ID ITB6_HUMAN Reviewed; 788 AA. AC P18564; B2R9W5; C9JA97; Q0VA95; Q16500; Q53RG5; Q53RR6; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 27-APR-2001, sequence version 2. DT 27-MAR-2024, entry version 224. DE RecName: Full=Integrin beta-6; DE Flags: Precursor; GN Name=ITGB6; 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 1). RC TISSUE=Pancreas; RX PubMed=2365683; DOI=10.1016/s0021-9258(19)38425-x; RA Sheppard D., Rozzo C., Starr L., Quaranta V., Erle D.J., Pytela R.; RT "Complete amino acid sequence of a novel integrin beta subunit (beta 6) RT identified in epithelial cells using the polymerase chain reaction."; RL J. Biol. Chem. 265:11502-11507(1990). RN [2] RP SEQUENCE REVISION TO 18-24; 158; 642 AND 719. RA Askins J.; RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 116-197. RX PubMed=1382574; DOI=10.1093/intimm/4.9.1031; RA Jiang W.-M., Jenkins D., Yuan Q., Leung E., Choo K.H., Watson J.D., RA Krissansen G.W.; RT "The gene organization of the human beta 7 subunit, the common beta subunit RT of the leukocyte integrins HML-1 and LPAM-1."; RL Int. Immunol. 4:1031-1040(1992). RN [8] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH COXSACKIEVIRUS B1 RP CAPSID PROTEINS. RX PubMed=9426447; DOI=10.1006/viro.1997.8831; RA Agrez M.V., Shafren D.R., Gu X., Cox K., Sheppard D., Barry R.D.; RT "Integrin alpha v beta 6 enhances coxsackievirus B1 lytic infection of RT human colon cancer cells."; RL Virology 239:71-77(1997). RN [9] RP INTERACTION WITH FLNB. RC TISSUE=Keratinocyte, and Skeletal muscle; RX PubMed=11807098; DOI=10.1083/jcb.200103037; RA van Der Flier A., Kuikman I., Kramer D., Geerts D., Kreft M., Takafuta T., RA Shapiro S.S., Sonnenberg A.; RT "Different splice variants of filamin-B affect myogenesis, subcellular RT distribution, and determine binding to integrin (beta) subunits."; RL J. Cell Biol. 156:361-376(2002). RN [10] RP FUNCTION. RX PubMed=15184403; DOI=10.1083/jcb.200312172; RA Annes J.P., Chen Y., Munger J.S., Rifkin D.B.; RT "Integrin alphaVbeta6-mediated activation of latent TGF-beta requires the RT latent TGF-beta binding protein-1."; RL J. Cell Biol. 165:723-734(2004). RN [11] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH COXSACKIEVIRUS A9 RP CAPSID PROTEINS. RX PubMed=15194773; DOI=10.1128/jvi.78.13.6967-6973.2004; RA Williams C.H., Kajander T., Hyypia T., Jackson T., Sheppard D., Stanway G.; RT "Integrin alpha v beta 6 is an RGD-dependent receptor for coxsackievirus RT A9."; RL J. Virol. 78:6967-6973(2004). RN [12] RP INTERACTION WITH HAX1, AND FUNCTION. RX PubMed=17545607; DOI=10.1158/0008-5472.can-07-0318; RA Ramsay A.G., Keppler M.D., Jazayeri M., Thomas G.J., Parsons M., RA Violette S., Weinreb P., Hart I.R., Marshall J.F.; RT "HS1-associated protein X-1 regulates carcinoma cell migration and invasion RT via clathrin-mediated endocytosis of integrin alphavbeta6."; RL Cancer Res. 67:5275-5284(2007). RN [13] RP FUNCTION, INTERACTION WITH FBN1, AND SUBCELLULAR LOCATION. RX PubMed=17158881; DOI=10.1074/jbc.m607008200; RA Jovanovic J., Takagi J., Choulier L., Abrescia N.G., Stuart D.I., RA van der Merwe P.A., Mardon H.J., Handford P.A.; RT "alphaVbeta6 is a novel receptor for human fibrillin-1. Comparative studies RT of molecular determinants underlying integrin-rgd affinity and RT specificity."; RL J. Biol. Chem. 282:6743-6751(2007). RN [14] RP FUNCTION, AND INTERACTION WITH TGFB1. RX PubMed=22278742; DOI=10.1091/mbc.e11-12-1018; RA Wang R., Zhu J., Dong X., Shi M., Lu C., Springer T.A.; RT "GARP regulates the bioavailability and activation of TGFbeta."; RL Mol. Biol. Cell 23:1129-1139(2012). RN [15] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HERPES SIMPLES-1/HHV-1 RP GH:GL PROTEINS. RX PubMed=24367260; DOI=10.1371/journal.ppat.1003806; RA Gianni T., Salvioli S., Chesnokova L.S., Hutt-Fletcher L.M., RA Campadelli-Fiume G.; RT "alphavbeta6- and alphavbeta8-integrins serve as interchangeable receptors RT for HSV gH/gL to promote endocytosis and activation of membrane fusion."; RL PLoS Pathog. 9:E1003806-E1003806(2013). RN [16] {ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 18-491 IN COMPLEX WITH ITGAV; RP TGFB3 PEPTIDE; CALCIUM AND MANGANESE, FUNCTION, GLYCOSYLATION AT ASN-48; RP ASN-97; ASN-260 AND ASN-387, AND DISULFIDE BONDS. RX PubMed=25383667; DOI=10.1038/nsmb.2905; RA Dong X., Hudson N.E., Lu C., Springer T.A.; RT "Structural determinants of integrin beta-subunit specificity for latent RT TGF-beta."; RL Nat. Struct. Mol. Biol. 21:1091-1096(2014). RN [17] {ECO:0007744|PDB:5FFG, ECO:0007744|PDB:5FFO} RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 128-378 IN COMPLEX WITH TGFB1 AND RP ITGAV, INTERACTION WITH TGFB1, CALCIUM-BINDING, FUNCTION, DISULFIDE BONDS, RP AND GLYCOSYLATION AT ASN-260. RX PubMed=28117447; DOI=10.1038/nature21035; RA Dong X., Zhao B., Iacob R.E., Zhu J., Koksal A.C., Lu C., Engen J.R., RA Springer T.A.; RT "Force interacts with macromolecular structure in activation of TGF-beta."; RL Nature 542:55-59(2017). RN [18] RP INVOLVEMENT IN AI1H, AND VARIANT AI1H THR-196. RX PubMed=24319098; DOI=10.1093/hmg/ddt616; RA Poulter J.A., Brookes S.J., Shore R.C., Smith C.E., Abi Farraj L., RA Kirkham J., Inglehearn C.F., Mighell A.J.; RT "A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis RT imperfecta."; RL Hum. Mol. Genet. 23:2189-2197(2014). RN [19] RP INVOLVEMENT IN AI1H, AND VARIANTS AI1H THR-143 AND GLN-275. RX PubMed=24305999; DOI=10.1093/hmg/ddt611; RA Wang S.K., Choi M., Richardson A.S., Reid B.M., Lin B.P., Wang S.J., RA Kim J.W., Simmer J.P., Hu J.C.; RT "ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis RT imperfecta."; RL Hum. Mol. Genet. 23:2157-2163(2014). CC -!- FUNCTION: Integrin alpha-V:beta-6 (ITGAV:ITGB6) is a receptor for CC fibronectin and cytotactin (PubMed:17545607, PubMed:17158881). It CC recognizes the sequence R-G-D in its ligands (PubMed:17545607, CC PubMed:17158881). Internalization of integrin alpha-V/beta-6 via CC clathrin-mediated endocytosis promotes carcinoma cell invasion CC (PubMed:17545607, PubMed:17158881). ITGAV:ITGB6 acts as a receptor for CC fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 CC (PubMed:17158881). Integrin alpha-V:beta-6 (ITGAV:ITGB6) mediates R-G- CC D-dependent release of transforming growth factor beta-1 (TGF-beta-1) CC from regulatory Latency-associated peptide (LAP), thereby playing a key CC role in TGF-beta-1 activation (PubMed:15184403, PubMed:22278742, CC PubMed:28117447). {ECO:0000269|PubMed:15184403, CC ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:17545607, CC ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:25383667, CC ECO:0000269|PubMed:28117447}. CC -!- FUNCTION: (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor CC for Coxsackievirus A9 and Coxsackievirus B1. CC {ECO:0000269|PubMed:15194773, ECO:0000269|PubMed:9426447}. CC -!- FUNCTION: (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor CC for Herpes simplex virus-1/HHV-1 (PubMed:24367260). CC {ECO:0000269|PubMed:24367260}. CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit (PubMed:11807098, CC PubMed:17545607, PubMed:17158881). Interacts with FLNB CC (PubMed:11807098). Interacts with HAX1 (PubMed:17545607). ITGAV:ITGB6 CC interacts with FBN1 (PubMed:17158881). ITGAV:ITGB6 interacts with TGFB1 CC (PubMed:22278742, PubMed:28117447). {ECO:0000269|PubMed:11807098, CC ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:17545607, CC ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:28117447}. CC -!- SUBUNIT: (Microbial infection) Integrin ITGAV:ITGB6 interacts with CC coxsackievirus A9, coxsackievirus B1 capsid proteins (PubMed:9426447, CC PubMed:15194773). {ECO:0000269|PubMed:15194773, CC ECO:0000269|PubMed:9426447}. CC -!- SUBUNIT: (Microbial infection) Integrin ITGAV:ITGB6 interacts with CC herpes simplex virus-1/HHV-1 gH:gL proteins. CC {ECO:0000269|PubMed:24367260}. CC -!- INTERACTION: CC P18564; P06756: ITGAV; NbExp=8; IntAct=EBI-2568070, EBI-298282; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17545607}; CC Single-pass type I membrane protein {ECO:0000305}. Cell junction, focal CC adhesion {ECO:0000269|PubMed:17158881}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P18564-1; Sequence=Displayed; CC Name=2; CC IsoId=P18564-2; Sequence=VSP_055189; 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 -!- DISEASE: Amelogenesis imperfecta 1H (AI1H) [MIM:616221]: A disorder CC characterized by defective enamel formation, resulting in hypoplastic CC and hypomineralized tooth enamel that may be rough, pitted, and/or CC discolored. {ECO:0000269|PubMed:24305999, ECO:0000269|PubMed:24319098}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the integrin beta chain family. {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; M35198; AAA36122.2; -; mRNA. DR EMBL; AC092153; AAX93093.1; -; Genomic_DNA. DR EMBL; AK313944; BAG36662.1; -; mRNA. DR EMBL; AC080166; AAY24053.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11390.1; -; Genomic_DNA. DR EMBL; BC121178; AAI21179.1; -; mRNA. DR EMBL; S49380; AAB23690.1; -; Genomic_DNA. DR CCDS; CCDS2212.1; -. [P18564-1] DR CCDS; CCDS63040.1; -. [P18564-2] DR PIR; A37057; A37057. DR RefSeq; NP_000879.2; NM_000888.4. [P18564-1] DR RefSeq; NP_001269282.1; NM_001282353.1. [P18564-1] DR RefSeq; NP_001269284.1; NM_001282355.1. [P18564-2] DR RefSeq; NP_001269317.1; NM_001282388.1. DR PDB; 4UM8; X-ray; 2.85 A; B/D=1-788. DR PDB; 4UM9; X-ray; 2.50 A; B/D=18-491. DR PDB; 5FFG; X-ray; 2.25 A; B=128-378. DR PDB; 5FFO; X-ray; 3.49 A; B/F=128-378. DR PDB; 5NEM; EM; 3.10 A; B=22-491. DR PDB; 5NER; EM; 3.10 A; B=22-491. DR PDB; 5NET; EM; 3.10 A; B=22-491. DR PDB; 5NEU; EM; 3.10 A; B=22-491. DR PDB; 8TCG; EM; 3.40 A; B=130-371. DR PDBsum; 4UM8; -. DR PDBsum; 4UM9; -. DR PDBsum; 5FFG; -. DR PDBsum; 5FFO; -. DR PDBsum; 5NEM; -. DR PDBsum; 5NER; -. DR PDBsum; 5NET; -. DR PDBsum; 5NEU; -. DR PDBsum; 8TCG; -. DR AlphaFoldDB; P18564; -. DR EMDB; EMD-3632; -. DR EMDB; EMD-3633; -. DR EMDB; EMD-3634; -. DR EMDB; EMD-3635; -. DR EMDB; EMD-41154; -. DR SMR; P18564; -. DR BioGRID; 109900; 11. DR ComplexPortal; CPX-1820; Integrin alphav-beta6 complex. DR CORUM; P18564; -. DR DIP; DIP-59187N; -. DR ELM; P18564; -. DR IntAct; P18564; 4. DR STRING; 9606.ENSP00000283249; -. DR BindingDB; P18564; -. DR ChEMBL; CHEMBL2111416; -. DR DrugBank; DB16515; PLN-74809. DR GuidetoPHARMACOLOGY; 2460; -. DR GlyConnect; 1419; 7 N-Linked glycans (2 sites). DR GlyCosmos; P18564; 9 sites, 7 glycans. DR GlyGen; P18564; 10 sites, 7 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; P18564; -. DR PhosphoSitePlus; P18564; -. DR SwissPalm; P18564; -. DR BioMuta; ITGB6; -. DR DMDM; 13432176; -. DR EPD; P18564; -. DR jPOST; P18564; -. DR MassIVE; P18564; -. DR MaxQB; P18564; -. DR PaxDb; 9606-ENSP00000283249; -. DR PeptideAtlas; P18564; -. DR ProteomicsDB; 53577; -. [P18564-1] DR ProteomicsDB; 9297; -. DR Pumba; P18564; -. DR ABCD; P18564; 49 sequenced antibodies. DR Antibodypedia; 33727; 399 antibodies from 28 providers. DR DNASU; 3694; -. DR Ensembl; ENST00000283249.7; ENSP00000283249.2; ENSG00000115221.12. [P18564-1] DR Ensembl; ENST00000409872.1; ENSP00000386367.1; ENSG00000115221.12. [P18564-1] DR Ensembl; ENST00000409967.6; ENSP00000386828.2; ENSG00000115221.12. [P18564-2] DR GeneID; 3694; -. DR KEGG; hsa:3694; -. DR MANE-Select; ENST00000283249.7; ENSP00000283249.2; NM_000888.5; NP_000879.2. DR UCSC; uc010fou.4; human. [P18564-1] DR AGR; HGNC:6161; -. DR CTD; 3694; -. DR DisGeNET; 3694; -. DR GeneCards; ITGB6; -. DR HGNC; HGNC:6161; ITGB6. DR HPA; ENSG00000115221; Tissue enhanced (kidney, skeletal muscle, tongue). DR MalaCards; ITGB6; -. DR MIM; 147558; gene. DR MIM; 616221; phenotype. DR neXtProt; NX_P18564; -. DR OpenTargets; ENSG00000115221; -. DR Orphanet; 2850; Alopecia-intellectual disability syndrome. DR Orphanet; 100032; Hypocalcified amelogenesis imperfecta. DR Orphanet; 100031; Hypoplastic amelogenesis imperfecta. DR PharmGKB; PA29960; -. DR VEuPathDB; HostDB:ENSG00000115221; -. DR eggNOG; KOG1226; Eukaryota. DR GeneTree; ENSGT01100000263555; -. DR InParanoid; P18564; -. DR OMA; WIYTVEG; -. DR OrthoDB; 5475862at2759; -. DR PhylomeDB; P18564; -. DR TreeFam; TF105392; -. DR PathwayCommons; P18564; -. DR Reactome; R-HSA-1566948; Elastic fibre formation. DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres. DR Reactome; R-HSA-216083; Integrin cell surface interactions. DR Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs. DR Reactome; R-HSA-3000178; ECM proteoglycans. DR SignaLink; P18564; -. DR SIGNOR; P18564; -. DR BioGRID-ORCS; 3694; 13 hits in 1149 CRISPR screens. DR ChiTaRS; ITGB6; human. DR GeneWiki; Integrin,_beta_6; -. DR GenomeRNAi; 3694; -. DR Pharos; P18564; Tbio. DR PRO; PR:P18564; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P18564; Protein. DR Bgee; ENSG00000115221; Expressed in visceral pleura and 135 other cell types or tissues. DR ExpressionAtlas; P18564; baseline and differential. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0009986; C:cell surface; IBA:GO_Central. DR GO; GO:0005813; C:centrosome; IDA:HPA. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0034685; C:integrin alphav-beta6 complex; IDA:UniProtKB. DR GO; GO:0008305; C:integrin complex; TAS:ProtInc. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0043235; C:receptor complex; IDA:MGI. DR GO; GO:0005178; F:integrin binding; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0140677; F:molecular function activator activity; IEP:DisProt. DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW. DR GO; GO:0060348; P:bone development; IEA:Ensembl. DR GO; GO:0060435; P:bronchiole development; IEA:Ensembl. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0033627; P:cell adhesion mediated by integrin; IDA:UniProtKB. DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl. DR GO; GO:0007160; P:cell-matrix adhesion; NAS:ComplexPortal. DR GO; GO:0071479; P:cellular response to ionizing radiation; IEA:Ensembl. DR GO; GO:0070166; P:enamel mineralization; IEA:Ensembl. DR GO; GO:0060022; P:hard palate development; IEA:Ensembl. DR GO; GO:0006955; P:immune response; IEA:Ensembl. DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0061520; P:Langerhans cell differentiation; IEA:Ensembl. DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl. DR GO; GO:0055091; P:phospholipid homeostasis; IEA:Ensembl. DR GO; GO:1901388; P:regulation of transforming growth factor beta activation; IDA:UniProtKB. DR GO; GO:0009615; P:response to virus; IEA:Ensembl. DR GO; GO:0043588; P:skin development; IEA:Ensembl. DR GO; GO:0043129; P:surfactant homeostasis; IEA:Ensembl. DR GO; GO:0071604; P:transforming growth factor beta production; IEA:Ensembl. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl. DR GO; GO:0042060; P:wound healing; IEA:Ensembl. DR DisProt; DP02530; -. DR Gene3D; 4.10.1240.30; -; 1. DR Gene3D; 1.20.5.100; Cytochrome c1, transmembrane anchor, C-terminal; 1. DR Gene3D; 2.10.25.10; Laminin; 4. 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; IPR013111; EGF_extracell. DR InterPro; IPR040622; I-EGF_1. DR InterPro; IPR033760; Integrin_beta_N. DR InterPro; IPR015812; Integrin_bsu. DR InterPro; IPR014836; Integrin_bsu_cyt_dom. DR InterPro; IPR012896; Integrin_bsu_tail. DR InterPro; IPR036349; Integrin_bsu_tail_dom_sf. DR InterPro; IPR002369; Integrin_bsu_VWA. DR InterPro; IPR032695; Integrin_dom_sf. DR InterPro; IPR016201; PSI. DR InterPro; IPR036465; vWFA_dom_sf. DR PANTHER; PTHR10082; INTEGRIN BETA SUBUNIT; 1. DR PANTHER; PTHR10082:SF11; INTEGRIN BETA-6; 1. DR Pfam; PF07974; EGF_2; 2. DR Pfam; PF18372; I-EGF_1; 1. DR Pfam; PF08725; Integrin_b_cyt; 1. DR Pfam; PF07965; Integrin_B_tail; 1. DR Pfam; PF00362; Integrin_beta; 1. DR Pfam; PF17205; PSI_integrin; 1. DR PIRSF; PIRSF002512; Integrin_B; 1. DR PRINTS; PR01186; INTEGRINB. DR SMART; SM00187; INB; 1. DR SMART; SM01241; Integrin_b_cyt; 1. DR SMART; SM01242; Integrin_B_tail; 1. DR SMART; SM00423; PSI; 1. DR SUPFAM; SSF57196; EGF/Laminin; 2. DR SUPFAM; SSF69687; Integrin beta tail domain; 1. DR SUPFAM; SSF69179; Integrin domains; 2. DR SUPFAM; SSF103575; Plexin repeat; 1. DR SUPFAM; SSF53300; vWA-like; 1. DR PROSITE; PS00022; EGF_1; 2. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS00243; INTEGRIN_BETA; 3. DR Genevisible; P18564; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Amelogenesis imperfecta; Calcium; KW Cell adhesion; Cell junction; Cell membrane; Disease variant; KW Disulfide bond; EGF-like domain; Glycoprotein; KW Host cell receptor for virus entry; Host-virus interaction; Integrin; KW Magnesium; Membrane; Metal-binding; Receptor; Reference proteome; Repeat; KW Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..788 FT /note="Integrin beta-6" FT /id="PRO_0000016350" FT TOPO_DOM 22..709 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 710..730 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 731..788 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 22..71 FT /note="PSI" FT /evidence="ECO:0000255" FT DOMAIN 131..371 FT /note="VWFA" FT /evidence="ECO:0000250|UniProtKB:P05106" FT DOMAIN 456..501 FT /note="EGF-like 1" FT /evidence="ECO:0000250|UniProtKB:P05106" FT DOMAIN 502..543 FT /note="EGF-like 2" FT /evidence="ECO:0000250|UniProtKB:P05106" FT DOMAIN 544..582 FT /note="EGF-like 3" FT /evidence="ECO:0000250|UniProtKB:P05106" FT DOMAIN 583..619 FT /note="EGF-like 4" FT /evidence="ECO:0000250|UniProtKB:P05106" FT REGION 731..758 FT /note="Interaction with HAX1" FT /evidence="ECO:0000269|PubMed:17545607" FT BINDING 140 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /note="in MIDAS binding site" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8" FT BINDING 142 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /note="in MIDAS binding site" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" 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:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8" FT BINDING 144 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /note="in MIDAS binding site" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 147 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /note="in ADMIDAS binding site" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT BINDING 148 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /note="in ADMIDAS binding site" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT BINDING 179 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="in LIMBS binding site" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM9" FT BINDING 235 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="in LIMBS binding site" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM9" FT BINDING 237 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="in LIMBS binding site" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM9" FT BINDING 239 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="in LIMBS binding site" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM9" FT BINDING 240 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /note="in LIMBS binding site" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM9" FT BINDING 240 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /note="in MIDAS binding site" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT BINDING 271 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /note="in ADMIDAS binding site and liganded-open FT conformation" FT /evidence="ECO:0000250|UniProtKB:P05106" FT BINDING 355 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /note="in ADMIDAS binding site and unliganded-closed FT conformation" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8" FT CARBOHYD 48 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT CARBOHYD 97 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT CARBOHYD 260 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0000269|PubMed:28117447, ECO:0007744|PDB:4UM8, FT ECO:0007744|PDB:4UM9" FT CARBOHYD 387 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT CARBOHYD 396 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 463 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 471 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 541 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 575 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 23..41 FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT DISULFID 31..454 FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT DISULFID 34..59 FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT DISULFID 44..70 FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT DISULFID 197..204 FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0000269|PubMed:28117447, ECO:0007744|PDB:4UM8, FT ECO:0007744|PDB:4UM9, ECO:0007744|PDB:5FFG, FT ECO:0007744|PDB:5FFO" FT DISULFID 252..293 FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0000269|PubMed:28117447, ECO:0007744|PDB:4UM8, FT ECO:0007744|PDB:4UM9, ECO:0007744|PDB:5FFG, FT ECO:0007744|PDB:5FFO" FT DISULFID 394..406 FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT DISULFID 426..452 FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM8, ECO:0007744|PDB:4UM9" FT DISULFID 456..476 FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM9" FT DISULFID 467..479 FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM9" FT DISULFID 481..490 FT /evidence="ECO:0000269|PubMed:25383667, FT ECO:0007744|PDB:4UM9" FT DISULFID 492..519 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 502..517 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 511..522 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 524..537 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 539..560 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 544..558 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 552..563 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 565..574 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 576..599 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 583..597 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 591..602 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 604..614 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 617..620 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 624..670 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 630..649 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 633..645 FT /evidence="ECO:0000250|UniProtKB:P05106" FT DISULFID 678..702 FT /evidence="ECO:0000250|UniProtKB:P05106" FT VAR_SEQ 554..660 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_055189" FT VARIANT 143 FT /note="A -> T (in AI1H; dbSNP:rs140015315)" FT /evidence="ECO:0000269|PubMed:24305999" FT /id="VAR_073328" FT VARIANT 196 FT /note="P -> T (in AI1H; dbSNP:rs730880298)" FT /evidence="ECO:0000269|PubMed:24319098" FT /id="VAR_073329" FT VARIANT 275 FT /note="H -> Q (in AI1H; dbSNP:rs730882118)" FT /evidence="ECO:0000269|PubMed:24305999" FT /id="VAR_073330" FT VARIANT 437 FT /note="P -> T (in dbSNP:rs2305820)" FT /id="VAR_049636" FT TURN 24..26 FT /evidence="ECO:0007829|PDB:4UM9" FT HELIX 31..34 FT /evidence="ECO:0007829|PDB:4UM9" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:4UM9" FT HELIX 62..68 FT /evidence="ECO:0007829|PDB:4UM9" FT TURN 72..74 FT /evidence="ECO:0007829|PDB:4UM9" FT STRAND 81..86 FT /evidence="ECO:0007829|PDB:4UM9" FT HELIX 98..100 FT /evidence="ECO:0007829|PDB:4UM9" FT STRAND 108..113 FT /evidence="ECO:0007829|PDB:4UM9" FT STRAND 119..126 FT /evidence="ECO:0007829|PDB:4UM9" FT STRAND 133..140 FT /evidence="ECO:0007829|PDB:5FFG" FT HELIX 143..145 FT /evidence="ECO:0007829|PDB:5FFG" FT HELIX 146..151 FT /evidence="ECO:0007829|PDB:5FFG" FT HELIX 152..154 FT /evidence="ECO:0007829|PDB:5FFG" FT HELIX 155..166 FT /evidence="ECO:0007829|PDB:5FFG" FT STRAND 170..177 FT /evidence="ECO:0007829|PDB:5FFG" FT TURN 183..185 FT /evidence="ECO:0007829|PDB:4UM9" FT HELIX 190..194 FT /evidence="ECO:0007829|PDB:5FFG" FT TURN 196..201 FT /evidence="ECO:0007829|PDB:5FFG" FT STRAND 209..218 FT /evidence="ECO:0007829|PDB:5FFG" FT HELIX 220..229 FT /evidence="ECO:0007829|PDB:5FFG" FT STRAND 236..241 FT /evidence="ECO:0007829|PDB:4UM9" FT HELIX 242..251 FT /evidence="ECO:0007829|PDB:5FFG" FT HELIX 253..256 FT /evidence="ECO:0007829|PDB:5FFG" FT STRAND 262..272 FT /evidence="ECO:0007829|PDB:5FFG" FT HELIX 277..283 FT /evidence="ECO:0007829|PDB:5FFG" FT STRAND 297..301 FT /evidence="ECO:0007829|PDB:5FFG" FT TURN 302..306 FT /evidence="ECO:0007829|PDB:5FFG" FT HELIX 312..321 FT /evidence="ECO:0007829|PDB:5FFG" FT STRAND 324..330 FT /evidence="ECO:0007829|PDB:5FFG" FT HELIX 332..344 FT /evidence="ECO:0007829|PDB:5FFG" FT STRAND 349..352 FT /evidence="ECO:0007829|PDB:5FFG" FT HELIX 360..371 FT /evidence="ECO:0007829|PDB:5FFG" FT STRAND 375..382 FT /evidence="ECO:0007829|PDB:4UM9" FT STRAND 387..393 FT /evidence="ECO:0007829|PDB:4UM9" FT TURN 395..397 FT /evidence="ECO:0007829|PDB:4UM8" FT STRAND 399..401 FT /evidence="ECO:0007829|PDB:4UM9" FT STRAND 414..422 FT /evidence="ECO:0007829|PDB:4UM9" FT STRAND 431..437 FT /evidence="ECO:0007829|PDB:4UM9" FT STRAND 444..450 FT /evidence="ECO:0007829|PDB:4UM9" FT HELIX 455..457 FT /evidence="ECO:0007829|PDB:4UM8" FT STRAND 467..475 FT /evidence="ECO:0007829|PDB:4UM9" FT STRAND 478..481 FT /evidence="ECO:0007829|PDB:4UM9" SQ SEQUENCE 788 AA; 85936 MW; EDB7D533EC4C8C4D CRC64; MGIELLCLFF LFLGRNDHVQ GGCALGGAET CEDCLLIGPQ CAWCAQENFT HPSGVGERCD TPANLLAKGC QLNFIENPVS QVEILKNKPL SVGRQKNSSD IVQIAPQSLI LKLRPGGAQT LQVHVRQTED YPVDLYYLMD LSASMDDDLN TIKELGSRLS KEMSKLTSNF RLGFGSFVEK PVSPFVKTTP EEIANPCSSI PYFCLPTFGF KHILPLTNDA ERFNEIVKNQ KISANIDTPE GGFDAIMQAA VCKEKIGWRN DSLHLLVFVS DADSHFGMDS KLAGIVIPND GLCHLDSKNE YSMSTVLEYP TIGQLIDKLV QNNVLLIFAV TQEQVHLYEN YAKLIPGATV GLLQKDSGNI LQLIISAYEE LRSEVELEVL GDTEGLNLSF TAICNNGTLF QHQKKCSHMK VGDTASFSVT VNIPHCERRS RHIIIKPVGL GDALELLVSP ECNCDCQKEV EVNSSKCHHG NGSFQCGVCA CHPGHMGPRC ECGEDMLSTD SCKEAPDHPS CSGRGDCYCG QCICHLSPYG NIYGPYCQCD NFSCVRHKGL LCGGNGDCDC GECVCRSGWT GEYCNCTTST DSCVSEDGVL CSGRGDCVCG KCVCTNPGAS GPTCERCPTC GDPCNSKRSC IECHLSAAGQ AREECVDKCK LAGATISEEE DFSKDGSVSC SLQGENECLI TFLITTDNEG KTIIHSINEK DCPKPPNIPM IMLGVSLAIL LIGVVLLCIW KLLVSFHDRK EVAKFEAERS KAKWQTGTNP LYRGSTSTFK NVTYKHREKQ KVDLSTDC //