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 27-MAR-2024, entry version 264. 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 JEB5B 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 JEB5B 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 JEB5B 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 JEB5B 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 JEB5B 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 JEB5B. 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 JEB5B 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=5; 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 VWFA domain (or beta I domain) contains three cation- CC binding sites: the ligand-associated metal ion-binding site (LIMBS or CC SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent CC MIDAS site (ADMIDAS). This domain is also part of the ligand-binding CC site. {ECO:0000250|UniProtKB:P05106}. 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, junctional 5B, with pyloric atresia CC (JEB5B) [MIM:226730]: 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 Junctional epidermolysis bullosa is characterized by blistering that CC occurs at the level of the lamina lucida in the skin basement membrane. CC JEB5B is an autosomal recessive, severe, frequently lethal form with CC variable involvement of skin, nails, mucosa, and with variable effects CC on the digestive system. It is characterized by mucocutaneous CC fragility, aplasia cutis congenita, and gastrointestinal atresia, which CC most commonly affects the pylorus. Pyloric atresia is a primary CC manifestation rather than a scarring process secondary to epidermolysis CC bullosa. {ECO:0000269|PubMed:10873890, ECO:0000269|PubMed:11251584, CC ECO:0000269|PubMed:11328943, ECO:0000269|PubMed:9422533, CC ECO:0000269|PubMed:9546354, ECO:0000269|PubMed:9792864, CC ECO:0000269|PubMed:9892956}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the integrin beta chain family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA37656.1; Type=Frameshift; Evidence={ECO:0000305}; 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; 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; 115. 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 GlyCosmos; P16144; 7 sites, 1 glycan. DR GlyGen; P16144; 9 sites, 1 O-linked glycan (4 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; 9606-ENSP00000200181; -. DR PeptideAtlas; 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 Pumba; P16144; -. DR ABCD; P16144; 3 sequenced antibodies. DR Antibodypedia; 3934; 1159 antibodies from 44 providers. DR DNASU; 3691; -. DR Ensembl; ENST00000200181.8; ENSP00000200181.3; ENSG00000132470.14. [P16144-1] DR Ensembl; ENST00000449880.7; 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 AGR; HGNC:6158; -. 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; ENSGT01100000263555; -. DR HOGENOM; CLU_237558_0_0_1; -. DR InParanoid; P16144; -. DR OMA; HTKFRQQ; -. DR OrthoDB; 5475862at2759; -. 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 1160 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 188 other cell types or tissues. DR ExpressionAtlas; P16144; baseline and differential. 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; IBA:GO_Central. 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:HPA. 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:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006914; P:autophagy; IMP:UniProtKB. DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc. 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; 2.60.40.2030; -; 1. DR Gene3D; 4.10.1240.30; -; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 4. DR Gene3D; 2.10.25.10; Laminin; 3. DR Gene3D; 3.30.1680.10; ligand-binding face of the semaphorins, domain 2; 1. DR Gene3D; 2.60.40.1510; ntegrin, alpha v. Chain A, domain 3; 1. DR Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 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; INTEGRIN BETA SUBUNIT; 1. DR PANTHER; PTHR10082:SF42; INTEGRIN BETA-4; 1. 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; PR00014; FNTYPEIII. 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; CalX-like; 1. DR SUPFAM; SSF57196; EGF/Laminin; 2. DR SUPFAM; SSF49265; Fibronectin type III; 2. DR SUPFAM; SSF69687; Integrin beta tail domain; 1. DR SUPFAM; SSF103575; Plexin repeat; 1. DR SUPFAM; SSF53300; vWA-like; 1. DR PROSITE; PS00022; EGF_1; 2. DR PROSITE; PS01186; EGF_2; 2. DR PROSITE; PS50853; FN3; 4. DR PROSITE; PS00243; INTEGRIN_BETA; 2. DR Genevisible; P16144; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cell adhesion; Cell junction; KW Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond; KW Epidermolysis bullosa; Glycoprotein; Integrin; Lipoprotein; Magnesium; KW Membrane; Metal-binding; Palmitate; Phosphoprotein; Receptor; KW Reference proteome; Repeat; Signal; 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 /evidence="ECO:0000255" FT DOMAIN 131..329 FT /note="VWFA" FT /evidence="ECO:0000250|UniProtKB:P05106" FT DOMAIN 456..502 FT /note="EGF-like 1" FT /evidence="ECO:0000250|UniProtKB:P05106" FT DOMAIN 503..542 FT /note="EGF-like 2" FT /evidence="ECO:0000250|UniProtKB:P05106" FT DOMAIN 543..581 FT /note="EGF-like 3" FT /evidence="ECO:0000250|UniProtKB:P05106" FT DOMAIN 582..619 FT /note="EGF-like 4" FT /evidence="ECO:0000250|UniProtKB:P05106" 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 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 BINDING 139 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /note="in MIDAS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 141 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /note="in ADMIDAS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 141 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /note="in MIDAS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 144 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /note="in ADMIDAS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 145 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /note="in ADMIDAS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 176 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="in LIMBS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 228 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="in LIMBS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 230 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="in LIMBS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 232 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="in LIMBS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 233 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="in LIMBS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 233 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /note="in MIDAS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 350 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /note="in ADMIDAS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" 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..48 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 38..455 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 41..61 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 51..72 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 245..288 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 457..476 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 468..479 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 481..490 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 492..520 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 503..518 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 512..523 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 525..536 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 543..557 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 551..562 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 564..573 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 575..598 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 582..596 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 590..601 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 603..614 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 626..671 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 632..651 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 635..648 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 680..706 FT /evidence="ECO:0000250|UniProtKB:P05106" 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 JEB5B; dbSNP:rs121912465)" FT /evidence="ECO:0000269|PubMed:9892956" FT /id="VAR_010652" FT VARIANT 61 FT /note="C -> Y (in JEB5B; 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 JEB5B)" FT /evidence="ECO:0000269|PubMed:11328943" FT /id="VAR_011293" FT VARIANT 156 FT /note="L -> P (in JEB5B; dbSNP:rs121912461)" FT /evidence="ECO:0000269|PubMed:9546354" FT /id="VAR_004007" FT VARIANT 245 FT /note="C -> G (in JEB5B)" FT /evidence="ECO:0000269|PubMed:9422533" FT /id="VAR_004008" FT VARIANT 252 FT /note="R -> C (in JEB5B; 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 JEB5B; dbSNP:rs1476568580)" FT /evidence="ECO:0000269|PubMed:11328943" FT /id="VAR_011294" FT VARIANT 283 FT /note="R -> C (in JEB5B; dbSNP:rs1422797135)" FT /evidence="ECO:0000269|PubMed:11328943" FT /id="VAR_011295" FT VARIANT 325 FT /note="V -> D (in JEB5B; dbSNP:rs1304888529)" FT /evidence="ECO:0000269|PubMed:11328943" FT /id="VAR_011296" FT VARIANT 336 FT /note="L -> P (in JEB5B)" 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 JEB5B; 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 JEB5B; dbSNP:rs121912468)" FT /evidence="ECO:0000269|PubMed:11328943" FT /id="VAR_011301" FT VARIANT 1281 FT /note="R -> W (in JEB5B; abolishes interaction with FT 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 //