ID CO4A1_HUMAN Reviewed; 1669 AA.
AC P02462; A7E2W4; B1AM70; F5H5K0; Q1P9S9; Q5VWF6; Q86X41; Q8NF88; Q9NYC5;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-MAY-2018, sequence version 4.
DT 27-MAR-2024, entry version 233.
DE RecName: Full=Collagen alpha-1(IV) chain {ECO:0000305};
DE Contains:
DE RecName: Full=Arresten;
DE Flags: Precursor;
GN Name=COL4A1 {ECO:0000312|HGNC:HGNC:2202};
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 [GENOMIC DNA].
RX PubMed=2701944; DOI=10.1016/s0021-9258(18)80034-5;
RA Soininen R., Huotari M., Ganguly A., Prockop D.J., Tryggvason K.;
RT "Structural organization of the gene for the alpha 1 chain of human type IV
RT collagen.";
RL J. Biol. Chem. 264:13565-13571(1989).
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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-1334.
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-943.
RC TISSUE=Placenta;
RX PubMed=3311751; DOI=10.1111/j.1432-1033.1987.tb13450.x;
RA Brazel D., Oberbaeumer I., Dieringer H., Babel W., Glanville R.W.,
RA Deutzmann R., Kuehn K.;
RT "Completion of the amino acid sequence of the alpha 1 chain of human
RT basement membrane collagen (type IV) reveals 21 non-triplet interruptions
RT located within the collagenous domain.";
RL Eur. J. Biochem. 168:529-536(1987).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
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 PROTEIN SEQUENCE OF 28-243.
RX PubMed=4043082; DOI=10.1111/j.1432-1033.1985.tb09186.x;
RA Glanville R.W., Qian R.Q., Siebold B., Risteli J., Kuehn K.;
RT "Amino acid sequence of the N-terminal aggregation and cross-linking region
RT (7S domain) of the alpha 1 (IV) chain of human basement membrane
RT collagen.";
RL Eur. J. Biochem. 152:213-219(1985).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 46-1257.
RC TISSUE=Placenta;
RX PubMed=3691802; DOI=10.1016/0014-5793(87)81155-9;
RA Soininen R., Haka-Risku T., Prockop D.J., Tryggvason K.;
RT "Complete primary structure of the alpha 1-chain of human basement membrane
RT (type IV) collagen.";
RL FEBS Lett. 225:188-194(1987).
RN [8]
RP PROTEIN SEQUENCE OF 534-1447, PROLINE HYDROXYLATION, AND LYSINE
RP HYDROXYLATION.
RX PubMed=6434307; DOI=10.1111/j.1432-1033.1984.tb08404.x;
RA Babel W., Glanville R.W.;
RT "Structure of human-basement-membrane (type IV) collagen. Complete amino-
RT acid sequence of a 914-residue-long pepsin fragment from the alpha 1(IV)
RT chain.";
RL Eur. J. Biochem. 143:545-556(1984).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1256-1669.
RX PubMed=2581969; DOI=10.1016/s0021-9258(17)39662-x;
RA Pihlajaniemi T., Tryggvason K., Myers J.C., Kurkinen M., Lebo R.,
RA Cheung M.-C., Prockop D.J., Boyd C.D.;
RT "cDNA clones coding for the pro-alpha1(IV) chain of human type IV
RT procollagen reveal an unusual homology of amino acid sequences in two
RT halves of the carboxyl-terminal domain.";
RL J. Biol. Chem. 260:7681-7687(1985).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1259-1669.
RX PubMed=2582422; DOI=10.1073/pnas.82.11.3649;
RA Brinker J.M., Gudas L.J., Loidl H.R., Wang S.-Y., Rosenbloom J.,
RA Kefalides N.A., Myers J.C.;
RT "Restricted homology between human alpha 1 type IV and other procollagen
RT chains.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:3649-3653(1985).
RN [11]
RP PROTEIN SEQUENCE OF 1441-1669, AND DISULFIDE BONDS.
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 1441-1669, FUNCTION OF ARRESTEN, AND TISSUE
RP SPECIFICITY.
RX PubMed=10811134;
RA Colorado P.C., Torre A., Kamphaus G., Maeshima Y., Hopfer H., Takahashi K.,
RA Volk R., Zamborsky E.D., Herman S., Sarkar P.K., Ericksen M.B.,
RA Dhanabal M., Simons M., Post M., Kufe D.W., Weichselbaum R.R.,
RA Sukhatme V.P., Kalluri R.;
RT "Anti-angiogenic cues from vascular basement membrane collagen.";
RL Cancer Res. 60:2520-2526(2000).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669.
RA Fu J., Bai X., Wang W., Ruan C.;
RT "Arresten, a collagen-derived inhibitor of angiogenesis.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669.
RA Peng X., Yin B., Yuan J., Qiang B.;
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669.
RA Zheng Q.C., Song Z.F., Zheng Y.W., Li Y.Q., Shu X.;
RT "Molecular cloning and sequencing of human arresten gene.";
RL Zhonghua Shi Yan Wai Ke Za Zhi 19:46-47(2002).
RN [16]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669.
RA He A.B.;
RT "Cloning and expression of arresten in Escherichia coli and Pachia
RT pastoris.";
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [17]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1441-1669, FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=16481288;
RA Zheng J.P., Tang H.Y., Chen X.J., Yu B.F., Xie J., Wu T.C.;
RT "Construction of recombinant plasmid and prokaryotic expression in E. coli
RT and biological activity analysis of human placenta arresten gene.";
RL Hepatobiliary Pancreat. Dis. Int. 5:74-79(2006).
RN [18]
RP RETRACTED PAPER.
RX PubMed=16151532; DOI=10.1172/jci24813;
RA Sudhakar A., Nyberg P., Keshamouni V.G., Mannam A.P., Li J., Sugimoto H.,
RA Cosgrove D., Kalluri R.;
RT "Human alpha1 type IV collagen NC1 domain exhibits distinct antiangiogenic
RT activity mediated by alpha1beta1 integrin.";
RL J. Clin. Invest. 115:2801-2810(2005).
RN [19]
RP RETRACTION NOTICE OF PUBMED:16151532.
RX PubMed=31895054; DOI=10.1172/jci135305;
RA Sudhakar A., Nyberg P., Keshamouni V.G., Mannam A.P., Li J., Sugimoto H.,
RA Cosgrove D., Kalluri R.;
RL J. Clin. Invest. 130:552-552(2020).
RN [20]
RP IDENTIFICATION OF RECEPTOR, AND FUNCTION OF ARRESTEN.
RX PubMed=18775695; DOI=10.1016/j.yexcr.2008.08.011;
RA Nyberg P., Xie L., Sugimoto H., Colorado P., Sund M., Holthaus K.,
RA Sudhakar A., Salo T., Kalluri R.;
RT "Characterization of the anti-angiogenic properties of arresten, an
RT alpha1beta1 integrin-dependent collagen-derived tumor suppressor.";
RL Exp. Cell Res. 314:3292-3305(2008).
RN [21]
RP INVOLVEMENT IN ICH, VARIANTS ICH LEU-352 AND GLY-538, VARIANTS VAL-144 AND
RP VAL-1531, AND CHARACTERIZATION OF VARIANTS ICH LEU-352 AND GLY-538.
RX PubMed=22522439; DOI=10.1002/ana.22682;
RA Weng Y.C., Sonni A., Labelle-Dumais C., de Leau M., Kauffman W.B.,
RA Jeanne M., Biffi A., Greenberg S.M., Rosand J., Gould D.B.;
RT "COL4A1 mutations in patients with sporadic late-onset intracerebral
RT hemorrhage.";
RL Ann. Neurol. 71:470-477(2012).
RN [22]
RP INVOLVEMENT IN BSVD1, AND VARIANTS BSVD1 ARG-755; ARG-773; ASP-882 AND
RP ARG-1266.
RX PubMed=22574627; DOI=10.1111/j.1469-8749.2011.04198.x;
RA Shah S., Ellard S., Kneen R., Lim M., Osborne N., Rankin J., Stoodley N.,
RA van der Knaap M., Whitney A., Jardine P.;
RT "Childhood presentation of COL4A1 mutations.";
RL Dev. Med. Child. Neurol. 54:569-574(2012).
RN [23]
RP INVOLVEMENT IN BSVD1, AND VARIANT BSVD1 LYS-1627.
RX PubMed=23394911; DOI=10.1016/j.ajo.2012.11.028;
RA Rodahl E., Knappskog P.M., Majewski J., Johansson S., Telstad W.,
RA Krakenes J., Boman H.;
RT "Variants of anterior segment dysgenesis and cerebral involvement in a
RT large family with a novel COL4A1 mutation.";
RL Am. J. Ophthalmol. 155:946-953(2013).
RN [24]
RP INVOLVEMENT IN SCHZ, AND VARIANTS SCHZC ARG-655; ARG-870; SER-897; SER-948;
RP GLU-1041; GLU-1082; ARG-1326; ASP-1332 AND LYS-1615.
RX PubMed=23225343; DOI=10.1002/ana.23736;
RA Yoneda Y., Haginoya K., Kato M., Osaka H., Yokochi K., Arai H., Kakita A.,
RA Yamamoto T., Otsuki Y., Shimizu S., Wada T., Koyama N., Mino Y., Kondo N.,
RA Takahashi S., Hirabayashi S., Takanashi J., Okumura A., Kumagai T.,
RA Hirai S., Nabetani M., Saitoh S., Hattori A., Yamasaki M., Kumakura A.,
RA Sugo Y., Nishiyama K., Miyatake S., Tsurusaki Y., Doi H., Miyake N.,
RA Matsumoto N., Saitsu H.;
RT "Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly.";
RL Ann. Neurol. 73:48-57(2013).
RN [25]
RP INVOLVEMENT IN RATOR, AND VARIANT RATOR ARG-510.
RX PubMed=25228067; DOI=10.1007/s00417-014-2800-6;
RA Zenteno J.C., Crespi J., Buentello-Volante B., Buil J.A., Bassaganyas F.,
RA Vela-Segarra J.I., Diaz-Cascajosa J., Marieges M.T.;
RT "Next generation sequencing uncovers a missense mutation in COL4A1 as the
RT cause of familial retinal arteriolar tortuosity.";
RL Graefes Arch. Clin. Exp. Ophthalmol. 252:1789-1794(2014).
RN [26]
RP INVOLVEMENT IN BSVD1, AND VARIANTS BSVD1 ARG-708 AND ARG-773.
RX PubMed=24628545; DOI=10.1111/cge.12379;
RA Deml B., Reis L.M., Maheshwari M., Griffis C., Bick D., Semina E.V.;
RT "Whole exome analysis identifies dominant COL4A1 mutations in patients with
RT complex ocular phenotypes involving microphthalmia.";
RL Clin. Genet. 86:475-481(2014).
RN [27]
RP INVOLVEMENT IN PADMAL.
RX PubMed=27666438; DOI=10.1002/ana.24782;
RA Verdura E., Herve D., Bergametti F., Jacquet C., Morvan T.,
RA Prieto-Morin C., Mackowiak A., Manchon E., Hosseini H., Cordonnier C.,
RA Girard-Buttaz I., Rosenstingl S., Hagel C., Kuhlenbauemer G., Leca-Radu E.,
RA Goux D., Fleming L., Van Agtmael T., Chabriat H., Chapon F.,
RA Tournier-Lasserve E.;
RT "Disruption of a miR-29 binding site leading to COL4A1 upregulation causes
RT pontine autosomal dominant microangiopathy with leukoencephalopathy.";
RL Ann. Neurol. 80:741-753(2016).
RN [28]
RP INVOLVEMENT IN PADMAL.
RX PubMed=28369186; DOI=10.1093/brain/awx062;
RA Siitonen M., Boerjesson-Hanson A., Poeyhoenen M., Ora A., Pasanen P.,
RA Bras J., Kern S., Kern J., Andersen O., Stanescu H., Kleta R., Baumann M.,
RA Kalaria R., Kalimo H., Singleton A., Hardy J., Viitanen M., Myllykangas L.,
RA Guerreiro R.;
RT "Multi-infarct dementia of Swedish type is caused by a 3'UTR mutation of
RT COL4A1.";
RL Brain 140:E29-E29(2017).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1441-1669, AND ADDITIONAL
RP INTERCHAIN LINKS.
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 [30]
RP VARIANTS BSVD1 SER-749 AND ARG-1236.
RX PubMed=15905400; DOI=10.1126/science.1109418;
RA Gould D.B., Phalan F.C., Breedveld G.J., van Mil S.E., Smith R.S.,
RA Schimenti J.C., Aguglia U., van der Knaap M.S., Heutink P., John S.W.M.;
RT "Mutations in Col4a1 cause perinatal cerebral hemorrhage and
RT porencephaly.";
RL Science 308:1167-1171(2005).
RN [31]
RP VARIANTS BSVD1 ASP-1130 AND ARG-1423.
RX PubMed=16107487; DOI=10.1136/jmg.2005.035584;
RA Breedveld G., de Coo I.F., Lequin M.H., Arts W.F.M., Heutink P.,
RA Gould D.B., John S.W.M., Oostra B., Mancini G.M.S.;
RT "Novel mutations in three families confirm a major role of COL4A1 in
RT hereditary porencephaly.";
RL J. Med. Genet. 43:490-495(2006).
RN [32]
RP VARIANT BSVD1 GLU-562.
RX PubMed=16598045; DOI=10.1056/nejmoa053727;
RA Gould D.B., Phalan F.C., van Mil S.E., Sundberg J.P., Vahedi K., Massin P.,
RA Bousser M.G., Heutink P., Miner J.H., Tournier-Lasserve E., John S.W.M.;
RT "Role of COL4A1 in small-vessel disease and hemorrhagic stroke.";
RL N. Engl. J. Med. 354:1489-1496(2006).
RN [33]
RP VARIANT BSVD1 ASP-720.
RX PubMed=17696175; DOI=10.1002/ana.21191;
RA Sibon I., Coupry I., Menegon P., Bouchet J.P., Gorry P., Burgelin I.,
RA Calvas P., Orignac I., Dousset V., Lacombe D., Orgogozo J.M., Arveiler B.,
RA Goizet C.;
RT "COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and
RT stroke.";
RL Ann. Neurol. 62:177-184(2007).
RN [34]
RP VARIANTS HANAC VAL-498; ARG-519 AND GLU-528.
RX PubMed=18160688; DOI=10.1056/nejmoa071906;
RA Plaisier E., Gribouval O., Alamowitch S., Mougenot B., Prost C.,
RA Verpont M.C., Marro B., Desmettre T., Cohen S.Y., Roullet E., Dracon M.,
RA Fardeau M., Van Agtmael T., Kerjaschki D., Antignac C., Ronco P.;
RT "COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and
RT muscle cramps.";
RL N. Engl. J. Med. 357:2687-2695(2007).
RN [35]
RP VARIANT BSVD1 ARG-805.
RX PubMed=17379824; DOI=10.1161/strokeaha.106.475194;
RA Vahedi K., Kubis N., Boukobza M., Arnoult M., Massin P.,
RA Tournier-Lasserve E., Bousser M.G.;
RT "COL4A1 mutation in a patient with sporadic, recurrent intracerebral
RT hemorrhage.";
RL Stroke 38:1461-1464(2007).
RN [36]
RP VARIANT BSVD1 ARG-1580.
RX PubMed=19194877; DOI=10.1002/ana.21525;
RA de Vries L.S., Koopman C., Groenendaal F., Van Schooneveld M.,
RA Verheijen F.W., Verbeek E., Witkamp T.D., van der Worp H.B., Mancini G.;
RT "COL4A1 mutation in two preterm siblings with antenatal onset of
RT parenchymal hemorrhage.";
RL Ann. Neurol. 65:12-18(2009).
RN [37]
RP VARIANTS HANAC ARG-498; ARG-510 AND LEU-525.
RX PubMed=20818663; DOI=10.1002/ajmg.a.33659;
RA Plaisier E., Chen Z., Gekeler F., Benhassine S., Dahan K., Marro B.,
RA Alamowitch S., Paques M., Ronco P.;
RT "Novel COL4A1 mutations associated with HANAC syndrome: a role for the
RT triple helical CB3[IV] domain.";
RL Am. J. Med. Genet. A 152:2550-2555(2010).
RN [38]
RP VARIANTS BSVD1 ASP-720 AND ARG-755.
RX PubMed=20385946; DOI=10.1001/archophthalmol.2010.42;
RA Coupry I., Sibon I., Mortemousque B., Rouanet F., Mine M., Goizet C.;
RT "Ophthalmological features associated with COL4A1 mutations.";
RL Arch. Ophthalmol. 128:483-489(2010).
RN [39]
RP VARIANT BSVD1 ARG-755.
RX PubMed=19477666; DOI=10.1016/j.ejpn.2009.04.010;
RA Shah S., Kumar Y., McLean B., Churchill A., Stoodley N., Rankin J.,
RA Rizzu P., van der Knaap M., Jardine P.;
RT "A dominantly inherited mutation in collagen IV A1 (COL4A1) causing
RT childhood onset stroke without porencephaly.";
RL Eur. J. Paediatr. Neurol. 14:182-187(2010).
RN [40]
RP VARIANTS LEU-7 AND HIS-1334.
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).
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 {ECO:0000250|UniProtKB:P02463}.
CC -!- FUNCTION: Arresten, comprising the C-terminal NC1 domain, inhibits
CC angiogenesis and tumor formation. The C-terminal half is found to
CC possess the anti-angiogenic activity. Specifically inhibits endothelial
CC cell proliferation, migration and tube formation.
CC {ECO:0000269|PubMed:10811134, ECO:0000269|PubMed:18775695}.
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:P02463,
CC ECO:0000250|UniProtKB:Q7SIB2}.
CC -!- INTERACTION:
CC P02462; P08572: COL4A2; NbExp=2; IntAct=EBI-2432478, EBI-2432506;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000250|UniProtKB:P02463}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P02462-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P02462-2; Sequence=VSP_059564, VSP_059565;
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta.
CC {ECO:0000269|PubMed:10811134, ECO:0000269|PubMed:16481288}.
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 NC1 domain mediates hexamerization of alpha chains of type IV collagen
CC (By similarity). {ECO:0000250|UniProtKB:P02463, ECO:0000305}.
CC -!- PTM: Lysines at the third position of the tripeptide repeating unit (G-
CC X-Y) are hydroxylated. The modified lysines can be O-glycosylated.
CC {ECO:0000269|PubMed:6434307}.
CC -!- PTM: Contains 4-hydroxyproline (Probable). Prolines at the third
CC position of the tripeptide repeating unit (G-X-Y) are hydroxylated in
CC some or all of the chains (By similarity).
CC {ECO:0000250|UniProtKB:P02463, ECO:0000305|PubMed:6434307}.
CC -!- PTM: Contains 3-hydroxyproline. This modification occurs on the first
CC proline residue in the sequence motif Gly-Pro-Hyp, where Hyp is 4-
CC hydroxyproline. {ECO:0000250|UniProtKB:P02463,
CC ECO:0000250|UniProtKB:Q7SIB2}.
CC -!- PTM: Type IV collagens contain numerous cysteine residues which are
CC involved in inter- and intramolecular disulfide bonding
CC (PubMed:2844531). 12 of these, located in the NC1 domain, are conserved
CC in all known type IV collagens. {ECO:0000269|PubMed:2844531,
CC ECO:0000305}.
CC -!- PTM: The trimeric structure of the NC1 domains is stabilized by
CC covalent bonds (sulfilimine cross-links) between Lys and Met residues
CC (PubMed:12011424). These cross-links are important for the mechanical
CC stability of the basement membrane (By similarity). Sulfilimine cross-
CC link is catalyzed by PXDN (By similarity).
CC {ECO:0000250|UniProtKB:P02463, ECO:0000269|PubMed:12011424}.
CC -!- PTM: Proteolytic processing produces the C-terminal NC1 peptide,
CC arresten. {ECO:0000269|PubMed:10811134}.
CC -!- DISEASE: Hereditary angiopathy with nephropathy aneurysms and muscle
CC cramps (HANAC) [MIM:611773]: The clinical renal manifestations include
CC hematuria and bilateral large cysts. Histologic analysis revealed
CC complex basement membrane defects in kidney and skin. The systemic
CC angiopathy appears to affect both small vessels and large arteries.
CC {ECO:0000269|PubMed:18160688, ECO:0000269|PubMed:20818663}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Brain small vessel disease 1 with or without ocular anomalies
CC (BSVD1) [MIM:175780]: An autosomal dominant cerebrovascular disorder
CC with variable manifestations reflecting the location and severity of
CC the vascular defect. BSVD1 features include cerebral hemorrage,
CC unilateral fluid-filled cysts or cavities within the cerebral
CC hemispheres, leukoencephalopathy, hemiplegia, seizures, intellectual
CC disability, and facial paresis. Affected individuals may manifest
CC variable visual defects and ocular anomalies.
CC {ECO:0000269|PubMed:15905400, ECO:0000269|PubMed:16107487,
CC ECO:0000269|PubMed:16598045, ECO:0000269|PubMed:17379824,
CC ECO:0000269|PubMed:17696175, ECO:0000269|PubMed:19194877,
CC ECO:0000269|PubMed:19477666, ECO:0000269|PubMed:20385946,
CC ECO:0000269|PubMed:22574627, ECO:0000269|PubMed:23394911,
CC ECO:0000269|PubMed:24628545}. 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:22522439}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Tortuosity of retinal arteries (RATOR) [MIM:180000]: A disease
CC characterized by marked tortuosity of second- and third-order retinal
CC arteries with normal first-order arteries and venous system. Most
CC patients manifest variable degrees of symptomatic transient vision loss
CC due to retinal hemorrhage following minor stress or trauma.
CC {ECO:0000269|PubMed:25228067}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Schizencephaly (SCHZC) [MIM:269160]: Extremely rare human
CC congenital disorder characterized by a full-thickness cleft within the
CC cerebral hemispheres. These clefts are lined with gray matter and most
CC commonly involve the parasylvian regions. Large portions of the
CC cerebral hemispheres may be absent and replaced by cerebro-spinal
CC fluid. {ECO:0000269|PubMed:23225343}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Microangiopathy and leukoencephalopathy, pontine, autosomal
CC dominant (PADMAL) [MIM:618564]: A form of cerebral small vessel disease
CC characterized by the recurrence of ischemic strokes starting in the
CC thirties or forties, and associated with progressive imbalance and
CC cognitive impairment. MRI examination shows ischemic lacunas in the
CC pons and cerebral hemispheres, and diffuse leukoencephalopathy
CC affecting various brain regions. {ECO:0000269|PubMed:27666438,
CC ECO:0000269|PubMed:28369186}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. Causative mutations
CC affect a binding site for miR-29 microRNA located within the 3'UTR of
CC COL4A1 and lead to an up-regulation of this gene.
CC {ECO:0000269|PubMed:27666438}.
CC -!- SIMILARITY: Belongs to the type IV collagen family.
CC {ECO:0000255|PROSITE-ProRule:PRU00736}.
CC -!- CAUTION: Was shown to inhibit expression of hypoxia-inducible factor
CC 1alpha and ERK1/2 and p38 MAPK activation, and to function as a ligand
CC for alpha1/beta1 integrin. However, this study was later retracted.
CC {ECO:0000305|PubMed:16151532, ECO:0000305|PubMed:31895054}.
CC ---------------------------------------------------------------------------
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DR EMBL; M26576; AAA53098.1; -; Genomic_DNA.
DR EMBL; J04217; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26550; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26540; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26542; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26543; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26544; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26545; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26546; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26547; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26537; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26538; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26548; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26549; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26551; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26552; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26553; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26554; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26555; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26556; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26557; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26539; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26558; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26559; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26560; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26561; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26562; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26536; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26563; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26541; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26564; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26565; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26566; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26567; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26568; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26569; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26570; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26571; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26572; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26573; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26574; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; M26575; AAA53098.1; JOINED; Genomic_DNA.
DR EMBL; AL161773; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL390755; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455822; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC047305; AAH47305.1; -; mRNA.
DR EMBL; BC151220; AAI51221.1; -; mRNA.
DR EMBL; X05561; CAA29075.1; -; mRNA.
DR EMBL; Y00706; CAA68698.1; -; mRNA.
DR EMBL; M10940; AAA52006.1; -; mRNA.
DR EMBL; M11315; AAA52042.1; -; mRNA.
DR EMBL; AF258349; AAF72630.1; -; mRNA.
DR EMBL; AF363672; AAK53382.1; -; mRNA.
DR EMBL; AF400431; AAK92480.1; -; mRNA.
DR EMBL; AY285780; AAP43112.1; -; mRNA.
DR EMBL; AF536207; AAM97359.1; -; mRNA.
DR EMBL; DQ464183; ABE73157.1; -; mRNA.
DR CCDS; CCDS76649.1; -. [P02462-2]
DR CCDS; CCDS9511.1; -. [P02462-1]
DR PIR; S16876; CGHU4B.
DR RefSeq; NP_001290039.1; NM_001303110.1. [P02462-2]
DR RefSeq; NP_001836.3; NM_001845.5. [P02462-1]
DR PDB; 1LI1; X-ray; 1.90 A; A/B/D/E=1441-1669.
DR PDB; 5NAX; X-ray; 2.82 A; A/B/D/F=1441-1669.
DR PDB; 5NAY; X-ray; 1.80 A; A/B/C/D/E/F=1441-1669.
DR PDB; 6MPX; X-ray; 1.90 A; A=1438-1666.
DR PDBsum; 1LI1; -.
DR PDBsum; 5NAX; -.
DR PDBsum; 5NAY; -.
DR PDBsum; 6MPX; -.
DR AlphaFoldDB; P02462; -.
DR SMR; P02462; -.
DR BioGRID; 107679; 34.
DR ComplexPortal; CPX-1723; Collagen type IV trimer variant 1.
DR IntAct; P02462; 31.
DR MINT; P02462; -.
DR STRING; 9606.ENSP00000364979; -.
DR ChEMBL; CHEMBL2364188; -.
DR GlyCosmos; P02462; 3 sites, 1 glycan.
DR GlyGen; P02462; 3 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P02462; -.
DR PhosphoSitePlus; P02462; -.
DR SwissPalm; P02462; -.
DR BioMuta; COL4A1; -.
DR DMDM; 125987809; -.
DR EPD; P02462; -.
DR jPOST; P02462; -.
DR MassIVE; P02462; -.
DR PaxDb; 9606-ENSP00000364979; -.
DR PeptideAtlas; P02462; -.
DR ProteomicsDB; 26899; -.
DR ProteomicsDB; 51524; -. [P02462-1]
DR ProteomicsDB; 51525; -. [P02462-2]
DR Pumba; P02462; -.
DR Antibodypedia; 3436; 967 antibodies from 39 providers.
DR DNASU; 1282; -.
DR Ensembl; ENST00000375820.10; ENSP00000364979.4; ENSG00000187498.16. [P02462-1]
DR Ensembl; ENST00000543140.6; ENSP00000443348.1; ENSG00000187498.16. [P02462-2]
DR GeneID; 1282; -.
DR KEGG; hsa:1282; -.
DR MANE-Select; ENST00000375820.10; ENSP00000364979.4; NM_001845.6; NP_001836.3.
DR UCSC; uc001vqw.4; human. [P02462-1]
DR AGR; HGNC:2202; -.
DR DisGeNET; 1282; -.
DR GeneCards; COL4A1; -.
DR GeneReviews; COL4A1; -.
DR HGNC; HGNC:2202; COL4A1.
DR HPA; ENSG00000187498; Tissue enhanced (placenta).
DR MalaCards; COL4A1; -.
DR MIM; 120130; gene.
DR MIM; 175780; phenotype.
DR MIM; 180000; phenotype.
DR MIM; 269160; phenotype.
DR MIM; 611773; phenotype.
DR MIM; 614519; phenotype.
DR MIM; 618564; phenotype.
DR neXtProt; NX_P02462; -.
DR OpenTargets; ENSG00000187498; -.
DR Orphanet; 36383; COL4A1-related familial vascular leukoencephalopathy.
DR Orphanet; 99810; Familial porencephaly.
DR Orphanet; 481986; Familial schizencephaly.
DR Orphanet; 73229; HANAC syndrome.
DR Orphanet; 477749; Pontine autosomal dominant microangiopathy with leukoencephalopathy.
DR Orphanet; 75326; Retinal arterial tortuosity.
DR Orphanet; 899; Walker-Warburg syndrome.
DR PharmGKB; PA26717; -.
DR VEuPathDB; HostDB:ENSG00000187498; -.
DR eggNOG; KOG3544; Eukaryota.
DR GeneTree; ENSGT00940000157678; -.
DR HOGENOM; CLU_002023_1_0_1; -.
DR InParanoid; P02462; -.
DR OMA; MIPPCPQ; -.
DR OrthoDB; 2882192at2759; -.
DR PhylomeDB; P02462; -.
DR TreeFam; TF316865; -.
DR PathwayCommons; P02462; -.
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; P02462; -.
DR SIGNOR; P02462; -.
DR BioGRID-ORCS; 1282; 10 hits in 1144 CRISPR screens.
DR ChiTaRS; COL4A1; human.
DR EvolutionaryTrace; P02462; -.
DR GeneWiki; Collagen,_type_IV,_alpha_1; -.
DR GenomeRNAi; 1282; -.
DR Pharos; P02462; Tbio.
DR PRO; PR:P02462; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P02462; Protein.
DR Bgee; ENSG00000187498; Expressed in visceral pleura and 205 other cell types or tissues.
DR ExpressionAtlas; P02462; baseline and differential.
DR Genevisible; P02462; HS.
DR GO; GO:0005604; C:basement membrane; IBA:GO_Central.
DR GO; GO:0005587; C:collagen type IV trimer; IMP:BHF-UCL.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
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; IMP:BHF-UCL.
DR GO; GO:0030020; F:extracellular matrix structural constituent conferring tensile strength; IMP:BHF-UCL.
DR GO; GO:0048407; F:platelet-derived growth factor binding; IDA:MGI.
DR GO; GO:0071711; P:basement membrane organization; IMP:BHF-UCL.
DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:BHF-UCL.
DR GO; GO:0007420; P:brain development; IMP:BHF-UCL.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:BHF-UCL.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0007528; P:neuromuscular junction development; IEA:Ensembl.
DR GO; GO:0061333; P:renal tubule morphogenesis; IMP:BHF-UCL.
DR GO; GO:0061304; P:retinal blood vessel morphogenesis; IMP:BHF-UCL.
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:SF854; COLLAGEN ALPHA-1(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.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Angiogenesis; Basement membrane;
KW Collagen; Direct protein sequencing; Disease variant; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Hydroxylation; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000269|PubMed:4043082"
FT PROPEP 28..172
FT /note="N-terminal propeptide (7S domain)"
FT /id="PRO_0000005748"
FT CHAIN 173..1669
FT /note="Collagen alpha-1(IV) chain"
FT /id="PRO_0000005749"
FT CHAIN 1445..1669
FT /note="Arresten"
FT /id="PRO_0000390482"
FT DOMAIN 1445..1669
FT /note="Collagen IV NC1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT REGION 48..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..1440
FT /note="Triple-helical region"
FT REGION 504..1382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1404..1431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 109..123
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..154
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..215
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 281..299
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 353..380
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 409..423
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 627..655
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 802..817
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1341..1366
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1417..1431
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 204
FT /note="3-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q7SIB2"
FT MOD_RES 207
FT /note="3-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q7SIB2"
FT MOD_RES 210
FT /note="3-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q7SIB2"
FT MOD_RES 587
FT /note="3-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q7SIB2"
FT MOD_RES 602
FT /note="3-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q7SIB2"
FT MOD_RES 603
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:P02463"
FT MOD_RES 605
FT /note="3-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q7SIB2"
FT MOD_RES 606
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:P02463"
FT MOD_RES 623
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:P02463"
FT MOD_RES 626
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:P02463"
FT MOD_RES 629
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:P02463"
FT MOD_RES 632
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:P02463"
FT MOD_RES 647
FT /note="3-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q7SIB2"
FT MOD_RES 1214
FT /note="3-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q7SIB2"
FT MOD_RES 1424
FT /note="3-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q7SIB2"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 1460..1551
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736,
FT ECO:0000269|PubMed:2844531"
FT DISULFID 1493..1548
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736,
FT ECO:0000269|PubMed:2844531"
FT DISULFID 1505..1511
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736,
FT ECO:0000269|PubMed:2844531"
FT DISULFID 1570..1665
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736,
FT ECO:0000269|PubMed:2844531"
FT DISULFID 1604..1662
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736,
FT ECO:0000269|PubMed:2844531"
FT DISULFID 1616..1622
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736,
FT ECO:0000269|PubMed:2844531"
FT CROSSLNK 1533
FT /note="S-Lysyl-methionine sulfilimine (Met-Lys) (interchain
FT with K-1651)"
FT /evidence="ECO:0000269|PubMed:12011424"
FT CROSSLNK 1651
FT /note="S-Lysyl-methionine sulfilimine (Lys-Met) (interchain
FT with M-1533)"
FT /evidence="ECO:0000269|PubMed:12011424"
FT VAR_SEQ 513..519
FT /note="GPQGTPG -> LLFQIHK (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_059564"
FT VAR_SEQ 520..1669
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_059565"
FT VARIANT 7
FT /note="V -> L (in dbSNP:rs9515185)"
FT /evidence="ECO:0000269|PubMed:21527998"
FT /id="VAR_030027"
FT VARIANT 144
FT /note="A -> V"
FT /evidence="ECO:0000269|PubMed:22522439"
FT /id="VAR_073809"
FT VARIANT 304
FT /note="P -> L (in dbSNP:rs34843786)"
FT /id="VAR_044158"
FT VARIANT 352
FT /note="P -> L (in ICH; the mutant protein is retained
FT intracellularly and is not secreted normally;
FT dbSNP:rs200786329)"
FT /evidence="ECO:0000269|PubMed:22522439"
FT /id="VAR_073810"
FT VARIANT 498
FT /note="G -> R (in HANAC; dbSNP:rs267606744)"
FT /evidence="ECO:0000269|PubMed:20818663"
FT /id="VAR_064493"
FT VARIANT 498
FT /note="G -> V (in HANAC; dbSNP:rs113994104)"
FT /evidence="ECO:0000269|PubMed:18160688"
FT /id="VAR_044159"
FT VARIANT 510
FT /note="G -> R (in HANAC and RATOR; dbSNP:rs267606743)"
FT /evidence="ECO:0000269|PubMed:20818663,
FT ECO:0000269|PubMed:25228067"
FT /id="VAR_064494"
FT VARIANT 519
FT /note="G -> R (in HANAC; dbSNP:rs113994105)"
FT /evidence="ECO:0000269|PubMed:18160688"
FT /id="VAR_044160"
FT VARIANT 525
FT /note="G -> L (in HANAC; requires 2 nucleotide
FT substitutions; dbSNP:rs281865426)"
FT /evidence="ECO:0000269|PubMed:20818663"
FT /id="VAR_064495"
FT VARIANT 528
FT /note="G -> E (in HANAC; dbSNP:rs113994106)"
FT /evidence="ECO:0000269|PubMed:18160688"
FT /id="VAR_044161"
FT VARIANT 538
FT /note="R -> G (in ICH; the mutant protein is retained
FT intracellularly and is not secreted normally;
FT dbSNP:rs397514624)"
FT /evidence="ECO:0000269|PubMed:22522439"
FT /id="VAR_073811"
FT VARIANT 555
FT /note="P -> T (in dbSNP:rs536174)"
FT /id="VAR_030511"
FT VARIANT 562
FT /note="G -> E (in BSVD1; dbSNP:rs121912857)"
FT /evidence="ECO:0000269|PubMed:16598045"
FT /id="VAR_030028"
FT VARIANT 655
FT /note="G -> R (in SCHZC)"
FT /evidence="ECO:0000269|PubMed:23225343"
FT /id="VAR_073812"
FT VARIANT 708
FT /note="G -> R (in BSVD1; dbSNP:rs672601349)"
FT /evidence="ECO:0000269|PubMed:24628545"
FT /id="VAR_073813"
FT VARIANT 720
FT /note="G -> D (in BSVD1; dbSNP:rs113994108)"
FT /evidence="ECO:0000269|PubMed:17696175,
FT ECO:0000269|PubMed:20385946"
FT /id="VAR_064496"
FT VARIANT 749
FT /note="G -> S (in BSVD1; dbSNP:rs113994109)"
FT /evidence="ECO:0000269|PubMed:15905400"
FT /id="VAR_030029"
FT VARIANT 755
FT /note="G -> R (in BSVD1; dbSNP:rs672601346)"
FT /evidence="ECO:0000269|PubMed:19477666,
FT ECO:0000269|PubMed:20385946, ECO:0000269|PubMed:22574627"
FT /id="VAR_064497"
FT VARIANT 773
FT /note="G -> R (in BSVD1; dbSNP:rs672601347)"
FT /evidence="ECO:0000269|PubMed:22574627,
FT ECO:0000269|PubMed:24628545"
FT /id="VAR_073814"
FT VARIANT 805
FT /note="G -> R (in BSVD1; dbSNP:rs113994110)"
FT /evidence="ECO:0000269|PubMed:17379824"
FT /id="VAR_064498"
FT VARIANT 870
FT /note="G -> R (in SCHZC; dbSNP:rs1877962670)"
FT /evidence="ECO:0000269|PubMed:23225343"
FT /id="VAR_073815"
FT VARIANT 882
FT /note="G -> D (in BSVD1)"
FT /evidence="ECO:0000269|PubMed:22574627"
FT /id="VAR_073816"
FT VARIANT 897
FT /note="G -> S (in SCHZC)"
FT /evidence="ECO:0000269|PubMed:23225343"
FT /id="VAR_073817"
FT VARIANT 948
FT /note="G -> S (in SCHZC; dbSNP:rs1555303073)"
FT /evidence="ECO:0000269|PubMed:23225343"
FT /id="VAR_073818"
FT VARIANT 1041
FT /note="G -> E (in SCHZC)"
FT /evidence="ECO:0000269|PubMed:23225343"
FT /id="VAR_073819"
FT VARIANT 1082
FT /note="G -> E (in SCHZC)"
FT /evidence="ECO:0000269|PubMed:23225343"
FT /id="VAR_073820"
FT VARIANT 1130
FT /note="G -> D (in BSVD1; dbSNP:rs113994111)"
FT /evidence="ECO:0000269|PubMed:16107487"
FT /id="VAR_030030"
FT VARIANT 1236
FT /note="G -> R (in BSVD1; dbSNP:rs113994112)"
FT /evidence="ECO:0000269|PubMed:15905400"
FT /id="VAR_030031"
FT VARIANT 1266
FT /note="G -> R (in BSVD1)"
FT /evidence="ECO:0000269|PubMed:22574627"
FT /id="VAR_073821"
FT VARIANT 1326
FT /note="G -> R (in SCHZC; dbSNP:rs587777379)"
FT /evidence="ECO:0000269|PubMed:23225343"
FT /id="VAR_073822"
FT VARIANT 1332
FT /note="G -> D (in SCHZC; dbSNP:rs1877331560)"
FT /evidence="ECO:0000269|PubMed:23225343"
FT /id="VAR_073823"
FT VARIANT 1334
FT /note="Q -> H (in dbSNP:rs3742207)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:21527998"
FT /id="VAR_020013"
FT VARIANT 1423
FT /note="G -> R (in BSVD1; dbSNP:rs113994113)"
FT /evidence="ECO:0000269|PubMed:16107487"
FT /id="VAR_030032"
FT VARIANT 1531
FT /note="M -> V (in dbSNP:rs1343193102)"
FT /evidence="ECO:0000269|PubMed:22522439"
FT /id="VAR_073824"
FT VARIANT 1580
FT /note="G -> R (in BSVD1; dbSNP:rs113994114)"
FT /evidence="ECO:0000269|PubMed:19194877"
FT /id="VAR_064499"
FT VARIANT 1615
FT /note="E -> K (in SCHZC; dbSNP:rs1876543576)"
FT /evidence="ECO:0000269|PubMed:23225343"
FT /id="VAR_073825"
FT VARIANT 1627
FT /note="N -> K (in BSVD1; dbSNP:rs672601348)"
FT /evidence="ECO:0000269|PubMed:23394911"
FT /id="VAR_073826"
FT CONFLICT 237..238
FT /note="SG -> KE (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="G -> K (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="Q -> A (in Ref. 4; CAA29075)"
FT /evidence="ECO:0000305"
FT CONFLICT 719
FT /note="N -> D (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 837
FT /note="D -> Y (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 842
FT /note="K -> P (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 896
FT /note="V -> W (in Ref. 7; CAA68698)"
FT /evidence="ECO:0000305"
FT CONFLICT 904
FT /note="E -> Q (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 914
FT /note="S -> K (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 998
FT /note="S -> K (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1010
FT /note="K -> P (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1012
FT /note="S -> K (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1358
FT /note="E -> Q (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1490
FT /note="A -> T (in Ref. 17; ABE73157)"
FT /evidence="ECO:0000305"
FT CONFLICT 1507
FT /note="I -> T (in Ref. 17; ABE73157)"
FT /evidence="ECO:0000305"
FT CONFLICT 1519
FT /note="Y -> C (in Ref. 17; ABE73157)"
FT /evidence="ECO:0000305"
FT CONFLICT 1570
FT /note="C -> Y (in Ref. 16; AAM97359)"
FT /evidence="ECO:0000305"
FT STRAND 1446..1451
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1453..1456
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1465..1478
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1481..1484
FT /evidence="ECO:0007829|PDB:5NAY"
FT HELIX 1490..1492
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1493..1496
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1502..1505
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1511..1514
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1519..1524
FT /evidence="ECO:0007829|PDB:5NAY"
FT HELIX 1538..1544
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1547..1555
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1557..1561
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1563..1566
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1574..1587
FT /evidence="ECO:0007829|PDB:5NAY"
FT HELIX 1589..1591
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1593..1595
FT /evidence="ECO:0007829|PDB:5NAY"
FT HELIX 1601..1603
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1604..1607
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1613..1617
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1620..1623
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1629..1634
FT /evidence="ECO:0007829|PDB:5NAY"
FT HELIX 1638..1640
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1641..1643
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1648..1650
FT /evidence="ECO:0007829|PDB:5NAY"
FT HELIX 1655..1658
FT /evidence="ECO:0007829|PDB:5NAY"
FT STRAND 1661..1667
FT /evidence="ECO:0007829|PDB:5NAY"
SQ SEQUENCE 1669 AA; 160611 MW; 3BEBA6DFFB9B8A84 CRC64;
MGPRLSVWLL LLPAALLLHE EHSRAAAKGG CAGSGCGKCD CHGVKGQKGE RGLPGLQGVI
GFPGMQGPEG PQGPPGQKGD TGEPGLPGTK GTRGPPGASG YPGNPGLPGI PGQDGPPGPP
GIPGCNGTKG ERGPLGPPGL PGFAGNPGPP GLPGMKGDPG EILGHVPGML LKGERGFPGI
PGTPGPPGLP GLQGPVGPPG FTGPPGPPGP PGPPGEKGQM GLSFQGPKGD KGDQGVSGPP
GVPGQAQVQE KGDFATKGEK GQKGEPGFQG MPGVGEKGEP GKPGPRGKPG KDGDKGEKGS
PGFPGEPGYP GLIGRQGPQG EKGEAGPPGP PGIVIGTGPL GEKGERGYPG TPGPRGEPGP
KGFPGLPGQP GPPGLPVPGQ AGAPGFPGER GEKGDRGFPG TSLPGPSGRD GLPGPPGSPG
PPGQPGYTNG IVECQPGPPG DQGPPGIPGQ PGFIGEIGEK GQKGESCLIC DIDGYRGPPG
PQGPPGEIGF PGQPGAKGDR GLPGRDGVAG VPGPQGTPGL IGQPGAKGEP GEFYFDLRLK
GDKGDPGFPG QPGMPGRAGS PGRDGHPGLP GPKGSPGSVG LKGERGPPGG VGFPGSRGDT
GPPGPPGYGP AGPIGDKGQA GFPGGPGSPG LPGPKGEPGK IVPLPGPPGA EGLPGSPGFP
GPQGDRGFPG TPGRPGLPGE KGAVGQPGIG FPGPPGPKGV DGLPGDMGPP GTPGRPGFNG
LPGNPGVQGQ KGEPGVGLPG LKGLPGLPGI PGTPGEKGSI GVPGVPGEHG AIGPPGLQGI
RGEPGPPGLP GSVGSPGVPG IGPPGARGPP GGQGPPGLSG PPGIKGEKGF PGFPGLDMPG
PKGDKGAQGL PGITGQSGLP GLPGQQGAPG IPGFPGSKGE MGVMGTPGQP GSPGPVGAPG
LPGEKGDHGF PGSSGPRGDP GLKGDKGDVG LPGKPGSMDK VDMGSMKGQK GDQGEKGQIG
PIGEKGSRGD PGTPGVPGKD GQAGQPGQPG PKGDPGISGT PGAPGLPGPK GSVGGMGLPG
TPGEKGVPGI PGPQGSPGLP GDKGAKGEKG QAGPPGIGIP GLRGEKGDQG IAGFPGSPGE
KGEKGSIGIP GMPGSPGLKG SPGSVGYPGS PGLPGEKGDK GLPGLDGIPG VKGEAGLPGT
PGPTGPAGQK GEPGSDGIPG SAGEKGEPGL PGRGFPGFPG AKGDKGSKGE VGFPGLAGSP
GIPGSKGEQG FMGPPGPQGQ PGLPGSPGHA TEGPKGDRGP QGQPGLPGLP GPMGPPGLPG
IDGVKGDKGN PGWPGAPGVP GPKGDPGFQG MPGIGGSPGI TGSKGDMGPP GVPGFQGPKG
LPGLQGIKGD QGDQGVPGAK GLPGPPGPPG PYDIIKGEPG LPGPEGPPGL KGLQGLPGPK
GQQGVTGLVG IPGPPGIPGF DGAPGQKGEM GPAGPTGPRG FPGPPGPDGL PGSMGPPGTP
SVDHGFLVTR HSQTIDDPQC PSGTKILYHG YSLLYVQGNE RAHGQDLGTA GSCLRKFSTM
PFLFCNINNV CNFASRNDYS YWLSTPEPMP MSMAPITGEN IRPFISRCAV CEAPAMVMAV
HSQTIQIPPC PSGWSSLWIG YSFVMHTSAG AEGSGQALAS PGSCLEEFRS APFIECHGRG
TCNYYANAYS FWLATIERSE MFKKPTPSTL KAGELRTHVS RCQVCMRRT
//
