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 02-OCT-2024, entry version 236. 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 --------------------------------------------------------------------------- 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; 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; 35. 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 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; 936 antibodies from 40 providers. DR DNASU; 1282; -. DR Ensembl; ENST00000375820.10; ENSP00000364979.4; ENSG00000187498.17. [P02462-1] DR Ensembl; ENST00000543140.6; ENSP00000443348.1; ENSG00000187498.17. [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 CTD; 1282; -. 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; COL4A1/2-related familial vascular leukoencephalopathy. DR Orphanet; 75326; Familial isolated retinal arteriolar tortuosity. 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; 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 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; IPR050149; Collagen_superfamily. 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; KW Proteomics identification; Reference proteome; 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 //