ID COIA1_HUMAN Reviewed; 1754 AA. AC P39060; A8MVI4; Q58EX6; Q6RZ39; Q6RZ40; Q6RZ41; Q8N4S4; Q8WXI5; Q96T70; AC Q9UK38; Q9Y6Q7; Q9Y6Q8; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 5. DT 27-MAR-2024, entry version 234. DE RecName: Full=Collagen alpha-1(XVIII) chain {ECO:0000305}; DE Contains: DE RecName: Full=Endostatin {ECO:0000305}; DE Contains: DE RecName: Full=Non-collagenous domain 1 {ECO:0000305}; DE Short=NC1; DE Flags: Precursor; GN Name=COL18A1 {ECO:0000312|HGNC:HGNC:2195}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND VARIANT ILE-1076. RX PubMed=9503365; DOI=10.1016/s0945-053x(98)90003-8; RA Saarela J., Ylikarppa R., Rehn M., Purmonen S., Pihlajaniemi T.; RT "Complete primary structure of two variant forms of human type XVIII RT collagen and tissue-specific differences in the expression of the RT corresponding transcripts."; RL Matrix Biol. 16:319-328(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2 AND 3), AND VARIANTS RP ILE-1076 AND ASN-1675. RX PubMed=14614989; DOI=10.1016/s0945-053x(03)00073-8; RA Elamaa H., Snellman A., Rehn M., Autio-Harmainen H., Pihlajaniemi T.; RT "Characterization of the human type XVIII collagen gene and proteolytic RT processing and tissue location of the variant containing a frizzled RT motif."; RL Matrix Biol. 22:427-442(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U., RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ILE-1076. RC TISSUE=Kidney, and PNS; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1069-1754, AND VARIANT ARG-1121. RX PubMed=8188291; DOI=10.1006/geno.1994.1098; RA Oh S.P., Warman M.L., Seldin M.F., Cheng S., Knoll J.H., Timmons S., RA Olsen B.R.; RT "Cloning of cDNA and genomic DNA encoding human type XVIII collagen and RT localization of the alpha 1(XVIII) collagen gene to mouse chromosome 10 and RT human chromosome 21."; RL Genomics 19:494-499(1994). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1568-1754. RX PubMed=11517600; RA Feng Y., Cui L.B., Liu C.X., Ma Q.J.; RT "Inhibition effect in vitro of purified endostatin expressed in Pichia RT pastoris."; RL Sheng Wu Gong Cheng Xue Bao 17:278-282(2001). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1572-1754, AND VARIANT ASN-1675. RC TISSUE=Placenta; RA Zhi-Yong H., Biao L., Wei-Jie Z., Xiang-Fu W.; RT "Cloning and expression of human endostatin gene in Escherichia coli."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1642-1743. RA Deininger M.H., Trautmann K., Schluesener H.J.; RT "Endostatin promotes delayed secondary damage following traumatic brain RT injury."; RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases. RN [9] RP FUNCTION. RX PubMed=9459295; DOI=10.1016/s0014-5793(97)01503-2; RA Staendker L., Schrader M., Kanse S.M., Juergens M., Forssmann W.G., RA Preissner K.T.; RT "Isolation and characterization of the circulating form of human RT endostatin."; RL FEBS Lett. 420:129-133(1997). RN [10] RP GLYCOSYLATION AT THR-1567, GLYCOSYLATION, AND SUBCELLULAR LOCATION. RX PubMed=10441114; DOI=10.1021/bi990787+; RA John H., Preissner K.T., Forssmann W.G., Staendker L.; RT "Novel glycosylated forms of human plasma endostatin and circulating RT endostatin-related fragments of collagen XV."; RL Biochemistry 38:10217-10224(1999). RN [11] RP PROTEOLYTIC CLEAVAGE. RX PubMed=10626789; RA Wen W., Moses M.A., Wiederschain D., Arbiser J.L., Folkman J.; RT "The generation of endostatin is mediated by elastase."; RL Cancer Res. 59:6052-6056(1999). RN [12] RP FUNCTION, AND SUBUNIT. RX PubMed=11257123; DOI=10.1083/jcb.152.6.1233; RA Kuo C.J., LaMontagne K.R. Jr., Garcia-Cardena G., Ackley B.D., Kalman D., RA Park S., Christofferson R., Kamihara J., Ding Y.H., Lo K.M., Gillies S., RA Folkman J., Mulligan R.C., Javaherian K.; RT "Oligomerization-dependent regulation of motility and morphogenesis by the RT collagen XVIII NC1/endostatin domain."; RL J. Cell Biol. 152:1233-1246(2001). RN [13] RP BIOTECHNOLOGY. RX PubMed=17644065; DOI=10.1016/j.bbrc.2007.06.155; RA Ling Y., Yang Y., Lu N., You Q.D., Wang S., Gao Y., Chen Y., Guo Q.L.; RT "Endostar, a novel recombinant human endostatin, exerts antiangiogenic RT effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of RT endothelial cells."; RL Biochem. Biophys. Res. Commun. 361:79-84(2007). RN [14] RP INVOLVEMENT IN KNO1. RX PubMed=23667181; DOI=10.1136/jmedgenet-2013-101755; RA Aldahmesh M.A., Khan A.O., Mohamed J.Y., Levin A.V., Wuthisiri W., RA Lynch S., McCreery K., Alkuraya F.S.; RT "No evidence for locus heterogeneity in Knobloch syndrome."; RL J. Med. Genet. 50:565-566(2013). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-696, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [16] RP TISSUE SPECIFICITY, AND GLYCOSYLATION AT SER-889. RX PubMed=32337544; DOI=10.1093/glycob/cwaa039; RA Toledo A.G., Pihl J., Spliid C.B., Persson A., Nilsson J., Pereira M.A., RA Gustavsson T., Choudhary S., Oo H.Z., Black P.C., Daugaard M., Esko J.D., RA Larson G., Salanti A., Clausen T.M.; RT "An affinity chromatography and glycoproteomics workflow to profile the RT chondroitin sulfate proteoglycans that interact with malarial VAR2CSA in RT the placenta and in cancer."; RL Glycobiology 30:989-1002(2020). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1572-1749, AND ZINC-BINDING SITE. RX PubMed=9724722; DOI=10.1073/pnas.95.18.10443; RA Ding Y.-H., Javaherian K., Lo K.-M., Chopra R., Boehm T., Lanciotti J., RA Harris B.A., Li Y., Shapiro R., Hohenester E., Timpl R., Folkman J., RA Wiley D.C.; RT "Zinc-dependent dimers observed in crystals of human endostatin."; RL Proc. Natl. Acad. Sci. U.S.A. 95:10443-10448(1998). RN [18] RP INVOLVEMENT IN KNO1, AND FUNCTION. RX PubMed=10942434; DOI=10.1093/hmg/9.13.2051; RA Sertie A.L., Sossi V., Camargo A.A., Zatz M., Brahe C., Passos-Bueno M.R.; RT "Collagen XVIII, containing an endogenous inhibitor of angiogenesis and RT tumor growth, plays a critical role in the maintenance of retinal structure RT and in neural tube closure."; RL Hum. Mol. Genet. 9:2051-2058(2000). RN [19] RP VARIANTS ILE-1076 AND ASN-1675. RX PubMed=11606364; RA Iughetti P., Suzuki O., Godoi P.H., Alves V.A., Sertie A.L., Zorick T., RA Soares F., Camargo A.A., Moreira E.S., di Loreto C., Moreira-Filho C.A., RA Simpson A., Oliva G., Passos-Bueno M.R.; RT "A polymorphism in endostatin, an angiogenesis inhibitor, predisposes for RT the development of prostatic adenocarcinoma."; RL Cancer Res. 61:7375-7378(2001). RN [20] RP VARIANTS LEU-49; ARG-111; ILE-1076 AND ARG-1121, AND CHARACTERIZATION OF RP VARIANT ASN-1675. RX PubMed=14695535; DOI=10.1002/humu.10284; RA Menzel O., Bekkeheien R.C.J., Reymond A., Fukai N., Boye E., RA Kosztolanyi G., Aftimos S., Deutsch S., Scott H.S., Olsen B.R., RA Antonarakis S.E., Guipponi M.; RT "Knobloch syndrome: novel mutations in COL18A1, evidence for genetic RT heterogeneity, and a functionally impaired polymorphism in endostatin."; RL Hum. Mutat. 23:77-84(2004). RN [21] RP VARIANT [LARGE SCALE ANALYSIS] ARG-1121. RX PubMed=18987736; DOI=10.1038/nature07485; RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., RA DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). RN [22] RP INVOLVEMENT IN GLCC, AND VARIANT GLCC LYS-184. RX PubMed=30007336; DOI=10.1093/hmg/ddy256; RA Suri F., Yazdani S., Chapi M., Safari I., Rasooli P., Daftarian N., RA Jafarinasab M.R., Ghasemi Firouzabadi S., Alehabib E., Darvish H., RA Klotzle B., Fan J.B., Turk C., Elahi E.; RT "COL18A1 is a candidate eye iridocorneal angle-closure gene in humans."; RL Hum. Mol. Genet. 27:3772-3786(2018). CC -!- FUNCTION: Probably plays a major role in determining the retinal CC structure as well as in the closure of the neural tube. CC {ECO:0000269|PubMed:10942434}. CC -!- FUNCTION: [Non-collagenous domain 1]: May regulate extracellular CC matrix-dependent motility and morphogenesis of endothelial and non- CC endothelial cells; the function requires homotrimerization and CC implicates MAPK signaling. {ECO:0000269|PubMed:11257123}. CC -!- FUNCTION: [Endostatin]: Potently inhibits endothelial cell CC proliferation and angiogenesis (PubMed:9459295). May inhibit CC angiogenesis by binding to the heparan sulfate proteoglycans involved CC in growth factor signaling (By similarity). Inhibits VEGFA-induced CC endothelial cell proliferation and migration. Seems to inhibit VEGFA- CC mediated signaling by blocking the interaction of VEGFA to its receptor CC KDR/VEGFR2. Modulates endothelial cell migration in an integrin- CC dependent manner implicating integrin ITGA5:ITGB1 and to a lesser CC extent ITGAV:ITGB3 and ITGAV:ITGB5 (By similarity). May negatively CC regulate the activity of homotrimeric non-collagenous domain 1 CC (PubMed:11257123). {ECO:0000250|UniProtKB:P39061, CC ECO:0000269|PubMed:11257123, ECO:0000269|PubMed:9459295}. CC -!- SUBUNIT: [Non-collagenous domain 1]: Forms homotrimers CC (PubMed:11257123). Recombinant non-collagenous domain 1 has stronger CC affinity to NID1, HSPG2 and laminin-1:NID1 complex and lower affinity CC to FBLN1 and FBLN2 than endostatin (By similarity). CC {ECO:0000250|UniProtKB:P39061, ECO:0000269|PubMed:11257123}. CC -!- SUBUNIT: [Endostatin]: Monomeric (PubMed:11257123). Interacts with CC KDR/VEGFR2. Interacts with the ITGA5:ITGB1 complex. Interacts with CC NID1, HSPG2, laminin-1:NID1 complex, FBLN1 and FBLN2 (By similarity). CC {ECO:0000250|UniProtKB:P39061, ECO:0000269|PubMed:11257123}. CC -!- INTERACTION: CC PRO_0000005794; PRO_0000000092 [P05067]: APP; NbExp=2; IntAct=EBI-2566375, EBI-821758; CC PRO_0000005794; PRO_0000005794 [P39060]: COL18A1; NbExp=6; IntAct=EBI-2566375, EBI-2566375; CC PRO_0000005794; P19338: NCL; NbExp=12; IntAct=EBI-2566375, EBI-346967; CC PRO_0000005794; Q15113: PCOLCE; NbExp=4; IntAct=EBI-2566375, EBI-8869614; CC PRO_0000005794; P21980: TGM2; NbExp=2; IntAct=EBI-2566375, EBI-727668; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000250}. Secreted, extracellular space, extracellular CC matrix, basement membrane {ECO:0000250|UniProtKB:P39061}. CC -!- SUBCELLULAR LOCATION: [Non-collagenous domain 1]: Secreted, CC extracellular space, extracellular matrix, basement membrane CC {ECO:0000250|UniProtKB:P39061}. Secreted CC {ECO:0000250|UniProtKB:P39061}. CC -!- SUBCELLULAR LOCATION: [Endostatin]: Secreted CC {ECO:0000269|PubMed:10441114}. Secreted, extracellular space, CC extracellular matrix, basement membrane {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=NC1-728; CC IsoId=P39060-3; Sequence=Displayed; CC Name=2; Synonyms=Long, NC-493; CC IsoId=P39060-1; Sequence=VSP_023131; CC Name=3; Synonyms=Short, NC1-303; CC IsoId=P39060-2; Sequence=VSP_023130, VSP_023132; CC -!- TISSUE SPECIFICITY: Detected in placenta (at protein level) CC (PubMed:32337544). Present in multiple organs with highest levels in CC liver, lung and kidney. {ECO:0000269|PubMed:32337544}. CC -!- PTM: Prolines at the third position of the tripeptide repeating unit CC (G-X-Y) of the triple-helical regions are hydroxylated. CC -!- PTM: Circulating endostatins are found as sialoglycoprotein and CC asialoglycoprotein structures. {ECO:0000269|PubMed:10441114}. CC -!- PTM: Undergoes proteolytic processing by CTSL/cathepsin-L and elastase- CC like proteases to generate both non-collagenous domain 1 trimers and CC endostatin monomers (PubMed:10626789). In tissue extracts (brain, CC skeletal muscle, heart, kidney, testis and liver) predominantly bands CC of approximately 38 kDa are detected; recombinant non-collagenous CC domain 1 shows similar mobility. In vitro, several proteolytic cleavage CC sites in the non-collagenous domain 1 hinge region generating different CC endostatin-like peptides are reported (By similarity). CC {ECO:0000250|UniProtKB:P39061, ECO:0000269|PubMed:10626789}. CC -!- POLYMORPHISM: There is an association between a polymorphism in CC position 1675 and prostate cancer. Heterozygous Asn-1675 individuals CC have a 2.5 times increased chance of developing prostate cancer as CC compared with homozygous Asp-1675 individuals. CC -!- DISEASE: Knobloch syndrome 1 (KNO1) [MIM:267750]: A developmental CC disorder primarily characterized by typical eye abnormalities, CC including high myopia, cataracts, dislocated lens, vitreoretinal CC degeneration, and retinal detachment, with occipital skull defects, CC which can range from occipital encephalocele to occult cutis aplasia. CC {ECO:0000269|PubMed:10942434, ECO:0000269|PubMed:23667181}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Glaucoma, primary closed-angle (GLCC) [MIM:618880]: An CC autosomal dominant form of primary glaucoma, an ocular disease CC characterized by a marked increase of intraocular pressure causing CC damage to eye structures and function. GLCC is characterized by CC elevated intraocular pressure due to iridocorneal angle closure with CC retention of the aqueous humor in the anterior chamber. Iridocorneal CC angle changes are apparent in the fourth to fifth decade of life, and CC patients manifest age-related variation in the severity of glaucomatous CC damage. {ECO:0000269|PubMed:30007336}. Note=The disease may be caused CC by variants affecting the gene represented in this entry. CC -!- BIOTECHNOLOGY: [Endostatin]: Available under the name Endostar (Jiangsu CC Simcere Pharmaceutical) for the treatment of non-small-cell lung CC cancer. {ECO:0000269|PubMed:17644065, ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 1]: Produced by alternative promoter usage. CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing of isoform CC 1. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative promoter usage. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the multiplexin collagen family. {ECO:0000305}. CC -!- CAUTION: Non-collagenous domain 1 seems to be the predominant tissue CC form from which endostatin is cleaved. However, the proteolytic CC cleavage site to generate non-collagenous domain 1 is not known. CC Soluble recombinant non-collagenous domain 1 amenable to biochemical CC studies has been used instead. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF018081; AAC39658.1; -; mRNA. DR EMBL; AF018082; AAC39659.1; -; mRNA. DR EMBL; AY484971; AAR83296.1; -; Genomic_DNA. DR EMBL; AY484968; AAR83296.1; JOINED; Genomic_DNA. DR EMBL; AY484969; AAR83296.1; JOINED; Genomic_DNA. DR EMBL; AY484970; AAR83296.1; JOINED; Genomic_DNA. DR EMBL; AY484971; AAR83297.1; -; Genomic_DNA. DR EMBL; AY484968; AAR83297.1; JOINED; Genomic_DNA. DR EMBL; AY484969; AAR83297.1; JOINED; Genomic_DNA. DR EMBL; AY484970; AAR83297.1; JOINED; Genomic_DNA. DR EMBL; AY484971; AAR83298.1; -; Genomic_DNA. DR EMBL; AY484967; AAR83298.1; JOINED; Genomic_DNA. DR EMBL; AY484969; AAR83298.1; JOINED; Genomic_DNA. DR EMBL; AY484970; AAR83298.1; JOINED; Genomic_DNA. DR EMBL; AL163302; CAB90482.1; -; Genomic_DNA. DR EMBL; BX322561; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC033715; AAH33715.1; -; mRNA. DR EMBL; BC063833; AAH63833.1; -; mRNA. DR EMBL; L22548; AAA51864.1; -; mRNA. DR EMBL; AF416592; AAL37720.1; -; mRNA. DR EMBL; AF184060; AAF01310.1; -; mRNA. DR EMBL; AF333247; AAK50626.1; -; mRNA. DR CCDS; CCDS42971.1; -. [P39060-2] DR RefSeq; NP_085059.2; NM_030582.3. DR RefSeq; NP_569711.2; NM_130444.2. DR RefSeq; NP_569712.2; NM_130445.3. DR PDB; 1BNL; X-ray; 2.90 A; A/B/C/D=1572-1749. DR PDB; 3HON; X-ray; 3.00 A; A=1441-1496. DR PDB; 3HSH; X-ray; 1.80 A; A/B/C/D/E/F=1441-1496. DR PDBsum; 1BNL; -. DR PDBsum; 3HON; -. DR PDBsum; 3HSH; -. DR AlphaFoldDB; P39060; -. DR SMR; P39060; -. DR BioGRID; 123311; 130. DR ComplexPortal; CPX-1759; Collagen type XVIII trimer. DR CORUM; P39060; -. DR IntAct; P39060; 32. DR MINT; P39060; -. DR STRING; 9606.ENSP00000352798; -. DR ChEMBL; CHEMBL2364188; -. DR GlyConnect; 127; 1 N-Linked glycan (1 site), 1 O-Linked glycan (1 site). DR GlyCosmos; P39060; 29 sites, 10 glycans. DR GlyGen; P39060; 32 sites, 1 N-linked glycan (1 site), 10 O-linked glycans (27 sites). DR iPTMnet; P39060; -. DR PhosphoSitePlus; P39060; -. DR BioMuta; COL18A1; -. DR DMDM; 215274264; -. DR EPD; P39060; -. DR jPOST; P39060; -. DR MassIVE; P39060; -. DR MaxQB; P39060; -. DR PeptideAtlas; P39060; -. DR ProteomicsDB; 55311; -. [P39060-3] DR ProteomicsDB; 55312; -. [P39060-1] DR ProteomicsDB; 55313; -. [P39060-2] DR Pumba; P39060; -. DR Antibodypedia; 2814; 665 antibodies from 37 providers. DR DNASU; 80781; -. DR Ensembl; ENST00000355480.10; ENSP00000347665.5; ENSG00000182871.16. [P39060-1] DR Ensembl; ENST00000359759.8; ENSP00000352798.4; ENSG00000182871.16. [P39060-3] DR Ensembl; ENST00000651438.1; ENSP00000498485.1; ENSG00000182871.16. [P39060-2] DR GeneID; 80781; -. DR KEGG; hsa:80781; -. DR MANE-Select; ENST00000651438.1; ENSP00000498485.1; NM_001379500.1; NP_001366429.1. [P39060-2] DR UCSC; uc062awf.1; human. [P39060-3] DR AGR; HGNC:2195; -. DR CTD; 80781; -. DR DisGeNET; 80781; -. DR GeneCards; COL18A1; -. DR HGNC; HGNC:2195; COL18A1. DR HPA; ENSG00000182871; Tissue enhanced (liver). DR MalaCards; COL18A1; -. DR MIM; 120328; gene. DR MIM; 267750; phenotype. DR MIM; 618880; phenotype. DR neXtProt; NX_P39060; -. DR OpenTargets; ENSG00000182871; -. DR Orphanet; 1571; Knobloch syndrome. DR PharmGKB; PA26711; -. DR VEuPathDB; HostDB:ENSG00000182871; -. DR eggNOG; KOG3546; Eukaryota. DR GeneTree; ENSGT00940000158212; -. DR HOGENOM; CLU_004003_1_0_1; -. DR InParanoid; P39060; -. DR OMA; GTKQTNI; -. DR OrthoDB; 5363002at2759; -. DR PhylomeDB; P39060; -. DR TreeFam; TF315821; -. DR PathwayCommons; P39060; -. DR Reactome; R-HSA-1442490; Collagen degradation. DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases. DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes. DR Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures. DR Reactome; R-HSA-216083; Integrin cell surface interactions. DR Reactome; R-HSA-3000157; Laminin interactions. DR Reactome; R-HSA-8948216; Collagen chain trimerization. DR SignaLink; P39060; -. DR SIGNOR; P39060; -. DR BioGRID-ORCS; 80781; 6 hits in 1154 CRISPR screens. DR ChiTaRS; COL18A1; human. DR EvolutionaryTrace; P39060; -. DR GeneWiki; Collagen,_type_XVIII,_alpha_1; -. DR GenomeRNAi; 80781; -. DR Pharos; P39060; Tbio. DR PRO; PR:P39060; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; P39060; Protein. DR Bgee; ENSG00000182871; Expressed in right coronary artery and 189 other cell types or tissues. DR ExpressionAtlas; P39060; baseline and differential. DR GO; GO:0005604; C:basement membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005581; C:collagen trimer; IBA:GO_Central. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL. DR GO; GO:0030020; F:extracellular matrix structural constituent conferring tensile strength; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central. DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0030199; P:collagen fibril organization; IBA:GO_Central. DR GO; GO:0001886; P:endothelial cell morphogenesis; IBA:GO_Central. DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0030903; P:notochord development; IBA:GO_Central. DR GO; GO:0051599; P:response to hydrostatic pressure; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central. DR GO; GO:0007601; P:visual perception; TAS:ProtInc. DR CDD; cd07455; CRD_Collagen_XVIII; 1. DR CDD; cd00247; Endostatin-like; 1. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 3.40.1620.70; -; 1. DR Gene3D; 1.10.2000.10; Frizzled cysteine-rich domain; 1. DR Gene3D; 3.10.100.10; Mannose-Binding Protein A, subunit A; 1. DR InterPro; IPR016186; C-type_lectin-like/link_sf. DR InterPro; IPR008160; Collagen. DR InterPro; IPR035523; Collagen_XVIII_Fz. DR InterPro; IPR010515; Collagenase_NC10/endostatin. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR016187; CTDL_fold. DR InterPro; IPR010363; DUF959_COL18_N. DR InterPro; IPR020067; Frizzled_dom. DR InterPro; IPR036790; Frizzled_dom_sf. DR InterPro; IPR048287; TSPN-like_N. DR InterPro; IPR045463; XV/XVIII_trimerization_dom. DR PANTHER; PTHR24023; COLLAGEN ALPHA; 1. DR PANTHER; PTHR24023:SF1034; COLLAGEN ALPHA-1(XVIII) CHAIN; 1. DR Pfam; PF01391; Collagen; 3. DR Pfam; PF20010; Collagen_trimer; 1. DR Pfam; PF06121; DUF959; 1. DR Pfam; PF06482; Endostatin; 1. DR Pfam; PF01392; Fz; 1. DR SMART; SM00063; FRI; 1. DR SMART; SM00210; TSPN; 1. DR SUPFAM; SSF56436; C-type lectin-like; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF63501; Frizzled cysteine-rich domain; 1. DR PROSITE; PS50038; FZ; 1. DR Genevisible; P39060; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative promoter usage; Alternative splicing; KW Basement membrane; Cell adhesion; Collagen; Disulfide bond; KW Extracellular matrix; Glaucoma; Glycoprotein; Hydroxylation; Metal-binding; KW Phosphoprotein; Proteoglycan; Reference proteome; Repeat; Secreted; Signal; KW Zinc. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..1754 FT /note="Collagen alpha-1(XVIII) chain" FT /id="PRO_0000005793" FT CHAIN 1572..1754 FT /note="Endostatin" FT /id="PRO_0000005794" FT CHAIN ?..1754 FT /note="Non-collagenous domain 1" FT /id="PRO_0000441861" FT DOMAIN 329..446 FT /note="FZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DOMAIN 456..644 FT /note="Laminin G-like" FT REGION 42..104 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 152..256 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 645..1443 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 645..751 FT /note="Nonhelical region 1 (NC1)" FT REGION 752..785 FT /note="Triple-helical region 1 (COL1)" FT REGION 786..795 FT /note="Nonhelical region 2 (NC2)" FT REGION 796..875 FT /note="Triple-helical region 2 (COL2)" FT REGION 876..899 FT /note="Nonhelical region 3 (NC3)" FT REGION 900..1021 FT /note="Triple-helical region 3 (COL3)" FT REGION 1022..1044 FT /note="Nonhelical region 4 (NC4)" FT REGION 1045..1127 FT /note="Triple-helical region 4 (COL4)" FT REGION 1128..1141 FT /note="Nonhelical region 5 (NC5)" FT REGION 1142..1183 FT /note="Triple-helical region 5 (COL5)" FT REGION 1184..1196 FT /note="Nonhelical region 6 (NC6)" FT REGION 1197..1269 FT /note="Triple-helical region 6 (COL6)" FT REGION 1270..1279 FT /note="Nonhelical region 7 (NC7)" FT REGION 1280..1312 FT /note="Triple-helical region 7 (COL7)" FT REGION 1313..1324 FT /note="Nonhelical region 8 (NC8)" FT REGION 1325..1346 FT /note="Triple-helical region 8 (COL8)" FT REGION 1347..1353 FT /note="Nonhelical region 9 (NC9)" FT REGION 1354..1411 FT /note="Triple-helical region 9 (COL9)" FT REGION 1412..1424 FT /note="Nonhelical region 10 (NC10)" FT REGION 1425..1442 FT /note="Triple-helical region 10 (COL10)" FT REGION 1443..1754 FT /note="Nonhelical region 11 (NC11)" FT REGION 1456..1501 FT /note="Non-collagenous domain 1 association domain" FT /evidence="ECO:0000250|UniProtKB:P39061" FT REGION 1502..1571 FT /note="Non-collagenous domain 1 hinge region" FT /evidence="ECO:0000250|UniProtKB:P39061" FT REGION 1511..1556 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 1330..1332 FT /note="Cell attachment site" FT /evidence="ECO:0000255" FT COMPBIAS 54..75 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 157..183 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 189..211 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 235..249 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 716..740 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 764..791 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 799..813 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 861..875 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 903..917 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 938..962 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1004..1022 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1253..1269 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1320..1337 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1352..1369 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1378..1437 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1516..1530 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1572 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT BINDING 1574 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT BINDING 1582 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT BINDING 1647 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT MOD_RES 696 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT CARBOHYD 68 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 129 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 164 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 889 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000269|PubMed:32337544" FT CARBOHYD 926 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1567 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:10441114" FT /id="CAR_000150" FT DISULFID 334..397 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 344..390 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 381..419 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 408..443 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 412..432 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 1604..1744 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 1706..1736 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT VAR_SEQ 1..415 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9503365" FT /id="VSP_023130" FT VAR_SEQ 216..450 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9503365" FT /id="VSP_023131" FT VAR_SEQ 416..450 FT /note="QDACWSRLGGGRLPVACASLPTQEDGYCVLIGPAA -> MAPRCPWPWPRRR FT RLLDVLAPLVLLLGVRAASAEP (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9503365" FT /id="VSP_023132" FT VARIANT 49 FT /note="Q -> L (in dbSNP:rs61735029)" FT /evidence="ECO:0000269|PubMed:14695535" FT /id="VAR_018053" FT VARIANT 111 FT /note="G -> R (in dbSNP:rs114139997)" FT /evidence="ECO:0000269|PubMed:14695535" FT /id="VAR_018054" FT VARIANT 184 FT /note="E -> K (in GLCC; uncertain significance; FT dbSNP:rs749957649)" FT /evidence="ECO:0000269|PubMed:30007336" FT /id="VAR_084282" FT VARIANT 288 FT /note="A -> T (in dbSNP:rs11702494)" FT /id="VAR_059232" FT VARIANT 379 FT /note="T -> M (in dbSNP:rs8133886)" FT /id="VAR_061115" FT VARIANT 1076 FT /note="V -> I (in dbSNP:rs62000962)" FT /evidence="ECO:0000269|PubMed:11606364, FT ECO:0000269|PubMed:14614989, ECO:0000269|PubMed:14695535, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9503365" FT /id="VAR_018055" FT VARIANT 1121 FT /note="P -> R (in dbSNP:rs79980197)" FT /evidence="ECO:0000269|PubMed:14695535, FT ECO:0000269|PubMed:18987736, ECO:0000269|PubMed:8188291" FT /id="VAR_018056" FT VARIANT 1195 FT /note="Q -> H (in dbSNP:rs2230693)" FT /id="VAR_059233" FT VARIANT 1675 FT /note="D -> N (probable risk factor for prostate cancer; FT results in decreased affinity for laminin; FT dbSNP:rs12483377)" FT /evidence="ECO:0000269|PubMed:11606364, FT ECO:0000269|PubMed:14614989, ECO:0000269|PubMed:14695535, FT ECO:0000269|Ref.7" FT /id="VAR_012709" FT CONFLICT 299 FT /note="R -> K (in Ref. 2; AAR83296)" FT /evidence="ECO:0000305" FT CONFLICT 663 FT /note="S -> F (in Ref. 1; AAC39658/AAC39659)" FT /evidence="ECO:0000305" FT CONFLICT 1112 FT /note="V -> L (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1147 FT /note="P -> R (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1168 FT /note="R -> L (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1210 FT /note="P -> L (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1299 FT /note="A -> P (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1319 FT /note="L -> K (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1355 FT /note="P -> A (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1358 FT /note="P -> A (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1362..1364 FT /note="Missing (in Ref. 1; AAC39658/AAC39659, 2; FT AAR83296/AAR83297/AAR83298, 4; AAH33715/AAH63833 and 5; FT AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1444 FT /note="G -> GQ (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1542 FT /note="R -> G (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1552 FT /note="A -> G (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1561..1562 FT /note="LR -> CG (in Ref. 5; AAA51864)" FT /evidence="ECO:0000305" FT CONFLICT 1681 FT /note="R -> T (in Ref. 7; AAF01310)" FT /evidence="ECO:0000305" FT CONFLICT 1685 FT /note="W -> R (in Ref. 8; AAK50626)" FT /evidence="ECO:0000305" FT CONFLICT 1721 FT /note="S -> Y (in Ref. 7; AAF01310)" FT /evidence="ECO:0000305" FT CONFLICT 1736 FT /note="C -> S (in Ref. 8; AAK50626)" FT /evidence="ECO:0000305" FT STRAND 1445..1450 FT /evidence="ECO:0007829|PDB:3HSH" FT HELIX 1451..1457 FT /evidence="ECO:0007829|PDB:3HSH" FT HELIX 1458..1460 FT /evidence="ECO:0007829|PDB:3HSH" FT STRAND 1466..1469 FT /evidence="ECO:0007829|PDB:3HSH" FT TURN 1470..1473 FT /evidence="ECO:0007829|PDB:3HSH" FT STRAND 1474..1479 FT /evidence="ECO:0007829|PDB:3HSH" FT STRAND 1482..1486 FT /evidence="ECO:0007829|PDB:3HSH" FT STRAND 1488..1493 FT /evidence="ECO:0007829|PDB:3HSH" FT STRAND 1581..1585 FT /evidence="ECO:0007829|PDB:1BNL" FT HELIX 1597..1610 FT /evidence="ECO:0007829|PDB:1BNL" FT STRAND 1617..1621 FT /evidence="ECO:0007829|PDB:1BNL" FT HELIX 1629..1631 FT /evidence="ECO:0007829|PDB:1BNL" FT HELIX 1634..1636 FT /evidence="ECO:0007829|PDB:1BNL" FT STRAND 1649..1652 FT /evidence="ECO:0007829|PDB:1BNL" FT HELIX 1654..1657 FT /evidence="ECO:0007829|PDB:1BNL" FT HELIX 1679..1681 FT /evidence="ECO:0007829|PDB:1BNL" FT STRAND 1689..1691 FT /evidence="ECO:0007829|PDB:1BNL" FT HELIX 1706..1709 FT /evidence="ECO:0007829|PDB:1BNL" FT STRAND 1716..1722 FT /evidence="ECO:0007829|PDB:1BNL" FT HELIX 1723..1725 FT /evidence="ECO:0007829|PDB:1BNL" FT STRAND 1727..1729 FT /evidence="ECO:0007829|PDB:1BNL" FT STRAND 1732..1735 FT /evidence="ECO:0007829|PDB:1BNL" FT STRAND 1743..1747 FT /evidence="ECO:0007829|PDB:1BNL" SQ SEQUENCE 1754 AA; 178188 MW; 23A327DCBD3B328D CRC64; MAPYPCGCHI LLLLFCCLAA ARANLLNLNW LWFNNEDTSH AATTIPEPQG PLPVQPTADT TTHVTPRNGS TEPATAPGSP EPPSELLEDG QDTPTSAESP DAPEENIAGV GAEILNVAKG IRSFVQLWND TVPTESLARA ETLVLETPVG PLALAGPSST PQENGTTLWP SRGIPSSPGA HTTEAGTLPA PTPSPPSLGR PWAPLTGPSV PPPSSGRASL SSLLGGAPPW GSLQDPDSQG LSPAAAAPSQ QLQRPDVRLR TPLLHPLVMG SLGKHAAPSA FSSGLPGALS QVAVTTLTRD SGAWVSHVAN SVGPGLANNS ALLGADPEAP AGRCLPLPPS LPVCGHLGIS RFWLPNHLHH ESGEQVRAGA RAWGGLLQTH CHPFLAWFFC LLLVPPCGSV PPPAPPPCCQ FCEALQDACW SRLGGGRLPV ACASLPTQED GYCVLIGPAA ERISEEVGLL QLLGDPPPQQ VTQTDDPDVG LAYVFGPDAN SGQVARYHFP SLFFRDFSLL FHIRPATEGP GVLFAITDSA QAMVLLGVKL SGVQDGHQDI SLLYTEPGAG QTHTAASFRL PAFVGQWTHL ALSVAGGFVA LYVDCEEFQR MPLARSSRGL ELEPGAGLFV AQAGGADPDK FQGVIAELKV RRDPQVSPMH CLDEEGDDSD GASGDSGSGL GDARELLREE TGAALKPRLP APPPVTTPPL AGGSSTEDSR SEEVEEQTTV ASLGAQTLPG SDSVSTWDGS VRTPGGRVKE GGLKGQKGEP GVPGPPGRAG PPGSPCLPGP PGLPCPVSPL GPAGPALQTV PGPQGPPGPP GRDGTPGRDG EPGDPGEDGK PGDTGPQGFP GTPGDVGPKG DKGDPGVGER GPPGPQGPPG PPGPSFRHDK LTFIDMEGSG FGGDLEALRG PRGFPGPPGP PGVPGLPGEP GRFGVNSSDV PGPAGLPGVP GREGPPGFPG LPGPPGPPGR EGPPGRTGQK GSLGEAGAPG HKGSKGAPGP AGARGESGLA GAPGPAGPPG PPGPPGPPGP GLPAGFDDME GSGGPFWSTA RSADGPQGPP GLPGLKGDPG VPGLPGAKGE VGADGVPGFP GLPGREGIAG PQGPKGDRGS RGEKGDPGKD GVGQPGLPGP PGPPGPVVYV SEQDGSVLSV PGPEGRPGFA GFPGPAGPKG NLGSKGERGS PGPKGEKGEP GSIFSPDGGA LGPAQKGAKG EPGFRGPPGP YGRPGYKGEI GFPGRPGRPG MNGLKGEKGE PGDASLGFGM RGMPGPPGPP GPPGPPGTPV YDSNVFAESS RPGPPGLPGN QGPPGPKGAK GEVGPPGPPG QFPFDFLQLE AEMKGEKGDR GDAGQKGERG EPGGGGFFGS SLPGPPGPPG PPGPRGYPGI PGPKGESIRG QPGPPGPQGP PGIGYEGRQG PPGPPGPPGP PSFPGPHRQT ISVPGPPGPP GPPGPPGTMG ASSGVRLWAT RQAMLGQVHE VPEGWLIFVA EQEELYVRVQ NGFRKVQLEA RTPLPRGTDN EVAALQPPVV QLHDSNPYPR REHPHPTARP WRADDILASP PRLPEPQPYP GAPHHSSYVH LRPARPTSPP AHSHRDFQPV LHLVALNSPL SGGMRGIRGA DFQCFQQARA VGLAGTFRAF LSSRLQDLYS IVRRADRAAV PIVNLKDELL FPSWEALFSG SEGPLKPGAR IFSFDGKDVL RHPTWPQKSV WHGSDPNGRR LTESYCETWR TEAPSATGQA SSLLGGRLLG QSAASCHHAY IVLCIENSFM TASK //