CO4A2_HUMAN
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 03-AUG-2022, entry version 226.
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}.
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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; 52.
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 GlyGen; P08572; 2 sites, 2 O-linked glycans (1 site).
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; P08572; -.
DR PeptideAtlas; P08572; -.
DR PRIDE; P08572; -.
DR ProteomicsDB; 52123; -.
DR Antibodypedia; 4381; 232 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 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; HNGTEWI; -.
DR OrthoDB; 63831at2759; -.
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 1075 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 196 other tissues.
DR ExpressionAtlas; P08572; baseline and differential.
DR Genevisible; P08572; HS.
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:0031012; C:extracellular matrix; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0030020; F:extracellular matrix structural constituent conferring tensile strength; HDA:BHF-UCL.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
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: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 GO; GO:0006351; P:transcription, DNA-templated; IEA:Ensembl.
DR Gene3D; 2.170.240.10; -; 1.
DR InterPro; IPR008160; Collagen.
DR InterPro; IPR001442; Collagen_IV_NC.
DR InterPro; IPR036954; Collagen_IV_NC_sf.
DR InterPro; IPR016187; CTDL_fold.
DR Pfam; PF01413; C4; 2.
DR Pfam; PF01391; Collagen; 17.
DR SMART; SM00111; C4; 2.
DR SUPFAM; SSF56436; SSF56436; 2.
DR PROSITE; PS51403; NC1_IV; 1.
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 (associated with ICH susceptibility; results
FT in a 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 (associated with ICH susceptibility; results
FT in a 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 (probable disease-associated variant found in
FT a family with porencephaly and small-vessel disease in the
FT form of scattered white matter lesions; impairs COL4A2 and
FT COL4A1 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 (associated with ICH susceptibility; results
FT in a 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
