ITB4_HUMAN
ID ITB4_HUMAN Reviewed; 1822 AA.
AC P16144; A0AVL6; O14690; O14691; O15339; O15340; O15341; Q0VF97; Q9UIQ4;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 5.
DT 03-AUG-2022, entry version 255.
DE RecName: Full=Integrin beta-4;
DE AltName: Full=GP150;
DE AltName: CD_antigen=CD104;
DE Flags: Precursor;
GN Name=ITGB4;
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] (ISOFORM BETA-4A), AND VARIANT PRO-1779.
RX PubMed=2311577; DOI=10.1002/j.1460-2075.1990.tb08170.x;
RA Suzuki S., Naitoh Y.;
RT "Amino acid sequence of a novel integrin beta 4 subunit and primary
RT expression of the mRNA in epithelial cells.";
RL EMBO J. 9:757-763(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-4B), AND VARIANT PRO-1779.
RX PubMed=2311578; DOI=10.1002/j.1460-2075.1990.tb08171.x;
RA Hogervorst F., Kuikman I., von Dem Borne A.E.G.K., Sonnenberg A.;
RT "Cloning and sequence analysis of beta-4 cDNA: an integrin subunit that
RT contains a unique 118 kd cytoplasmic domain.";
RL EMBO J. 9:765-770(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-4C).
RC TISSUE=Pancreas;
RX PubMed=1976638; DOI=10.1083/jcb.111.4.1593;
RA Tamura R.N., Rozzo C., Starr L., Chambers J., Reichardt L.F., Cooper H.M.,
RA Quaranta V.;
RT "Epithelial integrin alpha 6 beta 4: complete primary structure of alpha 6
RT and variant forms of beta 4.";
RL J. Cell Biol. 111:1593-1604(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS BETA-4A; BETA-4B AND
RP BETA-4C), AND VARIANTS SER-1764 AND PRO-1779.
RX PubMed=9194858;
RA Pulkkinen L., Kurtz K.S., Xu Y., Bruckner-Tuderman L., Uitto J.;
RT "Genomic organization of the integrin beta 4 gene (ITGB4): a homozygous
RT splice-site mutation in a patient with junctional epidermolysis bullosa
RT associated with pyloric atresia.";
RL Lab. Invest. 76:823-833(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS BETA-4A; BETA-4B AND BETA-4C),
RP AND VARIANTS SER-1764 AND PRO-1779.
RC TISSUE=Lung;
RX PubMed=9166594; DOI=10.1007/s003359900467;
RA Iacovacci S., Gagnoux-Palacios L., Zambruno G., Meneguzzi G., D'Alessio M.;
RT "Genomic organization of the human integrin beta 4 gene.";
RL Mamm. Genome 8:448-450(1997).
RN [6]
RP SEQUENCE REVISION.
RA D'Alessio M.;
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM BETA-4E), AND VARIANT
RP PRO-1779.
RX PubMed=9207246; DOI=10.1006/bbrc.1997.6892;
RA van Leusden M.R., Kuikman I., Sonnenberg A.;
RT "The unique cytoplasmic domain of the human integrin variant beta4E is
RT produced by partial retention of intronic sequences.";
RL Biochem. Biophys. Res. Commun. 235:826-830(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-4A), AND VARIANT
RP PRO-1779.
RC TISSUE=Cerebellum;
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 [11]
RP PROTEIN SEQUENCE OF 28-46.
RX PubMed=2542022; DOI=10.1002/j.1460-2075.1989.tb03425.x;
RA Kajiji S., Tamura R.N., Quaranta V.;
RT "A novel integrin (alpha E beta 4) from human epithelial cells suggests a
RT fourth family of integrin adhesion receptors.";
RL EMBO J. 8:673-680(1989).
RN [12]
RP ALTERNATIVE SPLICING (ISOFORM BETA-4D).
RX PubMed=7982032; DOI=10.3109/15419069409014197;
RA Clarke A.S., Lotz M.M., Mercurio A.M.;
RT "A novel structural variant of the human beta 4 integrin cDNA.";
RL Cell Adhes. Commun. 2:1-6(1994).
RN [13]
RP INTERACTION WITH DSP.
RX PubMed=10637308; DOI=10.1091/mbc.11.1.277;
RA Hopkinson S.B., Jones J.C.;
RT "The N terminus of the transmembrane protein BP180 interacts with the N-
RT terminal domain of BP230, thereby mediating keratin cytoskeleton anchorage
RT to the cell surface at the site of the hemidesmosome.";
RL Mol. Biol. Cell 11:277-286(2000).
RN [14]
RP INTERACTION WITH DST.
RX PubMed=11375975; DOI=10.1074/jbc.m011005200;
RA Favre B., Fontao L., Koster J., Shafaatian R., Jaunin F., Saurat J.-H.,
RA Sonnenberg A., Borradori L.;
RT "The hemidesmosomal protein bullous pemphigoid antigen 1 and the integrin
RT beta 4 subunit bind to ERBIN. Molecular cloning of multiple alternative
RT splice variants of ERBIN and analysis of their tissue expression.";
RL J. Biol. Chem. 276:32427-32436(2001).
RN [15]
RP INVOLVEMENT IN JEB5A.
RX PubMed=12485428; DOI=10.1046/j.1523-1747.2002.19609.x;
RA Jonkman M.F., Pas H.H., Nijenhuis M., Kloosterhuis G., Steege G.;
RT "Deletion of a cytoplasmic domain of integrin beta4 causes epidermolysis
RT bullosa simplex.";
RL J. Invest. Dermatol. 119:1275-1281(2002).
RN [16]
RP FUNCTION, INTERACTION WITH COL17A1 AND DST, CHARACTERIZATION OF VARIANT
RP TRP-1281, AND SUBCELLULAR LOCATION.
RX PubMed=12482924; DOI=10.1242/jcs.00241;
RA Koster J., Geerts D., Favre B., Borradori L., Sonnenberg A.;
RT "Analysis of the interactions between BP180, BP230, plectin and the
RT integrin alpha6beta4 important for hemidesmosome assembly.";
RL J. Cell Sci. 116:387-399(2003).
RN [17]
RP PALMITOYLATION.
RX PubMed=15611341; DOI=10.1083/jcb.200404100;
RA Yang X., Kovalenko O.V., Tang W., Claas C., Stipp C.S., Hemler M.E.;
RT "Palmitoylation supports assembly and function of integrin-tetraspanin
RT complexes.";
RL J. Cell Biol. 167:1231-1240(2004).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-695.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1530, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [21]
RP FUNCTION, INTERACTION WITH RAC1, AND SUBCELLULAR LOCATION.
RX PubMed=19403692; DOI=10.1091/mbc.e09-01-0051;
RA Hamill K.J., Hopkinson S.B., DeBiase P., Jones J.C.;
RT "BPAG1e maintains keratinocyte polarity through beta4 integrin-mediated
RT modulation of Rac1 and cofilin activities.";
RL Mol. Biol. Cell 20:2954-2962(2009).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [23]
RP FUNCTION, BINDING TO NRG1, IDENTIFICATION IN A COMPLEX WITH NRG1 AND ERBB3,
RP AND NRG1-BINDING REGION.
RX PubMed=20682778; DOI=10.1074/jbc.m110.113878;
RA Ieguchi K., Fujita M., Ma Z., Davari P., Taniguchi Y., Sekiguchi K.,
RA Wang B., Takada Y.K., Takada Y.;
RT "Direct binding of the EGF-like domain of neuregulin-1 to integrins
RT ({alpha}v{beta}3 and {alpha}6{beta}4) is involved in neuregulin-1/ErbB
RT signaling.";
RL J. Biol. Chem. 285:31388-31398(2010).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP PALMITOYLATION BY DHHC3, AND SUBCELLULAR LOCATION.
RX PubMed=22314500; DOI=10.1007/s00018-012-0924-6;
RA Sharma C., Rabinovitz I., Hemler M.E.;
RT "Palmitoylation by DHHC3 is critical for the function, expression, and
RT stability of integrin alpha6beta4.";
RL Cell. Mol. Life Sci. 69:2233-2244(2012).
RN [26]
RP FUNCTION, BINDING TO IGF1, IDENTIFICATION IN A COMPLEX WITH IGF1 AND IGF1R,
RP AND IGF1-BINDING REGION.
RX PubMed=22351760; DOI=10.1074/jbc.m111.304170;
RA Fujita M., Ieguchi K., Davari P., Yamaji S., Taniguchi Y., Sekiguchi K.,
RA Takada Y.K., Takada Y.;
RT "Cross-talk between integrin alpha6beta4 and insulin-like growth factor-1
RT receptor (IGF1R) through direct alpha6beta4 binding to IGF1 and subsequent
RT alpha6beta4-IGF1-IGF1R ternary complex formation in anchorage-independent
RT conditions.";
RL J. Biol. Chem. 287:12491-12500(2012).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1069; SER-1454; SER-1457;
RP SER-1474; THR-1487 AND THR-1530, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP FUNCTION, AND INTERACTION WITH IGF2.
RX PubMed=28873464; DOI=10.1371/journal.pone.0184285;
RA Cedano Prieto D.M., Cheng Y., Chang C.C., Yu J., Takada Y.K., Takada Y.;
RT "Direct integrin binding to insulin-like growth factor-2 through the C-
RT domain is required for insulin-like growth factor receptor type 1 (IGF1R)
RT signaling.";
RL PLoS ONE 12:E0184285-E0184285(2017).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 1126-1320.
RX PubMed=10428948; DOI=10.1093/emboj/18.15.4087;
RA de Pereda J.M., Wiche G., Liddington R.C.;
RT "Crystal structure of a tandem pair of fibronectin type III domains from
RT the cytoplasmic tail of integrin alpha6beta4.";
RL EMBO J. 18:4087-4095(1999).
RN [30]
RP STRUCTURE BY NMR OF 1515-1622.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the fibronectin type III domain of human integrin
RT beta-4.";
RL Submitted (APR-2008) to the PDB data bank.
RN [31]
RP VARIANTS EB-PA TYR-61; CYS-252; ARG-562 AND TRP-1281.
RX PubMed=9792864; DOI=10.1086/302116;
RA Pulkkinen L., Rouan F., Bruckner-Tuderman L., Wallerstein R., Garzon M.,
RA Brown T., Smith L., Carter W.G., Uitto J.;
RT "Novel ITGB4 mutations in lethal and nonlethal variants of epidermolysis
RT bullosa with pyloric atresia: missense versus nonsense.";
RL Am. J. Hum. Genet. 63:1376-1387(1998).
RN [32]
RP VARIANT EB-PA GLY-245.
RX PubMed=9422533;
RA Pulkkinen L., Kim D.U., Uitto J.;
RT "Epidermolysis bullosa with pyloric atresia: novel mutations in the beta-4
RT integrin gene (ITGB4).";
RL Am. J. Pathol. 152:157-166(1998).
RN [33]
RP VARIANT EB-PA PRO-156.
RX PubMed=9546354;
RA Pulkkinen L., Bruckner-Tuderman L., August C., Uitto J.;
RT "Compound heterozygosity for missense (L156P) and nonsense (R554X)
RT mutations in the beta-4 integrin gene (ITGB4) underlies mild, nonlethal
RT phenotype of epidermolysis bullosa with pyloric atresia.";
RL Am. J. Pathol. 152:935-941(1998).
RN [34]
RP VARIANT EB-PA ARG-38.
RX PubMed=9892956; DOI=10.1046/j.1365-2133.1998.02515.x;
RA Mellerio J.E., Pulkkinen L., McMillan J.R., Lake B.D., Horn H.M.,
RA Tidman M.J., Harper J.I., McGrath J.A., Uitto J., Eady R.A.J.;
RT "Pyloric atresia-junctional epidermolysis bullosa syndrome: mutations in
RT the integrin beta4 gene (ITGB4) in two unrelated patients with mild
RT disease.";
RL Br. J. Dermatol. 139:862-871(1998).
RN [35]
RP VARIANT EB-PA TRP-1281.
RX PubMed=10873890; DOI=10.1053/ajkd.2000.8293;
RA Kambham N., Tanji N., Seigle R.L., Markowitz G.S., Pulkkinen L., Uitto J.,
RA D'Agati V.D.;
RT "Congenital focal segmental glomerulosclerosis associated with beta4
RT integrin mutation and epidermolysis bullosa.";
RL Am. J. Kidney Dis. 36:190-196(2000).
RN [36]
RP VARIANT JEB5A ASP-931.
RX PubMed=10792571; DOI=10.1046/j.1523-1747.2000.00960-3.x;
RA Inoue M., Tamai K., Shimizu H., Owaribe K., Nakama T., Hashimoto T.,
RA McGrath J.A.;
RT "A homozygous missense mutation in the cytoplasmic tail of beta4 integrin,
RT G931D, that disrupts hemidesmosome assembly and underlies non-Herlitz
RT junctional epidermolysis bullosa without pyloric atresia?";
RL J. Invest. Dermatol. 114:1061-1064(2000).
RN [37]
RP VARIANTS EB-PA.
RX PubMed=11251584; DOI=10.1046/j.1365-2133.2001.04038.x;
RA Ashton G.H.S., Sorelli P., Mellerio J.E., Keane F.M., Eady R.A.J.,
RA McGrath J.A.;
RT "Alpha 6 beta 4 integrin abnormalities in junctional epidermolysis bullosa
RT with pyloric atresia.";
RL Br. J. Dermatol. 144:408-414(2001).
RN [38]
RP VARIANTS HIS-98 AND LEU-844.
RX PubMed=11289717; DOI=10.1007/s100380170122;
RA Hirano A., Nagai H., Harada H., Terada Y., Haga S., Kajiwara T., Emi M.;
RT "Nine novel single-nucleotide polymorphisms in the integrin beta4 (ITGB4)
RT gene in the Japanese population.";
RL J. Hum. Genet. 46:35-37(2001).
RN [39]
RP VARIANTS EB-PA TYR-131; CYS-252; ASP-273; CYS-283; ASP-325; PRO-336 AND
RP HIS-1225, AND VARIANT GLN-1216.
RX PubMed=11328943; DOI=10.1203/00006450-200105000-00003;
RA Nakano A., Pulkkinen L., Murrell D., Rico J., Lucky A.W., Garzon M.,
RA Stevens C.A., Robertson S., Pfendner E., Uitto J.;
RT "Epidermolysis bullosa with congenital pyloric atresia: novel mutations in
RT the beta 4 integrin gene (ITGB4) and genotype/phenotype correlations.";
RL Pediatr. Res. 49:618-626(2001).
CC -!- FUNCTION: Integrin alpha-6/beta-4 is a receptor for laminin. Plays a
CC critical structural role in the hemidesmosome of epithelial cells. Is
CC required for the regulation of keratinocyte polarity and motility.
CC ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is
CC essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds
CC to IGF1 and this binding is essential for IGF1 signaling
CC (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is
CC essential for IGF2 signaling (PubMed:28873464).
CC {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692,
CC ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760,
CC ECO:0000269|PubMed:28873464}.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. Beta-4 associates
CC with alpha-6. Interacts (via cytoplasmic region) with COL17A1 (via
CC cytoplasmic region). Interacts (via cytoplasmic region) with DST
CC isoform 3 (via N-terminus). Isoform beta-4a interacts (via cytoplasmic
CC domain) with DST (via N-terminus). Interacts with RAC1. ITGA6:ITGB4 is
CC found in a ternary complex with NRG1 and ERBB3 (PubMed:20682778).
CC ITGA6:ITGB4 is found in a ternary complex with IGF1 and IGF1R
CC (PubMed:22351760). ITGA6:ITGB4 interacts with IGF2 (PubMed:28873464).
CC {ECO:0000269|PubMed:10637308, ECO:0000269|PubMed:11375975,
CC ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692,
CC ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760,
CC ECO:0000269|PubMed:28873464}.
CC -!- INTERACTION:
CC P16144; Q96B67: ARRDC3; NbExp=3; IntAct=EBI-948678, EBI-2875665;
CC P16144; P23229: ITGA6; NbExp=3; IntAct=EBI-948678, EBI-2436548;
CC P16144; Q15149: PLEC; NbExp=7; IntAct=EBI-948678, EBI-297903;
CC P16144; Q05397: PTK2; NbExp=7; IntAct=EBI-948678, EBI-702142;
CC P16144; O95136: S1PR2; NbExp=2; IntAct=EBI-948678, EBI-10634606;
CC P16144; Q99500: S1PR3; NbExp=3; IntAct=EBI-948678, EBI-10634734;
CC P16144; Q8R5M8-2: Cadm1; Xeno; NbExp=3; IntAct=EBI-948678, EBI-5651941;
CC P16144; Q9QXS1-3: Plec; Xeno; NbExp=4; IntAct=EBI-948678, EBI-16145475;
CC P16144-2; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-11051601, EBI-10173507;
CC P16144-2; Q92624: APPBP2; NbExp=3; IntAct=EBI-11051601, EBI-743771;
CC P16144-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11051601, EBI-3867333;
CC P16144-2; Q16610: ECM1; NbExp=3; IntAct=EBI-11051601, EBI-947964;
CC P16144-2; P49639: HOXA1; NbExp=3; IntAct=EBI-11051601, EBI-740785;
CC P16144-2; Q5T749: KPRP; NbExp=3; IntAct=EBI-11051601, EBI-10981970;
CC P16144-2; Q15323: KRT31; NbExp=3; IntAct=EBI-11051601, EBI-948001;
CC P16144-2; Q6A162: KRT40; NbExp=3; IntAct=EBI-11051601, EBI-10171697;
CC P16144-2; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-11051601, EBI-11959885;
CC P16144-2; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-11051601, EBI-11749135;
CC P16144-2; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-11051601, EBI-10172290;
CC P16144-2; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-11051601, EBI-10171774;
CC P16144-2; P60411: KRTAP10-9; NbExp=5; IntAct=EBI-11051601, EBI-10172052;
CC P16144-2; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-11051601, EBI-11953334;
CC P16144-2; Q3LI76: KRTAP15-1; NbExp=3; IntAct=EBI-11051601, EBI-11992140;
CC P16144-2; Q9BYP8: KRTAP17-1; NbExp=3; IntAct=EBI-11051601, EBI-11988175;
CC P16144-2; Q9BYR9: KRTAP2-4; NbExp=3; IntAct=EBI-11051601, EBI-14065470;
CC P16144-2; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-11051601, EBI-9996449;
CC P16144-2; Q9BYR5: KRTAP4-2; NbExp=3; IntAct=EBI-11051601, EBI-10172511;
CC P16144-2; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-11051601, EBI-11962084;
CC P16144-2; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-11051601, EBI-1044640;
CC P16144-2; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-11051601, EBI-1043191;
CC P16144-2; Q99750: MDFI; NbExp=3; IntAct=EBI-11051601, EBI-724076;
CC P16144-2; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-11051601, EBI-10172526;
CC P16144-2; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-11051601, EBI-11522433;
CC P16144-2; P13349: MYF5; NbExp=3; IntAct=EBI-11051601, EBI-17491620;
CC P16144-2; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-11051601, EBI-22310682;
CC P16144-2; Q9NRQ2: PLSCR4; NbExp=3; IntAct=EBI-11051601, EBI-769257;
CC P16144-2; Q16633: POU2AF1; NbExp=3; IntAct=EBI-11051601, EBI-943588;
CC P16144-2; P22735: TGM1; NbExp=3; IntAct=EBI-11051601, EBI-2562368;
CC P16144-2; Q15654: TRIP6; NbExp=3; IntAct=EBI-11051601, EBI-742327;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Cell membrane; Lipid-anchor. Cell junction, hemidesmosome.
CC Note=Colocalizes with DST at the leading edge of migrating
CC keratinocytes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=Beta-4C;
CC IsoId=P16144-1; Sequence=Displayed;
CC Name=Beta-4A;
CC IsoId=P16144-2; Sequence=VSP_002749;
CC Name=Beta-4B;
CC IsoId=P16144-3; Sequence=VSP_002749, VSP_002750;
CC Name=Beta-4D;
CC IsoId=P16144-4; Sequence=VSP_002749, VSP_002751;
CC Name=Beta-4E;
CC IsoId=P16144-5; Sequence=VSP_002747, VSP_002748;
CC -!- TISSUE SPECIFICITY: Integrin alpha-6/beta-4 is predominantly expressed
CC by epithelia. Isoform beta-4D is also expressed in colon and placenta.
CC Isoform beta-4E is also expressed in epidermis, lung, duodenum, heart,
CC spleen and stomach.
CC -!- DOMAIN: The fibronectin type-III-like domains bind BPAG1 and plectin
CC and probably also recruit BP230.
CC -!- PTM: Palmitoylated by DHHC3 at several cysteines of the membrane-
CC proximal region, enhancing stability and cell surface expression.
CC Palmitoylation also promotes secondary association with tertaspanins.
CC {ECO:0000269|PubMed:15611341, ECO:0000269|PubMed:22314500}.
CC -!- DISEASE: Epidermolysis bullosa, junctional 5A, intermediate (JEB5A)
CC [MIM:619816]: A form of epidermolysis bullosa, a genodermatosis
CC characterized by recurrent blistering, fragility of the skin and
CC mucosal epithelia, and erosions caused by minor mechanical trauma.
CC JEB5A is an autosomal recessive, intermediate form in which blistering
CC lesions occur between the epidermis and the dermis at the lamina lucida
CC level of the basement membrane zone. In intermediate forms of
CC junctional epidermolysis bullosa, blistering does not lead to the
CC formation of chronic granulation tissue and does not affect the
CC lifespan of affected individuals. Nail dystrophy and dental enamel
CC defects are present. Scarring or non-scarring alopecia and diffuse hair
CC loss may occur. {ECO:0000269|PubMed:10792571,
CC ECO:0000269|PubMed:12485428}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Epidermolysis bullosa letalis, with pyloric atresia (EB-PA)
CC [MIM:226730]: An autosomal recessive, frequently lethal, epidermolysis
CC bullosa with variable involvement of skin, nails, mucosa, and with
CC variable effects on the digestive system. It is characterized by
CC mucocutaneous fragility, aplasia cutis congenita, and gastrointestinal
CC atresia, which most commonly affects the pylorus. Pyloric atresia is a
CC primary manifestation rather than a scarring process secondary to
CC epidermolysis bullosa. {ECO:0000269|PubMed:10873890,
CC ECO:0000269|PubMed:11251584, ECO:0000269|PubMed:11328943,
CC ECO:0000269|PubMed:9422533, ECO:0000269|PubMed:9546354,
CC ECO:0000269|PubMed:9792864, ECO:0000269|PubMed:9892956}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the integrin beta chain family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA37656.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X51841; CAA36134.1; -; mRNA.
DR EMBL; X52186; CAA36433.1; -; mRNA.
DR EMBL; X53587; CAA37656.1; ALT_FRAME; mRNA.
DR EMBL; U66541; AAC51634.1; -; Genomic_DNA.
DR EMBL; U66530; AAC51634.1; JOINED; Genomic_DNA.
DR EMBL; U66531; AAC51634.1; JOINED; Genomic_DNA.
DR EMBL; U66532; AAC51634.1; JOINED; Genomic_DNA.
DR EMBL; U66533; AAC51634.1; JOINED; Genomic_DNA.
DR EMBL; U66534; AAC51634.1; JOINED; Genomic_DNA.
DR EMBL; U66535; AAC51634.1; JOINED; Genomic_DNA.
DR EMBL; U66536; AAC51634.1; JOINED; Genomic_DNA.
DR EMBL; U66537; AAC51634.1; JOINED; Genomic_DNA.
DR EMBL; U66538; AAC51634.1; JOINED; Genomic_DNA.
DR EMBL; U66539; AAC51634.1; JOINED; Genomic_DNA.
DR EMBL; U66540; AAC51634.1; JOINED; Genomic_DNA.
DR EMBL; U66541; AAC51633.1; -; Genomic_DNA.
DR EMBL; U66530; AAC51633.1; JOINED; Genomic_DNA.
DR EMBL; U66531; AAC51633.1; JOINED; Genomic_DNA.
DR EMBL; U66532; AAC51633.1; JOINED; Genomic_DNA.
DR EMBL; U66533; AAC51633.1; JOINED; Genomic_DNA.
DR EMBL; U66534; AAC51633.1; JOINED; Genomic_DNA.
DR EMBL; U66535; AAC51633.1; JOINED; Genomic_DNA.
DR EMBL; U66536; AAC51633.1; JOINED; Genomic_DNA.
DR EMBL; U66537; AAC51633.1; JOINED; Genomic_DNA.
DR EMBL; U66538; AAC51633.1; JOINED; Genomic_DNA.
DR EMBL; U66539; AAC51633.1; JOINED; Genomic_DNA.
DR EMBL; U66540; AAC51633.1; JOINED; Genomic_DNA.
DR EMBL; U66541; AAC51632.1; -; Genomic_DNA.
DR EMBL; U66530; AAC51632.1; JOINED; Genomic_DNA.
DR EMBL; U66531; AAC51632.1; JOINED; Genomic_DNA.
DR EMBL; U66532; AAC51632.1; JOINED; Genomic_DNA.
DR EMBL; U66533; AAC51632.1; JOINED; Genomic_DNA.
DR EMBL; U66534; AAC51632.1; JOINED; Genomic_DNA.
DR EMBL; U66535; AAC51632.1; JOINED; Genomic_DNA.
DR EMBL; U66536; AAC51632.1; JOINED; Genomic_DNA.
DR EMBL; U66537; AAC51632.1; JOINED; Genomic_DNA.
DR EMBL; U66538; AAC51632.1; JOINED; Genomic_DNA.
DR EMBL; U66539; AAC51632.1; JOINED; Genomic_DNA.
DR EMBL; U66540; AAC51632.1; JOINED; Genomic_DNA.
DR EMBL; AC087749; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89305.1; -; Genomic_DNA.
DR EMBL; BC118916; AAI18917.1; -; mRNA.
DR EMBL; BC126411; AAI26412.1; -; mRNA.
DR EMBL; AJ251004; CAB61345.1; -; Genomic_DNA.
DR EMBL; Y11107; CAB61345.1; JOINED; Genomic_DNA.
DR EMBL; AF011375; AAB65421.1; -; mRNA.
DR EMBL; AF011376; AAB65422.1; -; Genomic_DNA.
DR CCDS; CCDS11727.1; -. [P16144-1]
DR CCDS; CCDS32736.1; -. [P16144-3]
DR CCDS; CCDS58599.1; -. [P16144-2]
DR PIR; JC5545; JC5545.
DR PIR; S12380; A36429.
DR RefSeq; NP_000204.3; NM_000213.4. [P16144-1]
DR RefSeq; NP_001005619.1; NM_001005619.1. [P16144-3]
DR RefSeq; NP_001005731.1; NM_001005731.2. [P16144-2]
DR RefSeq; NP_001308052.1; NM_001321123.1. [P16144-2]
DR PDB; 1QG3; X-ray; 2.15 A; A/B=1126-1320.
DR PDB; 2YRZ; NMR; -; A=1518-1622.
DR PDB; 3F7P; X-ray; 2.75 A; C/D/E=1126-1369.
DR PDB; 3F7Q; X-ray; 1.75 A; A/B=1126-1355.
DR PDB; 3F7R; X-ray; 2.04 A; A=1126-1369.
DR PDB; 3FQ4; X-ray; 1.49 A; A/B=989-1107.
DR PDB; 3FSO; X-ray; 1.41 A; A/B=989-1107.
DR PDB; 3H6A; X-ray; 1.61 A; A/B=989-1107.
DR PDB; 4Q58; X-ray; 4.00 A; C/D=1126-1320.
DR PDB; 4WTW; X-ray; 1.61 A; A/B=1527-1618.
DR PDB; 4WTX; X-ray; 1.50 A; A=1642-1736.
DR PDB; 6GVK; X-ray; 1.55 A; A=1527-1736.
DR PDB; 6GVL; X-ray; 2.05 A; A=1527-1736.
DR PDBsum; 1QG3; -.
DR PDBsum; 2YRZ; -.
DR PDBsum; 3F7P; -.
DR PDBsum; 3F7Q; -.
DR PDBsum; 3F7R; -.
DR PDBsum; 3FQ4; -.
DR PDBsum; 3FSO; -.
DR PDBsum; 3H6A; -.
DR PDBsum; 4Q58; -.
DR PDBsum; 4WTW; -.
DR PDBsum; 4WTX; -.
DR PDBsum; 6GVK; -.
DR PDBsum; 6GVL; -.
DR AlphaFoldDB; P16144; -.
DR SASBDB; P16144; -.
DR SMR; P16144; -.
DR BioGRID; 109897; 101.
DR ComplexPortal; CPX-1822; Integrin alpha6-beta4 complex.
DR CORUM; P16144; -.
DR DIP; DIP-40182N; -.
DR ELM; P16144; -.
DR IntAct; P16144; 119.
DR MINT; P16144; -.
DR STRING; 9606.ENSP00000200181; -.
DR DrugBank; DB05122; R1295.
DR GlyConnect; 1417; 1 N-Linked glycan (1 site).
DR GlyGen; P16144; 7 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P16144; -.
DR PhosphoSitePlus; P16144; -.
DR SwissPalm; P16144; -.
DR BioMuta; ITGB4; -.
DR DMDM; 317373584; -.
DR CPTAC; CPTAC-530; -.
DR CPTAC; CPTAC-531; -.
DR EPD; P16144; -.
DR jPOST; P16144; -.
DR MassIVE; P16144; -.
DR MaxQB; P16144; -.
DR PaxDb; P16144; -.
DR PeptideAtlas; P16144; -.
DR PRIDE; P16144; -.
DR ProteomicsDB; 53292; -. [P16144-1]
DR ProteomicsDB; 53293; -. [P16144-2]
DR ProteomicsDB; 53294; -. [P16144-3]
DR ProteomicsDB; 53295; -. [P16144-4]
DR ProteomicsDB; 53296; -. [P16144-5]
DR ABCD; P16144; 3 sequenced antibodies.
DR Antibodypedia; 3934; 1064 antibodies from 44 providers.
DR DNASU; 3691; -.
DR Ensembl; ENST00000200181.8; ENSP00000200181.3; ENSG00000132470.14. [P16144-1]
DR Ensembl; ENST00000449880.6; ENSP00000400217.2; ENSG00000132470.14. [P16144-3]
DR Ensembl; ENST00000450894.7; ENSP00000405536.3; ENSG00000132470.14. [P16144-2]
DR Ensembl; ENST00000579662.5; ENSP00000463651.1; ENSG00000132470.14. [P16144-2]
DR GeneID; 3691; -.
DR KEGG; hsa:3691; -.
DR MANE-Select; ENST00000200181.8; ENSP00000200181.3; NM_000213.5; NP_000204.3.
DR UCSC; uc002jpg.3; human. [P16144-1]
DR CTD; 3691; -.
DR DisGeNET; 3691; -.
DR GeneCards; ITGB4; -.
DR GeneReviews; ITGB4; -.
DR HGNC; HGNC:6158; ITGB4.
DR HPA; ENSG00000132470; Tissue enhanced (salivary gland, skin).
DR MalaCards; ITGB4; -.
DR MIM; 147557; gene.
DR MIM; 226730; phenotype.
DR MIM; 619816; phenotype.
DR neXtProt; NX_P16144; -.
DR OpenTargets; ENSG00000132470; -.
DR Orphanet; 1114; Aplasia cutis congenita.
DR Orphanet; 158684; Epidermolysis bullosa simplex with pyloric atresia.
DR Orphanet; 79402; Intermediate generalized junctional epidermolysis bullosa.
DR Orphanet; 79403; Junctional epidermolysis bullosa with pyloric atresia.
DR Orphanet; 251393; Localized junctional epidermolysis bullosa.
DR PharmGKB; PA29957; -.
DR VEuPathDB; HostDB:ENSG00000132470; -.
DR eggNOG; KOG1226; Eukaryota.
DR GeneTree; ENSGT00980000198528; -.
DR HOGENOM; CLU_237558_0_0_1; -.
DR InParanoid; P16144; -.
DR OMA; YGPVNED; -.
DR OrthoDB; 473040at2759; -.
DR PhylomeDB; P16144; -.
DR TreeFam; TF105392; -.
DR PathwayCommons; P16144; -.
DR Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures.
DR Reactome; R-HSA-3000157; Laminin interactions.
DR Reactome; R-HSA-3000170; Syndecan interactions.
DR Reactome; R-HSA-446107; Type I hemidesmosome assembly.
DR SignaLink; P16144; -.
DR SIGNOR; P16144; -.
DR BioGRID-ORCS; 3691; 12 hits in 1080 CRISPR screens.
DR ChiTaRS; ITGB4; human.
DR EvolutionaryTrace; P16144; -.
DR GeneWiki; ITGB4; -.
DR GenomeRNAi; 3691; -.
DR Pharos; P16144; Tbio.
DR PRO; PR:P16144; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P16144; protein.
DR Bgee; ENSG00000132470; Expressed in tibial nerve and 186 other tissues.
DR ExpressionAtlas; P16144; baseline and differential.
DR Genevisible; P16144; HS.
DR GO; GO:0009925; C:basal plasma membrane; IEA:Ensembl.
DR GO; GO:0005604; C:basement membrane; IEA:Ensembl.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0031252; C:cell leading edge; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IBA:GO_Central.
DR GO; GO:0030056; C:hemidesmosome; IDA:UniProtKB.
DR GO; GO:0008305; C:integrin complex; TAS:ProtInc.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:UniProtKB.
DR GO; GO:0005178; F:integrin binding; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IMP:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc.
DR GO; GO:0033627; P:cell adhesion mediated by integrin; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0048870; P:cell motility; IMP:UniProtKB.
DR GO; GO:0007160; P:cell-matrix adhesion; IMP:UniProtKB.
DR GO; GO:0046847; P:filopodium assembly; IEA:Ensembl.
DR GO; GO:0031581; P:hemidesmosome assembly; IDA:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0048333; P:mesodermal cell differentiation; IEP:UniProtKB.
DR GO; GO:0035878; P:nail development; IMP:UniProtKB.
DR GO; GO:0032290; P:peripheral nervous system myelin formation; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; IDA:UniProtKB.
DR GO; GO:0043589; P:skin morphogenesis; IMP:UniProtKB.
DR GO; GO:0061450; P:trophoblast cell migration; IEA:Ensembl.
DR CDD; cd00063; FN3; 4.
DR Gene3D; 2.60.40.10; -; 4.
DR Gene3D; 2.60.40.2030; -; 1.
DR Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR038081; CalX-like_sf.
DR InterPro; IPR003644; Calx_beta.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR013111; EGF_extracell.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR040622; I-EGF_1.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR033760; Integrin_beta_N.
DR InterPro; IPR015812; Integrin_bsu.
DR InterPro; IPR012013; Integrin_bsu-4.
DR InterPro; IPR012896; Integrin_bsu_tail.
DR InterPro; IPR036349; Integrin_bsu_tail_dom_sf.
DR InterPro; IPR002369; Integrin_bsu_VWA.
DR InterPro; IPR016201; PSI.
DR InterPro; IPR036465; vWFA_dom_sf.
DR PANTHER; PTHR10082; PTHR10082; 2.
DR PANTHER; PTHR10082:SF42; PTHR10082:SF42; 2.
DR Pfam; PF03160; Calx-beta; 1.
DR Pfam; PF07974; EGF_2; 1.
DR Pfam; PF00041; fn3; 4.
DR Pfam; PF18372; I-EGF_1; 1.
DR Pfam; PF07965; Integrin_B_tail; 1.
DR Pfam; PF00362; Integrin_beta; 1.
DR Pfam; PF17205; PSI_integrin; 1.
DR PIRSF; PIRSF002513; Integrin_B4; 1.
DR PRINTS; PR01186; INTEGRINB.
DR SMART; SM00237; Calx_beta; 1.
DR SMART; SM00060; FN3; 4.
DR SMART; SM00187; INB; 1.
DR SMART; SM01242; Integrin_B_tail; 1.
DR SMART; SM00423; PSI; 1.
DR SUPFAM; SSF141072; SSF141072; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR SUPFAM; SSF53300; SSF53300; 1.
DR SUPFAM; SSF69687; SSF69687; 1.
DR PROSITE; PS00022; EGF_1; 2.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50853; FN3; 4.
DR PROSITE; PS00243; INTEGRIN_BETA; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Cell junction;
KW Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond;
KW Epidermolysis bullosa; Glycoprotein; Integrin; Lipoprotein; Membrane;
KW Palmitate; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000269|PubMed:2542022"
FT CHAIN 28..1822
FT /note="Integrin beta-4"
FT /id="PRO_0000016346"
FT TOPO_DOM 28..710
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 711..733
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 734..1822
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 29..73
FT /note="PSI"
FT DOMAIN 131..329
FT /note="VWFA"
FT REPEAT 456..502
FT /note="I"
FT REPEAT 503..542
FT /note="II"
FT REPEAT 543..581
FT /note="III"
FT REPEAT 582..619
FT /note="IV"
FT DOMAIN 979..1084
FT /note="Calx-beta"
FT DOMAIN 1129..1218
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1222..1321
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1530..1625
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1643..1739
FT /note="Fibronectin type-III 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 194..199
FT /note="Involved in NRG1- and IGF1-binding"
FT /evidence="ECO:0000269|PubMed:20682778,
FT ECO:0000269|PubMed:22351760"
FT REGION 456..619
FT /note="Cysteine-rich tandem repeats"
FT REGION 732..749
FT /note="Palmitoylated on several cysteines"
FT REGION 1113..1140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1400..1444
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1495..1525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 771
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64632"
FT MOD_RES 1069
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64632"
FT MOD_RES 1454
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1457
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1474
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1487
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1494
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64632"
FT MOD_RES 1530
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1791
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64632"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 491
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 579
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 617
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 695
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT DISULFID 30..455
FT /evidence="ECO:0000250"
FT DISULFID 38..48
FT /evidence="ECO:0000250"
FT DISULFID 41..72
FT /evidence="ECO:0000250"
FT DISULFID 51..61
FT /evidence="ECO:0000250"
FT DISULFID 245..288
FT /evidence="ECO:0000250"
FT DISULFID 424..671
FT /evidence="ECO:0000250"
FT DISULFID 452..457
FT /evidence="ECO:0000250"
FT DISULFID 468..479
FT /evidence="ECO:0000250"
FT DISULFID 476..512
FT /evidence="ECO:0000250"
FT DISULFID 481..490
FT /evidence="ECO:0000250"
FT DISULFID 492..503
FT /evidence="ECO:0000250"
FT DISULFID 518..523
FT /evidence="ECO:0000250"
FT DISULFID 520..551
FT /evidence="ECO:0000250"
FT DISULFID 525..536
FT /evidence="ECO:0000250"
FT DISULFID 557..562
FT /evidence="ECO:0000250"
FT DISULFID 564..573
FT /evidence="ECO:0000250"
FT DISULFID 575..582
FT /evidence="ECO:0000250"
FT DISULFID 596..601
FT /evidence="ECO:0000250"
FT DISULFID 598..648
FT /evidence="ECO:0000250"
FT DISULFID 603..614
FT /evidence="ECO:0000250"
FT DISULFID 626..635
FT /evidence="ECO:0000250"
FT DISULFID 632..706
FT /evidence="ECO:0000250"
FT DISULFID 651..680
FT /evidence="ECO:0000250"
FT VAR_SEQ 851..964
FT /note="LNEVYRQISGVHKLQQTKFRQQPNAGKKQDHTIVDTVLMAPRSAKPALLKLT
FT EKQVEQRAFHDLKVAPGYYTLTADQDARGMVEFQEGVELVDVRVPLFIRPEDDDEKQLL
FT VEA -> VRTQELGLAGDVAERGLQADLRCTQAPADQVPAAAQCREKARPHHCGHSADG
FT APLGQAGPAEAYREAGGTEGLPRPQGGPRLLHPHCRPGRPGHGGVPGGRGAGGRTGAPL
FT YPA (in isoform Beta-4E)"
FT /evidence="ECO:0000303|PubMed:9207246"
FT /id="VSP_002747"
FT VAR_SEQ 965..1822
FT /note="Missing (in isoform Beta-4E)"
FT /evidence="ECO:0000303|PubMed:9207246"
FT /id="VSP_002748"
FT VAR_SEQ 1370..1439
FT /note="Missing (in isoform Beta-4A, isoform Beta-4B and
FT isoform Beta-4D)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:2311577, ECO:0000303|PubMed:2311578,
FT ECO:0000303|PubMed:9194858"
FT /id="VSP_002749"
FT VAR_SEQ 1519
FT /note="H -> HGLPPIWEHGRSRLPLSWALGSRSRAQMKGFPPSRGPRDSIILAGRP
FT AAPSWGP (in isoform Beta-4B)"
FT /evidence="ECO:0000303|PubMed:2311578,
FT ECO:0000303|PubMed:9194858"
FT /id="VSP_002750"
FT VAR_SEQ 1678..1685
FT /note="CEMAQGGG -> W (in isoform Beta-4D)"
FT /evidence="ECO:0000305"
FT /id="VSP_002751"
FT VARIANT 38
FT /note="C -> R (in EB-PA; mild form; dbSNP:rs121912465)"
FT /evidence="ECO:0000269|PubMed:9892956"
FT /id="VAR_010652"
FT VARIANT 61
FT /note="C -> Y (in EB-PA; lethal form; dbSNP:rs80338755)"
FT /evidence="ECO:0000269|PubMed:9792864"
FT /id="VAR_004006"
FT VARIANT 98
FT /note="R -> H (in dbSNP:rs143114124)"
FT /evidence="ECO:0000269|PubMed:11289717"
FT /id="VAR_011292"
FT VARIANT 131
FT /note="D -> Y (in EB-PA; lethal form)"
FT /evidence="ECO:0000269|PubMed:11328943"
FT /id="VAR_011293"
FT VARIANT 156
FT /note="L -> P (in EB-PA; mild form; dbSNP:rs121912461)"
FT /evidence="ECO:0000269|PubMed:9546354"
FT /id="VAR_004007"
FT VARIANT 245
FT /note="C -> G (in EB-PA; lethal form)"
FT /evidence="ECO:0000269|PubMed:9422533"
FT /id="VAR_004008"
FT VARIANT 252
FT /note="R -> C (in EB-PA; mild form; dbSNP:rs201494421)"
FT /evidence="ECO:0000269|PubMed:11328943,
FT ECO:0000269|PubMed:9792864"
FT /id="VAR_004009"
FT VARIANT 273
FT /note="G -> D (in EB-PA; lethal form; dbSNP:rs1476568580)"
FT /evidence="ECO:0000269|PubMed:11328943"
FT /id="VAR_011294"
FT VARIANT 283
FT /note="R -> C (in EB-PA; dbSNP:rs1422797135)"
FT /evidence="ECO:0000269|PubMed:11328943"
FT /id="VAR_011295"
FT VARIANT 325
FT /note="V -> D (in EB-PA; dbSNP:rs1304888529)"
FT /evidence="ECO:0000269|PubMed:11328943"
FT /id="VAR_011296"
FT VARIANT 336
FT /note="L -> P (in EB-PA; mild form)"
FT /evidence="ECO:0000269|PubMed:11328943"
FT /id="VAR_011297"
FT VARIANT 478
FT /note="Q -> H (in dbSNP:rs8079267)"
FT /id="VAR_027803"
FT VARIANT 562
FT /note="C -> R (in EB-PA; mild form; dbSNP:rs121912463)"
FT /evidence="ECO:0000269|PubMed:9792864"
FT /id="VAR_004010"
FT VARIANT 844
FT /note="R -> L (in dbSNP:rs140819116)"
FT /evidence="ECO:0000269|PubMed:11289717"
FT /id="VAR_011298"
FT VARIANT 931
FT /note="G -> D (in JEB5A; dbSNP:rs121912466)"
FT /evidence="ECO:0000269|PubMed:10792571"
FT /id="VAR_011299"
FT VARIANT 1216
FT /note="H -> Q (in dbSNP:rs149284152)"
FT /evidence="ECO:0000269|PubMed:11328943"
FT /id="VAR_011300"
FT VARIANT 1225
FT /note="R -> H (in EB-PA; mild form; dbSNP:rs121912468)"
FT /evidence="ECO:0000269|PubMed:11328943"
FT /id="VAR_011301"
FT VARIANT 1281
FT /note="R -> W (in EB-PA; mild form; abolishes interaction
FT with PLEC and reduces interaction with COL17A1;
FT dbSNP:rs121912467)"
FT /evidence="ECO:0000269|PubMed:10873890,
FT ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:9792864"
FT /id="VAR_004011"
FT VARIANT 1764
FT /note="T -> S (in dbSNP:rs1051486)"
FT /evidence="ECO:0000269|PubMed:9166594,
FT ECO:0000269|PubMed:9194858"
FT /id="VAR_055971"
FT VARIANT 1779
FT /note="L -> P (in dbSNP:rs871443)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2311577, ECO:0000269|PubMed:2311578,
FT ECO:0000269|PubMed:9166594, ECO:0000269|PubMed:9194858,
FT ECO:0000269|PubMed:9207246"
FT /id="VAR_027804"
FT CONFLICT 27
FT /note="Missing (in Ref. 5; CAB61345)"
FT /evidence="ECO:0000305"
FT CONFLICT 43
FT /note="R -> Y (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 46
FT /note="K -> P (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 621..704
FT /note="IHPGLCEDLRSCVQCQAWGTGEKKGRTCEECNFKVKMVDELKRAEEVVVRCS
FT FRDEDDDCTYSYTMEGDGAPGPNSTVLVHKKK -> STRASARTYAPACSARRGAPARR
FT RGARVRNATSRSRWWTSLREARRWWCAAPSGTRMTTAPTATPWKVTAPLGPTALSWCTR
FT RR (in Ref. 5; CAB61345)"
FT /evidence="ECO:0000305"
FT CONFLICT 802..804
FT /note="GFA -> WLC (in Ref. 8; AAB65422)"
FT /evidence="ECO:0000305"
FT CONFLICT 1414..1429
FT /note="HGPPDDGGAGGKGGSL -> TAPRTTAARAGRAAAV (in Ref. 3;
FT CAA37656)"
FT /evidence="ECO:0000305"
FT CONFLICT 1755
FT /note="P -> L (in Ref. 10; AAI18917)"
FT /evidence="ECO:0000305"
FT CONFLICT 1777
FT /note="Missing (in Ref. 5; CAB61345)"
FT /evidence="ECO:0000305"
FT STRAND 990..995
FT /evidence="ECO:0007829|PDB:3FSO"
FT STRAND 997..1002
FT /evidence="ECO:0007829|PDB:3FSO"
FT HELIX 1003..1005
FT /evidence="ECO:0007829|PDB:3FSO"
FT STRAND 1006..1016
FT /evidence="ECO:0007829|PDB:3FSO"
FT STRAND 1022..1033
FT /evidence="ECO:0007829|PDB:3FSO"
FT TURN 1035..1037
FT /evidence="ECO:0007829|PDB:3FSO"
FT STRAND 1043..1048
FT /evidence="ECO:0007829|PDB:3FSO"
FT STRAND 1054..1061
FT /evidence="ECO:0007829|PDB:3FSO"
FT TURN 1070..1073
FT /evidence="ECO:0007829|PDB:3FQ4"
FT STRAND 1076..1087
FT /evidence="ECO:0007829|PDB:3FSO"
FT STRAND 1096..1103
FT /evidence="ECO:0007829|PDB:3FSO"
FT STRAND 1131..1137
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1139..1141
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1143..1148
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1156..1163
FT /evidence="ECO:0007829|PDB:3F7Q"
FT HELIX 1168..1170
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1172..1183
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1191..1200
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1203..1207
FT /evidence="ECO:0007829|PDB:3F7P"
FT STRAND 1211..1214
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1227..1230
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1232..1234
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1236..1239
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1252..1260
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1262..1264
FT /evidence="ECO:0007829|PDB:3F7R"
FT STRAND 1266..1268
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1271..1275
FT /evidence="ECO:0007829|PDB:1QG3"
FT STRAND 1282..1286
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1294..1302
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1310..1314
FT /evidence="ECO:0007829|PDB:3F7Q"
FT HELIX 1316..1318
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1334..1336
FT /evidence="ECO:0007829|PDB:3F7Q"
FT STRAND 1344..1348
FT /evidence="ECO:0007829|PDB:3F7P"
FT STRAND 1522..1524
FT /evidence="ECO:0007829|PDB:2YRZ"
FT STRAND 1532..1540
FT /evidence="ECO:0007829|PDB:6GVK"
FT STRAND 1543..1549
FT /evidence="ECO:0007829|PDB:6GVK"
FT STRAND 1558..1566
FT /evidence="ECO:0007829|PDB:6GVK"
FT TURN 1567..1569
FT /evidence="ECO:0007829|PDB:6GVK"
FT STRAND 1573..1577
FT /evidence="ECO:0007829|PDB:6GVK"
FT STRAND 1584..1587
FT /evidence="ECO:0007829|PDB:6GVK"
FT STRAND 1595..1604
FT /evidence="ECO:0007829|PDB:6GVK"
FT STRAND 1612..1620
FT /evidence="ECO:0007829|PDB:6GVK"
FT TURN 1632..1635
FT /evidence="ECO:0007829|PDB:6GVK"
FT STRAND 1636..1639
FT /evidence="ECO:0007829|PDB:6GVK"
FT STRAND 1648..1653
FT /evidence="ECO:0007829|PDB:4WTX"
FT STRAND 1656..1662
FT /evidence="ECO:0007829|PDB:4WTX"
FT STRAND 1671..1680
FT /evidence="ECO:0007829|PDB:4WTX"
FT STRAND 1683..1685
FT /evidence="ECO:0007829|PDB:4WTX"
FT STRAND 1688..1694
FT /evidence="ECO:0007829|PDB:4WTX"
FT STRAND 1697..1703
FT /evidence="ECO:0007829|PDB:4WTX"
FT STRAND 1712..1722
FT /evidence="ECO:0007829|PDB:4WTX"
FT STRAND 1724..1732
FT /evidence="ECO:0007829|PDB:4WTX"
SQ SEQUENCE 1822 AA; 202167 MW; 09710FFBBD719469 CRC64;
MAGPRPSPWA RLLLAALISV SLSGTLANRC KKAPVKSCTE CVRVDKDCAY CTDEMFRDRR
CNTQAELLAA GCQRESIVVM ESSFQITEET QIDTTLRRSQ MSPQGLRVRL RPGEERHFEL
EVFEPLESPV DLYILMDFSN SMSDDLDNLK KMGQNLARVL SQLTSDYTIG FGKFVDKVSV
PQTDMRPEKL KEPWPNSDPP FSFKNVISLT EDVDEFRNKL QGERISGNLD APEGGFDAIL
QTAVCTRDIG WRPDSTHLLV FSTESAFHYE ADGANVLAGI MSRNDERCHL DTTGTYTQYR
TQDYPSVPTL VRLLAKHNII PIFAVTNYSY SYYEKLHTYF PVSSLGVLQE DSSNIVELLE
EAFNRIRSNL DIRALDSPRG LRTEVTSKMF QKTRTGSFHI RRGEVGIYQV QLRALEHVDG
THVCQLPEDQ KGNIHLKPSF SDGLKMDAGI ICDVCTCELQ KEVRSARCSF NGDFVCGQCV
CSEGWSGQTC NCSTGSLSDI QPCLREGEDK PCSGRGECQC GHCVCYGEGR YEGQFCEYDN
FQCPRTSGFL CNDRGRCSMG QCVCEPGWTG PSCDCPLSNA TCIDSNGGIC NGRGHCECGR
CHCHQQSLYT DTICEINYSA IHPGLCEDLR SCVQCQAWGT GEKKGRTCEE CNFKVKMVDE
LKRAEEVVVR CSFRDEDDDC TYSYTMEGDG APGPNSTVLV HKKKDCPPGS FWWLIPLLLL
LLPLLALLLL LCWKYCACCK ACLALLPCCN RGHMVGFKED HYMLRENLMA SDHLDTPMLR
SGNLKGRDVV RWKVTNNMQR PGFATHAASI NPTELVPYGL SLRLARLCTE NLLKPDTREC
AQLRQEVEEN LNEVYRQISG VHKLQQTKFR QQPNAGKKQD HTIVDTVLMA PRSAKPALLK
LTEKQVEQRA FHDLKVAPGY YTLTADQDAR GMVEFQEGVE LVDVRVPLFI RPEDDDEKQL
LVEAIDVPAG TATLGRRLVN ITIIKEQARD VVSFEQPEFS VSRGDQVARI PVIRRVLDGG
KSQVSYRTQD GTAQGNRDYI PVEGELLFQP GEAWKELQVK LLELQEVDSL LRGRQVRRFH
VQLSNPKFGA HLGQPHSTTI IIRDPDELDR SFTSQMLSSQ PPPHGDLGAP QNPNAKAAGS
RKIHFNWLPP SGKPMGYRVK YWIQGDSESE AHLLDSKVPS VELTNLYPYC DYEMKVCAYG
AQGEGPYSSL VSCRTHQEVP SEPGRLAFNV VSSTVTQLSW AEPAETNGEI TAYEVCYGLV
NDDNRPIGPM KKVLVDNPKN RMLLIENLRE SQPYRYTVKA RNGAGWGPER EAIINLATQP
KRPMSIPIIP DIPIVDAQSG EDYDSFLMYS DDVLRSPSGS QRPSVSDDTG CGWKFEPLLG
EELDLRRVTW RLPPELIPRL SASSGRSSDA EAPHGPPDDG GAGGKGGSLP RSATPGPPGE
HLVNGRMDFA FPGSTNSLHR MTTTSAAAYG THLSPHVPHR VLSTSSTLTR DYNSLTRSEH
SHSTTLPRDY STLTSVSSHD SRLTAGVPDT PTRLVFSALG PTSLRVSWQE PRCERPLQGY
SVEYQLLNGG ELHRLNIPNP AQTSVVVEDL LPNHSYVFRV RAQSQEGWGR EREGVITIES
QVHPQSPLCP LPGSAFTLST PSAPGPLVFT ALSPDSLQLS WERPRRPNGD IVGYLVTCEM
AQGGGPATAF RVDGDSPESR LTVPGLSENV PYKFKVQART TEGFGPEREG IITIESQDGG
PFPQLGSRAG LFQHPLQSEY SSITTTHTSA TEPFLVDGLT LGAQHLEAGG SLTRHVTQEF
VSRTLTTSGT LSTHMDQQFF QT
