CO4A4_HUMAN
ID CO4A4_HUMAN Reviewed; 1690 AA.
AC P53420; A8MTZ1; Q53RW9; Q53S42; Q53WR1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 3.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Collagen alpha-4(IV) chain;
DE Flags: Precursor;
GN Name=COL4A4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS LEU-1004;
RP MET-1327 AND PRO-1403.
RC TISSUE=Kidney;
RX PubMed=7523402; DOI=10.1016/s0021-9258(18)47174-8;
RA Leinonen A., Mariyama M., Mochizuki T., Tryggvason K., Reeders S.T.;
RT "Complete primary structure of the human type IV collagen alpha 4(IV)
RT chain. Comparison with structure and expression of the other alpha (IV)
RT chains.";
RL J. Biol. Chem. 269:26172-26177(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INVOLVEMENT IN ATS2, VARIANTS ATS2
RP VAL-1030 AND LEU-1572, AND VARIANTS ALA-545; GLN-570; THR-931; LEU-1004;
RP MET-1327; SER-1402 AND PRO-1403.
RX PubMed=9792860; DOI=10.1086/302106;
RA Boye E., Mollet G., Forestier L., Cohen-Solal L., Heidet L., Cochat P.,
RA Gruenfeld J.-P., Palcoux J.-B., Gubler M.-C., Antignac C.;
RT "Determination of the genomic structure of the COL4A4 gene and of novel
RT mutations causing autosomal recessive Alport syndrome.";
RL Am. J. Hum. Genet. 63:1329-1340(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-23.
RX PubMed=9537506; DOI=10.1016/s0014-5793(98)00128-8;
RA Momota R., Sugimoto M., Oohashi T., Kigasawa K., Yoshioka H., Ninomiya Y.;
RT "Two genes, COL4A3 and COL4A4 coding for the human alpha3(IV) and
RT alpha4(IV) collagen chains are arranged head-to-head on chromosome 2q36.";
RL FEBS Lett. 424:11-16(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1219-1690, AND VARIANTS MET-1327 AND
RP PRO-1403.
RC TISSUE=Eye;
RX PubMed=8365481; DOI=10.1016/0014-5793(93)80256-t;
RA Sugimoto M., Oohashi T., Yoshioka H., Matsuo N., Ninomiya Y.;
RT "cDNA isolation and partial gene structure of the human alpha 4(IV)
RT collagen chain.";
RL FEBS Lett. 330:122-128(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1407-1507.
RX PubMed=1429714; DOI=10.1016/s0021-9258(18)35902-7;
RA Kamagata Y., Mattei M.-G., Ninomiya Y.;
RT "Isolation and sequencing of cDNAs and genomic DNAs encoding the alpha 4
RT chain of basement membrane collagen type IV and assignment of the gene to
RT the distal long arm of human chromosome 2.";
RL J. Biol. Chem. 267:23753-23758(1992).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=8083201; DOI=10.1016/s0021-9258(17)31612-5;
RA Mariyama M., Leinonen A., Mochizuki T., Tryggvason K., Reeders S.T.;
RT "Complete primary structure of the human alpha 3(IV) collagen chain.
RT Coexpression of the alpha 3(IV) and alpha 4(IV) collagen chains in human
RT tissues.";
RL J. Biol. Chem. 269:23013-23017(1994).
RN [8]
RP HEXAMERIZATION.
RX PubMed=12193605; DOI=10.1074/jbc.m207769200;
RA Borza D.B., Bondar O., Todd P., Sundaramoorthy M., Sado Y., Ninomiya Y.,
RA Hudson B.G.;
RT "Quaternary organization of the goodpasture autoantigen, the alpha 3(IV)
RT collagen chain. Sequestration of two cryptic autoepitopes by intrapromoter
RT interactions with the alpha4 and alpha5 NC1 domains.";
RL J. Biol. Chem. 277:40075-40083(2002).
RN [9]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=29777959; DOI=10.1016/j.actbio.2018.05.023;
RA Felemban M., Dorgau B., Hunt N.C., Hallam D., Zerti D., Bauer R., Ding Y.,
RA Collin J., Steel D., Krasnogor N., Al-Aama J., Lindsay S., Mellough C.,
RA Lako M.;
RT "Extracellular matrix component expression in human pluripotent stem cell-
RT derived retinal organoids recapitulates retinogenesis in vivo and reveals
RT an important role for IMPG1 and CD44 in the development of photoreceptors
RT and interphotoreceptor matrix.";
RL Acta Biomater. 74:207-221(2018).
RN [10]
RP REVIEW ON VARIANTS.
RX PubMed=9195222;
RX DOI=10.1002/(sici)1098-1004(1997)9:6<477::aid-humu1>3.0.co;2-#;
RA Lemmink H.H., Schroeder C.H., Monnens L.A.H., Smeets H.J.M.;
RT "The clinical spectrum of type IV collagen mutations.";
RL Hum. Mutat. 9:477-499(1997).
RN [11]
RP VARIANT ATS2 SER-1201.
RX PubMed=7987396; DOI=10.1038/ng0994-77;
RA Mochizuki T., Lemmink H.H., Mariyama M., Antignac C., Gubler M.-C.,
RA Pirson Y., Verellen-Dumoulin C., Chan B., Schroeder C.H., Smeets H.J.M.,
RA Reeders S.T.;
RT "Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen
RT genes in autosomal recessive Alport syndrome.";
RL Nat. Genet. 8:77-82(1994).
RN [12]
RP VARIANT BFH GLU-897.
RX PubMed=8787673; DOI=10.1172/jci118893;
RA Lemmink H.H., Nillesen W.N., Mochizuki T., Schroeder C.H., Brunner H.G.,
RA van Oost B.A., Monnens L.A.H., Smeets H.J.M.;
RT "Benign familial hematuria due to mutation of the type IV collagen alpha4
RT gene.";
RL J. Clin. Invest. 98:1114-1118(1996).
RN [13]
RP VARIANT BFH ARG-960, AND VARIANTS THR-6; SER-482 AND ALA-545.
RX PubMed=11961012; DOI=10.1681/asn.v1351248;
RA Badenas C., Praga M., Tazon B., Heidet L., Arrondel C., Armengol A.,
RA Andres A., Morales E., Camacho J.A., Lens X., Davila S., Mila M.,
RA Antignac C., Darnell A., Torra R.;
RT "Mutations in the COL4A4 and COL4A3 genes cause familial benign
RT hematuria.";
RL J. Am. Soc. Nephrol. 13:1248-1254(2002).
RN [14]
RP VARIANTS BFH GLU-116; ARG-960; GLU-999 AND LEU-1132, AND VARIANT SER-482.
RX PubMed=12631110; DOI=10.1046/j.1523-1755.2003.00780.x;
RA Buzza M., Dagher H., Wang Y.Y., Wilson D., Babon J.J., Cotton R.G.,
RA Savige J.;
RT "Mutations in the COL4A4 gene in thin basement membrane disease.";
RL Kidney Int. 63:447-453(2003).
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 -!- 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. The alpha 3(IV) chain
CC forms a triple helical protomer with alpha 4(IV) and alpha 5(IV); this
CC triple helical structure dimerizes through NC1-NC1 domain interactions
CC such that the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of one
CC protomer connect with the alpha 5(IV), alpha 4(IV) and alpha 3(IV)
CC chains of the opposite protomer, respectively. Associates with LAMB2 at
CC the neuromuscular junction and in GBM (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000255|PROSITE-ProRule:PRU00736}.
CC Note=Colocalizes with COL4A4 and COL4A5 in GBM, tubular basement
CC membrane (TBM) and synaptic basal lamina (BL). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in Bruch's membrane, outer plexiform
CC layer, inner nuclear layer, inner plexiform layer, ganglion cell layer,
CC inner limiting membrane and around the blood vessels of the retina (at
CC protein level) (PubMed:29777959). Alpha 3 and alpha 4 type IV collagens
CC are colocalized and present in kidney, eye, basement membranes of lens
CC capsule, cochlea, lung, skeletal muscle, aorta, synaptic fibers, fetal
CC kidney and fetal lung. PubMed:8083201 reports similar levels of
CC expression of alpha 3 and alpha 4 type IV collagens in kidney, but
CC PubMed:7523402 reports that in kidney levels of alpha 3 type IV
CC collagen are significantly lower than those of alpha 4 type IV
CC collagen. Highest levels of expression of alpha 4 type IV collagen are
CC detected in kidney, calvaria, neuroretina and cardiac muscle. Lower
CC levels of expression are observed in brain, lung and thymus, and no
CC expression is detected in choroid plexus, liver, adrenal, pancreas,
CC ileum or skin. {ECO:0000269|PubMed:29777959,
CC ECO:0000269|PubMed:7523402, ECO:0000269|PubMed:8083201}.
CC -!- DEVELOPMENTAL STAGE: At 6 weeks post-conception (WPC) expressed in the
CC hyaloid artery and lens capsule (at protein level) (PubMed:29777959).
CC Expressed between 6 and 19 WPC in the choroid and Bruch's membrane with
CC faint expression in the retinal pigment epithelium, outer neuroblastic
CC zone, inner plexiform layer, and the inner neuroblastic zone (at
CC protein level) (PubMed:29777959). {ECO:0000269|PubMed:29777959}.
CC -!- DOMAIN: Alpha chains of type IV collagen have a non-collagenous domain
CC (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats
CC in the long central triple-helical domain (which may cause flexibility
CC in the triple helix), and a short N-terminal triple-helical 7S domain.
CC -!- PTM: Prolines at the third position of the tripeptide repeating unit
CC (G-X-Y) are hydroxylated in some or all of the chains.
CC -!- PTM: Type IV collagens contain numerous cysteine residues which are
CC involved in inter- and intramolecular disulfide bonding. 12 of these,
CC located in the NC1 domain, are conserved in all known type IV
CC collagens.
CC -!- PTM: The trimeric structure of the NC1 domains is stabilized by
CC covalent bonds between Lys and Met residues. {ECO:0000250}.
CC -!- DISEASE: Alport syndrome 2, autosomal recessive (ATS2) [MIM:203780]: A
CC syndrome characterized by progressive glomerulonephritis, glomerular
CC basement membrane defects, renal failure, sensorineural deafness and
CC specific eye abnormalities (lenticonous and macular flecks). The
CC disorder shows considerable heterogeneity in that families differ in
CC the age of end-stage renal disease and the occurrence of deafness.
CC {ECO:0000269|PubMed:7987396, ECO:0000269|PubMed:9792860}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Hematuria, benign familial (BFH) [MIM:141200]: An autosomal
CC dominant condition characterized by non-progressive isolated
CC microscopic hematuria that does not result in renal failure. It is
CC characterized pathologically by thinning of the glomerular basement
CC membrane. {ECO:0000269|PubMed:11961012, ECO:0000269|PubMed:12631110,
CC ECO:0000269|PubMed:8787673}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the type IV collagen family.
CC {ECO:0000255|PROSITE-ProRule:PRU00736}.
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DR EMBL; X81053; CAA56943.1; -; mRNA.
DR EMBL; Y17397; CAA76763.1; -; Genomic_DNA.
DR EMBL; Y17398; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17399; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17400; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17401; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17402; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17403; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17404; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17405; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17406; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17407; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17408; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17409; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17410; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17411; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17412; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17413; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17427; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17426; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17414; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17415; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17416; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17417; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17418; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17419; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17420; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17443; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17442; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17441; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17440; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17439; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17438; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17437; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17436; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17435; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17434; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17433; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17432; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17431; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17430; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17429; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17428; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17421; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17422; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17423; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17424; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; Y17425; CAA76763.1; JOINED; Genomic_DNA.
DR EMBL; AC073149; AAY24061.1; -; Genomic_DNA.
DR EMBL; AC079235; AAY14670.1; -; Genomic_DNA.
DR EMBL; AB008496; BAA25065.1; -; Genomic_DNA.
DR EMBL; D17391; BAA04214.1; -; mRNA.
DR CCDS; CCDS42828.1; -.
DR PIR; A55360; CGHU1B.
DR RefSeq; NP_000083.3; NM_000092.4.
DR RefSeq; XP_005246338.1; XM_005246281.3.
DR PDB; 5NB1; X-ray; 2.82 A; A/B/C/D/E/F=1461-1690.
DR PDB; 6WKU; X-ray; 1.76 A; A=1465-1687.
DR PDBsum; 5NB1; -.
DR PDBsum; 6WKU; -.
DR AlphaFoldDB; P53420; -.
DR SMR; P53420; -.
DR BioGRID; 107683; 7.
DR ComplexPortal; CPX-1725; Collagen type IV trimer variant 3.
DR IntAct; P53420; 5.
DR MINT; P53420; -.
DR STRING; 9606.ENSP00000379866; -.
DR ChEMBL; CHEMBL3988505; -.
DR DrugBank; DB06356; TRC093.
DR GlyGen; P53420; 2 sites.
DR iPTMnet; P53420; -.
DR PhosphoSitePlus; P53420; -.
DR BioMuta; COL4A4; -.
DR DMDM; 259016360; -.
DR EPD; P53420; -.
DR jPOST; P53420; -.
DR MassIVE; P53420; -.
DR PaxDb; P53420; -.
DR PeptideAtlas; P53420; -.
DR PRIDE; P53420; -.
DR ProteomicsDB; 56583; -.
DR Antibodypedia; 54339; 138 antibodies from 23 providers.
DR DNASU; 1286; -.
DR Ensembl; ENST00000396625.5; ENSP00000379866.3; ENSG00000081052.14.
DR GeneID; 1286; -.
DR KEGG; hsa:1286; -.
DR MANE-Select; ENST00000396625.5; ENSP00000379866.3; NM_000092.5; NP_000083.3.
DR UCSC; uc061teu.1; human.
DR CTD; 1286; -.
DR DisGeNET; 1286; -.
DR GeneCards; COL4A4; -.
DR GeneReviews; COL4A4; -.
DR HGNC; HGNC:2206; COL4A4.
DR HPA; ENSG00000081052; Low tissue specificity.
DR MalaCards; COL4A4; -.
DR MIM; 120131; gene.
DR MIM; 141200; phenotype.
DR MIM; 203780; phenotype.
DR neXtProt; NX_P53420; -.
DR OpenTargets; ENSG00000081052; -.
DR Orphanet; 88918; Autosomal dominant Alport syndrome.
DR Orphanet; 88919; Autosomal recessive Alport syndrome.
DR Orphanet; 97562; NON RARE IN EUROPE: Benign familial hematuria.
DR PharmGKB; PA26721; -.
DR VEuPathDB; HostDB:ENSG00000081052; -.
DR eggNOG; KOG3544; Eukaryota.
DR GeneTree; ENSGT00940000153991; -.
DR HOGENOM; CLU_002023_1_0_1; -.
DR InParanoid; P53420; -.
DR OMA; KGFPGCD; -.
DR OrthoDB; 63831at2759; -.
DR PhylomeDB; P53420; -.
DR TreeFam; TF344135; -.
DR PathwayCommons; P53420; -.
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-419037; NCAM1 interactions.
DR Reactome; R-HSA-8948216; Collagen chain trimerization.
DR SignaLink; P53420; -.
DR SIGNOR; P53420; -.
DR BioGRID-ORCS; 1286; 9 hits in 1072 CRISPR screens.
DR ChiTaRS; COL4A4; human.
DR GeneWiki; COL4A4; -.
DR GenomeRNAi; 1286; -.
DR Pharos; P53420; Tbio.
DR PRO; PR:P53420; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P53420; protein.
DR Bgee; ENSG00000081052; Expressed in renal medulla and 123 other tissues.
DR ExpressionAtlas; P53420; baseline and differential.
DR Genevisible; P53420; HS.
DR GO; GO:0005604; C:basement membrane; IDA:UniProtKB.
DR GO; GO:0005587; C:collagen type IV trimer; IDA:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005201; F:extracellular matrix structural constituent; IMP:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0032836; P:glomerular basement membrane development; IMP:UniProtKB.
DR Gene3D; 2.170.240.10; -; 1.
DR InterPro; IPR008160; Collagen.
DR InterPro; IPR001442; Collagen_IV_NC.
DR InterPro; IPR036954; Collagen_IV_NC_sf.
DR InterPro; IPR016187; CTDL_fold.
DR Pfam; PF01413; C4; 2.
DR Pfam; PF01391; Collagen; 14.
DR SMART; SM00111; C4; 2.
DR SUPFAM; SSF56436; SSF56436; 2.
DR PROSITE; PS51403; NC1_IV; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alport syndrome; Basement membrane; Collagen; Deafness;
KW Disease variant; Disulfide bond; Extracellular matrix; Glycoprotein;
KW Hydroxylation; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..38
FT /evidence="ECO:0000255"
FT CHAIN 39..1690
FT /note="Collagen alpha-4(IV) chain"
FT /id="PRO_0000005850"
FT DOMAIN 1465..1690
FT /note="Collagen IV NC1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT REGION 39..64
FT /note="7S domain"
FT REGION 61..173
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..1459
FT /note="Triple-helical region"
FT REGION 187..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 405..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 469..1457
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 94..96
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 145..147
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 189..191
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 310..312
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 724..726
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 785..787
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 989..991
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 1212..1214
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT COMPBIAS 63..79
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 588..602
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 614..644
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 678..692
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 877..911
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1115..1129
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1218..1241
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1253..1278
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1295..1312
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1332..1375
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 1206..1207
FT /note="Cleavage; by collagenase"
FT /evidence="ECO:0000250"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 669
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 1480..1569
FT /note="Or C-1480 with C-1566"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1513..1566
FT /note="Or C-1513 with C-1569"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1525..1531
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1588..1686
FT /note="Or C-1588 with C-1683"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1622..1683
FT /note="Or C-1622 with C-1686"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1634..1641
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT VARIANT 6
FT /note="I -> T (in dbSNP:rs16823264)"
FT /evidence="ECO:0000269|PubMed:11961012"
FT /id="VAR_031622"
FT VARIANT 116
FT /note="G -> E (in BFH; dbSNP:rs1553696235)"
FT /evidence="ECO:0000269|PubMed:12631110"
FT /id="VAR_031623"
FT VARIANT 441..446
FT /note="Missing (in APSAR)"
FT /id="VAR_008148"
FT VARIANT 482
FT /note="P -> S (in dbSNP:rs2229814)"
FT /evidence="ECO:0000269|PubMed:11961012,
FT ECO:0000269|PubMed:12631110"
FT /id="VAR_022069"
FT VARIANT 545
FT /note="G -> A (in dbSNP:rs1800516)"
FT /evidence="ECO:0000269|PubMed:11961012,
FT ECO:0000269|PubMed:9792860"
FT /id="VAR_008149"
FT VARIANT 570
FT /note="E -> Q"
FT /evidence="ECO:0000269|PubMed:9792860"
FT /id="VAR_008150"
FT VARIANT 594
FT /note="E -> G (in dbSNP:rs35998949)"
FT /id="VAR_055680"
FT VARIANT 670
FT /note="V -> I (in dbSNP:rs34236495)"
FT /id="VAR_055681"
FT VARIANT 759
FT /note="P -> L (in dbSNP:rs36121515)"
FT /id="VAR_055682"
FT VARIANT 897
FT /note="G -> E (in BFH; dbSNP:rs121912860)"
FT /evidence="ECO:0000269|PubMed:8787673"
FT /id="VAR_001912"
FT VARIANT 931
FT /note="A -> T (in dbSNP:rs75875272)"
FT /evidence="ECO:0000269|PubMed:9792860"
FT /id="VAR_008151"
FT VARIANT 960
FT /note="G -> R (in BFH; dbSNP:rs769783985)"
FT /evidence="ECO:0000269|PubMed:11961012,
FT ECO:0000269|PubMed:12631110"
FT /id="VAR_031624"
FT VARIANT 999
FT /note="G -> E (in BFH; dbSNP:rs13027659)"
FT /evidence="ECO:0000269|PubMed:12631110"
FT /id="VAR_031625"
FT VARIANT 1004
FT /note="P -> L (in dbSNP:rs1800517)"
FT /evidence="ECO:0000269|PubMed:7523402,
FT ECO:0000269|PubMed:9792860"
FT /id="VAR_008152"
FT VARIANT 1030
FT /note="G -> V (in ATS2; dbSNP:rs772699709)"
FT /evidence="ECO:0000269|PubMed:9792860"
FT /id="VAR_008153"
FT VARIANT 1132
FT /note="P -> L (in BFH)"
FT /evidence="ECO:0000269|PubMed:12631110"
FT /id="VAR_031626"
FT VARIANT 1201
FT /note="G -> S (in ATS2; dbSNP:rs121912858)"
FT /evidence="ECO:0000269|PubMed:7987396"
FT /id="VAR_001913"
FT VARIANT 1327
FT /note="V -> M (in dbSNP:rs2229813)"
FT /evidence="ECO:0000269|PubMed:7523402,
FT ECO:0000269|PubMed:8365481, ECO:0000269|PubMed:9792860"
FT /id="VAR_031627"
FT VARIANT 1402
FT /note="P -> S"
FT /evidence="ECO:0000269|PubMed:9792860"
FT /id="VAR_008154"
FT VARIANT 1403
FT /note="S -> P (in dbSNP:rs3752895)"
FT /evidence="ECO:0000269|PubMed:7523402,
FT ECO:0000269|PubMed:8365481, ECO:0000269|PubMed:9792860"
FT /id="VAR_031628"
FT VARIANT 1572
FT /note="P -> L (in ATS2; dbSNP:rs121912863)"
FT /evidence="ECO:0000269|PubMed:9792860"
FT /id="VAR_008155"
FT CONFLICT 1361..1363
FT /note="GPR -> AIS (in Ref. 3; AAY24061)"
FT /evidence="ECO:0000305"
FT CONFLICT 1659..1660
FT /note="LQ -> FE (in Ref. 5; BAA04214)"
FT /evidence="ECO:0000305"
FT STRAND 1465..1471
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1473..1476
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1486..1498
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1501..1504
FT /evidence="ECO:0007829|PDB:6WKU"
FT HELIX 1510..1512
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1513..1516
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1522..1526
FT /evidence="ECO:0007829|PDB:6WKU"
FT TURN 1527..1529
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1530..1534
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1539..1544
FT /evidence="ECO:0007829|PDB:6WKU"
FT HELIX 1556..1562
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1565..1579
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1581..1584
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1592..1605
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1611..1613
FT /evidence="ECO:0007829|PDB:6WKU"
FT HELIX 1619..1621
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1622..1625
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1631..1634
FT /evidence="ECO:0007829|PDB:6WKU"
FT HELIX 1636..1638
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1640..1642
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1648..1653
FT /evidence="ECO:0007829|PDB:6WKU"
FT HELIX 1657..1659
FT /evidence="ECO:0007829|PDB:6WKU"
FT TURN 1660..1662
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1668..1670
FT /evidence="ECO:0007829|PDB:6WKU"
FT HELIX 1673..1677
FT /evidence="ECO:0007829|PDB:6WKU"
FT STRAND 1682..1687
FT /evidence="ECO:0007829|PDB:6WKU"
SQ SEQUENCE 1690 AA; 164038 MW; C55711CDF14A57DB CRC64;
MWSLHIVLMR CSFRLTKSLA TGPWSLILIL FSVQYVYGSG KKYIGPCGGR DCSVCHCVPE
KGSRGPPGPP GPQGPIGPLG APGPIGLSGE KGMRGDRGPP GAAGDKGDKG PTGVPGFPGL
DGIPGHPGPP GPRGKPGMSG HNGSRGDPGF PGGRGALGPG GPLGHPGEKG EKGNSVFILG
AVKGIQGDRG DPGLPGLPGS WGAGGPAGPT GYPGEPGLVG PPGQPGRPGL KGNPGVGVKG
QMGDPGEVGQ QGSPGPTLLV EPPDFCLYKG EKGIKGIPGM VGLPGPPGRK GESGIGAKGE
KGIPGFPGPR GDPGSYGSPG FPGLKGELGL VGDPGLFGLI GPKGDPGNRG HPGPPGVLVT
PPLPLKGPPG DPGFPGRYGE TGDVGPPGPP GLLGRPGEAC AGMIGPPGPQ GFPGLPGLPG
EAGIPGRPDS APGKPGKPGS PGLPGAPGLQ GLPGSSVIYC SVGNPGPQGI KGKVGPPGGR
GPKGEKGNEG LCACEPGPMG PPGPPGLPGR QGSKGDLGLP GWLGTKGDPG PPGAEGPPGL
PGKHGASGPP GNKGAKGDMV VSRVKGHKGE RGPDGPPGFP GQPGSHGRDG HAGEKGDPGP
PGDHEDATPG GKGFPGPLGP PGKAGPVGPP GLGFPGPPGE RGHPGVPGHP GVRGPDGLKG
QKGDTISCNV TYPGRHGPPG FDGPPGPKGF PGPQGAPGLS GSDGHKGRPG TPGTAEIPGP
PGFRGDMGDP GFGGEKGSSP VGPPGPPGSP GVNGQKGIPG DPAFGHLGPP GKRGLSGVPG
IKGPRGDPGC PGAEGPAGIP GFLGLKGPKG REGHAGFPGV PGPPGHSCER GAPGIPGQPG
LPGYPGSPGA PGGKGQPGDV GPPGPAGMKG LPGLPGRPGA HGPPGLPGIP GPFGDDGLPG
PPGPKGPRGL PGFPGFPGER GKPGAEGCPG AKGEPGEKGM SGLPGDRGLR GAKGAIGPPG
DEGEMAIISQ KGTPGEPGPP GDDGFPGERG DKGTPGMQGR RGEPGRYGPP GFHRGEPGEK
GQPGPPGPPG PPGSTGLRGF IGFPGLPGDQ GEPGSPGPPG FSGIDGARGP KGNKGDPASH
FGPPGPKGEP GSPGCPGHFG ASGEQGLPGI QGPRGSPGRP GPPGSSGPPG CPGDHGMPGL
RGQPGEMGDP GPRGLQGDPG IPGPPGIKGP SGSPGLNGLH GLKGQKGTKG ASGLHDVGPP
GPVGIPGLKG ERGDPGSPGI SPPGPRGKKG PPGPPGSSGP PGPAGATGRA PKDIPDPGPP
GDQGPPGPDG PRGAPGPPGL PGSVDLLRGE PGDCGLPGPP GPPGPPGPPG YKGFPGCDGK
DGQKGPVGFP GPQGPHGFPG PPGEKGLPGP PGRKGPTGLP GPRGEPGPPA DVDDCPRIPG
LPGAPGMRGP EGAMGLPGMR GPSGPGCKGE PGLDGRRGVD GVPGSPGPPG RKGDTGEDGY
PGGPGPPGPI GDPGPKGFGP GYLGGFLLVL HSQTDQEPTC PLGMPRLWTG YSLLYLEGQE
KAHNQDLGLA GSCLPVFSTL PFAYCNIHQV CHYAQRNDRS YWLASAAPLP MMPLSEEAIR
PYVSRCAVCE APAQAVAVHS QDQSIPPCPQ TWRSLWIGYS FLMHTGAGDQ GGGQALMSPG
SCLEDFRAAP FLECQGRQGT CHFFANKYSF WLTTVKADLQ FSSAPAPDTL KESQAQRQKI
SRCQVCVKYS
