Novel collectins

Abstract

Provided are isolated collectin (CL-L2s) genes including a base sequence set out in SEQ ID NO: 1, 3, 5, 7, 9, 12, 36, 38 or 40 relating to a novel collectin which are expected to exhibit an antibacterial activity, an antiviral activity and the like particularly in a human body; and isolated collectin proteins including an amino acid sequence set out in SEQ ID NO: 2, 4, 6, 8, 10, 13, 37, 39 or 41 and derivatives and fragments thereof.

What is claimed is:  
     
         1 . A protein comprising an amino acid sequence consisting of 271 amino acids set out in the amino acid position 1-271 of SEQ ID NO: 2, or a protein consisting of an amino acid sequence set out in SEQ ID NO: 2 having deletion, substitution or addition of one or several amino acids therein and having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-271 of SEQ ID NO: 2, or a derivative or a fragment thereof.  
     
     
         2 . A base sequence set out in SEQ ID NO: 45 (corresponding to a base sequence set out in the base position 265-1077 of SEQ ID NO: 1), a base sequence encoding an amino acid sequence set out in the amino acid position 1-271 of SEQ ID NO: 2 or a fragment thereof, or a base sequence that hybridizes to any one of said base sequences or a base sequence complementary thereto under a stringent condition and encodes a protein having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-271 of SEQ ID NO: 2.  
     
     
         3 . A protein comprising an amino acid sequence consisting of 245 amino acids set out in the amino acid position 1-245 of SEQ ID NO: 4, or a protein consisting of an amino acid sequence set out in the amino acid position 1-245 of SEQ ID NO: 4 having deletion, substitution or addition of one or several amino acids therein and having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-245 of SEQ ID NO: 4, or a derivative or a fragment thereof.  
     
     
         4 . A base sequence set out in SEQ ID NO: 46 (corresponding to a base sequence set out in the base position 141-875 of SEQ ID NO: 3), a base sequence encoding an amino acid sequence set out in the amino acid position 1-245 of SEQ ID NO: 4 or a fragment thereof, or a base sequence that hybridizes to any one of said base sequences or a base sequence complementary thereto under a stringent condition and encodes a protein having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-245 of SEQ ID NO: 4.  
     
     
         5 . A protein comprising an amino acid sequence consisting of 159 amino acids set out in SEQ ID NO: 47 (corresponding to an amino acid sequence set out in the amino acid position 113-271 of SEQ ID NO: 2), or a protein consisting of an amino acid sequence set out in SEQ ID NO: 2 having deletion, substitution or addition of one or several amino acids therein and having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 113-271 of SEQ ID NO: 2, or a derivative or a fragment thereof.  
     
     
         6 . A base sequence set out in SEQ ID NO: 48 (corresponding to a base sequence set out in the base position 601-1077 of SEQ ID NO: 1), a base sequence encoding an amino acid sequence set out in the amino acid position 113-271 of SEQ ID NO: 2 or a fragment thereof, or a base sequence that hybridizes to any one of said base sequences or a base sequence complementary thereto under a stringent condition and encodes a protein having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 113-271 of SEQ ID NO: 2.  
     
     
         7 . The protein further comprising a sequence (Gly-Xaa-Yaa)n, wherein n represents an integer of from 1 to 50, Xaa and Yaa represent an amino acid residue, which may be the same or different, at an N-terminal of the protein according to  claim 5 .  
     
     
         8 . The protein according to  claim 7  wherein said (Gly-Xaa-Yaa)n is selected from the group of sequences consisting of: 
 Gly-Leu-Lys-Gly-Asp-Ala-Gly-Glu-Lys-Gly-Asp-Lys-Gly-Ala-Pro-Gly-Arg-Pro-Gly-Arg—Val-Gly-Pro-Thr-Gly-Glu-Lys-Gly-Asp-Met-Gly-Asp-Lys-Gly-Gln-Lys-Gly-Ser-Val-Gly—Arg-His-Gly-Lys-Ile-Gly-Pro-Ile-Gly-Ser-Lys-Gly-Glu-Lys-Gly-Asp-Ser-Gly-Asp-Ile-Gly-Pro-Pro-Gly-Pro-Asn-Gly-Glu-Pro-Gly-Leu-Pro (SEQ ID NO: 49 (corresponding to the amino acid position 41-112 of SEQ ID NO: 2)),  
 Gly-Asp-Ala-Gly-Glu-Lys-Gly-Asp-Lys-Gly-Ala-Pro-Gly-Arg-Pro-Gly-Arg-Val-Gly-Pro—Thr-Gly-Glu-Lys-Gly-Asp-Met-Gly-Asp-Lys-Gly-Gln-Lys-Gly-Ser-Val-Gly-Arg-His-Gly—Lys-Ile-Gly-Pro-Ile-Gly-Ser-Lys-Gly-Glu-Lys-Gly-Asp-Ser-Gly-Asp-Ile-Gly-Pro-Pro-Gly-Pro-Asn-Gly-Glu-Pro-Gly-Leu-Pro (SEQ ID NO: 50 (corresponding to the amino acid position 44-112 of SEQ ID NO: 2, or the amino acid position 18-86 of SEQ ID NO: 4)) Gly-Glu-Lys-Gly-Asp-Ser-Gly-Asp-Ile-Gly-Pro-Pro-Gly-Pro-Asn-Gly-Glu-Pro-Gly-Leu-Pro (SEQ ID NO: 51 (corresponding to the amino acid position 92-112 of SEQ ID NO: 2 or the amino acid position 66-86 of SEQ ID NO: 4)),  
 Gly-Asp-Met-Gly-Asp-Lys-Gly-Gln-Lys-Gly-Ser-Val-Gly-Arg-His-Gly-Lys-Ile-Gly-Pro—Ile-Gly-Ser-Lys-Gly-Glu-Lys-Gly-Asp-Ser-Gly-Asp-Ile-Gly-Pro-Pro-Gly-Pro-Asn-Gly-Glu-Pro-Gly-Leu-Pro (SEQ ID NO: 52 (corresponding to the amino acid position 68-112 of SEQ ID NO: 2 or the amino acid position 42-86 of SEQ ID NO: 4)),  
 Gly-Asp-Ala-Gly-Glu-Lys-Gly-Asp-Lys-Gly-Ala-Pro-Gly-Arg-Pro-Gly-Arg-Val-Gly-Pro—Thr-Gly-Glu-Lys-Gly-Glu-Lys-Gly-Asp-Ser-Gly-Asp-Ile-Gly-Pro-Pro-Gly-Pro-Asn-Gly-Glu-Pro-Gly-Leu-Pro (SEQ ID NO: 11 (corresponding to the amino acid position 44-67 and 92-112 of SEQ ID NO: 2 or the amino acid position 18-41 and 66-86 of SEQ ID NO: 4)), Gly-Leu-Lys-Gly-Glu-Lys-Gly-Asp-Ser-Gly-Asp-Ile-Gly-Pro-Pro-Gly-Pro-Asn-Gly-Glu-Pro-Gly-Leu-Pro (SEQ ID NO: 43 (corresponding to the amino acid position 41-43 and 92-112 of SEQ ID NO: 2)),  
 Gly-Leu-Lys-Gly-Asp-Met-Gly-Asp-Lys-Gly-Gln-Lys-Gly-Ser-Val-Gly-Arg-His-Gly-Lys—Ile-Gly-Pro-Ile-Gly-Ser-Lys-Gly-Glu-Lys-Gly-Asp-Ser-Gly-Asp-Ile-Gly-Pro-Pro-Gly-Pro-Asn-Gly-Glu-Pro-Gly-Leu-Pro (SEQ ID NO: 42 (corresponding to the amino acid position 41-43 and 68-112 of SEQ ID NO: 2)), or  
 Gly-Leu-Lys-Gly-Asp-Ala-Gly-Glu-Lys-Gly-Asp-Lys-Gly-Ala-Pro-Gly-Arg-Pro-Gly-Arg—Val-Gly-Pro-Thr-Gly-Glu-Lys-Gly-Glu-Lys-Gly-Asp-Ser-Gly-Asp-Ile-Gly-Pro-Pro-Gly-Pro-Asn-Gly-Glu-Pro-Gly-Leu-Pro (SEQ ID NO: 44 (corresponding to the amino acid position 41-67 and 92-112 of SEQ ID NO: 2)).  
 
     
     
         9 . A base sequence encoding the protein according to  claim 7  or  8 .  
     
     
         10 . A protein comprising an amino acid sequence of: 
 Met-Arg-Gly-Asn-Leu-Ala-Leu-Val-Gly-Val-Leu-Ile-Ser-Leu-Ala-Phe-Leu-Ser-Leu—Leu-Pro-Ser-Gly-His-Pro-Gln-Pro-Ala-Gly-Asp-Asp-Ala-Cys-Ser-Val-Gln-Ile-Leu-Val-Pro (SEQ ID NO: 53 (corresponding to the amino acid position 1-40 of SEQ ID NO: 2)) at an N-terminal of the sequence (Gly-Xaa-Yaa)n of the protein according to  claim 7  or  8  in addition thereto.    
     
     
         11 . A protein comprising a sequence of: Met-Trp-Trp-Val-Pro-Pro-Ser-Pro-Tyr-Gly-Cys-Leu-Pro-Cys-Ala-Leu-Pro (SEQ ID NO: 54 (corresponding to the amino acid position 1-17 of SEQ ID NO: 4)) at an N-terminal of the sequence (Gly-Xaa-Yaa)n of the protein according to  claim 7  or  8  in addition thereto.  
     
     
         12 . A base sequence encoding the protein according to  claim 10  or  11 .  
     
     
         13 . A protein comprising an amino acid sequence consisting of 197 amino acids set out in the amino acid position 1-197 of SEQ ID NO: 6, or a protein consisting of an amino acid sequence set out in the amino acid position 1-197 of SEQ ID NO: 6 having deletion, substitution or addition of one or several amino acids therein and having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-197 of SEQ ID NO: 6, or a derivative or a fragment thereof.  
     
     
         14 . A base sequence set out in SEQ ID NO: 55 (corresponding to a base sequence set out in the base position 141-731 of SEQ ID NO: 5), a base sequence encoding an amino acid sequence set out in the amino acid position 1-197 of SEQ ID NO: 6 or a fragment thereof, or a base sequence that hybridizes to any one of said base sequences or a base sequence complementary thereto under a stringent condition and encodes a protein having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-197 of SEQ ID NO: 6.  
     
     
         15 . A protein comprising an amino acid sequence consisting of 221 amino acids set out in the amino acid position 1-221 of SEQ ID NO: 8, or a protein consisting of an amino acid sequence set out in the amino acid position 1-221 of SEQ ID NO: 8 having deletion, substitution or addition of one or several amino acids therein and having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-221 of SEQ ID NO: 8, or a derivative or a fragment thereof.  
     
     
         16 . A base sequence set out in SEQ ID NO: 56 (corresponding to a base sequence set out in the base position 141-803 of SEQ ID NO: 7), a base sequence encoding an amino acid sequence set out in the amino acid position 1-221 of SEQ ID NO: 8 or a fragment thereof, or a base sequence that hybridizes to any one of said base sequences or a base sequence complementary thereto under a stringent condition and encodes a protein having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-221 of SEQ ID NO: 8.  
     
     
         17 . A protein comprising an amino acid sequence consisting of 221 amino acids set out in the amino acid position 1-221 of SEQ ID NO: 10, or a protein consisting of an amino acid sequence set out in the amino acid position 1-221 of SEQ ID NO: 10 having deletion, substitution or addition of one or several amino acids therein and having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-221 of SEQ ID NO: 10, or a derivative or a fragment thereof.  
     
     
         18 . A base sequence set out in SEQ ID NO: 57 (corresponding to a base sequence set out in the base position 141-803 of SEQ ID NO: 9), a base sequence encoding an amino acid sequence set out in the amino acid position 1-221 of SEQ ID NO: 10 or a fragment thereof, or a base sequence that hybridizes to any one of said base sequences or a base sequence complementary thereto under a stringent condition and encodes a protein having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-221 of SEQ ID NO: 10.  
     
     
         19 . A protein comprising an amino acid sequence consisting of 271 amino acids set out in the amino acid position 1-271 of SEQ ID NO: 13, or a protein consisting of an amino acid sequence set out in the amino acid position 1-271 of SEQ ID NO: 13 having deletion, substitution or addition of one or several amino acids therein and having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-271 of SEQ ID NO: 13, or a derivative or a fragment thereof.  
     
     
         20 . A base sequence set out in SEQ ID NO: 58 (corresponding to a base sequence set out in the base position 157-969 of SEQ ID NO: 12), a base sequence encoding an amino acid sequence set out in the amino acid position 1-271 of SEQ ID NO: 13 or a fragment thereof, or a base sequence that hybridizes to any one of said base sequences or a base sequence complementary thereto under a stringent condition and encodes a protein having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-271 of SEQ ID NO: 13.  
     
     
         21 . A protein comprising an amino acid sequence consisting of 223 amino acids set out in the amino acid position 1-223 of SEQ ID NO: 37, or a protein consisting of an amino acid sequence set out in the amino acid position 1-223 of SEQ ID NO: 37 having deletion, substitution or addition of one or several amino acids therein and having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-223 of SEQ ID NO: 37, or a derivative or a fragment thereof.  
     
     
         22 . A base sequence set out in SEQ ID NO: 59 (corresponding to a base sequence set out in the base position 265-933 of SEQ ID NO: 36), a base sequence encoding an amino acid sequence set out in the amino acid position 1-223 of SEQ ID NO: 37 or a fragment thereof, or a base sequence that hybridizes to any one of said base sequences or a base sequence complementary thereto under a stringent condition and encodes a protein having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-223 of SEQ ID NO: 37.  
     
     
         23 . A protein comprising an amino acid sequence consisting of 247 amino acids set out in the amino acid position 1-247 of SEQ ID NO: 39, or a protein consisting of an amino acid sequence set out in the amino acid position 1-247 of SEQ ID NO: 39 having deletion, substitution or addition of one or several amino acids therein and having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-247 of SEQ ID NO: 39, or a derivative or a fragment thereof.  
     
     
         24 . A base sequence set out in SEQ ID NO: 60 (corresponding to a base sequence set out in the base position 265-1005 of SEQ ID NO: 38), a base sequence encoding an amino acid sequence set out in the amino acid position 1-247 of SEQ ID NO: 39 or a fragment thereof, or a base sequence that hybridizes to any one of said base sequences or a base sequence complementary thereto under a stringent condition and encodes a protein having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-247 of SEQ ID NO: 39.  
     
     
         25 . A protein comprising an amino acid sequence consisting of 247 amino acids set out in the amino acid position 1-247 of SEQ ID NO: 41, or a protein consisting of an amino acid sequence set out in the amino acid position 1-247 of SEQ ID NO: 41 having deletion, substitution or addition of one or several amino acids therein and having an equal property to that of the protein having an amino acid sequence set out in the amino acid position 1-247 of SEQ ID NO: 41, or a derivative or a fragment thereof.  
     
     
         26 . A base sequence set out in SEQ ID NO: 61 (corresponding to a base sequence set out in the base position 265-1005 of SEQ ID NO: 40), a base sequence encoding an amino acid sequence set out in the amino acid position 1-247 of SEQ ID NO: 41 or a fragment thereof, or a base sequence that hybridizes to any one of said base sequences or a base sequence complementary thereto under a stringent condition and encodes a protein having an equal property to that of the protein having an amino acid sequence set out in amino acid position 1-247 of SEQ ID NO: 41.  
     
     
         27 . A vector comprising a base sequence according to  claim 2 ,  4 ,  6 ,  9 ,  12 ,  14 ,  16 ,  18 ,  20 ,  22 ,  24  or  26 .  
     
     
         28 . A transformed cell carrying a base sequence according to  claim 2 ,  4 ,  6 ,  9 ,  12 ,  14 ,  16 ,  18 ,  20 ,  22 ,  24  or  26  in a manner to allow the expression.  
     
     
         29 . A process for the production of a protein which comprises the steps of: culturing a cell transformed with the base sequence according to  claim 2 ,  4 ,  6 ,  9 ,  12 ,  14 ,  16 ,  18 ,  22 ,  24  or  26 ; and harvesting thus produced hCL-L2s protein.  
     
     
         30 . A process for the production of a protein which comprises the steps of: culturing a cell transformed with the base sequence according to  claim 20;  and harvesting thus produced mCL-L2s protein.  
     
     
         31 . The process according to  claim 29  or  30  wherein said cell is  Escherichia coli , an animal cell or an insect cell.  
     
     
         32 . A transgenic non-human animal having an altered expression level of CL-L2s gene.  
     
     
         33 . A knockout mouse wherein a function of mCL-L2s gene is deficient.  
     
     
         34 . An antibody to the protein according to  claim 1 ,  3 ,  5 ,  7 ,  8 ,  10 ,  11 ,  13 ,  15 ,  17 ,  19 ,  21 ,  23  or  25 , or a fragment thereof.  
     
     
         35 . The antibody according to  claim 34 , which is a polyclonal antibody, a monoclonal antibody or a peptide antibody.  
     
     
         36 . A process for measuring a CL-L2s protein or a fragment thereof on the basis of an immunological binding between the antibody according to  claim 34  or  35  and the CL-L2s protein or a fragment thereof.  
     
     
         37 . An agonist that stimulates a function of the protein according to  claim 1 ,  3 ,  5 ,  7 ,  8 ,  10 ,  11 ,  13 ,  15 ,  17 ,  19 ,  21 ,  23  or  25 .  
     
     
         38 . An antagonist that inhibits a function of the protein according to  claim 1 ,  3 ,  5 ,  7 ,  8 ,  10 ,  11 ,  13 ,  15 ,  17 ,  19 ,  21 ,  23  or  25 .  
     
     
         39 . A process for screening a drug wherein the protein according to  claim 1 ,  3 ,  5 ,  7 ,  8 ,  10 ,  11 ,  13 ,  15 ,  17 ,  19 ,  21 ,  23  or  25  is used.  
     
     
         40 . A drug which is obtained by the process for the screening according to  claim 39.