ID CO4A2_HUMAN Reviewed; 1712 AA. AC P08572; Q14052; Q548C3; Q5VZA9; Q66K23; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 03-APR-2007, sequence version 4. DT 27-MAR-2024, entry version 235. DE RecName: Full=Collagen alpha-2(IV) chain {ECO:0000305}; DE Contains: DE RecName: Full=Canstatin; DE Flags: Precursor; GN Name=COL4A2 {ECO:0000312|HGNC:HGNC:2203}; 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]. RX PubMed=3198637; DOI=10.1016/s0021-9258(19)77660-1; RA Hostikka S.L., Tryggvason K.; RT "The complete primary structure of the alpha 2 chain of human type IV RT collagen and comparison with the alpha 1(IV) chain."; RL J. Biol. Chem. 263:19488-19493(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1042, AND VARIANTS LYS-517 AND ALA-683. RC TISSUE=Placenta; RX PubMed=3345760; DOI=10.1111/j.1432-1033.1988.tb13852.x; RA Brazel D., Pollner R., Oberbaeumer I., Kuehn K.; RT "Human basement membrane collagen (type IV). The amino acid sequence of the RT alpha 2(IV) chain and its comparison with the alpha 1(IV) chain reveals RT deletions in the alpha 1(IV) chain."; RL Eur. J. Biochem. 172:35-42(1988). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33. RX PubMed=2846280; DOI=10.1002/j.1460-2075.1988.tb03122.x; RA Poeschl E., Pollner R., Kuehn K.; RT "The genes for the alpha 1(IV) and alpha 2(IV) chains of human basement RT membrane collagen type IV are arranged head-to-head and separated by a RT bidirectional promoter of unique structure."; RL EMBO J. 7:2687-2695(1988). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33. RX PubMed=3182844; DOI=10.1016/s0021-9258(19)77818-1; RA Soininen R., Huotari M., Hostikka S.L., Prockop D.J., Tryggvason K.; RT "The structural genes for alpha 1 and alpha 2 chains of human type IV RT collagen are divergently encoded on opposite DNA strands and have an RT overlapping promoter region."; RL J. Biol. Chem. 263:17217-17220(1988). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33. RC TISSUE=Skin; RX PubMed=8317999; DOI=10.1042/bj2920687; RA Fischer G., Schmidt C., Opitz J., Cully Z., Kuehn K., Poeschl E.; RT "Identification of a novel sequence element in the common promoter region RT of human collagen type IV genes, involved in the regulation of divergent RT transcription."; RL Biochem. J. 292:687-695(1993). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1040-1712. RC TISSUE=Placenta; RX PubMed=3692475; DOI=10.1007/bf00291418; RA Killen P.D., Francomano C.A., Yamada Y., Modi W.S., O'Brien S.J.; RT "Partial structure of the human alpha 2(IV) collagen chain and chromosomal RT localization of the gene (COL4A2)."; RL Hum. Genet. 77:318-324(1987). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1254-1712, AND VARIANT ILE-1399. RX PubMed=3582677; DOI=10.1016/0014-5793(87)80706-8; RA Hostikka S.L., Kurkinen M., Tryggvason K.; RT "Nucleotide sequence coding for the human type IV collagen alpha 2 chain RT cDNA reveals extensive homology with the NC-1 domain of alpha 1 (IV) but RT not with the collagenous domain or 3'-untranslated region."; RL FEBS Lett. 216:281-286(1987). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1351-1712. RC TISSUE=Eye; 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 [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1451-1485. RX PubMed=3025878; DOI=10.1073/pnas.84.2.512; RA Griffin C.A., Emanuel B.S., Hansen J.R., Cavenee W.K., Myers J.C.; RT "Human collagen genes encoding basement membrane alpha 1 (IV) and alpha 2 RT (IV) chains map to the distal long arm of chromosome 13."; RL Proc. Natl. Acad. Sci. U.S.A. 84:512-516(1987). RN [11] RP PROTEIN SEQUENCE OF 1480-1535; 1545-1614; 1617-1701 AND 1705-1712. RC TISSUE=Placenta; RX PubMed=2844531; DOI=10.1111/j.1432-1033.1988.tb14321.x; RA Siebold B., Deutzmann R., Kuehn K.; RT "The arrangement of intra- and intermolecular disulfide bonds in the RT carboxyterminal, non-collagenous aggregation and cross-linking domain of RT basement-membrane type IV collagen."; RL Eur. J. Biochem. 176:617-624(1988). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1486-1712. RX PubMed=2439508; DOI=10.1016/s0021-9258(18)48071-4; RA Myers J.C., Howard P.S., Jelen A.M., Dion A.S., Macarak E.J.; RT "Duplication of type IV collagen COOH-terminal repeats and species-specific RT expression of alpha 1(IV) and alpha 2(IV) collagen genes."; RL J. Biol. Chem. 262:9231-9238(1987). RN [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1486-1712, AND FUNCTION. RX PubMed=10625665; DOI=10.1074/jbc.275.2.1209; RA Kamphaus G.D., Colorado P.C., Panka D.J., Hopfer H., Ramchandran R., RA Torre A., Maeshima Y., Mier J.W., Sukhatme V.P., Kalluri R.; RT "Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor RT growth."; RL J. Biol. Chem. 275:1209-1215(2000). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1486-1712. RA Peng X., Sun W., Yin B., Yuan J., Qiang B.; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [15] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1486-1712. RC TISSUE=Hepatocyte; RA Li Y., Huang G., Qian G.; RT "Molecular cloning and homologous sequence analysis of canstatin cDNA RT derived from Chinese hepatocytes."; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1486-1712. RA Shan Z.X., Yu X.Y., Lin Q.X., Fu Y.H., Yang M., Tan H.H.; RT "Cloning and expression of canstatin in yeast."; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [17] RP FUNCTION OF CANSTATIN. RX PubMed=12876280; DOI=10.1074/jbc.m307339200; RA Panka D.J., Mier J.W.; RT "Canstatin inhibits Akt activation and induces Fas-dependent apoptosis in RT endothelial cells."; RL J. Biol. Chem. 278:37632-37636(2003). RN [18] RP FUNCTION OF CANSTATIN. RX PubMed=15899827; DOI=10.1158/0008-5472.can-04-3536; RA Magnon C., Galaup A., Mullan B., Rouffiac V., Bouquet C., Bidart J.M., RA Griscelli F., Opolon P., Perricaudet M.; RT "Canstatin acts on endothelial and tumor cells via mitochondrial damage RT initiated through interaction with alphavbeta3 and alphavbeta5 integrins."; RL Cancer Res. 65:4353-4361(2005). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [20] RP IDENTIFICATION BY 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 [21] RP BROMINATION AT TYR-1490, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=32571911; DOI=10.1073/pnas.2007749117; RA He C., Song W., Weston T.A., Tran C., Kurtz I., Zuckerman J.E., RA Guagliardo P., Miner J.H., Ivanov S.V., Bougoure J., Hudson B.G., Colon S., RA Voziyan P.A., Bhave G., Fong L.G., Young S.G., Jiang H.; RT "Peroxidasin-mediated bromine enrichment of basement membranes."; RL Proc. Natl. Acad. Sci. U.S.A. 117:15827-15836(2020). RN [22] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1485-1712. RX PubMed=12011424; DOI=10.1073/pnas.062183499; RA Than M.E., Henrich S., Huber R., Ries A., Mann K., Kuhn K., Timpl R., RA Bourenkov G.P., Bartunik H.D., Bode W.; RT "The 1.9-A crystal structure of the noncollagenous (NC1) domain of human RT placenta collagen IV shows stabilization via a novel type of covalent Met- RT Lys cross-link."; RL Proc. Natl. Acad. Sci. U.S.A. 99:6607-6612(2002). RN [23] RP VARIANTS PHE-192; LYS-517; ALA-683; ARG-701 AND SER-718. RX PubMed=21527998; RA Karolak J.A., Kulinska K., Nowak D.M., Pitarque J.A., Molinari A., RA Rydzanicz M., Bejjani B.A., Gajecka M.; RT "Sequence variants in COL4A1 and COL4A2 genes in Ecuadorian families with RT keratoconus."; RL Mol. Vis. 17:827-843(2011). RN [24] RP VARIANTS BSVD2 GLU-1037 AND ASP-1152. RX PubMed=22209246; DOI=10.1016/j.ajhg.2011.11.016; RA Yoneda Y., Haginoya K., Arai H., Yamaoka S., Tsurusaki Y., Doi H., RA Miyake N., Yokochi K., Osaka H., Kato M., Matsumoto N., Saitsu H.; RT "De novo and inherited mutations in COL4A2, encoding the type IV collagen RT alpha2 chain cause porencephaly."; RL Am. J. Hum. Genet. 90:86-90(2012). RN [25] RP INVOLVEMENT IN SUSCEPTIBILITY TO ICH, VARIANTS PHE-192; LYS-517; ALA-683; RP ARG-701; SER-718; GLN-1109; GLY-1123; LYS-1150; ILE-1399 AND THR-1690, AND RP CHARACTERIZATION OF VARIANTS GLY-1123; LYS-1150 AND THR-1690. RX PubMed=22209247; DOI=10.1016/j.ajhg.2011.11.022; RA Jeanne M., Labelle-Dumais C., Jorgensen J., Kauffman W.B., Mancini G.M., RA Favor J., Valant V., Greenberg S.M., Rosand J., Gould D.B.; RT "COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic RT stroke."; RL Am. J. Hum. Genet. 90:91-101(2012). RN [26] RP VARIANT ARG-1389. RX PubMed=22333902; DOI=10.1038/ejhg.2012.20; RA Verbeek E., Meuwissen M.E., Verheijen F.W., Govaert P.P., Licht D.J., RA Kuo D.S., Poulton C.J., Schot R., Lequin M.H., Dudink J., Halley D.J., RA de Coo R.I., den Hollander J.C., Oegema R., Gould D.B., Mancini G.M.; RT "COL4A2 mutation associated with familial porencephaly and small-vessel RT disease."; RL Eur. J. Hum. Genet. 20:844-851(2012). CC -!- FUNCTION: Type IV collagen is the major structural component of CC glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork CC together with laminins, proteoglycans and entactin/nidogen. CC -!- FUNCTION: Canstatin, a cleavage product corresponding to the collagen CC alpha 2(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor CC cell activity. It inhibits proliferation and migration of endothelial CC cells, reduces mitochondrial membrane potential, and induces apoptosis. CC Specifically induces Fas-dependent apoptosis and activates procaspase-8 CC and -9 activity. Ligand for alphavbeta3 and alphavbeta5 integrins. CC -!- SUBUNIT: There are six type IV collagen isoforms, alpha 1(IV)-alpha CC 6(IV), each of which can form a triple helix structure with 2 other CC chains to generate type IV collagen network. Interacts with EFEMP2 (By CC similarity). {ECO:0000250|UniProtKB:P08122}. CC -!- INTERACTION: CC P08572; P02462: COL4A1; NbExp=2; IntAct=EBI-2432506, EBI-2432478; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix, basement membrane. CC -!- DOMAIN: Alpha chains of type IV collagen have a non-collagenous domain CC (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats CC in the long central triple-helical domain (which may cause flexibility CC in the triple helix), and a short N-terminal triple-helical 7S domain. CC -!- PTM: Prolines at the third position of the tripeptide repeating unit CC (G-X-Y) are hydroxylated in some or all of the chains. CC -!- PTM: Type IV collagens contain numerous cysteine residues which are CC involved in inter- and intramolecular disulfide bonding. 12 of these, CC located in the NC1 domain, are conserved in all known type IV CC collagens. CC -!- PTM: The trimeric structure of the NC1 domains is stabilized by CC covalent bonds between Lys and Met residues. {ECO:0000250}. CC -!- PTM: Proteolytic processing produces the C-terminal NC1 peptide, CC canstatin. CC -!- DISEASE: Brain small vessel disease 2 (BSVD2) [MIM:614483]: An CC autosomal dominant cerebrovascular disorder with variable CC manifestations reflecting the location and severity of the vascular CC defect. BSVD2 features include intracranial hemorrage, fluid-filled CC cysts or cavities within the cerebral hemispheres, delayed psychomotor CC development, hemiplegia, spasticity and seizures. CC {ECO:0000269|PubMed:22209246}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Intracerebral hemorrhage (ICH) [MIM:614519]: A pathological CC condition characterized by bleeding into one or both cerebral CC hemispheres including the basal ganglia and the cerebral cortex. It is CC often associated with hypertension and craniocerebral trauma. CC Intracerebral bleeding is a common cause of stroke. CC {ECO:0000269|PubMed:22209247}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the type IV collagen family. CC {ECO:0000255|PROSITE-ProRule:PRU00736}. 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; AL139385; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL159153; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL161773; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; X05562; CAA29076.1; -; mRNA. DR EMBL; M36963; AAA53099.1; -; Genomic_DNA. DR EMBL; J04217; AAA53097.1; -; Genomic_DNA. DR EMBL; X12784; CAA31275.1; -; Genomic_DNA. DR EMBL; M24766; AAA52043.1; -; mRNA. DR EMBL; X05610; CAA29098.1; -; mRNA. DR EMBL; BC080644; AAH80644.1; -; mRNA. DR EMBL; J02760; AAA58422.1; -; mRNA. DR EMBL; AF258350; AAF72631.1; -; mRNA. DR EMBL; AF400430; AAK92479.1; -; mRNA. DR EMBL; AY450357; AAR20245.1; -; mRNA. DR EMBL; AY455978; AAR18250.1; -; mRNA. DR CCDS; CCDS41907.1; -. DR PIR; A32024; CGHU2B. DR RefSeq; NP_001837.2; NM_001846.3. DR PDB; 1LI1; X-ray; 1.90 A; C/F=1485-1712. DR PDB; 5NAX; X-ray; 2.82 A; C/E=1485-1712. DR PDB; 5NB2; X-ray; 2.50 A; A/B=1485-1712. DR PDB; 6MPX; X-ray; 1.90 A; A=1489-1709. DR PDBsum; 1LI1; -. DR PDBsum; 5NAX; -. DR PDBsum; 5NB2; -. DR PDBsum; 6MPX; -. DR AlphaFoldDB; P08572; -. DR SMR; P08572; -. DR BioGRID; 107681; 54. DR ComplexPortal; CPX-1723; Collagen type IV trimer variant 1. DR IntAct; P08572; 37. DR MINT; P08572; -. DR STRING; 9606.ENSP00000353654; -. DR ChEMBL; CHEMBL2364188; -. DR GlyCosmos; P08572; 2 sites, 2 glycans. DR GlyGen; P08572; 9 sites, 4 O-linked glycans (8 sites). DR iPTMnet; P08572; -. DR PhosphoSitePlus; P08572; -. DR SwissPalm; P08572; -. DR BioMuta; COL4A2; -. DR DMDM; 143811377; -. DR EPD; P08572; -. DR jPOST; P08572; -. DR MassIVE; P08572; -. DR MaxQB; P08572; -. DR PaxDb; 9606-ENSP00000353654; -. DR PeptideAtlas; P08572; -. DR ProteomicsDB; 52123; -. DR Pumba; P08572; -. DR Antibodypedia; 4381; 263 antibodies from 28 providers. DR DNASU; 1284; -. DR Ensembl; ENST00000360467.7; ENSP00000353654.5; ENSG00000134871.19. DR GeneID; 1284; -. DR KEGG; hsa:1284; -. DR MANE-Select; ENST00000360467.7; ENSP00000353654.5; NM_001846.4; NP_001837.2. DR UCSC; uc001vqx.4; human. DR AGR; HGNC:2203; -. DR CTD; 1284; -. DR DisGeNET; 1284; -. DR GeneCards; COL4A2; -. DR HGNC; HGNC:2203; COL4A2. DR HPA; ENSG00000134871; Tissue enhanced (placenta). DR MalaCards; COL4A2; -. DR MIM; 120090; gene. DR MIM; 614483; phenotype. DR MIM; 614519; phenotype. DR neXtProt; NX_P08572; -. DR OpenTargets; ENSG00000134871; -. DR Orphanet; 99810; Familial porencephaly. DR PharmGKB; PA26718; -. DR VEuPathDB; HostDB:ENSG00000134871; -. DR eggNOG; KOG3544; Eukaryota. DR GeneTree; ENSGT00940000157234; -. DR HOGENOM; CLU_002023_1_0_1; -. DR InParanoid; P08572; -. DR OMA; ATEPIWS; -. DR OrthoDB; 2882192at2759; -. DR PhylomeDB; P08572; -. DR TreeFam; TF344135; -. DR PathwayCommons; P08572; -. DR Reactome; R-HSA-1442490; Collagen degradation. DR Reactome; R-HSA-1474244; Extracellular matrix organization. DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes. DR Reactome; R-HSA-186797; Signaling by PDGF. 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-2214320; Anchoring fibril formation. DR Reactome; R-HSA-2243919; Crosslinking of collagen fibrils. DR Reactome; R-HSA-3000157; Laminin interactions. DR Reactome; R-HSA-3000171; Non-integrin membrane-ECM interactions. DR Reactome; R-HSA-3000178; ECM proteoglycans. DR Reactome; R-HSA-3000480; Scavenging by Class A Receptors. DR Reactome; R-HSA-419037; NCAM1 interactions. DR Reactome; R-HSA-8948216; Collagen chain trimerization. DR SignaLink; P08572; -. DR SIGNOR; P08572; -. DR BioGRID-ORCS; 1284; 14 hits in 1154 CRISPR screens. DR ChiTaRS; COL4A2; human. DR EvolutionaryTrace; P08572; -. DR GeneWiki; COL4A2; -. DR GenomeRNAi; 1284; -. DR Pharos; P08572; Tbio. DR PRO; PR:P08572; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; P08572; Protein. DR Bgee; ENSG00000134871; Expressed in saphenous vein and 198 other cell types or tissues. DR ExpressionAtlas; P08572; baseline and differential. DR GO; GO:0005604; C:basement membrane; IBA:GO_Central. DR GO; GO:0005587; C:collagen type IV 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; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005201; F:extracellular matrix structural constituent; TAS:UniProtKB. DR GO; GO:0030020; F:extracellular matrix structural constituent conferring tensile strength; HDA:BHF-UCL. DR GO; GO:0060090; F:molecular adaptor activity; EXP:DisProt. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; IBA:GO_Central. DR GO; GO:0006351; P:DNA-templated transcription; IEA:Ensembl. DR GO; GO:0035987; P:endodermal cell differentiation; IEP:UniProtKB. DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central. DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR DisProt; DP02953; -. DR Gene3D; 2.170.240.10; Collagen IV, non-collagenous; 1. DR InterPro; IPR008160; Collagen. DR InterPro; IPR001442; Collagen_IV_NC. DR InterPro; IPR036954; Collagen_IV_NC_sf. DR InterPro; IPR016187; CTDL_fold. DR PANTHER; PTHR24023; COLLAGEN ALPHA; 1. DR PANTHER; PTHR24023:SF714; COLLAGEN ALPHA-4(IV) CHAIN; 1. DR Pfam; PF01413; C4; 2. DR Pfam; PF01391; Collagen; 18. DR SMART; SM00111; C4; 2. DR SUPFAM; SSF56436; C-type lectin-like; 2. DR PROSITE; PS51403; NC1_IV; 1. DR Genevisible; P08572; HS. PE 1: Evidence at protein level; KW 3D-structure; Angiogenesis; Basement membrane; Bromination; Collagen; KW Direct protein sequencing; Disease variant; Disulfide bond; KW Extracellular matrix; Glycoprotein; Hydroxylation; Reference proteome; KW Repeat; Secreted; Signal. FT SIGNAL 1..25 FT PROPEP 26..183 FT /note="N-terminal propeptide (7S domain)" FT /id="PRO_0000005824" FT CHAIN 184..1712 FT /note="Collagen alpha-2(IV) chain" FT /id="PRO_0000005825" FT CHAIN 1486..1712 FT /note="Canstatin" FT /id="PRO_0000283775" FT DOMAIN 1489..1712 FT /note="Collagen IV NC1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736" FT REGION 60..237 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 184..1484 FT /note="Triple-helical region" FT REGION 271..448 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 507..640 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 690..906 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1157..1480 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 171..186 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 427..444 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 592..606 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 754..768 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1490 FT /note="3'-bromotyrosine" FT /evidence="ECO:0000269|PubMed:32571911" FT CARBOHYD 138 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:3198637" FT DISULFID 1504..1593 FT DISULFID 1537..1590 FT DISULFID 1549..1555 FT DISULFID 1612..1708 FT DISULFID 1646..1705 FT DISULFID 1658..1665 FT VARIANT 192 FT /note="V -> F (does not affect COL4A2 and COL4A1 secretion; FT dbSNP:rs62621885)" FT /evidence="ECO:0000269|PubMed:21527998, FT ECO:0000269|PubMed:22209247" FT /id="VAR_067551" FT VARIANT 517 FT /note="R -> K (in dbSNP:rs7990383)" FT /evidence="ECO:0000269|PubMed:21527998, FT ECO:0000269|PubMed:22209247, ECO:0000269|PubMed:3345760" FT /id="VAR_048796" FT VARIANT 683 FT /note="G -> A (in dbSNP:rs3803230)" FT /evidence="ECO:0000269|PubMed:21527998, FT ECO:0000269|PubMed:22209247, ECO:0000269|PubMed:3345760" FT /id="VAR_048797" FT VARIANT 701 FT /note="K -> R (does not affect COL4A2 and COL4A1 secretion; FT dbSNP:rs78829338)" FT /evidence="ECO:0000269|PubMed:21527998, FT ECO:0000269|PubMed:22209247" FT /id="VAR_067552" FT VARIANT 718 FT /note="P -> S (does not affect COL4A2 and COL4A1 secretion; FT dbSNP:rs9583500)" FT /evidence="ECO:0000269|PubMed:21527998, FT ECO:0000269|PubMed:22209247" FT /id="VAR_067836" FT VARIANT 1037 FT /note="G -> E (in BSVD2; dbSNP:rs387906603)" FT /evidence="ECO:0000269|PubMed:22209246" FT /id="VAR_067837" FT VARIANT 1109 FT /note="R -> Q (does not affect COL4A2 and COL4A1 secretion; FT dbSNP:rs184812559)" FT /evidence="ECO:0000269|PubMed:22209247" FT /id="VAR_067553" FT VARIANT 1123 FT /note="E -> G (risk factor for ICH; results in a FT significantly decreased extracellular-to-intracellular FT ratio of COL4A2 and COL4A1 proteins, indicating FT interference with the proper secretion of both these FT proteins; dbSNP:rs117412802)" FT /evidence="ECO:0000269|PubMed:22209247" FT /id="VAR_067554" FT VARIANT 1150 FT /note="Q -> K (risk factor for ICH; results in a FT significantly decreased extracellular-to-intracellular FT ratio of COL4A2 and COL4A1 proteins, indicating FT interference with the proper secretion of both these FT proteins; dbSNP:rs62621875)" FT /evidence="ECO:0000269|PubMed:22209247" FT /id="VAR_067555" FT VARIANT 1152 FT /note="G -> D (in BSVD2; incomplete penetrance; FT dbSNP:rs387906602)" FT /evidence="ECO:0000269|PubMed:22209246" FT /id="VAR_067838" FT VARIANT 1389 FT /note="G -> R (found in a family with porencephaly and FT small-vessel disease in the form of scattered white matter FT lesions; likely pathogenic; impairs COL4A2 and COL4A1 FT secretion; the mutant protein is retained in the FT endoplasmic reticulum)" FT /evidence="ECO:0000269|PubMed:22333902" FT /id="VAR_067556" FT VARIANT 1399 FT /note="V -> I (in dbSNP:rs45520539)" FT /evidence="ECO:0000269|PubMed:22209247, FT ECO:0000269|PubMed:3582677" FT /id="VAR_067557" FT VARIANT 1690 FT /note="A -> T (risk factor for ICH; results in a FT significantly decreased extracellular-to-intracellular FT ratio of COL4A2 and COL4A1 proteins, indicating FT interference with the proper secretion of both these FT proteins; dbSNP:rs201105747)" FT /evidence="ECO:0000269|PubMed:22209247" FT /id="VAR_067558" FT CONFLICT 471 FT /note="R -> P (in Ref. 3; CAA29076)" FT /evidence="ECO:0000305" FT CONFLICT 1041 FT /note="V -> L (in Ref. 7; AAA52043)" FT /evidence="ECO:0000305" FT CONFLICT 1419 FT /note="M -> I (in Ref. 8; CAA29098)" FT /evidence="ECO:0000305" FT CONFLICT 1575 FT /note="M -> I (in Ref. 12; AAA58422)" FT /evidence="ECO:0000305" FT CONFLICT 1636 FT /note="G -> V (in Ref. 7; AAA52043)" FT /evidence="ECO:0000305" FT CONFLICT 1663 FT /note="G -> H (in Ref. 11; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 1701 FT /note="H -> G (in Ref. 11; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 1490..1495 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1497..1500 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1509..1522 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1525..1528 FT /evidence="ECO:0007829|PDB:1LI1" FT HELIX 1534..1536 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1537..1540 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1546..1550 FT /evidence="ECO:0007829|PDB:1LI1" FT TURN 1551..1553 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1554..1558 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1563..1568 FT /evidence="ECO:0007829|PDB:1LI1" FT HELIX 1580..1586 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1589..1597 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1599..1603 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1605..1608 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1616..1629 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1635..1637 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1640..1642 FT /evidence="ECO:0007829|PDB:5NAX" FT HELIX 1643..1645 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1646..1649 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1655..1659 FT /evidence="ECO:0007829|PDB:1LI1" FT TURN 1660..1663 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1664..1666 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1672..1677 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1680..1684 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1691..1694 FT /evidence="ECO:0007829|PDB:1LI1" FT HELIX 1695..1697 FT /evidence="ECO:0007829|PDB:6MPX" FT HELIX 1699..1701 FT /evidence="ECO:0007829|PDB:1LI1" FT STRAND 1704..1710 FT /evidence="ECO:0007829|PDB:1LI1" SQ SEQUENCE 1712 AA; 167553 MW; E0DABEEAB349D8AF CRC64; MGRDQRAVAG PALRRWLLLG TVTVGFLAQS VLAGVKKFDV PCGGRDCSGG CQCYPEKGGR GQPGPVGPQG YNGPPGLQGF PGLQGRKGDK GERGAPGVTG PKGDVGARGV SGFPGADGIP GHPGQGGPRG RPGYDGCNGT QGDSGPQGPP GSEGFTGPPG PQGPKGQKGE PYALPKEERD RYRGEPGEPG LVGFQGPPGR PGHVGQMGPV GAPGRPGPPG PPGPKGQQGN RGLGFYGVKG EKGDVGQPGP NGIPSDTLHP IIAPTGVTFH PDQYKGEKGS EGEPGIRGIS LKGEEGIMGF PGLRGYPGLS GEKGSPGQKG SRGLDGYQGP DGPRGPKGEA GDPGPPGLPA YSPHPSLAKG ARGDPGFPGA QGEPGSQGEP GDPGLPGPPG LSIGDGDQRR GLPGEMGPKG FIGDPGIPAL YGGPPGPDGK RGPPGPPGLP GPPGPDGFLF GLKGAKGRAG FPGLPGSPGA RGPKGWKGDA GECRCTEGDE AIKGLPGLPG PKGFAGINGE PGRKGDRGDP GQHGLPGFPG LKGVPGNIGA PGPKGAKGDS RTITTKGERG QPGVPGVPGM KGDDGSPGRD GLDGFPGLPG PPGDGIKGPP GDPGYPGIPG TKGTPGEMGP PGLGLPGLKG QRGFPGDAGL PGPPGFLGPP GPAGTPGQID CDTDVKRAVG GDRQEAIQPG CIGGPKGLPG LPGPPGPTGA KGLRGIPGFA GADGGPGPRG LPGDAGREGF PGPPGFIGPR GSKGAVGLPG PDGSPGPIGL PGPDGPPGER GLPGEVLGAQ PGPRGDAGVP GQPGLKGLPG DRGPPGFRGS QGMPGMPGLK GQPGLPGPSG QPGLYGPPGL HGFPGAPGQE GPLGLPGIPG REGLPGDRGD PGDTGAPGPV GMKGLSGDRG DAGFTGEQGH PGSPGFKGID GMPGTPGLKG DRGSPGMDGF QGMPGLKGRP GFPGSKGEAG FFGIPGLKGL AGEPGFKGSR GDPGPPGPPP VILPGMKDIK GEKGDEGPMG LKGYLGAKGI QGMPGIPGLS GIPGLPGRPG HIKGVKGDIG VPGIPGLPGF PGVAGPPGIT GFPGFIGSRG DKGAPGRAGL YGEIGATGDF GDIGDTINLP GRPGLKGERG TTGIPGLKGF FGEKGTEGDI GFPGITGVTG VQGPPGLKGQ TGFPGLTGPP GSQGELGRIG LPGGKGDDGW PGAPGLPGFP GLRGIRGLHG LPGTKGFPGS PGSDIHGDPG FPGPPGERGD PGEANTLPGP VGVPGQKGDQ GAPGERGPPG SPGLQGFPGI TPPSNISGAP GDKGAPGIFG LKGYRGPPGP PGSAALPGSK GDTGNPGAPG TPGTKGWAGD SGPQGRPGVF GLPGEKGPRG EQGFMGNTGP TGAVGDRGPK GPKGDPGFPG APGTVGAPGI AGIPQKIAVQ PGTVGPQGRR GPPGAPGEMG PQGPPGEPGF RGAPGKAGPQ GRGGVSAVPG FRGDEGPIGH QGPIGQEGAP GRPGSPGLPG MPGRSVSIGY LLVKHSQTDQ EPMCPVGMNK LWSGYSLLYF EGQEKAHNQD LGLAGSCLAR FSTMPFLYCN PGDVCYYASR NDKSYWLSTT APLPMMPVAE DEIKPYISRC SVCEAPAIAI AVHSQDVSIP HCPAGWRSLW IGYSFLMHTA AGDEGGGQSL VSPGSCLEDF RATPFIECNG GRGTCHYYAN KYSFWLTTIP EQSFQGSPSA DTLKAGLIRT HISRCQVCMK NL //