US2004171115A1PendingUtilityA1
Multi-functional hematopoietic fusion proteins between sequence rearranged G-CSF receptor agonists and other hematopoietic factors
Priority: Oct 5, 1995Filed: Oct 27, 2003Published: Sep 2, 2004
Est. expiryOct 5, 2015(expired)· nominal 20-yr term from priority
Inventors:Yiqing FengNicholas StatenCharles M. BaumNeena SummersMaire Helena CaparonS. Christopher BauerLinda L. ZurfluhJohn MckearnBarbara Kure KleinStephen C. LeeCharles A. McwherterJudith G. Giri
A61K 38/00A61K 2039/51C07K 14/53A61K 48/00A61K 2035/124C07K 2319/75C07K 14/524C07K 14/5403C07K 2319/00C12N 15/62
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Claims
Abstract
Disclosed are novel multi-functional hematopoietic receptor agonist proteins, DNAs which encode the multi-functional hematopoietic receptor agonists proteins, methods of making the multi-functional hematopoietic receptor agonists proteins and methods of using the multi-functional hematopoietic receptor agonists proteins.
Claims
exact text as granted — not AI-modifiedWe claim the following:
1 . A hematopoietic protein comprising; an amino acid sequence of the formula:
R 1 -L 1 -R 2 , R 2 -L 1 -R 1 , R 1 -R 2 , or R 2 -R 1 wherein R 1 and R 2 are independently selected from the group consisting of: (I) A polypeptide comprising a modified human G-CSF amino acid sequence selected from the group consisting of:
(a) an amino acid sequence of the formula:
1 10 (SEQ ID NO: 1) Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro
wherein
Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly; Xaa at position 2 is Pro or Leu; Xaa at position 3 is Leu, Arg, Tyr or Ser; Xaa at position 13 is Phe, Ser, His, Thr or Pro; Xaa at position 16 is Lys, Pro, Ser, Thr or His; Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg; Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys; Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala; Xaa at position 24 is Ile, Pro, Tyr or Leu; Xaa at position 27 is Asp, or Gly; Xaa at position 30 is Ala, Ile, Leu or Gly; Xaa at position 34 is Lys or Ser; Xaa at position 36 is Cys or Ser; Xaa at position 42 is Cys or Ser; Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu; Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr; Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala; Xaa at position 47 is Leu or Thr; Xaa at position 49 is Leu, Phe, Arg or Ser; Xaa at position 50 is Leu, Ile, His, Pro or Tyr; Xaa at position 54 is Leu or His; Xaa at position 64 is Cys or Ser; Xaa at position 67 is Gln, Lys, Leu or Cys; Xaa at position 70 is Gln, Pro, Leu, Arg or Ser; Xaa at position 74 is Cys or Ser; Xaa at position 104 is Asp, Gly or Val; Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly; Xaa at position 115 is Thr, His, Leu or Ala; Xaa at position 120 is Gln, Gly, Arg, Lys or His Xaa at position 123 is Glu, Arg, Phe or Thr Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu; Xaa at position 146 is Arg or Gln; Xaa at position 147 is Arg or Gln; Xaa at position 156 is His, Gly or Ser; Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly; Xaa at position 162 is Glu, Leu, Gly or Trp; Xaa at position 163 is Val, Gly, Arg or Ala; Xaa at position 169 is Arg, Ser, Leu, Arg or Cys; Xaa at position 170 is His, Arg or Ser; wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can optionally be deleted from said modified human G-CSF amino acid sequence; and wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 38-39 39-40 40-41 41-42 42-43 43-44 45-46 48-49 49-50 52-53 53-54 54-55 55-56 56-57 57-58 58-59 59-60 60-61 61-62 62-63 63-64 64-65 65-66 66-67 67-68 68-69 69-70 70-71 71-72 91-92 92-93 93-94 94-95 95-96 96-97 97-98 98-99 99-100 123-124 124-125 125-126 126-127 128-129 128-129 129-130 130-131 131-132 132-133 133-134 134-135 135-136 136-137 137-138 138-139 139-140 140-141 141-142 or 142-143 respectively; and (b) an amino acid sequence of the formula: 1 10 (SEQ ID NO: 1) Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro wherein Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly; Xaa at position 2 is Pro or Leu; Xaa at position 3 is Leu, Arg, Tyr or Ser; Xaa at position 13 is Phe, Ser, His, Thr or Pro; Xaa at position 16 is Lys, Pro, Ser, Thr or His; Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg; Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys; Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala; Xaa at position 24 is Ile, Pro, Tyr or Leu; Xaa at position 27 is Asp, or Gly; Xaa at position 30 is Ala, Ile, Leu or Gly; Xaa at position 34 is Lys or Ser; Xaa at position 36 is Cys or Ser; Xaa at position 42 is Cys or Ser; Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu; Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr; Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala; Xaa at position 47 is Leu or Thr; Xaa at position 49 is Leu, Phe, Arg or Ser; Xaa at position 50 is Leu, Ile, His, Pro or Tyr; Xaa at position 54 is Leu or His; Xaa at position 64 is Cys or Ser; Xaa at position 67 is Gln, Lys, Leu or Cys; Xaa at position 70 is Gln, Pro, Leu, Arg or Ser; Xaa at position 74 is Cys or Ser; Xaa at position 104 is Asp, Gly or Val; Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly; Xaa at position 115 is Thr, His, Leu or Ala; Xaa at position 120 is Gln, Gly, Arg, Lys or His Xaa at position 123 is Glu, Arg, Phe or Thr Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu; Xaa at position 146 is Arg or Gln; Xaa at position 147 is Arg or Gln; Xaa at position 156 is His, Gly or Ser; Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly; Xaa at position 162 is Glu, Leu, Gly or Trp; Xaa at position 163 is Val, Gly, Arg or Ala; Xaa at position 169 is Arg, Ser, Leu, Arg or Cys; Xaa at position 170 is His, Arg or Ser, wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted; wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-terminus at amino acids: 2-3 10-11 12-13 18-19 122-123 158-159 169-170; (II) A polypeptide comprising; a modified human IL-3 amino acid sequence of the formula: Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO: 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130 wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu; wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence; wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and wherein the N-terminus is joined to the C-terminus directly or through a linker (L 2 ), capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 26-27 27-28 28-29 29-30 30-31 31-32 32-33 33-34 34-35 35-36 36-37 37-38 38-39 39-40 40-41 41-42 49-50 50-51 51-52 52-53 53-54 54-55 64-65 65-66 66-67 67-68 68-69 69-70 70-71 71-72 72-73 82-83 83-84 84-85 85-86 86-87 87-88 88-89 89-90 90-91 91-92 92-93 97-98 98-99 99-100 100-101 101-102 102-103 or 103-104 respectively; (III) A polypeptide comprising; a modified human c-mpl ligand amino acid sequence selected from the group consisiting of: (a) an amino acid sequence of the formula: SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO: 256) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlepheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 Arg 153 wherein Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met; Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn; and wherein the N-terminus is joined to the C-terminus directly or through a linker (L 2 ) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 26-27 27-28 28-29 29-30 30-31 32-33 33-34 34-35 36-37 37-38 38-39 40-41 41-42 42-43 43-44 44-45 46-47 47-48 48-49 50-51 51-52 52-53 53-54 54-55 55-56 56-57 57-58 58-59 59-60 78-79 79-80 80-81 81-82 82-83 83-84 84-85 85-86 86-87 87-88 88-89 108-109 109-110 110-111 111-112 112-113 113-114 114-115 115-116 116-117 117-118 118-119 119-120 120-121 121-122 122-123 123-124 124-125 125-126 126-127 or 127-128 respectively; and (b) an amino acid sequence of the formula: SerProAlaProProAlaXaaAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO: 283) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuXaaVal 135 140 145 150 Arg 153 wherein Xaa at position 7 is Ser or Ala; Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met; Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn; Xaa at position 151 is Ser or Ala, wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 26-27 27-28 28-29 29-30 30-31 32-33 33-34 34-35 36-37 37-38 38-39 40-41 41-42 42-43 43-44 44-45 46-47 47-48 48-49 50-51 51-52 52-53 53-54 54-55 55-56 56-57 57-58 58-59 59-60 78-79 79-80 80-81 81-82 82-83 83-84 84-85 85-86 86-87 87-88 88-89 108-109 109-110 110-111 111-112 112-113 113-114 114-115 115-116 116-117 117-118 118-119 119-120 120-121 121-122 122-123 123-124 124-125 125-126 126-127 or 127-128; (IV) A polypeptide comprising; a modified human IL-3 amino acid sequence of the formula: Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO: 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130 wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu, wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence; and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and (V) a colony stimulating factor; and wherein L 1 is a linker capable of linking R 1 to R 2 ; with the proviso that at least R 1 or R 2 is selected from the polypeptide of formula (I), (II), or (III); and said hematopoietic protein can optionally be immediately preceded by (methionine −1 ), (alanine −1 ) or (methionine −2 , alanine −1 ).
2 . A hematopoietic protein comprising; an amino acid sequence of the formula:
R 1 -L 1 -R 2 , R 2 -L 1 -R 1 , R 1 -R 2 , or R 2 -R 1 wherein R 1 and R 2 are independently selected from the group consisting of: (I) A polypeptide comprising; a modified human G-CSF amino acid sequence of the formula: 1 10 (SEQ ID NO: 1) Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro wherein Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly; Xaa at position 2 is Pro or Leu; Xaa at position 3 is Leu, Arg, Tyr or Ser; Xaa at position 13 is Phe, Ser, His, Thr or Pro; Xaa at position 16 is Lys, Pro, Ser, Thr or His; Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg; Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys; Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala; Xaa at position 24 is Ile, Pro, Tyr or Leu; Xaa at position 27 is Asp, or Gly; Xaa at position 30 is Ala, Ile, Leu or Gly; Xaa at position 34 is Lys or Ser; Xaa at position 36 is Cys or Ser; Xaa at position 42 is Cys or Ser; Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu; Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr; Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala; Xaa at position 47 is Leu or Thr; Xaa at position 49 is Leu, Phe, Arg or Ser; Xaa at position 50 is Leu, Ile, His, Pro or Tyr; Xaa at position 54 is Leu or His; Xaa at position 64 is Cys or Ser; Xaa at position 67 is Gln, Lys, Leu or Cys; Xaa at position 70 is Gln, Pro, Leu, Arg or Ser; Xaa at position 74 is Cys or Ser; Xaa at position 104 is Asp, Gly or Val; Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly; Xaa at position 115 is Thr, His, Leu or Ala; Xaa at position 120 is Gln, Gly, Arg, Lys or His Xaa at position 123 is Glu, Arg, Phe or Thr Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu; Xaa at position 146 is Arg or Gln; Xaa at position 147 is Arg or Gln; Xaa at position 156 is His, Gly or Ser; Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly; Xaa at position 162 is Glu, Leu, Gly or Trp; Xaa at position 163 is Val, Gly, Arg or Ala; Xaa at position 169 is Arg, Ser, Leu, Arg or Cys; Xaa at position 170 is His, Arg or Ser, wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can optionally be deleted from said modified human G-CSF amino acid sequence; and wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids; 38-39 39-40 40-41 41-42 42-43 43-44 45-46 48-49 49-50 52-53 53-54 54-55 55-56 56-57 57-58 58-59 59-60 60-61 61-62 62-63 63-64 64-65 65-66 66-67 67-68 68-69 69-70 70-71 71-72 91-92 92-93 93-94 94-95 95-96 96-97 97-98 98-99 99-100 123-124 124-125 125-126 126-127 128-129 128-129 129-130 130-131 131-132 132-133 133-134 134-135 135-136 136-137 137-138 138-139 139-140 140-141 141-142 or 142-143 respectively; (II) A polypeptide comprising; a modified human IL-3 amino acid sequence of the formula: Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO: 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130 wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe; Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu, wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence; wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and wherein the N-terminus is joined to the C-terminus directly or through a linker (L 2 ), capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 26-27 49-50 83-84 27-28 50-51 84-85 28-29 51-52 85-86 29-30 52-53 86-87 30-31 53-54 87-88 31-32 54-55 88-89 32-33 64-65 89-90 33-34 65-66 90-91 34-35 66-67 91-92 35-36 67-68 92-93 36-37 68-69 97-98 37-38 69-70 98-99 38-39 70-71 99-100 39-40 71-72 100-101 40-41 72-73 101-102 41-42 82-83 102-103 or 103-104 respectively; (III) A polypeptide comprising; a modified human c-mpl ligand amino acid sequence of the formula: SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO: 256) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 Arg 153 wherein Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met; Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn, wherein the N-terminus is joined to the C-terminus directly or through a linker (L 2 ) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 26-27 51-52 108-109 27-28 52-53 109-110 28-29 53-54 110-111 29-30 54-55 111-112 30-31 55-56 112-113 32-33 56-57 113-114 33-34 57-58 114-115 34-35 58-59 115-116 36-37 59-60 116-117 37-38 78-79 117-118 38-39 79-80 118-119 40-41 80-81 119-120 41-42 81-82 120-121 42-43 82-83 121-122 43-44 83-84 122-123 44-45 84-85 123-124 46-47 85-86 124-125 47-48 86-87 125-126 48-49 87-88 126-127 50-51 88-89 or 127-128 respectively; (IV) A polypeptide comprising; a modified human IL-3 amino acid sequence of the formula: Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO: 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130 wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu; wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence; and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and (V) a colony stimulating factor wherein L 1 is a linker capable of linking R 1 to R 2 with the proviso that at least R 1 or R 2 is selected from the polypeptide of formula (I), (II), or (III) and said hematopoietic protein can optionally be immediately preceded by (methionine −1 ), (alanine −1 ) or (methionine −2 , alanine −1 ).
3 . A hematopoietic protein comprising an amino acid sequence of the formula:
R 1 -L 1 -R 2 , R 2 -L 1 -R 1 , R 1 -R 2 , or R 2 -R 1 wherein R 1 and R 2 are independently selected from the group consisting of: (I) A polypeptide comprising; a modified human G-CSF amino acid sequence of the formula: 1 10 Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa (SEQ ID NO: 1) 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro wherein Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly; Xaa at position 2 is Pro or Leu; Xaa at position 3 is Leu, Arg, Tyr or Ser; Xaa at position 13 is Phe, Ser, His, Thr or Pro; Xaa at position 16 is Lys, Pro, Ser, Thr or His; Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg; Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys; Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala; Xaa at position 24 is Ile, Pro, Tyr or Leu; Xaa at position 27 is Asp, or Gly; Xaa at position 30 is Ala, Ile, Leu or Gly; Xaa at position 34 is Lys or Ser; Xaa at position 36 is Cys or Ser; Xaa at position 42 is Cys or Ser; Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu; Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr; Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala; Xaa at position 47 is Leu or Thr; Xaa at position 49 is Leu, Phe, Arg or Ser; Xaa at position 50 is Leu, Ile, His, Pro or Tyr; Xaa at position 54 is Leu or His; Xaa at position 64 is Cys or Ser; Xaa at position 67 is Gln, Lys, Leu or Cys; Xaa at position 70 is Gln, Pro, Leu, Arg or Ser; Xaa at position 74 is Cys or Ser; Xaa at position 104 is Asp, Gly or Val; Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly; Xaa at position 115 is Thr, His, Leu or Ala; Xaa at position 120 is Gln, Gly, Arg, Lys or His Xaa at position 123 is Glu, Arg, Phe or Thr Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu; Xaa at position 146 is Arg or Gln; Xaa at position 147 is Arg or Gln; Xaa at position 156 is His, Gly or Ser; Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly; Xaa at position 162 is Glu, Leu, Gly or Trp; Xaa at position 163 is Val, Gly, Arg or Ala; Xaa at position 169 is Arg, Ser, Leu, Arg or Cys; Xaa at position 170 is His, Arg or Ser, wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted from said modified human G-CSF amino acid sequence; and wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 38-39 62-63 123-124 39-40 63-64 124-125 40-41 64-65 125-126 41-42 65-66 126-127 42-43 66-67 128-129 43-44 67-68 128-129 45-46 68-69 129-130 48-49 69-70 130-131 49-50 70-71 131-132 52-53 71-72 132-133 53-54 91-92 133-134 54-55 92-93 134-135 55-56 93-94 135-136 56-57 94-95 136-137 57-58 95-96 137-138 58-59 96-97 138-139 59-60 97-98 139-140 60-61 98-99 140-141 61-62 99-100 141-142 or 142-143 respectively; (II) A polypeptide comprising; a modified human IL-3 amino acid sequence of the formula: Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO: 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130 wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu, wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence; and wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and wherein the N-terminus is joined to the C-terminus directly or through a linker (L 2 ) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 26-27 49-50 83-84 27-28 50-51 84-85 28-29 51-52 85-86 29-30 52-53 86-87 30-31 53-54 87-88 31-32 54-55 88-89 32-33 64-65 89-90 33-34 65-66 90-91 34-35 66-67 91-92 35-36 67-68 92-93 36-37 68-69 97-98 37-38 69-70 98-99 38-39 70-71 99-100 39-40 71-72 100-101 40-41 72-73 101-102 41-42 82-83 102-103 or 103-104 respectively; (III) A polypeptide comprising; a modified human c-mpl ligand amino acid sequence of the formula: SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO: 256) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 Arg 153 wherein Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met; Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn; and wherein the N-terminus is joined to the C-terminus directly or through a linker (L 2 ) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 52-53 108-109 53-54 109-110 54-55 110-111 55-56 111-112 56-57 112-113 57-58 113-114 58-59 114-115 59-60 115-116 78-79 116-117 79-80 117-118 80-81 118-119 81-82 119-120 82-83 120-121 83-84 121-122 84-85 122-123 85-86 123-124 86-87 124-125 87-88 125-126 88-89 126-127 or 127-128 respectively; (IV) A polypeptide comprising; a modified human IL-3 amino acid sequence of the formula: Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO: 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130 wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu, wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence; and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3, and (V) a colony stimulating factor; and wherein L 1 is a linker capable of linking R 1 to R 2 with the proviso that at least R 1 or R 2 is selected from the polypeptide of formula (I), (II), or (III); and said hematopoietic protein can optionally be immediately preceded by (methionine −1 ), (alanine −1 ) or (methionine −2 , alanine −1 ).
4 . The hematopoietic protein as recited in claim 1 wherein the polypeptide of (IV) is selected from the from the group consisting of:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO: 225)
Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu
Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu
Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO: 226)
Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu
Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu
Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO: 227)
Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu
Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu
Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
and
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO: 228)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln.
5 . The hematopoietic protein as recited in claim 2 wherein the polypeptide of (IV) is selected from the from the group consisting of:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO: 225)
Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu
Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu
Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO: 226)
Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu
Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu
Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO: 227)
Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu
Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu
Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
and
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO: 228)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln.
6 . The hematopoietic protein as recited in claim 3 wherein the polypeptide of (IV) is selected from the from the group consisting of:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO: 225)
Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu
Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu
Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO: 226)
Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu
Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu
Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO: 227)
Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu
Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu
Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
and
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO: 228)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln.
7 . A hematopoietic protein comprising; an amino acid sequence of the formula:
R 1 -L 1 -R 2 , R 2 -L 1 -R 1 , R 1 -R 2 , or R 2 -R 1 wherein R 1 is a polypeptide comprising; a modified human G-CSF amino acid sequence of the formula: 1 10 Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa (SEQ ID NO: 1) 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro wherein Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly; Xaa at position 2 is Pro or Leu; Xaa at position 3 is Leu, Arg, Tyr or Ser; Xaa at position 13 is Phe, Ser, His, Thr or Pro; Xaa at position 16 is Lys, Pro, Ser, Thr or His; Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg; Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys; Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala; Xaa at position 24 is Ile, Pro, Tyr or Leu; Xaa at position 27 is Asp, or Gly; Xaa at position 30 is Ala, Ile, Leu or Gly; Xaa at position 34 is Lys or Ser; Xaa at position 36 is Cys or Ser; Xaa at position 42 is Cys or Ser; Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu; Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr; Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala; Xaa at position 47 is Leu or Thr; Xaa at position 49 is Leu, Phe, Arg or Ser; Xaa at position 50 is Leu, Ile, His, Pro or Tyr; Xaa at position 54 is Leu or His; Xaa at position 64 is Cys or Ser; Xaa at position 67 is Gln, Lys, Leu or Cys; Xaa at position 70 is Gln, Pro, Leu, Arg or Ser; Xaa at position 74 is Cys or Ser; Xaa at position 104 is Asp, Gly or Val; Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly; Xaa at position 115 is Thr, His, Leu or Ala; Xaa at position 120 is Gln, Gly, Arg, Lys or His Xaa at position 123 is Glu, Arg, Phe or Thr Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu; Xaa at position 146 is Arg or Gln; Xaa at position 147 is Arg or Gln; Xaa at position 156 is His, Gly or Ser; Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly; Xaa at position 162 is Glu, Leu, Gly or Trp; Xaa at position 163 is Val, Gly, Arg or Ala; Xaa at position 169 is Arg, Ser, Leu, Arg or Cys; Xaa at position 170 is His, Arg or Ser, wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted from said modified human G-CSF amino acid sequence; and wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 38-39 62-63 123-124 39-40 63-64 124-125 40-41 64-65 125-126 41-42 65-66 126-127 42-43 66-67 128-129 43-44 67-68 128-129 45-46 68-69 129-130 48-49 69-70 130-131 49-50 70-71 131-132 52-53 71-72 132-133 53-54 91-92 133-134 54-55 92-93 134-135 55-56 93-94 135-136 56-57 94-95 136-137 57-58 95-96 137-138 58-59 96-97 138-139 59-60 97-98 139-140 60-61 98-99 140-141 61-62 99-100 141-142 or 142-143 respectively, wherein R 2 is a polypeptide comprising; a modified human IL-3 amino acid sequence of the formula: Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO: 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130 wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu, wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human interleukin-3 amino acid sequence; and wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3 and wherein the N-terminus is joined to the C-terminus directly or through a linker (L 2 ) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 26-27 49-50 83-84 27-28 50-51 84-85 28-29 51-52 85-86 29-30 52-53 86-87 30-31 53-54 87-88 31-32 54-55 88-89 32-33 64-65 89-90 33-34 65-66 90-91 34-35 66-67 91-92 35-36 67-68 92-93 36-37 68-69 97-98 37-38 69-70 98-99 38-39 70-71 99-100 39-40 71-72 100-101 40-41 72-73 101-102 41-42 82-83 102-103 or 103-104 respectively; wherein L 1 is a linker capable of linking R 1 to R 2 and said hematopoietic protein can optionally be immediately preceded by (methionine −1 ), (alanine −1 ) or (methionine −2 , alanine −1 ).
8 . A hematopoietic protein comprising; an amino acid sequence of the formula:
R 1 -L 1 -R 2 , R 2 -L 1 -R 1 , R 1 -R 2 , or R 2 -R 1 wherein R 1 is a polypeptide comprising; a modified human G-CSF amino acid sequence of the formula: 1 10 Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa (SEQ ID NO: 1) 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro wherein Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly; Xaa at position 2 is Pro or Leu; Xaa at position 3 is Leu, Arg, Tyr or Ser; Xaa at position 13 is Phe, Ser, His, Thr or Pro; Xaa at position 16 is Lys, Pro, Ser, Thr or His; Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg; Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys; Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala; Xaa at position 24 is Ile, Pro, Tyr or Leu; Xaa at position 27 is Asp, or Gly; Xaa at position 30 is Ala, Ile, Leu or Gly; Xaa at position 34 is Lys or Ser; Xaa at position 36 is Cys or Ser; Xaa at position 42 is Cys or Ser; Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu; Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr; Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala; Xaa at position 47 is Leu or Thr; Xaa at position 49 is Leu, Phe, Arg or Ser; Xaa at position 50 is Leu, Ile, His, Pro or Tyr; Xaa at position 54 is Leu or His; Xaa at position 64 is Cys or Ser; Xaa at position 67 is Gln, Lys, Leu or Cys; Xaa at position 70 is Gln, Pro, Leu, Arg or Ser; Xaa at position 74 is Cys or Ser; Xaa at position 104 is Asp, Gly or Val; Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly; Xaa at position 115 is Thr, His, Leu or Ala; Xaa at position 120 is Gln, Gly, Arg, Lys or His Xaa at position 123 is Glu, Arg, Phe or Thr Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu; Xaa at position 146 is Arg or Gln; Xaa at position 147 is Arg or Gln; Xaa at position 156 is His, Gly or Ser; Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly; Xaa at position 162 is Glu, Leu, Gly or Trp; Xaa at position 163 is Val, Gly, Arg or Ala; Xaa at position 169 is Arg, Ser, Leu, Arg or Cys; Xaa at position 170 is His, Arg or Ser; wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted from said modified human G-CSF amino acid sequence and wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 38-39 62-63 123-124 39-40 63-64 124-125 40-41 64-65 125-126 41-42 65-66 126-127 42-43 66-67 128-129 43-44 67-68 128-129 45-46 68-69 129-130 48-49 69-70 130-131 49-50 70-71 131-132 52-53 71-72 132-133 53-54 91-92 133-134 54-55 92-93 134-135 55-56 93-94 135-136 56-57 94-95 136-137 57-58 95-96 137-138 58-59 96-97 138-139 59-60 97-98 139-140 60-61 98-99 140-141 61-62 99-100 141-142 or 142-143 respectively; R 2 is a polypeptide comprising a modified human IL-3 amino acid sequence of the formula: Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO:2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130 wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu, wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus; and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3 and L 1 is a linker capable of linking R 1 to R 2 and additionally said hematopoietic protein can be immediately preceded by (methionine −1 ), (alanine −1 ) or (methionine −2 , alanine −1 ).
9 . A hematopoietic protein comprising an amino acid sequence of the formula:
R 1 -L 1 -R 2 , R 2 -L 1 -R 1 , R 1 -R 2 , or R 2 -R 1 wherein R 1 is a polypeptide comprising; a modified human G-CSF amino acid sequence of the formula: 1 10 (SEQ ID NO:1) Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro wherein Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly; Xaa at position 2 is Pro or Leu; Xaa at position 3 is Leu, Arg, Tyr or Ser; Xaa at position 13 is Phe, Ser, His, Thr or Pro; Xaa at position 16 is Lys, Pro, Ser, Thr or His; Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg; Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys; Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala; Xaa at position 24 is Ile, Pro, Tyr or Leu; Xaa at position 27 is Asp, or Gly; Xaa at position 30 is Ala, Ile, Leu or Gly; Xaa at position 34 is Lys or Ser; Xaa at position 36 is Cys or Ser; Xaa at position 42 is Cys or Ser; Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu; Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr; Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala; Xaa at position 47 is Leu or Thr; Xaa at position 49 is Leu, Phe, Arg or Ser; Xaa at position 50 is Leu, Ile, His, Pro or Tyr; Xaa at position 54 is Leu or His; Xaa at position 64 is Cys or Ser; Xaa at position 67 is Gln, Lys, Leu or Cys; Xaa at position 70 is Gln, Pro, Leu, Arg or Ser; Xaa at position 74 is Cys or Ser; Xaa at position 104 is Asp, Gly or Val; Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly; Xaa at position 115 is Thr, His, Leu or Ala; Xaa at position 120 is Gln, Gly, Arg, Lys or His Xaa at position 123 is Glu, Arg, Phe or Thr Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu; Xaa at position 146 is Arg or Gln; Xaa at position 147 is Arg or Gln; Xaa at position 156 is His, Gly or Ser; Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly; Xaa at position 162 is Glu, Leu, Gly or Trp; Xaa at position 163 is Val, Gly, Arg or Ala; Xaa at position 169 is Arg, Ser, Leu, Arg or Cys; Xaa at position 170 is His, Arg or Ser, wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted from said modified human G-CSF amino acid sequence and wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 38-39 62-63 123-124 39-40 63-64 124-125 40-41 64-65 125-126 41-42 65-66 126-127 42-43 66-67 128-129 43-44 67-68 128-129 45-46 68-69 129-130 48-49 69-70 130-131 49-50 70-71 131-132 52-53 71-72 132-133 53-54 91-92 133-134 54-55 92-93 134-135 55-56 93-94 135-136 56-57 94-95 136-137 57-58 95-96 137-138 58-59 96-97 138-139 59-60 97-98 139-140 60-61 98-99 140-141 61-62 99-100 141-142 or 142-143 respectively; R 2 is a polypeptide comprising a modified human c-mpl ligand amino acid sequence of the formula: SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO:256) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 Arg wherein Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met; Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn, and wherein the N-terminus is joined to the C-terminus directly or through a linker (L 2 ) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 26-27 51-52 108-109 27-28 52-53 109-110 28-29 53-54 110-111 29-30 54-55 111-112 30-31 55-56 112-113 32-33 56-57 113-114 33-34 57-58 114-115 34-35 58-59 115-116 36-37 59-60 116-117 37-38 78-79 117-118 38-39 79-80 118-119 40-41 80-81 119-120 41-42 81-82 120-121 42-43 82-83 121-122 43-44 83-84 122-123 44-45 84-85 123-124 46-47 85-86 124-125 47-48 86-87 125-126 48-49 87-88 126-127 50-51 88-89 or 127-128; wherein L 1 is a linker capable of linking R 1 to R 2 and additionally said hematopoietic protein can be immediately preceded by (methionine −1 ), (alanine −1 ) or (methionine −2 , alanine −1 ).
10 . A hematopoietic protein comprising; an amino acid sequence of the formula:
R 1 —L 1 —R 2 , R 2 —L 1 —R 1 , R 1 —R 2 , or R 2 —R 1 wherein R 1 is a polypeptide comprising a modified human c-mpl ligand amino acid sequence of the formula: SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO:256) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 Arg 153 wherein Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met; Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn, and wherein the N-terminus is joined to the C-terminus directly or through a linker (L 2 ) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 26-27 27-28 28-29 29-30 30-31 32-33 33-34 34-35 36-37 37-38 38-39 40-41 41-42 42-43 43-44 44-45 46-47 47-48 48-49 50-51 51-52 52-53 53-54 54-55 55-56 56-57 57-58 58-59 59-60 78-79 79-80 80-81 81-82 82-83 83-84 84-85 85-86 86-87 87-88 88-89 108-109 109-110 110-111 111-112 112-113 113-114 114-115 115-116 116-117 117-118 118-119 119-120 120-121 121-122 122-123 123-124 124-125 125-126 126-127 or 127-128; wherein R 2 is a polypeptide comprising a modified human IL-3 amino acid sequence of the formula: Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO:2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130 wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa at position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu, or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, or Ser; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu, wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human interleukin-3 amino acid sequence; and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; wherein L 1 is a linker capable of linking R 1 to R 2 ; and said hematopoietic protein can optionally be immediately preceded by (methionine −1 ), (alanine −1 ) or (methionine −2 , alanine −1 ).
11 . The hematopoeitic protein of claim 8 or 10 wherein R 2 is selected from the group consisting of:
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO:225)
Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu
Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu
Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO:226)
Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu
Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu
Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO:227)
Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu
Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu
Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln;
and
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:228)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln.
12 . A hematopoietic protein comprising; an amino acid sequence of the formula:
R 1 -L 1 -R 2 , R 2 -L 1 -R 1 , R 1 -R 2 , or R 2 -R 1 wherein R 1 is a polypeptide comprising; a modified human c-mpl ligand amino acid sequence of the formula: SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO:256) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 Arg 153 wherein Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met; Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met; Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn; and wherein the N-terminus is joined to the C-terminus directly or through a linker (L 2 ) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids: 26-27 27-28 28-29 29-30 30-31 32-33 33-34 34-35 36-37 37-38 38-39 40-41 41-42 42-43 43-44 44-45 46-47 47-48 48-49 50-51 51-52 52-53 53-54 54-55 55-56 56-57 57-58 58-59 59-60 78-79 79-80 80-81 81-82 82-83 83-84 84-85 85-86 86-87 87-88 88-89 108-109 109-110 110-111 111-112 112-113 113-114 114-115 115-116 116-117 117-118 118-119 119-120 120-121 121-122 122-123 123-124 124-125 125-126 126-127 or 127-128 respectively; wherein R 2 is G-CSF or G-CSF Ser 17 wherein L 1 is a linker capable of linking R 1 to R 2 ; and said hematopoietic protein can optionally be immediately preceded by (methionine −1 ), (alanine −1 ) or (methionine −2 , alanine −1 ).
13 . The hematopoietic protein as recited in claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 or 12 wherein said linker (L 2 ) is selected from the group consisting of;
GlyGlyGlySer;
(SEQ ID NO:12)
GlyGlyGlySerGlyGlyGlySer;
(SEQ ID NO:242)
GlyGlyGlySerGlyGlyGlySerGlyGlyGly
(SEQ ID NO:243)
Ser;
SerGlyGlySerGlyGlySer;
(SEQ ID NO:244)
GluPheGlyAsnMetAla;
(SEQ ID NO:245)
GluPheGlyGlyAsnMetAla;
(SEQ ID NO:246)
GluPheGlyGlyAsnGlyGlyAsnMetAla;
(SEQ ID NO:247)
and
GlyGlySerAspMetAlaGly.
(SEQ ID NO:248)
14 . The hematopoietic protein as recited in claim 11 wherein said linker (L2) is selected from the group consisting of:
GlyGlyGlySer;
(SEQ ID NO:12)
GlyGlyGlySerGlyGlyGlySer;
(SEQ ID NO:242)
GlyGlyGlySerGlyGlyGlySerGlyGlyGly
(SEQ ID NO:243)
Ser;
SerGlyGlySerGlyGlySer;
(SEQ ID NO:244)
GluPheGlyAsnMetAla;
(SEQ ID NO:245)
GluPheGlyGlyAsnMetAla;
(SEQ ID NO:246)
GluPheGlyGlyAsnGlyGlyAsnMetAla;
(SEQ ID NO:247)
and
GlyGlySerAspMetAlaGly.
(SEQ ID NO:248)
15 . The hematopoietic protein as recited in claim 1 wherein said protein is selected from the group consisting of:
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:166)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu Cys
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys
Ala Thr;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:167)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu Cys
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys
Ala Thr;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:168)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Pro Glu Leu Gly
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly
Ile Ser;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:169)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu Gly
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly
Ile Ser;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:170)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Met Ala Pro Ala
Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu
Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val
Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser
Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu
His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu
Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu
Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu
Leu Gly;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:171)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro Ala
Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu
Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val
Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser
Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu
His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu
Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu
Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu
Leu Gly;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:172)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly Ala
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg
Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser
Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln
Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys
Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly
Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln
Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr
Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu
Gln Pro;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:173)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg
Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser
Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln
Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys
Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly
Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln
Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr
Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu
Gln Pro;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:177)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe Gln
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly
Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu
Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala
Phe Ala;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:175)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Ala Phe Gln
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser
Gly Gly Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly
Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu
Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala
Phe Ala;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:176)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Tyr Lys Leu Cys
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu
Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu
Lys Leu Cys Ala Thr;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:177)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Tyr Lys Leu Cys
His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro
Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu
Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu
Lys Leu Cys Ala Thr;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:179)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Glu Leu Gly
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr
Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu
Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala
Leu Glu Gly Ile Ser;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:181)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro Ala
Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe
Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu
Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala
Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu
Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro
Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu
Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln
Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr
Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln
Met Glu Glu Leu Gly;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:182)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gln Gly Ala
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg
Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala Ser
Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg
Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala
Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His
Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln
Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu
Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro
Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp
Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala
Pro Ala Leu Gln Pro;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:183)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg
Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala Ser
Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg
Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala
Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His
Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln
Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu
Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro
Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp
Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala
Pro Ala Leu Gln Pro;
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
(SEQ ID NO:184)
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile
Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr
Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp
Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu
Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro
Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Ser Ala Phe Gln
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr
Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys
Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu
Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu
Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala
Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu
Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met
Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala
Met Pro Ala Phe Ala;
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
(SEQ ID NO:194)
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaTyrLysLeuCysHisProGluGluLeuValLeuLeu
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGly
ValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHis
LeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeu
ProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAla
AlaLeuGlnGluLysLeuCysAlaThr;
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
(SEQ ID NO:195)
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaProGluLeuGlyProThrLeuAspThrLeuGlnLeu
AspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaPro
AlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAla
GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeu
ArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSer
SerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAsp
GlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeu
ValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGln
AlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly
LeuLeuGlnAlaLeuGluGlyIleSer;
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
(SEQ ID NO:196)
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuVal
AlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGln
ProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSer
PheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGln
GluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHis
SerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAla
GlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeu
GluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAsp
PheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro
ThrGlnGlyAlaMetProAlaPheAla;
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
(SEQ ID NO:197)
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaMetAlaProAlaLeuGlnProThrGlnGlyAlaMet
ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeu
GlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGly
SerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLys
SerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys
AlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlyIle
ProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer
GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSer
ProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThr
IleTrpGlnGlnMetGluGluLeuGly;
MetAlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAla
(SEQ ID NO:198)
ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsn
LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer
GlyIleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro
SerArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr
PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeu
GlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLys
IleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHis
ProGluGluLeuValLeuLeuGlyHisSerLeuGlyIleProTrpAlaProLeuSerSer
CysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPhe
LeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlyIleSerProGluLeuGlyProThrLeu
AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrIleTrpGlnGlnMetGluGlu
LeuGlyMetAlaProAlaLeuGlnPro;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO:209)
Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu
Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu
Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Gly Pro Thr Cys Leu
Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu
Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly
Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe
Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly
Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala Ser
Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu
Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu
Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe
Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln
Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala
Ala Arg Gly Gln Leu;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO:210)
Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu
Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu
Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Gly Thr Gln Leu Pro
Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala Ile Phe
Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu Met
Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn
Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser
Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln
Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala
Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr
Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly
Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser
Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala
Leu Gln Ser Leu Leu;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO:211)
Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu
Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu
Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Gly Arg Thr Thr Ala
His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu
Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu
Cys Val Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro
Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His
Val Leu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu
Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu
Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly
Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln
Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly
Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr
Gln Leu Pro Pro Gln;
Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys
(SEQ ID NO:212)
Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu
Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu
Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly
Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala
Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp
Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu
Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Ser Pro
Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro
Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala His Lys Asp Pro
Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val
Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu
Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu
Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser
Arg Leu Ser Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val
Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln
Met Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu
Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gln Leu Gly Pro Thr
Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu
Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro
Gln Gly Arg Thr Thr;
Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met
(SEQ ID NO:186)
Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala
Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg
Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln
Gln Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp Glu Ile Ile
His His Leu Lys Arg Pro Pro Ala Pro Leu Tyr Val Glu Gly Gly
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly
Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met
Ala Pro Ala Leu Gln Pro;
Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys
(SEQ ID NO:187)
Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile
Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr
Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg
Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp
Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu
Ser Phe Val Arg Ala Val Lys Asn Leu Glu Tyr Val Glu Gly Gly
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly
Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met
Ala Pro Ala Leu Gln Pro;
Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln
(SEQ ID NO:189)
Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln
Ala Gln Glu Gln Gln Gly Gly Gly Ser Asn Cys Ser Ile Met Ile
Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu
Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp
Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val
Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn
Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Tyr Val Glu Gly Gly
Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn
Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Ser Gly Gly
Ser Gly Gly Ser Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val
Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys
Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly
His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly
Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser
Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met
Ala Pro Ala Leu Gln Pro;
Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met
(SEQ ID NO:190)
Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala
Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg
Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg
His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu
Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln
Gln Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asn Cys
Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro
Ala Pro Leu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro
Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu
Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg
His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro;
Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys
(SEQ ID NO:191)
Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile
Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr
Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Gly Gly Gly Ser
Gly Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser Ile Met Ile Asp
Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp
Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp Arg
Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys
Asn Leu Glu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro
Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu
Ser His Lys Ser Pro Asn Met Ala Thr Gln Gly Ala Met Pro Ala
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg
His Leu Ala Gln Pro Ser Gly Gly Ser Gly Gly Ser Gln Ser Phe
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro;
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu
(SEQ ID NO:199)
ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsn
LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer
AlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro
ThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThr
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe
LeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu
LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer
LeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly
CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu
GlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe
AlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro;
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu
(SEQ ID NO:200)
ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsn
LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer
AlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro
ThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThr
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro
GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla
LeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
GlnPro;
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu
(SEQ ID NO:201)
ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsn
LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer
AlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro
ThrArgHisProIleIleIleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThr
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe
LeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu
LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer
LeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly
CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu
GlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe
AlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro;
MetAlaAsnCysSerAsnMetIleAspGluIleIleThrHisLeuLysGlnProProLeu
(SEQ ID NO:202)
ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsn
LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer
AlaIleGluSerIleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro
ThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThr
PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly
SerProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGlu
SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe
GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer
TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro
GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla
LeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu
GlyHisSerLeuGlyIleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln
LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln
AlaLeuGluGlyIleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal
AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu
GlnPro;
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
(SEQ ID NO:221)
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln
GlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeu
ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe
GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu
ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro
ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
AlaArgGlyGlnLeu;
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
(SEQ ID NO:222)
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAla
ProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHis
SerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAla
ValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIle
LeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyPro
ThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAla
LeuGlnSerLeuLeu;
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
(SEQ ID NO:223
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly
GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln
GlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeu
ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe
GlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeu
SerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluVal
HisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys
ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu
GlyValMetAlaAlaArgGlyGlnLeu;
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
(SEQ ID NO: 234)
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys
AspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu
MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMet
AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal
LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys
AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly
GlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu
LeuLeuGlyAlaLeuGlnSerLeuLeu;
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
(SEQ ID NO:235)
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeu
SerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr
LeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAla
CysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeu
SerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPhe
SerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAla
ValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeu
SerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSer
LeuLeuGlyThrGlnLeuProProGln;
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
(SEQ ID NO:236)
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg
GluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArg
ValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysPro
GluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGlu
TrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeu
LeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeu
GlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThr
GlnLeuProProGlnGlyArgThrThr;
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
(SEQ ID NO:237)
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly
GlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis
ProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr
GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly
ValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu
SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro
ProGlnGlyArgThrThrAlaHisLys;
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
(SEQ ID NO:238)
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysVal
ArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGly
GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu
ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro
ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly
ArgThrThrAlaHisLysAspProAsn;
AlaAsnCysSerIleMetIleAspGluIleIleHisHisLeuLysArgProProAlaPro
(SEQ ID NO:239)
LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerIleLeuMetAspArgAsnLeu
ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly
IleGluAlaIleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer
ArgHisProIleIleIleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe
TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer
ProGlyGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSer
HisLysSerProAsnMetAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArg
GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly
GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu
ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro
ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu
GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla
AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln
ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAla
HisLys;
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:271)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
91
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Leu Gly
151
Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu
166
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
181
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu
196
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
211
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
226
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly
241
Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp
256
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu
271
Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala
286
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala
301
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg
316
His Leu Ala Gln Pro Asp Met Ala Thr Pro;
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:272)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
31
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Leu Gly
151
Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu
176
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
191
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu
206
Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys
221
Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
236
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly
251
Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp
266
Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu
281
Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala
296
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala
311
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg
326
His Leu Ala Gln Pro Asp Met Ala Thr Pro;
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:273)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
91
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Phe Leu
151
Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala
166
Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro
181
Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala
196
Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys
211
Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu
226
Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp
241
Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln
256
Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln
271
Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly
286
Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser
301
Tyr Arg Val Leu Arg His Leu Ala Gln Pro Asp Met Ala Thr Pro
316
Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser;
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:274)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
91
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Glu Gln
151
Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu
166
Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu
181
Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro
196
Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser
211
Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile
226
Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val
241
Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly
256
Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe
271
Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser
286
His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His
301
Leu Ala Gln Pro Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Ser
316
Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu;
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:275)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
91
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Leu Leu
151
Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro
166
Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser
181
Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile
196
Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val
211
Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly
226
Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe
241
Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser
256
His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His
271
Leu Ala Gln Pro Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Ser
286
Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys
301
Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr
316
Tyr Lys Leu Cys His Pro Glu Glu Leu Val;
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:276)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
91
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Pro Leu
151
Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser
166
Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala
181
Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu
196
Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met
211
Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala
226
Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val
241
Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg
256
Val Leu Arg His Leu Ala Gln Pro Asp Met Ala Thr Pro Leu Gly
271
Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu
286
Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
301
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu
316
Leu Gly His Ser Leu Gly Ile Pro Trp Ala;
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:277)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
91
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Gln Ala
151
Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe
166
Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu
181
Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe
196
Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro
211
Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala
226
Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln
241
Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln
256
Pro Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln
271
Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly
286
Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu
301
Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile
316
Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser;
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:278)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
91
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Leu Gln
151
Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr
166
Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly
181
Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr
196
Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu
211
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln
226
Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe
241
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Asp
256
Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe
271
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly
286
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His
301
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp
316
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala;
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:279)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
91
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Leu Ala
151
Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly
166
Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr
181
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile
196
Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro
211
Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg
226
Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
241
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Asp Met Ala
256
Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu
271
Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala
286
Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu
301
Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro
316
Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln;
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:280)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
91
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Glu Leu
151
Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala
166
Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala
181
Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg
196
His Leu Ala Gln Pro Asp Met Ala Thr Pro Leu Gly Pro Ala Ser
211
Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg
226
Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala
241
Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His
256
Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln
271
Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu
286
Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro
301
Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp
316
Phe Ala Thr Thr Ile Trp Gln Gln Met Glu;
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:281)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
91
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Gly Met
151
Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala
166
Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His
181
Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu
196
Ala Gln Pro Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu
211
Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile
226
Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr
241
Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu
256
Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu
271
Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu
286
Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu
301
Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala
316
Thr Thr Ile Trp Gln Gln Met Glu Glu Leu;
and
1
Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu
(SEQ ID NO:282)
16
Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp
31
Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn
46
Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser
61
Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser
76
Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly
91
Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr
106
Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly
121
Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser
136
Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Phe
151
Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Asp
166
Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe
181
Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly
196
Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His
211
Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp
226
Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly
241
Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu
256
Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu
271
Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp
286
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr
301
Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala
316
Gly Gly Val Leu Val Ala Ser His Leu Gln.
16 . The hematopoeitic protein as recieted in claim 1 wherein said c-mpl receptor agonist is selected from the group consisiting of:
MetAlaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis
(SEQ ID NO: 284)
LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuAlaValArg
GluPheGlyGlyAsnMetAlaSerProAlaProProAlaAlaAspLeuArgValLeuSer
LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis
ProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr
GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly
ValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu
SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro
ProGln;
and
MetAlaGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu
(SEQ ID NO: 285)
LeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThr
AlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHisLeuLeuArgGlyLysVal
ArgPheLeuMetLeuValGlyGlySerThrLeuAlaValArgGluPheGlyGlyAsnMet
AlaSerProAlaProProAlaAlaAspLeuArgValLeuSerLysLeuLeuArgAspSer
HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal
LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys
AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly
GlnLeu
17 . The hematopoietic protein of claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 or 12 wherein said colony stimulating factor is selected from the group consisting of GM-CSF, G-CSF, G-CSF Ser 17 , c-mpl ligand (TPO), M-CSF, erythropoietin (EPO), IL-1, IL-4, IL-2, IL-3, IL-5, IL 6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, LIF, flt3/flk2 ligand, human growth hormone, B-cell growth factor, B-cell differentiation factor, eosinophil differentiation factor and stem cell factor (SCF).
18 . The hematopoietic protein of claim 17 wherein said colony stimulating factor is selected from the group consisting of G-CSF, G-CSF Ser 17 and c-mpl ligand (TPO).
19 . A nucleic acid molecule encoding said hematopoietic protein of claim 1 .
20 . A nucleic acid molecule encoding said hematopoietic protein of claim 2 .
21 . A nucleic acid molecule encoding said hematopoietic protein of claim 3 .
22 . A nucleic acid molecule encoding said hematopoietic protein of claim 4 .
23 . A nucleic acid molecule encoding said hematopoietic protein of claim 5 .
24 . A nucleic acid molecule encoding said hematopoietic protein of claim 6 .
25 . A nucleic acid molecule encoding said hematopoietic protein of claim 7 .
26 . A nucleic acid molecule encoding said hematopoietic protein of claim 8 .
27 . A nucleic acid molecule encoding said hematopoietic protein of claim 9 .
28 . A nucleic acid molecule encoding said hematopoietic protein of claim 10 .
29 . A nucleic acid molecule encoding said hematopoietic protein of claim 11 .
30 . A nucleic acid molecule encoding said hematopoietic protein of claim 12 .
31 . A nucleic acid molecule encoding said hematopoietic protein of claim 13 .
32 . A nucleic acid molecule encoding said hematopoietic protein of claim 14 .
33 . A nucleic acid molecule encoding said hematopoietic protein of claim 15 .
34 . A nucleic acid molecule encoding said hematopoietic protein of claim 16 .
35 . A nucleic acid molecule encoding said hematopoietic protein of claim 17 .
36 . The nucleic acid molecule according to claim 30 selected from group consisting of:
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 94)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
GTGGTTCTGG
CGGCGGCTCC
AACATGGCTT
401
ACAAGCTGTG
CCACCCCGAG
GAGCTGGTGC
TGCTCGGACA
CTCTCTGGGC
451
ATCCCCTGGG
CTCCCCTGAG
CTCCTGCCCC
AGCCAGGCCC
TGCAGCTGGC
501
AGGCTGCTTG
AGCCAACTCC
ATAGCGGCCT
TTTCCTCTAC
CAGGGGCTCC
551
TGCAGGCCCT
GGAAGGGATA
TCCCCCGAGT
TGGGTCCCAC
CTTGGACACA
601
CTGCAGCTGG
ACCTCCCCGA
CTTTGCCACC
ACCATCTGGC
AGCAGATGGA
651
AGAACTGGGA
ATGGCCCCTG
CCCTGCAGCC
CACCCAGGGT
GCCATGCCGG
701
CCTTCGCCTC
TGCTTTCCAC
CGCCGGGCAG
GAGGGGTCCT
GGTTGCTAGC
751
CATCTGCAGA
GCTTCCTGGA
GGTGTCGTAC
CGCGTTCTAC
GCCACCTTGC
801
GCAGCCCTCT
GGCGGCTCTG
GCGGCTCTCA
GAGCTTCCTG
CTCAAGTCTT
851
TAGAGCAAGT
GAGAAACATC
CAGGGCGATG
GCGCAGCGCT
CCAGGAGAAG
901
CTGTGTGCCA
CCTAATAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 95)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAACCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTTACAAG
451
CTGTGCCACC
CCGAGGAGCT
GGTGCTGCTC
GGACACTCTC
TGGGCATCCC
501
CTGGGCTCCC
CTGAGCTCCT
GCCCCAGCCA
GGCCCTGCAG
CTGGCAGGCT
551
GCTTGAGCCA
ACTCCATAGC
GGCCTTTTCC
TCTACCAGGG
GCTCCTGCAG
601
GCCCTGCAAG
GGATATCCCC
CGAGTTGGGT
CCCACCTTGG
ACACACTGCA
651
GCTGGACGTC
GCCGACTTTG
CCACCACCAT
CTGGCAGCAG
ATGGAAGAAC
701
TGGGAATGGC
CCCTGCCCTG
CAGCCCACCC
AGGGTGCCAT
GCCGGCCTTC
751
GCCTCTGCTT
TCCAGCGCCG
GGCAGGAGGG
GTCCTGGTTG
CTAGCCATCT
801
GCAGAGCTTC
CTGGAGGTGT
CGTACCGCGT
TCTACGCCAC
CTTGCGCAGC
851
CCTCTGGCGG
CTCTGGCGGC
TCTCAGAGCT
TCCTGCTCAA
GTCTTTAGAG
901
CAAGTGAGAA
AGATCCAGGG
CGATGGCGCA
GCGCTCCAGG
AGAAGCTGTG
951
TGCCACCTAA
TAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 96)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
GTGGTTCTGG
CGGCGGCTCC
AACATGGCTC
401
CCGAGTTGGG
TCCCACCTTG
GACACACTGC
AGCTGGACGT
CGCCGACTTT
451
GCCACCACCA
TCTGGCAGCA
GATGGAAGAA
CTGGGAATGG
CCCCTGCCCT
501
GCAGCCCACC
CAGGGTGCCA
TGCCGGCCTT
CGCCTCTGCT
TTCCAGCGCC
551
GGGCAGGAGG
GGTCCTGGTT
GCTAGCCATC
TGCAGAGCTT
CCTGGAGGTG
601
TCGTACCGCG
TTCTACGCCA
CCTTGCGCAG
CCCTCTGGCG
GCTCTGGCGG
651
CTCTCAGAGC
TTCCTGCTCA
AGTCTTTAGA
GCAAGTGAGA
AAGATCCAGG
701
GCGATGGCGC
AGCGCTCCAG
GAGAAGCTGT
GTGCCACCTA
CAAGCTGTGC
751
CACCCCGACG
AGCTGGTGCT
GCTCGGACAC
TCTCTGGGCA
TCCCCTGGGC
801
TCCCCTGAGC
TCCTGCCCCA
GCCAGGCCCT
GCAGCTGGCA
GGCTGCTTGA
851
GCCAACTCCA
TAGCGGCCTT
TTCCTCTACC
AGGGGCTCCT
GCAGGCCCTG
901
GAAGGGATAT
CCTAATAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAC
(SEQ ID NO: 97)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCCAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCACGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGC
TTACCCTTGA
GCAAGCCCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTCCCGAG
451
TTGGGTCCCA
CCTTGGACAC
ACTGCAGCTG
GACGTCGCCG
ACTTTGCCAC
501
CACCATCTGG
CAGCAGATGG
AAGAACTGGG
AATGGCCCCT
GCCCTGCAGC
551
CCACCCAGGG
TGCCATGCCG
GCCTTCCCCT
CTGCTTTCCA
GCGCCGGGCA
601
GGAGGGCTCC
TGGTTGCTAG
CCATCTGCAG
AGCTTCCTGG
AGGTGTCGTA
651
CCGCGTTCTA
CGCCACCTTG
CGCAGCCCTC
TGGCGGCTCT
GGCGGCTCTC
701
AGAGCTTCCT
GCTCAAGTCT
TTAGAGCAAG
TGAGAAAGAT
CCAGGGCGAT
751
GGCGCAGCGC
TCCAGGAGAA
GCTGTGTGCC
ACCTACAAGC
TGTCCCACCC
801
CGAGGAGCTG
GTGCTGCTCG
GACACTCTCT
GGGCATCCCC
TGGGCTCCCC
851
TGAGCTCCTG
CCCCAGCCAG
GCCCTGCAGC
TGGCAGGCTG
CTTGAGCCAA
901
CTCCATAGCG
GCCTTTTCCT
CTACCAGGGG
CTCCTGCAGG
CCCTGGAAGG
951
GATATCCTAA
TAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 98)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
GTGGTTCTGG
CGGCGGCTCC
AACATGGCTA
401
TGGCCCCTGC
CCTGCAGCCC
ACCCAGGGTG
CCATGCCGGC
CTTCGCCTCT
451
GCTTTCCAGC
GCCGGGCAGG
AGGGGTCCTG
GTTGCTAGCC
ATCTGCAGAG
501
CTTCCTGGAG
GTGTCGTACC
GCGTTCTACG
CCACCTTGCG
CAGCCCTCTG
551
GCGGCTCTGG
CGGCTCTCAG
AGCTTCCTGC
TCAAGTCTTT
AGAGCAAGTG
601
AGAAAGATCC
AGGGCGATGG
CGCAGCGCTC
CAGGAGAAGC
TGTGTGCCAC
651
CTACAAGCTG
TGCCACCCCG
AGGAGCTGGT
GCTGCTCGGA
CACTCTCTGG
701
GCATCCCCTG
GGCTCCCCTG
AGCTCCTGCC
CCAGCCAGGC
CCTGCAGCTG
751
GCAGGCTGCT
TGAGCCAACT
CCATAGCGGC
CTTTTCCTCT
ACCAGGGGCT
801
CCTGCAGGCC
CTGGAAGGGA
TATCCCCCGA
GTTGGGTCCC
ACCTTGGACA
851
CACTGCAGCT
GGACGTCGCC
GACTTTGCCA
CCACCATCTG
GCAGCAGATG
901
GAAGAACTGG
GATAATAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 99)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCCTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTATGGCC
451
CCTGCCCTGC
AGCCCACCCA
GGGTGCCATG
CCGGCCTTCG
CCTCTGCTTT
501
CCAGCGCCGG
GCAGGAGGGG
TCCTGGTTGC
TAGCCATCTG
CAGAGCTTCC
551
TGGAGGTGTC
GTACCGCGTT
CTACGCCACC
TTGCGCAGCC
CTCTGGCGGC
601
TCTGGCGGCT
CTCAGAGCTT
CCTGCTCAAG
TCTTTAGAGC
AAGTGAGAAA
651
GATCCAGGGC
GATGGCGCAG
CGCTCCAGGA
GAAGCTGTGT
GCCACCTACA
701
AGCTGTGCCA
CCCCGAGGAG
CTGGTGCTGC
TCGGACACTC
TCTGGGCATC
751
CCCTGGGCTC
CCCTGAGCTC
CTGCCCCAGC
CAGGCCCTGC
AGCTGGCAGG
801
CTGCTTGAGC
CAACTCCATA
GCGGCCTTTT
CCTCTACCAG
GGGCTCCTGC
851
AGGCCCTGGA
AGGGATATCC
CCCGAGTTGG
GTCCCACCTT
GGACACACTG
901
CAGCTGGACG
TCGCCGACTT
TGCCACCACC
ATCTGGCAGC
AGATGGAAGA
951
ACTGGGATAA
TAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 100)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
GTGGTTCTGG
CGGCGGCTCC
AACATGGCTA
401
CCCAGGGTGC
CATGCCGGCC
TTCGCCTCTG
CTTTCCAGCG
CCGGGCAGGA
451
GGGGTCCTGG
TTGCTAGCCA
TCTGCAGAGC
TTCCTGGAGG
TGTCGTACCG
501
CGTTCTACGC
CACCTTGCGC
AGCCCTCTGG
CGGCTCTGGC
GGCTCTCAGA
551
GCTTCCTGCT
CAAGTCTTTA
GAGCAAGTGA
GAAAGATCCA
GGGCGATGGC
601
GCAGCGCTCC
AGGAGAAGCT
GTGTGCCACC
TACAAGCTGT
GCCACCCCGA
651
GGAGCTGGTG
CTGCTCGGAC
ACTCTCTGGG
CATCCCCTGG
GCTCCCCTGA
701
GCTCCTGCCC
CAGCCAGGCC
CTGCAGCTGG
CAGGCTGCTT
GAGCCAACTC
751
CATAGCGGCC
TTTTCCTCTA
CCAGGGGCTC
CTGCAGGCCC
TGGAAGGGAT
801
ATCCCCCGAG
TTGGGTCCCA
CCTTGGACAC
ACTGCAGCTG
GACGTCGCCG
851
ACTTTGCCAC
CACCATCTGG
CAGCAGATGG
AAGAACTGGG
AATGGCCCCT
901
GCCCTGCAGC
CCTAATAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 101)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTACCCAG
451
GGTGCCATGC
CGGCCTTCGC
CTCTGCTTTC
CAGCGCCGGG
CAGGAGGGGT
501
CCTGGTTGCT
AGCCATCTGC
AGAGCTTCCT
GGAGGTGTCG
TACCGCGTTC
551
TACGCCACCT
TGCGCAGCCC
TCTGGCGGCT
CTGGCGGCTC
TCAGAGCTTC
601
CTGCTCAAGT
CTTTAGAGCA
AGTGAGAAAG
ATCCAGGGCG
ATGGCGCAGC
651
GCTCCAGGAG
AAGCTGTGTG
CCACCTACAA
GCTGTGCCAC
CCCGAGGAGC
701
TGGTGCTGCT
CGGACACTCT
CTGCGCATCC
CCTGGGCTCC
CCTGAGCTCC
751
TGCCCCAGCC
AGGCCCTGCA
GCTGGCAGGC
TGCTTGAGCC
AACTCCATAG
801
CGGCCTTTTC
CTCTACCAGG
GGCTCCTGCA
GGCCCTGGAA
GGGATATCCC
851
CCGAGTTGGG
TCCCACCTTG
GACACACTGC
AGCTGGACGT
CGCCGACTTT
901
GCCACCACCA
TCTGGCAGCA
GATGGAAGAA
CTGGGAATGG
CCCCTGCCCT
951
GCAGCCCTAA
TAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 102)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
GTGGTTCTGG
CGGCGGCTCC
AACATGGCTT
401
CTGCTTTCCA
GCGCCGGGCA
GGAGGGGTCC
TGGTTGCTAG
CCATCTGCAG
451
AGCTTCCTGG
AGGTGTCGTA
CCGCGTTCTA
CGCCACCTTG
CGCAGCCCTC
501
TGGCGGCTCT
GGCGGCTCTC
AGAGCTTCCT
GCTCAAGTCT
TTAGAGCAAG
551
TGAGAAAGAT
CCAGGGCGAT
GGCGCAGCGC
TCCAGGAGAA
GCTGTGTGCC
601
ACCTACAAGC
TGTGCCACCC
CGAGGAGCTG
GTGCTGCTCG
GACACTCTCT
651
GGGCATCCCC
TGGGCTCCCC
TGAGCTCCTG
CCCCAGCCAG
GCCCTGCAGC
701
TGGCAGGCTG
CTTGAGCCAA
CTCCATAGCG
GCCTTTTCCT
CTACCAGGGG
751
CTCCTGCAGG
CCCTGGAAGG
GATATCCCCC
GAGTTGGGTC
CCACCTTGGA
801
CACACTGCAG
CTGGACGTCG
CCGACTTTGC
CACCACCATC
TGGCAGCAGA
851
TGGAAGAACT
GGGAATGGCC
CCTGCCCTGC
AGCCCACCCA
GGGTGCCATG
901
CCGGCCTTCG
CCTAATAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 107)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTCCCGAG
451
TTGGGTCCCA
CCTTGGACAC
ACTGCAGCTG
GACGTCGCCG
ACTTTGCCAC
501
CACCATCTGG
CAGCAGATGG
AAGAACTGGG
AATGGCCCCT
GCCCTGCAGC
551
CCACCCAGGG
TGCCATGCCG
GCCTTCGCCT
CTGCTTTCCA
GCGCCGGGCA
601
GGAGGGGTCC
TGGTTGCTAG
CCATCTGCAG
AGCTTCCTGG
AGGTGTCGTA
651
CCGCGTTCTA
CGCCACCTTG
CGCAGCCCAC
ACCATTGGGC
CCTGCCAGCT
701
CCCTGCCCCA
GAGCTTCCTG
CTCAAGTCTT
TAGAGCAAGT
GAGAAAGATC
751
CAGGGCGATG
GCGCAGCGCT
CCAGGAGAAG
CTGTGTGCCA
CCTACAAGCT
801
GTGCCACCCC
GAGGAGCTGG
TGCTGCTCGG
ACACTCTCTG
GGCATCCCCT
851
GGGCTCCCCT
GAGCTCCTGC
CCCAGCCAGG
CCCTGCAGCT
GGCAGGCTGC
901
TTGAGCCAAC
TCCATAGCGG
CCTTTTCCTC
TACCAGGGGC
TCCTGCAGGC
951
CCTGGAAGGG
ATATCCTAAT
AA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 103)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTTCTGCT
451
TTCCAGCGCC
GGGCAGGAGG
GGTCCTGGTT
GCTAGCCATC
TGCAGAGCTT
501
CCTGGAGGTG
TCGTACCGCG
TTCTACGCCA
CCTTGCGCAG
CCCTCTGGCG
551
GCTCTGGCGG
CTCTCAGAGC
TTCCTGCTCA
AGTCTTTAGA
GCAAGTGAGA
601
AAGATCCAGG
GCGATGGCGC
AGCGCTCCAG
GAGAAGCTGT
GTGCCACCTA
651
CAAGCTGTGC
CACCCCGAGG
AGCTGGTGCT
GCTCGGACAC
TCTCTGGGCA
701
TCCCCTGGGC
TCCCCTGAGC
TCCTGCCCCA
GCCAGGCCCT
GCAGCTGGCA
751
GGCTGCTTGA
GCCAACTCCA
TAGCGGCCTT
TTCCTCTACC
AGGGGCTCCT
801
GCAGGCCCTG
GAAGGGATAT
CCCCCGAGTT
GGGTCCCACC
TTGGACACAC
851
TGCAGCTGGA
CGTCGCCGAC
TTTGCCACCA
CCATCTGGCA
GCAGATGGAA
901
GAACTGGGAA
TGGCCCCTGC
CCTGCAGCCC
ACCCAGGGTG
CCATGCCGGC
951
CTTCGCCTAA
TAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 104)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
GTGGTTCTGG
CGGCGGCTCC
AACATGGCTT
401
ACAAGCTGTG
CCACCCCGAG
GAGCTGGTGC
TGCTCGGACA
CTCTCTGGGC
451
ATCCCCTGGG
CTCCCCTGAG
CTCCTGCCCC
AGCCACGCCC
TGCAGCTGGC
501
AGGCTGCTTG
AGCCAACTCC
ATAGCGGCCT
TTTCCTCTAC
CAGGGGCTCC
551
TGCAGGCCCT
GGAAGGGATA
TCCCCCGAGT
TGCGTCCCAC
CTTGGACACA
601
CTGCAGCTGG
ACGTCGCCGA
CTTTGCCACC
ACCATCTGGC
AGCAGATGGA
651
AGAACTGGGA
ATGGCCCCTG
CCCTGCAGCC
CACCCAGGGT
GCCATGCCGG
701
CCTTCGCCTC
TGCTTTCCAG
CGCCGGGCAG
GAGGGGTCCT
GGTTGCTAGC
751
CATCTGCAGA
GCTTCCTGGA
GGTGTCGTAC
CGCGTTCTAC
GCCACCTTGC
801
GCAGCCCACA
CCATTGGGCC
CTCCCAGCTC
CCTGCCCCAG
AGCTTCCTGC
851
TCAAGTCTTT
AGAGCAAGTG
AGAAAGATCC
AGGGCGATGG
CGCAGCGCTC
901
CAGGAGAAGC
TGTGTGCCAC
CTAATAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 105)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
ACAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAC
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
CGCTTACAAG
451
CTGTGCCACC
COGAGGAGCT
GGTGCTGCTC
GGACACTCTC
TGGGCATCCC
501
CTGGGCTCCC
CTGAGCTCCT
GCCCCAGCCA
GGCCCTGCAG
CTGGCAGGCT
551
GCTTGAGCCA
ACTCCATAGC
GGCCTTTTCC
TCTACCAGGG
GCTCCTGCAG
601
GCCCTGGAAG
GGATATCCCC
CGAGTTGGGT
CCCACCTTGG
ACACACTGCA
651
GCTGGACGTC
GCCGACTTTG
CCACCACCAT
CTGGCAGCAG
ATGGAAGAAC
701
TGGGAATGGC
CCCTGCCCTG
CAGCCCACCC
AGGGTGCCAT
GCCGGCCTTC
751
GCCTCTGCTT
TCCAGCGCCG
GGCAGGAGGG
GTCCTGGTTG
CTAGCCATCT
801
GCAGAGCTTC
CTGGAGGTGT
CGTACCGCGT
TCTACGCCAC
CTTGCGCAGC
851
CCACACCATT
GGGCCCTGCC
AGCTCCCTGC
CCCAGAGCTT
CCTGCTCAAG
901
TCTTTAGAGC
AAGTGAGAAA
GATCCAGGGC
GATGGCGCAG
CGCTCCAGGA
951
GAAGCTGTGT
GCCACCTAAT
AA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 109)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTATGGCC
451
CCTGCCCTGC
AGCCCACCCA
GGGTGCCATG
CCGGCCTTCG
CCTCTGCTTT
501
CCAGCGCCCG
GCAGGAGGGG
TCCTGGTTGC
TAGCCATCTG
CAGAGCTTCC
551
TGGAGGTGTC
GTACCGCGTT
CTACGCCACC
TTGCGCAGCC
CACACCATTG
601
GGCCCTGCCA
GCTCCCTGCC
CCAGAGCTTC
CTGCTCAAGT
CTTTAGAGCA
651
AGTGAGAAAG
ATCCAGGGCG
ATGGCGCAGC
GCTCCAGGAG
AAGCTGTGTG
701
CCACCTACAA
GCTGTGCCAC
CCCGAGGAGC
TGGTGCTGCT
CGGACACTCT
751
CTGGGCATCC
CCTGGGCTCC
CCTGAGCTCC
TGCCCCAGCC
AGGCCCTGCA
801
GCTGGCAGGC
TGCTTGAGCC
AACTCCATAG
CGGCCTTTTC
CTCTACCAGG
851
GGCTCCTGCA
GGCCCTGGAA
GGGATATCCC
CCGAGTTGGG
TCCCACCTTG
901
GACACACTGC
AGCTGGACGT
CGCCGACTTT
GCCACCACCA
TCTGGCAGCA
951
GATGGAAGAA
CTGGGATAAT
AA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 110)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
GTGGTTCTGG
CGGCGGCTCC
AACATGGCTA
401
CCCAGGGTGC
CATGCCGGCC
TTCGCCTCTG
CTTTCCAGCG
CCGGGCAGGA
451
GGGGTCCTGG
TTGCTAGCCA
TCTGCAGAGC
TTCCTGGAGG
TGTCGTACCG
501
CGTTCTACGC
CACCTTGCGC
AGCCCACACC
ATTGGGCCCT
GCCAGCTCCC
551
TGCCCCAGAG
CTTCCTGCTC
AAGTCTTTAG
AGCAAGTGAG
AAAGATCCAG
601
GGCGATGGCG
CAGCGCTCCA
GGAGAAGCTG
TGTGCCACCT
ACAAGCTGTG
651
CCACCCCGAG
GAGCTGGTGC
TGCTCGGACA
CTCTCTGGGC
ATCCCCTGGG
701
CTCCCCTGAG
CTCCTGCCCC
AGCCAGGCCC
TGCAGCTGGC
AGGCTGCTTG
751
AGCCAACTCC
ATAGCGGCCT
TTTCCTCTAC
CAGGGGCTCC
TGCAGGCCCT
801
GGAAGGGATA
TCCCCCGAGT
TGGGTCCCAC
CTTGGACACA
CTGCAGCTGG
851
ACGTCGCCGA
CTTTGCCACC
ACCATCTGGC
AGCAGATGGA
AGAACTGGGA
901
ATGGCCGCTG
CCCTGCAGCC
CTAATAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 111)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTACCCAG
451
GGTGCCATGC
CGGCCTTCGC
CTCTGCTTTC
CAGCGCCGGG
CAGGAGGGGT
501
CCTGGTTGCT
AGCCATCTGC
AGAGCTTCCT
GGAGGTGTCG
TACCGCGTTC
551
TACGCCACCT
TGCGCAGCCC
ACACCATTGG
GCCCTGCCAG
CTCCCTGCCC
601
CAGAGCTTCC
TGCTCAAGTC
TTTAGAGCAA
GTGAGAAAGA
TCCAGGGCGA
651
TGGCGCAGCG
CTCCAGGAGA
AGCTGTGTGC
CACCTACAAG
CTGTGCCACC
701
CCGAGGAGCT
GGTGCTGCTC
GGACACTCTC
TGGGCATCCC
CTGGGCTCCC
751
CTGAGCTCCT
GCCCCAGCCA
GGCCCTGCAG
CTGCCAGGCT
GCTTGAGCCA
801
ACTCCATAGC
GGCCTTTTCC
TCTACCAGGG
GCTCCTGCAG
GCCCTGGAAG
851
GGATATCCCC
CGAGTTGGGT
CCCACCTTCG
ACACACTGCA
GCTGGACGTC
901
GCCGACTTTG
CCACCACCAT
CTGGCAGCAG
ATGGAAGAAC
TGGGAATGGC
951
CCCTGCCCTG
CAGCCCTAAT
AA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 112)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
GTGGTTCTGG
CGGCGGCTCC
AACATGGCTT
401
CTGCTTTCCA
GCGCCGGGCA
GGAGGGGTCC
TGGTTGCTAG
CCATCTGCAG
451
AGCTTCCTGG
AGGTGTCGTA
CCGCGTTCTA
CGCCACCTTG
CGCAGCCCAC
501
ACCATTGGGC
CCTGCCAGCT
CCCTGCCCCA
GAGCTTCCTG
CTCAAGTCTT
551
TAGAGCAAGT
GAGAAAGATC
CAGGGCGATG
GCGCAGCGCT
CCAGGAGAAG
601
CTGTGTGCCA
CCTACAAGCT
GTGCCACCCC
GAGGAGCTGG
TGCTGCTCGG
651
ACACTCTCTG
GGCATCCCCT
GGGCTCCCCT
GAGCTCCTGC
CCCAGCCAGG
701
CCCTGCAGCT
GGCAGGCTGC
TTGAGCCAAC
TCCATAGCGG
CCTTTTCCTC
751
TACCAGGGGC
TCCTGCAGGC
CCTGGAAGGG
ATATCCCCCG
AGTTGGGTCC
801
CACCTTGGAC
ACACTGCAGC
TGGACGTCGC
CGACTTTGCC
ACCACCATCT
851
GGCAGCAGAT
GGAAGAACTG
GGAATGGCCC
CTGCCCTGCA
GCCCACCCAC
901
GGTGCCATGC
CGGCCTTCGC
CTAATAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 155)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GTCTTACAAG
451
CTGTGCCACC
CCGAGCAGCT
GGTGCTGCTC
GGACACTCTC
TGGGCATCCC
501
CTGGGCTCCC
CTGAGCTCCT
GCCCCAGCCA
GGCCCTGCAG
CTGGCAGGCT
551
GCTTGAGCCA
ACTCCATAGC
GGCCTTTTCC
TCTACCAGGG
GCTCCTGCAG
601
GCCCTGGAAG
GGATATCCCC
CGAGTTGGGT
CCCACCTTGG
ACACACTGCA
651
GCTGGACGTC
GCCGACTTTG
CCACCACCAT
CTGGCAGCAG
ATGGAAGAAC
701
TGGGAATGGC
CCCTGCCCTG
CAGCCCACCC
AGGGTGCCAT
GCCGGCCTTC
751
GCCTCTGCTT
TCCAGCGCCC
GGCAGGAGGG
GTCCTGGTTG
CTAGCCATCT
801
GCAGAGCTTC
CTGGAGGTGT
CGTACCGCGT
TCTACGCCAC
CTTGCGCAGC
851
CCGGCGGCGG
CTCTGACATG
GCTACACCAT
TAGGCCCTGC
CAGCTCCCTG
901
CCCCAGAGCT
TCCTGCTCAA
GTCTTTAGAG
CAACTGAGGA
AGATCCAGGG
951
CGATGGCGCA
GCGCTCCAGG
AGAAGCTGTG
TGCCACCTAA
TAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 156)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTGG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GTCTCCCGAG
451
TTGGGTCCCA
CCTTGGACAC
ACTGCAGCTG
GACGTCGCCG
ACTTTGCCAC
501
CACCATCTGG
CAGCAGATGG
AAGAACTGGG
AATGGCCCCT
GCCCTCCAGC
551
CCACCCAGGG
TGCCATGCCG
GCCTTCGCCT
CTGCTTTCCA
GCGCCGGGCA
601
GGAGGGGTCC
TGGTTGCTAG
CCATCTGCAG
AGCTTCCTGG
AGGTGTCGTA
651
CCGCGTTCTA
CGCCACCTTG
CGCAGCCCGG
CGGCGGCTCT
GACATGGCTA
701
CACCATTAGG
CCCTGCCAGC
TCCCTGCCCC
AGAGCTTCCT
GCTCAAGTCT
751
TTAGAGCAAG
TGAGGAAGAT
CCAGGGCGAT
GGCGCAGCGC
TCCAGGAGAA
801
GCTGTGTGCC
ACCTACAAGC
TGTGCCACCC
CGAGGAGCTG
GTGCTGCTCG
851
GACACTCTCT
GGGCATCCCC
TGGGCTCCCC
TGAGCTCCTG
CCCCAGCCAG
901
GCCCTGCAGC
TGGCAGGCTG
CTTGAGCCAA
CTCCATAGCG
GCCTTTTCCT
951
CTACCAGGGG
CTCCTGCAGG
CCCTGGAAGG
GATATCCTAA
TAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 157)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GTCTTCTGCT
451
TTCCAGCGCC
GGGCAGGAGG
GGTCCTGGTT
GCTAGCCATC
TGCAGAGCTT
501
CCTCGAGGTG
TCGTACCGCG
TTCTACGCCA
CCTTGCCCAG
CCCGGCGGCG
551
GCTCTGACAT
GGCTACACCA
TTAGGCCCTG
CCAGCTCCCT
GCCCCAGAGC
601
TTCCTGCTCA
AGTCTTTAGA
GCAAGTGAGG
AAGATCCAGG
GCGATGGCGC
651
AGCGCTCCAG
GAGAAGCTGT
GTGCCACCTA
CAAGCTGTGC
CACCCCGAGG
701
AGCTGGTGCT
GCTCGGACAC
TCTCTGGGCA
TCCCCTGGGC
TCCCCTGAGC
751
TCCTGCCCCA
GCCAGGCCCT
GCAGCTGGCA
GGCTGCTTGA
GCCAACTCCA
801
TAGCGGCCTT
TTCCTCTACC
AGGGGCTCCT
GCAGGCCCTG
GAAGGGATAT
851
CCCCCGAGTT
GGGTCCCACC
TTGGACACAC
TGCAGCTGGA
CGTCGCCGAC
901
TTTGCCACCA
CCATCTGGCA
GCAGATGGAA
GAACTGGGAA
TGGCCCCTGC
951
CCTGCAGCCC
ACCCAGGGTG
CCATGCCGGC
CTTCGCCTAA
TAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 158)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GTCTATGGCC
451
CCTGCCCTGC
AGCCCACCCA
GGGTGCCATG
CCGGCCTTCG
CCTCTGCTTT
501
CCAGCGCCGG
GCAGGAGGGG
TCCTGGTTGC
TAGCCATCTG
CAGAGCTTCC
551
TGGAGGTGTC
GTACCGCGTT
CTACGCCACC
TTGCGCAGCC
CGGCGGCGGC
601
TCTGACATGG
CTACACCATT
AGGCCCTGCC
AGCTCCCTGC
CCCAGAGCTT
651
CCTGCTCAAG
TCTTTAGAGC
AAGTGAGGAA
GATCCAGGGC
GATGGCGCAG
701
CGCTCCAGGA
GAAGCTGTGT
GCCACCTACA
AGCTGTGCCA
CCCCGAGGAG
751
CTGGTGCTGC
TCGGACACTC
TCTGGGCATC
CCCTGGGCTC
CCCTGAGCTC
801
CTGCCCCAGC
CAGGCCCTGC
AGCTGGCAGG
CTGCTTGAGC
CAACTCCATA
851
GCGGCCTTTT
CCTCTACCAG
GGGCTCCTGC
AGGCCCTGGA
AGGGATATCC
901
CCCGAGTTGG
GTCCCACCTT
GGACACACTG
CAGCTGGACG
TCGCCGACTT
951
TGCCACCACC
ATCTGGCAGC
AGATGGAAGA
ACTGGGATAA
TAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 159)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GTCTACCCAG
451
GGTGCCATGC
CGGCCTTCGC
CTCTGCTTTC
CAGCGCCGGG
CAGGAGGGGT
501
CCTGGTTGCT
AGCCATCTGC
AGAGCTTCCT
GGAGGTGTCG
TACCGCGTTC
551
TACGCCACCT
TGCGCAGCCC
GGCGGCGGCT
CTGACATGGC
TACACCATTA
601
GGCCCTGCCA
GCTCCCTGCC
CCAGAGCTTC
CTGCTCAAGT
CTTTAGAGCA
651
AGTGAGGAAG
ATCCAGGGCG
ATGGCGCAGC
GCTCCAGGAG
AAGCTGTGTG
701
CCACCTACAA
GCTCTGCCAC
CCCGAGGAGC
TGGTGCTGCT
CGGACACTCT
751
CTGGGCATCC
CCTGGGCTCC
CCTGAGCTCC
TGCCCCAGCC
AGGCCCTGCA
801
GCTGGCAGGC
TGCTTGAGCC
AACTCCATAG
CGGCCTTTTC
CTCTACCAGG
851
GGCTCCTGCA
GGCCCTGGAA
GGGATATCCC
CCGAGTTGGG
TCCCACCTTG
901
GACACACTGC
AGCTGGACGT
CGCCGACTTT
GCCACCACCA
TCTGGCAGCA
951
GATGGAAGAA
CTGGGAATGG
CCCCTGCCCT
GCAGCCCTAA
TAA;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT
(SEQ ID NO: 124)
TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT
CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT
ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT
CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC
CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT
CATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGA
CAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG
GGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTC
CGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTC
GGCGGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTG
CTTCGTGACTCCCATGTCCTTCACAGCAGACTGACCCAGTGCCCAGAGGTTCACCCTTTG
CCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATG
GAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATG
GCAGCACGGGGACAACTG;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT
(SEQ ID NO: 125)
TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT
CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT
ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT
CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC
CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT
CATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG
GATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTG
ATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCG
GCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTT
CACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCT
GCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGAC
ATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGA
CCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGG
GCCCTGCAGAGCCTCCTT;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT
(SEQ ID NO: 126)
TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT
CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT
ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT
CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC
CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT
CATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTG
AGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACC
CTCTGCGTCAGGGAATTCGCCGGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTC
CGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGC
CCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTCGACTTTAGCTTGGGA
GAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTT
CTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTC
CTGCGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGA
ACCCAGCTTCCTCCACAG;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT
(SEQ ID NO: 127)
TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT
CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGATCTTAGAAAATGCATCAGGT
ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT
CGACATCCAATCATCATCAAGGCAGGTGACTGCCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC
CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT
CATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACAC
CTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG
GAATTCGGCGGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGT
AAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCAC
CCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACC
CAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGA
GTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTT
TCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCACCTTCCT
CCACAGGGCAGGACCACA;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT
(SEQ ID NO: 128)
TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT
CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT
ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT
CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC
TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC
CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT
CATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA
GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC
GGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT
CGTGACTCCCATCTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCT
ACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG
GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA
GCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG
GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGC
AGGACCACAGCTCACAAG;
1
ATGGCTAACT
GCTCTAACAT
GATCGATGAA
ATCATCACCC
ACCTGAAGCA
(SEQ ID NO: 114)
51
GCCACCGCTG
CCGCTGCTGG
ACTTCAACAA
CCTCAATGGT
GAAGACCAAG
101
ATATCCTAAT
GGACAATAAC
CTTCGTCGTC
CAAACCTCGA
GGCATTCAAC
151
CGTGCTGTCA
AGTCTCTGCA
GAATGCATCA
GCAATTGAGA
GCATTCTTAA
201
AAATCTCCTG
CCATGTCTGC
CGCTAGCCAC
GGCCGCACCC
ACGCGACATC
251
CAATCCATAT
CAAGGACGGT
GACTGGAATG
AATTCCGTCG
TAAACTGACC
301
TTCTATCTGA
AAACCTTGGA
GAACGCGCAG
GCTCAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTACCCAG
451
GGTGCCATGC
CGGCCTTCGC
CTCTGCTTTC
CAGCGCCGGG
CAGGAGGGGT
501
CCTGGTTGCT
AGCCATCTGC
AGAGCTTCCT
GGAGGTGTCG
TACCGCGTTC
551
TACGCCACCT
TGCGCAGCCC
TCTGGCGGCT
CTGGCGGCTC
TCAGAGCTTC
601
CTGCTCAAGT
CTTTAGAGCA
AGTGAGAAAG
ATCCAGGGCG
ATGGCGCAGC
651
GCTCCAGGAG
AAGCTGTGTG
CCACCTACAA
GCTGTGCCAC
CCCGAGGAGC
701
TGGTGCTGCT
CGGACACTCT
CTGGGCATCC
CCTGGGCTCC
CCTGAGCTCC
751
TGCCCCAGCC
AGGCCCTGCA
GCTGGCAGGC
TGCTTGAGCC
AACTCCATAG
801
CGGCCTTTTC
CTCTACCAGG
GGCTCCTGCA
GGCCCTGGAA
GGGATATCCC
851
CCGAGTTGGG
TCCCACCTTG
GACACACTGC
AGCTGGACGT
CGCCGACTTT
901
GCCACCACCA
TCTGGCAGCA
GATGGAAGAA
CTGGGAATGG
CCCCTGCCCT
951
GCAGCCCTAA
TAA;
1
ATGGCTAACT
GCTCTAACAT
GATCGATGAA
ATCATCACCC
ACCTGAAGCA
(SEQ ID NO: 115)
51
GCCACCGCTG
CCGCTGCTGG
ACTTCAACAA
CCTCAATGGT
GAAGACCAAG
101
ATATCCTGAT
GGAAAATAAC
CTTCGTCGTC
CAAACCTCGA
GGCATTCAAC
151
CGTGCTGTCA
AGTCTCTGCA
GAATGCATCA
GCAATTGAGA
GCATTCTTAA
201
AAATCTCCTG
CCATGTCTGC
CCCTGGCCAC
GGCCGCACCC
ACGCGACATC
251
CAATCATCAT
CCGTGACGGT
GACTGGAATG
AATTCCGTCG
TAAACTGACC
301
TTCTATCTGA
AAACCTTGGA
GAACGCGCAG
GCTCAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTACCCAG
451
GGTGCCATGC
CGGCCTTCGC
CTCTGCTTTC
CAGCGCCGGG
CAGGAGGGGT
501
CCTGGTTGCT
AGCCATCTGC
AGAGCTTCCT
GGAGGTGTCG
TACCGCGTTC
551
TACGCCACCT
TGCGCAGCCC
ACACCATTGG
GCCCTGCCAG
CTCCCTGCCC
601
CAGAGCTTCC
TGCTCAAGTC
TTTAGAGCAA
GTGAGAAAGA
TCCAGGGCGA
651
TGGCGCAGCG
CTCCAGGAGA
AGCTGTGTGC
CACCTACAAG
CTGTGCCACC
701
CCGAGGAGCT
GGTGCTGCTC
GGACACTCTC
TGGGCATCCC
CTGGGCTCCC
751
CTGAGCTCCT
GCCCCAGCCA
GGCCCTGCAG
CTGGCAGGCT
GCTTGAGCCA
801
ACTCCATAGC
GGCCTTTTCC
TCTACCAGGG
GCTCCTGCAG
GCCCTGGAAG
851
GGATATCCCC
CGAGTTGGGT
CCCACCTTGG
ACACACTGCA
GCTGGACGTC
901
GCCGACTTTG
CCACCACCAT
CTGGCAGCAG
ATGGAAGAAC
TGGGAATGGC
951
CCCTGCCCTG
CAGCCCTAAT
AA;
1
ATGGCTAACT
GCTCTAACAT
GATCGATGAA
ATCATCACCC
ACCTGAAGCA
(SEQ ID NO: 116)
51
GCCACCGCTG
CCGCTGCTGG
ACTTCAACAA
CCTCAATGGT
GAAGACCAAG
101
ATATCCTGAT
GGAAAATAAC
CTTCGTCGTC
CAAACCTCGA
GGCATTCAAC
151
CGTGCTGTCA
AGTCTCTGCA
GAATGCATCA
GCAATTGAGA
GCATTCTTAA
201
AAATCTCCTG
CCATGTCTGC
CCCTGGCCAC
GGCCGCACCC
ACGCGACATC
251
CAATCATCAT
CCGTGACGCT
GACTGGAATG
AATTCCGTCG
TAAACTGACC
301
TTCTATCTGA
AAACCTTGGA
GAACGCGCAG
GCTCAACAGT
ACGTAGAGGG
351
CGGTGGAGCC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTACCCAG
451
GGTGCCATGC
CGGCCTTCGC
CTCTGCTTTC
CAGCGCCGGG
CAGGAGGGGT
501
CCTGGTTGCT
AGCCATCTGC
AGAGCTTCCT
GGAGGTGTCG
TACCGCGTTC
551
TACGCCACCT
TGCGCAGCCC
TCTGGCGGCT
CTGGCGGCTC
TCAGAGCTTC
601
CTGCTCAAGT
CTTTAGAGCA
AGTGAGAAAG
ATCCAGGGCG
ATGGCGCAGC
651
GCTCCAGGAG
AAGCTGTGTG
CCACCTACAA
GCTGTGCCAC
CCCGAGGAGC
701
TGGTGCTGCT
CGGACACTCT
CTGGGCATCC
CCTGGGCTCC
CCTGAGCTCC
751
TGCCCCAGCC
AGGCCCTGCA
GCTGGCAGGC
TGCTTGAGCC
AACTCCATAG
801
CGGCCTTTTC
CTCTACCAGG
GGCTCCTGCA
GGCCCTGGAA
GGGATATCCC
851
CCGAGTTGGG
TCCCACCTTG
GACACACTGC
AGCTGGACGT
CGCCGACTTT
901
GCCACCACCA
TCTGGCAGCA
GATGGAAGAA
CTGGGAATGG
CCCCTGCCCT
951
GCAGCCCTAA
TAA;
1
ATGGCTAACT
GCTCTAACAT
GATCGATGAA
ATCATCACCC
ACCTGAAGCA
(SEQ ID NO: 117)
51
GCCACCGCTG
CCGCTGCTGG
ACTTCAACAA
CCTCAATGGT
GAAGACCAAG
101
ATATCCTAAT
GGACAATAAC
CTTCGTCGTC
CAAACCTCGA
GGCATTCAAC
151
CGTGCTGTCA
AGTCTCTGCA
GAATGCATCA
GCAATTGAGA
GCATTCTTAA
201
AAATCTCCTG
CCATGTCTGC
CGCTAGCCAC
GGCCGCACCC
ACGCGACATC
251
CAATCCATAT
CAAGGACGGT
GACTGGAATG
AATTCCGTCG
TAAACTGACC
301
TTCTATCTGA
AAACCTTGGA
GAACGCGCAG
GCTCAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTACCCAG
451
GGTGCCATGC
CGGCCTTCGC
CTCTGCTTTC
CAGCGCCGGG
CAGGAGGGGT
501
CCTGGTTGCT
AGCCATCTGC
AGAGCTTCCT
GGAGGTGTCG
TACCGCGTTC
551
TACGCCACCT
TGCGCAGCCC
ACACCATTGG
GCCCTGCCAG
CTCCCTGCCC
601
CAGAGCTTCC
TGCTCAAGTC
TTTAGAGCAA
GTGAGAAAGA
TCCAGGGCGA
651
TGGCGCAGCG
CTCCAGGAGA
AGCTGTGTGC
CACCTACAAG
CTGTGCCACC
701
CCGAGGAGCT
GGTGCTGCTC
GGACACTCTC
TGGGCATCCC
CTGGGCTCCC
751
CTGAGCTCCT
GCCCCAGCCA
GGCCCTGCAG
CTGGCAGGCT
GCTTGAGCCA
801
ACTCCATAGC
GGCCTTTTCC
TCTACCAGGG
GCTCCTGCAG
GCCCTGGAAG
851
GGATATCCCC
CGAGTTGGGT
CCCACCTTGG
ACACACTGCA
GCTGGACGTC
901
GCCGACTTTG
CCACCACCAT
CTGGCAGCAG
ATGGAAGAAC
TGGGAATGGC
951
CCCTGCCCTG
CAGCCCTAAT
AA;
1
ATGGCTCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
CTATCCTGAT
(SEQ ID NO: 86)
51
GGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
AGGGCTGTCA
101
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
TAATCTCCAA
151
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
CAATCATCAT
201
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
TTCTATCTGG
251
TTACCCTTGA
GCAAGCGCAG
GAACAACAGG
GTGGTGGCTC
TAACTGCTCT
301
ATAATGATCG
ATGAAATTAT
ACATCACTTA
AAGAGACCAC
CTGCACCTTT
351
GTACGTAGAG
GGCGGTGGAG
GCTCCCCGGG
TGAACCGTCT
GGTCCAATCT
401
CTACTATCAA
CCCGTCTCCT
CCGTCTAAAG
AATCTCATAA
ATCTCCAAAC
451
ATGGCTACCC
AGGGTGCCAT
GCCGGCCTTC
GCCTCTGCTT
TCCAGCGCCG
501
GGCAGGAGGG
GTCCTGGTTG
CTAGCCATCT
GCAGAGCTTC
CTGGAGGTGT
551
CGTACCGCGT
TCTACGCCAC
CTTGCGCAGC
CCTCTGGCGG
CTCTGGCGGC
601
TCTCAGAGCT
TCCTGCTCAA
GTCTTTAGAG
CAAGTGAGAA
AGATCCAGGG
651
CGATGGCGCA
GCGCTCCAGG
AGAAGCTGTG
TGCCACCTAC
AAGCTGTGCC
701
ACCCCGAGGA
GCTGGTGCTG
CTCGGACACT
CTCTGGGCAT
CCCCTGGGCT
751
CCCCTGAGCT
CCTGCCCCAG
CCAGGCCCTG
CAGCTGGCAG
GCTGCTTGAG
801
CCAACTCCAT
AGCGGCCTTT
TCCTCTACCA
GGGGCTCCTG
CAGGCCCTGG
851
AAGGGATATC
CCCCGAGTTG
GGTCCCACCT
TGGACACACT
GCAGCTGGAC
901
GTCGCCGACT
TTGCCACCAC
CATCTGGCAG
CAGATGGAAG
AACTGGGAAT
951
GGCCCCTGCC
CTGCAGCCCT
AATAA;
1
ATGGCTAATG
CATCAGGTAT
TGAGGCAATT
CTTCGTAATC
TCCAACCATG
(SEQ ID NO: 87)
51
TCTGCCCTCT
GCCACGGCCG
CACCCTCTCG
ACATCCAATC
ATCATCAAGG
101
CAGGTGACTG
GCAAGAATTC
CGGGAAAAAC
TGACGTTCTA
TCTGGTTACC
151
CTTGAGCAAG
CGCAGGAACA
ACAGGGTGGT
GGCTCTAACT
GCTCTATAAT
201
GATCGATGAT
ATTATACATC
ACTTAAAGAG
ACCACCTGCA
CCTTTGCTGG
251
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
CTATCCTGAT
GGACCGAAAC
301
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
AGGGCTGTCA
AGAACTTAGA
351
ATACGTAGAG
GGCGGTGGAG
GCTCCCCGGG
TGAACCGTCT
GGTCCAATCT
401
CTACTATCAA
CCCGTCTCCT
CCGTCTAAAG
AATCTCATAA
ATCTCCAAAC
451
ATGGCTACCC
AGGGTGCCAT
GCCGGCCTTC
GCCTCTGCTT
TCCAGCGCCG
501
GGCAGGAGGG
GTCCTGGTTG
CTAGCCATCT
GCAGAGCTTC
CTGGAGGTGT
551
CGTACCGCGT
TCTACGCCAC
CTTGCGCAGC
CCTCTGGCGG
CTCTGGCGGC
601
TCTCAGAGCT
TCCTGCTCAA
GTCTTTAGAG
CAAGTGAGAA
AGATCCAGGG
651
CGATGGCGCA
GCGCTCCAGG
AGAAGCTGTG
TGCCACCTAC
AAGCTGTGCC
701
ACCCCGAGGA
GCTGGTGCTG
CTCGGACACT
CTCTGGGCAT
CCCCTGGGCT
751
CCCCTGAGCT
CCTGCCCCAG
CCAGGCCCTG
CAGCTGGCAG
GCTGCTTGAG
801
CCAACTCCAT
AGCGGCCTTT
TCCTCTACCA
GGGGCTCCTG
CAGGCCCTGG
851
AAGGGATATC
CCCCGAGTTG
GGTCCCACCT
TGGACACACT
GCAGCTGGAC
901
GTCGCCGACT
TTGCCACCAC
CATCTGGCAG
CAGATGGAAG
AACTGGGAAT
951
GGCCCCTGCC
CTGCAGCCCT
AATAA;
1
ATGGCTGCAC
CCTCTCGACA
TCCAATCATC
ATCAAGGCAG
GTGACTGGCA
(SEQ ID NO: 88)
51
AGAATTCCGG
GAAAAACTGA
CGTTCTATCT
GGTTACCCTT
GAGCAAGCGC
101
AGGAACAACA
GGGTGGTGGC
TCTAACTGCT
CTATAATGAT
CGATGAAATT
151
ATACATCACT
TAAAGAGACC
ACCTGCACCT
TTGCTGGACC
CGAACAACCT
201
CAATGACGAA
GACGTCTCTA
TCCTGATGGA
CCGAAACCTT
CGACTTCCAA
251
ACCTGGAGAG
CTTCGTAAGG
GCTGTCAAGA
ACTTAGAAAA
TGCATCAGGT
301
ATTGAGGCAA
TTCTTCGTAA
TCTCCAACCA
TGTCTGCCCT
CTGCCACGGC
351
CTACGTAGAG
GGCGGTGGAG
GCTCCCCGGG
TGAACCGTCT
GGTCCAATCT
401
CTACTATCAA
CCCGTCTCCT
CCGTCTAAAG
AATCTCATAA
ATCTCCAAAC
451
ATGGCTACCC
AGGGTGCCAT
GCCGGCCTTC
GCCTCTGCTT
TCCAGCGCCG
501
GGCAGGAGGG
GTCCTGGTTG
CTAGCCATCT
GCAGAGCTTC
CTGGAGGTGT
551
CGTACCGCGT
TCTACGCCAC
CTTGCGCAGC
CCTCTGGCGC
CTCTGGCGGC
601
TCTCAGAGCT
TCCTGCTCAA
GTCTTTAGAG
CAAGTGAGAA
AGATCCAGGG
651
CGATCGCGCA
GCGCTCCAGG
AGAAGCTGTG
TGCCACCTAC
AAGCTGTGCC
701
ACCCCGAGGA
GCTGGTGCTG
CTCGGACACT
CTCTGGGCAT
CCCCTGGGCT
751
CCCCTGAGCT
CCTGCCCCAG
CCAGGCCCTG
CAGCTGGCAG
GCTGCTTGAG
801
CCAACTCCAT
AGCGGCCTTT
TCCTCTACCA
GGGGCTCCTG
CAGGCCCTGG
851
AAGGGATATC
CCCCCAGTTG
GGTCCCACCT
TGGACACACT
GCAGCTGGAC
901
GTCGCCGACT
TTGCCACCAC
CATCTGGCAG
CAGATGGAAG
AACTGGGAAT
951
GGCCCCTGCC
CTGCAGCCCT
AATAA;
1
ATGGCTCTGC
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
CTATCCTGAT
(SEQ ID NO: 90)
51
CGACCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCCTA
AGGGCTCTCA
101
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
TAATCTCCAA
151
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
CAATCATCAT
201
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
TTCTATCTGG
251
TTACCCTTGA
GCAAGCGCAG
GAACAACAGG
GTGGTGGCTC
TGGCGGTGGC
301
AGCGGCGGCG
GTTCTAACTG
CTCTATAATG
ATCGATGAAA
TTATACATCA
351
CTTAAAGAGA
CCACCTGCAC
CTTTGTACGT
AGAGGGCGGT
GGAGGCTCCC
401
CGGGTGAACC
GTCTGGTCCA
ATCTCTACTA
TCAACCCGTC
TCCTCCGTCT
451
AAAGAATCTC
ATAAATCTCC
AAACATGGCT
ACCCAGGGTG
CCATGCCGGC
501
CTTCGCCTCT
GCTTTCCAGC
GCCGGGCAGG
AGGGGTCCTG
GTTGCTAGCC
551
ATCTGCAGAG
CTTCCTGGAG
GTGTCGTACC
GCGTTCTACG
CCACCTTGCG
601
CAGCCCTCTG
GCGGCTCTGG
CGGCTCTCAG
AGCTTCCTGC
TCAAGTCTTT
651
AGAGCAAGTG
AGAAAGATCC
AGGGCGATGG
CGCAGCGCTC
CAGGAGAAGC
701
TGTGTGCCAC
CTACAAGCTG
TGCCACCCCG
AGGAGCTGGT
GCTGCTCGGA
751
CACTCTCTGG
GCATCCCCTG
GGCTCCCCTG
AGCTCCTGCC
CCAGCCAGGC
801
CCTGCAGCTG
GCAGGCTGCT
TGAGCCAACT
CCATAGCGGC
CTTTTCCTCT
851
ACCAGGGGCT
CCTGCAGGCC
CTGGAAGGGA
TATCCCCCGA
GTTGGGTCCC
901
ACCTTGGACA
CACTGCAGCT
GGACGTCGCC
GACTTTGCCA
CCACCATCTG
951
GCAGCAGATG
GAAGAACTGG
GAATGGCCCC
TGCCCTGCAG
CCCTAATAA;
1
ATGGCTAATG
CATCAGGTAT
TGAGGCAATT
CTTCGTAATC
TCCAACCATG
(SEQ ID NO: 91)
51
TCTGCCCTCT
GCCACGGCCG
CACCCTCTCG
ACATCCAATC
ATCATCAAGG
101
CAGGTGACTG
GCAAGAATTC
CGGGAAAAAC
TGACGTTCTA
TCTGGTTACC
151
CTTGAGCAAG
CGCAGGAACA
ACAGGGTGGT
GGCTCTGGCG
GTGGCAGCGG
201
CGGCGGTTCT
AACTGCTCTA
TAATGATCGA
TGAAATTATA
CATCACTTAA
251
AGAGACCACC
TGCACCTTTG
CTGGACCCGA
ACAACCTCAA
TGACGAAGAC
301
CTCTCTATCC
TGATGGACCG
AAACCTTCGA
CTTCCAAACC
TGGAGAGCTT
351
CGTAAGGGCT
GTCAAGAACT
TAGAATACGT
AGAGGGCGGT
GGAGGCTCCC
401
CGGGTGAACC
GTCTGGTCCA
ATCTCTACTA
TCAACCCGTC
TCCTCCGTCT
451
AAAGAATCTC
ATAAATCTCC
AAACATGGCT
ACCCAGGGTG
CCATGCCGGC
501
CTTCGCCTCT
GCTTTCCAGC
GCCGGGCAGG
AGGGGTCCTG
GTTGCTACCC
551
ATCTGCAGAG
CTTCCTGGAG
GTGTCGTACC
GCGTTCTACG
CCACCTTGCG
601
CAGCCCTCTG
GCGGCTCTGG
CGGCTCTCAG
AGCTTCCTGC
TCAAGTCTTT
651
AGAGCAAGTG
AGAAAGATCC
ACGGCGATGG
CGCAGCGCTC
CAGGAGAAGC
701
TGTGTGCCAC
CTACAAGCTG
TGCCACCCCG
AGGAGCTGGT
GCTGCTCGGA
751
CACTCTCTGG
GCATCCCCTG
GGCTCCCCTG
AGCTCCTGCC
CCAGCCAGGC
801
CCTGCAGCTG
GCAGGCTGCT
TGAGCCAACT
CCATAGCGGC
CTTTTCCTCT
851
ACCAGGGGCT
CCTGCAGGCC
CTGGAAGGGA
TATCCCCCGA
GTTGGGTCCC
901
ACCTTGGACA
CACTGCAGCT
GGACGTCGCC
GACTTTGCCA
CCACCATCTG
951
GCAGCAGATG
GAAGAACTGG
CAATGGCCCC
TGCCCTGCAG
CCCTAATAA;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTT
(SEQ ID NO: 136)
GCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGAC
TTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAG
CCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCC
AATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTA
CCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCG
TCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAA
CATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCC
TTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCAC
AAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCT
GATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTC
CGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGC
AGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGA
CTTTACCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAG
CAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTT
(SEQ ID NO: 137)
GCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGAC
TTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAG
GCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCC
AATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTA
CCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCG
TCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAA
CATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCT
TCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCC
ACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCG
AGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAG
AGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGG
AAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGA
GGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGC
TTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTT
(SEQ ID NO: 148)
GCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGAC
TTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAG
GCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCC
AATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTA
CCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCG
TCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAA
CATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCC
TTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACACCTCAC
AAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCT
GATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGG
CGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT
GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCT
GCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGG
ACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTT
(SEQ ID NO: 149)
GCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGAC
TTCCAAACCTGGACAGCTTCGTAAGGGCTCTCAAGAACTTAGAAAATGCATCAGGTATTGAG
GCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCC
AATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTA
CCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCG
TCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAA
CATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCT
TCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCC
ACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCCCCTGC
TTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGA
GCCAGTGCCCAGAGCTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGC
TTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCAGAGGACATTCTGGGAGCAGTGAC
CCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCC
TCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTT
(SEQ ID NO: 150)
GCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGAC
TTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAG
GCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCC
AATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTA
CCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCG
TCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAA
CATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGC
TCCGAGGAAAGCTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTC
GGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAG
TAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACC
CTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAG
ATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGAT
GGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGAC
AGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTT
(SEQ ID NO: 151)
GCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGAC
TTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAG
GCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCC
AATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTA
CCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCG
TCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAA
CATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGG
TGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGC
GGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCG
TGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACAC
CTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACC
AAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGG
ACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCC
TCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACA;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTT
(SEQ ID NO: 152)
GCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCGTGATGGACCGAAACCTTCGAC
TTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAG
GCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCC
AATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTA
CCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCG
TCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAA
CATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCC
TGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATG
GCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCA
TGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGC
TGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAG
GACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGG
ACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGG
CCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTT
(SEQ ID NO: 153)
GCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGAC
TTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAG
GCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCC
AATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTA
CCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCG
TCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAA
CATGGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTG
TAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCA
GCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCA
CAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTG
TGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTG
GGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGCGACCCACTTG
CCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGA
GCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAAT;
GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCTTT
(SEQ ID NO: 154)
GCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTTCGAC
TTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTATTGAG
GCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCGACATCC
AATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTATCTGGTTA
CCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGGGTGAACCG
TCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAATCTCCAAA
CATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCC
TGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCC
GCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCA
CAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTG
TGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTG
GGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTG
CCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGA
GCCTCCTTGGAACCCAGGGCAGGACCACAGCTCACAAG;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 259)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTTTAGGC
451
CCTGCCAGCT
CCCTGCCCCA
GAGCTTCCTG
CTCAAGTCTT
TAGAGCAAGT
501
GAGGAAGATC
CAGGGCGATG
GCGCAGCGCT
CCAGGAGAAG
CTGTGTGCCA
551
CCTACAAGCT
GTGCCACCCC
GAGGAGCTGG
TGCTGCTCGG
ACACTCTCTG
601
GGCATCCCCT
GGGCTCCCCT
GAGCTCCTGC
CCCAGCCAGG
CCCTGCAGCT
651
GGCAGGCTGC
TTGAGCCAAC
TCCATAGCGG
CCTTTTCCTC
TACCAGGGGC
701
TCCTGCAGGC
CCTGGAAGGG
ATATCCCCCG
AGTTGGGTCC
CACCTTGGAC
751
ACACTGCAGC
TGGACGTCGC
CGACTTTGCC
ACCACCATCT
GGCAGCAGAT
801
GGAAGAACTG
GGAATGGCCC
CTGCCCTGCA
GCCCACCCAG
GGTGCCATGC
851
CGGCCTTCGC
CTCTGCTTTC
CAGCGCCGGG
CAGGAGGGGT
CCTGGTTGCT
901
AGCCATCTGC
AGAGCTTCCT
GGAGGTGTCG
TACCGCGTTC
TACGCCACCT
951
TGCGCAGCCC
GACATGGCTA
CACCA;
1
ATGGCTAACT
GCTCTATAAT
GATCCATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 260)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTCAGAGC
451
TTCCTGCTCA
AGTCTTTAGA
GCAAGTGAGG
AAGATCCAGG
CCGATGGCGC
501
AGCGCTCCAG
GAGAAGCTGT
GTGCCACCTA
CAAGCTGTGC
CACCCCGAGG
551
AGCTGGTGCT
GCTCGGACAC
TCTCTGGGCA
TCCCCTGGGC
TCCCCTGAGC
601
TCCTGCCCCA
GCCAGGCCCT
GCAGCTGGCA
GGCTGCTTGA
GCCAACTCCA
651
TAGCGGCCTT
TTCCTCTACC
AGGGGCTCCT
GCAGGCCCTG
GAAGGGATAT
701
CCCCCGAGTT
CGGTCCCACC
TTGGACACAC
TGCAGCTGGA
CGTCGCCGAC
751
TTTGCCACCA
CCATCTGGCA
GCAGATGGAA
GAACTGGGAA
TGGCCCCTGC
801
CCTGCAGCCC
ACCCAGGGTG
CCATGCCGGC
CTTCGCCTCT
GCTTTCCAGC
851
GCCGGGCAGG
AGGGGTCCTG
GTTGCTAGCC
ATCTGCAGAG
CTTCCTGGAG
901
GTGTCGTACC
GCGTTCTACG
CCACCTTGCG
CAGCCCGACA
TGGCTACACC
951
ATTAGGCCCT
GCCAGCTCCC
TGCCC;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 261)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTTTCCTG
451
CTCAAGTCTT
TAGAGCAAGT
GAGGAAGATC
CAGGGCGATG
GCGCAGCGCT
501
CCAGGAGAAG
CTGTGTGCCA
CCTACAAGCT
GTGCCACCCC
GAGGAGCTGG
551
TGCTGCTCGG
ACACTCTCTG
GGCATCCCCT
GGGCTCCCCT
GAGCTCCTGC
601
CCCAGCCAGG
CCCTGCAGCT
GGCAGGCTGC
TTGAGCCAAC
TCCATAGCGG
651
CCTTTTCCTC
TACCAGGGCC
TCCTGCAGGC
CCTGGAAGGG
ATATCCCCCG
701
AGTTGGGTCC
CACCTTGGAC
ACACTGCAGC
TGGACGTCGC
CGACTTTGCC
751
ACCACCATCT
GGCAGCAGAT
GGAAGAACTG
GGAATGGCCC
CTGCCCTGCA
801
GCCCACCCAG
GGTGCCATGC
CGGCCTTCGC
CTCTGCTTTC
CAGCGCCGGG
851
CAGGAGGGGT
CCTGGTTGCT
AGCCATCTGC
AGAGCTTCCT
GGAGGTGTCG
901
TACCGCGTTC
TACGCCACCT
TGCGCAGCCC
GACATGGCTA
CACCATTAGG
951
CCCTGCCAGC
TCCCTGCCCC
AGAGC;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 262)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACACT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTGAGCAA
451
GTGAGGAAGA
TCCAGGGCGA
TGGCGCAGCG
CTCCAGGAGA
AGCTGTGTGC
501
CACCTACAAG
CTGTGCCACC
CCGAGGAGCT
GGTGCTGCTC
GGACACTCTC
551
TGGGCATCCC
CTGGGCTCCC
CTGAGCTCCT
GCCCCAGCCA
GGCCCTGCAG
601
CTGGCAGGCT
GCTTGAGCCA
ACTCCATAGC
GGCCTTTTCC
TCTACCAGGG
651
GCTCCTGCAG
GCCCTGGAAG
GGATATCCCC
CGAGTTGGGT
CCCACCTTGG
701
ACACACTGCA
GCTGGACGTC
GCCGACTTTG
CCACCACCAT
CTGGCAGCAG
751
ATGGAAGAAC
TGGGAATGGC
CCCTGCCCTG
CAGCCCACCC
AGGGTGCCAT
801
GCCGGCCTTC
GCCTCTGCTT
TCCAGCGCCG
GGCAGGAGGG
GTCCTGGTTG
851
CTAGCCATCT
GCAGAGCTTC
CTGGAGGTGT
CGTACCGCGT
TCTACGCCAC
901
CTTGCGCAGC
CCGACATGGC
TACACCATTA
GGCCCTGCCA
GCTCCCTGCC
951
CCAGAGCTTC
CTGCTCAAGT
CTTTA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 263)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTCTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTCTGCTC
451
GGACACTCTC
TGGGCATCCC
CTGGGCTCCC
CTGAGCTCCT
GCCCCAGCCA
501
GGCCCTGCAG
CTGGCAGGCT
GCTTGAGCCA
ACTCCATAGC
GGCCTTTTCC
551
TCTACCAGGG
GCTCCTGCAG
GCCCTGGAAG
GGATATCCCC
CGAGTTGGGT
601
CCCACCTTGG
ACACACTGCA
GCTGGACGTC
GCCGACTTTG
CCACCACCAT
651
CTGGCAGCAG
ATGGAAGAAC
TGGGAATGGC
CCCTGCCCTG
CAGCCCACCC
701
AGGGTGCCAT
GCCGGCCTTC
GCCTCTGCTT
TCCAGCGCCG
GGCAGGAGGG
751
GTCCTGGTTG
CTAGCCATCT
GCAGAGCTTC
CTGGAGGTGT
CGTACCGCGT
801
TCTACGCCAC
CTTGCGCAGC
CCGACATGGC
TACACCATTA
GGCCCTGCCA
851
GCTCCCTGCC
CCAGAGCTTC
CTGCTCAAGT
CTTTAGAGCA
AGTGAGGAAG
901
ATCCAGGGCG
ATGGCGCAGC
GCTCCAGGAG
AAGCTGTGTG
CCACCTACAA
951
GCTGTGCCAC
CCCGAGGAGC
TGGTG;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 264)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTCCCCTG
451
AGCTCCTGCC
CCAGCCAGGC
CCTGCAGCTG
GCAGGCTGCT
TGAGCCAACT
501
CCATAGCGGC
CTTTTCCTCT
ACCAGGGGCT
CCTGCAGGCC
CTGGAAGGGA
551
TATCCCCCGA
GTTGGGTCCC
ACCTTGGACA
CACTGCAGCT
GGACGTCGCC
601
GACTTTGCCA
CCACCATCTG
GCAGCAGATG
GAAGAACTGG
GAATGGCCCC
651
TGCCCTGCAG
CCCACCCAGG
GTGCCATGCC
GGCCTTCGCC
TCTGCTTTCC
701
AGCGCCGGGC
AGGAGGGGTC
CTGGTTGCTA
GCCATCTGCA
GAGCTTCCTG
751
GAGGTGTCGT
ACCGCGTTCT
ACGCCACCTT
GCGCAGCCCG
ACATGGCTAC
801
ACCATTAGGC
CCTGCCAGCT
CCCTGCCCCA
GAGCTTCCTG
CTCAAGTCTT
851
TAGAGCAAGT
GAGGAAGATC
CAGGGCGATG
GCGCAGCGCT
CCAGGAGAAG
901
CTGTGTGCCA
CCTACAAGCT
GTGCCACCCC
GAGGAGCTGG
TGCTGCTCGG
951
ACACTCTCTG
GGCATCCCCT
GGGCT;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 265)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTCAGGCC
451
CTGCAGCTGG
CAGGCTGCTT
GAGCCAACTC
CATAGCGGCC
TTTTCCTCTA
501
CCAGGGGCTC
CTGCAGGCCC
TGGAAGGGAT
ATCCCCCGAG
TTGGGTCCCA
551
CCTTGGACAC
ACTGCAGCTG
GACGTCGCCG
ACTTTGCCAC
CACCATCTGG
601
CAGCAGATGG
AAGAACTGGG
AATGGCCCCT
GCCCTGCAGC
CCACCCAGGG
651
TGCCATGCCG
GCCTTCGCCT
CTGCTTTCCA
GCGCCGGGCA
GGAGGGGTCC
701
TGGTTGCTAG
CCATCTGCAG
AGCTTCCTGG
AGGTGTCGTA
CCGCGTTCTA
751
CGCCACCTTG
CGCAGCCCGA
CATGGCTACA
CCATTAGGCC
CTGCCAGCTC
801
CCTGCCCCAG
AGCTTCCTGC
TCAAGTCTTT
AGAGCAAGTG
AGGAAGATCC
851
AGGGCGATGG
CGCAGCCCTC
CAGGAGAAGC
TGTGTGCCAC
CTACAAGCTG
901
TGCCACCCCG
AGGAGCTGGT
GCTGCTCGGA
CACTCTCTGG
GCATCCCCTG
951
GGCTCCCCTG
AGCTCCTGCC
CCAGC;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 266)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTCGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTCG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTCTGCAG
451
CTGGCAGGCT
GCTTGAGCCA
ACTCCATAGC
GGCCTTTTCC
TCTACCAGGG
501
GCTCCTGCAG
GCCCTGGAAG
GGATATCCCC
CGAGTTGGGT
CCCACCTTGG
551
ACACACTGCA
GCTGGACGTC
GCCGACTTTG
CCACCACCAT
CTGGCAGCAG
601
ATGGAAGAAC
TGGGAATGGC
CCCTGCCCTG
CAGCCCACCC
AGGGTGCCAT
651
GCCGGCCTTC
GCCTCTGCTT
TCCAGCGCCG
GGCAGGAGGG
GTCCTGGTTG
701
CTAGCCATCT
GCAGAGCTTC
CTGGAGGTGT
CGTACCGCGT
TCTACGCCAC
751
CTTGCGCAGC
CCGACATGGC
TACACCATTA
GGCCCTCCCA
GCTCCCTGCC
801
CCAGAGCTTC
CTGCTCAAGT
CTTTAGAGCA
AGTGAGGAAG
ATCCAGGGCG
851
ATGGCGCAGC
GCTCCAGGAG
AAGCTGTGTG
CCACCTACAA
GCTGTGCCAC
901
CCCGAGGAGC
TGGTGCTGCT
CGGACACTCT
CTGGGCATCC
CCTGGGCTCC
951
CCTGAGCTCC
TGCCCCAGCC
AGGCC;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 267)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAACCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTCTGGCA
451
GGCTGCTTGA
GCCAACTCCA
TAGCGGCCTT
TTCCTCTACC
AGGGGCTCCT
501
GCAGGCCCTG
GAAGGGATAT
CCCCCGAGTT
GGGTCCCACC
TTGGACACAC
551
TGCAGCTGGA
CGTCGCCGAC
TTTGCCACCA
CCATCTGGCA
GCAGATGGAA
601
GAACTGGGAA
TGGCCCCTGC
CCTGCAGCCC
ACCCAGGGTG
CCATGCCGGC
651
CTTCGCCTCT
GCTTTCCAGC
GCCGGGCAGG
AGGGGTCCTG
GTTGCTAGCC
701
ATCTGCAGAG
CTTCCTGGAG
GTGTCGTACC
GCGTTCTACG
CCACCTTGCG
751
CAGCCCGACA
TGGCTACACC
ATTAGGCCCT
GCCAGCTCCC
TGCCCCAGAG
801
CTTCCTGCTC
AAGTCTTTAG
AGCAAGTGAG
GAAGATCCAG
GGCGATGGCG
851
CAGCGCTCCA
GGAGAAGCTG
TGTGCCACCT
ACAAGCTGTG
CCACCCCGAG
901
GAGCTGGTGC
TGCTCGGACA
CTCTCTGGGC
ATCCCCTGGG
CTCCCCTGAG
951
CTCCTGCCCC
AGCCAGGCCC
TGCAG;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 268)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTGAACTG
451
GGAATGGCCC
CTGCCCTGCA
GCCCACCCAG
GGTGCCATGC
CGGCCTTCGC
501
CTCTGCTTTC
CAGCGCCGGG
CAGGAGGGGT
CCTGGTTGCT
AGCCATCTGC
551
AGAGCTTCCT
GGAGGTGTCG
TACCGCGTTC
TACGCCACCT
TGCGCAGCCC
601
GACATGGCTA
CACCATTAGG
CCCTGCCAGC
TCCCTGCCCC
AGAGCTTCCT
651
GCTCAAGTCT
TTACAGCAAG
TGAGGAAGAT
CCAGGGCGAT
GGCGCAGCGC
701
TCCAGGAGAA
GCTGTGTGCC
ACCTACAAGC
TGTGCCACCC
CGAGGAGCTG
751
GTGCTGCTCG
GACACTCTCT
GGGCATCCCC
TGGGCTCCCC
TGAGCTCCTG
801
CCCCAGCCAG
GCCCTGCAGC
TGGCAGGCTG
CTTGAGCCAA
CTCCATAGCG
851
GCCTTTTCCT
CTACCAGGGG
CTCCTGCAGG
CCCTGGAAGG
GATATCCCCC
901
GAGTTGGGTC
CCACCTTGGA
CACACTGCAG
CTGGACGTCG
CCGACTTTGC
951
CACCACCATC
TGGCAGCAGA
TGGAA;
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 269)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTGGAATG
451
GCCCCTGCCC
TGCAGCCCAC
CCAGGGTGCC
ATGCCGGCCT
TCGCCTCTGC
501
TTTCCAGCGC
CGGGCAGGAG
GGGTCCTGGT
TGCTAGCCAT
CTGCAGAGCT
551
TCCTGGAGGT
GTCGTACCGC
GTTCTACGCC
ACCTTGCGCA
GCCCGACATG
601
GCTACACCAT
TAGGCCCTGC
CAGCTCCCTG
CCCCAGAGCT
TCCTGCTCAA
651
GTCTTTAGAG
CAAGTGAGGA
AGATCCAGGG
CGATGGCGCA
GCGCTCCAGG
701
AGAAGCTGTG
TGCCACCTAC
AAGCTGTGCC
ACCCCGAGGA
GCTGGTGCTG
751
CTCGGACACT
CTCTGGGCAT
CCCCTGGGCT
CCCCTGAGCT
CCTGCCCCAG
801
CCAGGCCCTG
CAGCTGGCAG
GCTGCTTGAG
CCAACTCCAT
AGCGGCCTTT
851
TCCTCTACCA
GGGGCTCCTG
CAGGCCCTGG
AAGGGATATC
CCCCGAGTTG
901
GGTCCCACCT
TGGACACACT
GCAGCTGGAC
GTCGCCGACT
TTGCCACCAC
951
CATCTGGCAG
CAGATGGAAG
AACTG;
and
1
ATGGCTAACT
GCTCTATAAT
GATCGATGAA
ATTATACATC
ACTTAAAGAG
(SEQ ID NO: 270)
51
ACCACCTGCA
CCTTTGCTGG
ACCCGAACAA
CCTCAATGAC
GAAGACGTCT
101
CTATCCTGAT
GGATCGAAAC
CTTCGACTTC
CAAACCTGGA
GAGCTTCGTA
151
AGGGCTGTCA
AGAACTTAGA
AAATGCATCA
GGTATTGAGG
CAATTCTTCG
201
TAATCTCCAA
CCATGTCTGC
CCTCTGCCAC
GGCCGCACCC
TCTCGACATC
251
CAATCATCAT
CAAGGCAGGT
GACTGGCAAG
AATTCCGGGA
AAAACTGACG
301
TTCTATCTGG
TTACCCTTGA
GCAAGCGCAG
GAACAACAGT
ACGTAGAGGG
351
CGGTGGAGGC
TCCCCGGGTG
AACCGTCTGG
TCCAATCTCT
ACTATCAACC
401
CGTCTCCTCC
GTCTAAAGAA
TCTCATAAAT
CTCCAAACAT
GGCTAGCTTC
451
CTGGAGGTGT
CGTACCGCGT
TCTACGCCAC
CTTGCGCAGC
CCGACATGGC
501
TACACCATTA
GGCCCTGCCA
GCTCCCTGCC
CCAGAGCTTC
CTGCTCAAGT
551
CTTTAGAGCA
AGTGAGGAAG
ATCCAGGGCG
ATGGCGCAGC
GCTCCAGGAG
601
AAGCTGTGTG
CCACCTACAA
GCTGTGCCAC
CCCCAGGAGC
TGGTGCTGCT
651
CGGACACTCT
CTGGGCATCC
CCTGGGCTCC
CCTGAGCTCC
TGCCCCAGCC
701
AGGCCCTCCA
GCTGGCAGGC
TGCTTGAGCC
AACTCCATAG
CGGCCTTTTC
751
CTCTACCAGG
GGCTCCTGCA
GGCCCTGGAA
GGGATATCCC
CCGAGTTGGG
801
TCCCACCTTG
GACACACTGC
AGCTGGACGT
CGCCGACTTT
GCCACCACCA
851
TCTGGCAGCA
GATGGAAGAA
CTGGGAATGG
CCCCTGCCCT
GCAGCCCACC
901
CAGGGTGCCA
TGCCGGCCTT
CGCCTCTGCT
TTCCAGCGCC
GGGCAGGAGG
951
GGTCCTGGTT
GCTAGCCATC
TGCAG.
37 . The nucleic acid molecule according to claim 34 selected from group consisting of:
1
ATGGCTGGAC CCACTTGCCT CTCATCCCTC CTGGGGCAGC TTTCTGGACA
(SEQ ID NO:286)
51
GGTCCGTCTC CTCCTTGGGG CCCTGCAGAG CCTCCTTGGA ACCCAGCTTC
101
CTCCACAGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CATCTTCCTG
151
AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG
201
AGGGTCCACC CTCGCCGTCA GGGAATTCGG CGGCAACATG GCGTCTCCGG
251
CGCCGCCTGC TGCTGACCTC CGAGTCCTCA GTAAACTGCT TCGTGACTCC
301
CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC
351
TACACCTGTC CTGCTGCCTG CTGTGGACTT TAGCTTGGGA GAATGGAAAA
401
CCCAGATGGA GGAGACCAAG GCACAGGACA TTCTGGGAGC AGTGACCCTT
451
CTGCTGGAGG GAGTGATGGC AGCACGGGGA CAACTG;
and
1
ATGGCTGGCA GGACCACAGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG
(SEQ ID NO:287)
51
CTTCCAACAC CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG
101
GGTCCACCCT CGCCGTCAGG GAATTCGGCG GCAACATGGC GTCTCCGGCG
151
CCGCCTGCTG CTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA
201
TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AGAGGTTCAC CCTTTGCCTA
251
CACCTGTCCT GCTGCCTGCT GTGGACTTTA GCTTGGGAGA ATGGAAAACC
301
CAGATGGAGG AGACCAAGGC ACAGGACATT CTGGGAGCAG TGACCCTTCT
351
GCTGGAGGGA GTGATGGCAG CACGGGGACA ACTGGGACCC ACTTGCCTCT
401
CATCCCTCCT GGGGCAGCTT TCTGGACAGG TCCGTCTCCT CCTTGGGGCC
451
CTGCAGAGCC TCCTTGGAAC CCAGCTTCCT CCACAG.
38 . A method of producing a hematopoietic protein comprising: growing under suitable nutrient conditions, a host cell transformed or transfected with a replicable vector comprising a nucleic acid molecule of claim 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 30 , 33 , 34 , 36 or 37 in a manner allowing expression of said hematopoietic protein and recovering said hematopoietic protein.
39 . A pharmaceutical composition comprising; the hematopoietic protein according to claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 12 , 15 or 16 and a pharmaceutically acceptable carrier.
40 . A method of stimulating the production of hematopoietic cells in a patient comprising the step of; administering an effective amount of the hematopoietic protein as recited in claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 12 , 15 , or 16 to said patient.
41 . A method of stimulating the production of hematopoietic cells in a patient comprising the step of administering an effective amount of the hematopoietic protein as recited in claim 13 to said patient.
42 . A method for selective ex vivo expansion of stem cells, comprising the steps of:
(a) separating stem cells from other cells; (b) culturing said separated stem cells with a selected culture medium-comprising; the hematopoietic protein of claim 1; and (c) harvesting said cultured cells.
43 . A method for treatment of a patient having a hematopoietic disorder, comprising the steps of:
(a) removing stem cells; (b) separating stem cells from other cells; (c) culturing said separated stem cells with a selected culture medium comprising; the hematopoietic protein of claim 1; (d) harvesting said cultured cells; and (e) transplanting said cultured cells into said patient.
44 . A method of human gene therapy, comprising the steps of:
(a) removing stem cells from a patient; (b) separating said stem cells from other cells; (c) culturing said separated stem cells with a selected culture medium comprising; the hematopoietic protein of claim 1; (d) introducing DNA into said cultured cells; (e) harvesting said transduced cells; and (f) transplanting said transduced cells into said patient.
45 . A method of human gene therapy, comprising the steps of:
(a) removing stem cells from a patient; (b) separating said stem cells from other cells; (c) culturing said separated stem cells with a selected culture medium comprising; the hematopoietic protein of claim 1; (d) introducing DNA into said cultured cells; (e) harvesting said transduced cells; and (f) transplanting said transduced cells into said patient.
46 . A method of human gene therapy, comprising the steps of:
(a) removing stem cells from a patient; (b) separating said stem cells from other cells; (c) culturing said separated stem cells with a selected culture medium comprising; the hematopoietic protein of claim 11; (d) introducing DNA into said cultured cells; (e) harvesting said transduced cells; and (f) transplanting said transduced cells into said patient.
47 . A method of human gene therapy, comprising the steps of:
(a) removing stem cells from a patient; (b) separating said stem cells from other cells; (c) culturing said separated stem cells with a selected culture medium comprising; the hematopoietic protein of claim 11; (d) introducing DNA into said cultured cells; (e) harvesting said transduced cells; and (f) transplanting said transduced cells into said patient.Cited by (0)
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