ID ITA6_HUMAN Reviewed; 1130 AA. AC P23229; Q08443; Q14646; Q16508; Q9UN03; DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 3. DT 10-JUN-2008, entry version 94. DE Integrin alpha-6 precursor (VLA-6) (CD49 antigen-like family member F) DE (CD49f antigen) [Contains: Integrin alpha-6 heavy chain; Integrin DE alpha-6 light chain]. GN Name=ITGA6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-6X1A). RC TISSUE=Pancreas; RX MEDLINE=91009492; PubMed=1976638; DOI=10.1083/jcb.111.4.1593; RA Tamura R.N., Rozzo C., Starr L., Chambers J., Reichardt L.F., RA Cooper H.M., Quaranta V.; RT "Epithelial integrin alpha 6 beta 4: complete primary structure of RT alpha 6 and variant forms of beta 4."; RL J. Cell Biol. 111:1593-1604(1990). RN [2] RP SEQUENCE REVISION TO 78 AND 362. RA Quaranta V.; RL Submitted (JUN-1991) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE (ISOFORM ALPHA-6X1A). RA Pulkkinen L., Uitto J.; RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-6X1A). RC TISSUE=Keratinocyte; RX MEDLINE=91301154; PubMed=2070796; RA Hogervorst F., Kuikman I., Geurts van Kessel A., Sonnenberg A.; RT "Molecular cloning of the human alpha 6 integrin subunit. Alternative RT splicing of alpha 6 mRNA and chromosomal localization of the alpha 6 RT and beta 4 genes."; RL Eur. J. Biochem. 199:425-433(1991). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 748-849. RX MEDLINE=93119630; PubMed=1476731; RA Starr L., Quaranta V.; RT "An efficient and reliable method for cloning PCR-amplification RT products: a survey of point mutations in integrin cDNA."; RL BioTechniques 13:612-618(1992). RN [6] RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-6X1A AND RP ALPHA-6X1B). RX MEDLINE=92052235; PubMed=1946438; RA Tamura R.N., Cooper H.M., Collo G., Quaranta V.; RT "Cell type-specific integrin variants with alternative alpha chain RT cytoplasmic domains."; RL Proc. Natl. Acad. Sci. U.S.A. 88:10183-10187(1991). RN [7] RP PARTIAL NUCLEOTIDE SEQUENCE (ISOFORMS ALPHA-6X1 AND ALPHA-6X2). RC TISSUE=Leukocyte; RX MEDLINE=94075378; PubMed=8253814; RA Ziober B.L., Vu M.P., Waleh N., Crawford J., Lin C.-S., Kramer R.H.; RT "Alternative extracellular and cytoplasmic domains of the integrin RT alpha 7 subunit are differentially expressed during development."; RL J. Biol. Chem. 268:26773-26783(1993). RN [8] RP PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM ALPHA-6X1A). RX PubMed=8496190; RA Shaw L.M., Lotz M.M., Mercurio A.M.; RT "Inside-out integrin signaling in macrophages. Analysis of the role of RT the alpha 6A beta 1 and alpha 6B beta 1 integrin variants in laminin RT adhesion by cDNA expression in an alpha 6 integrin-deficient RT macrophage cell line."; RL J. Biol. Chem. 268:11401-11408(1993). RN [9] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS ALPHA-6X1 AND RP ALPHA-6X1X2). RC TISSUE=Lymphoma; RX MEDLINE=96026914; PubMed=7583007; RA Delwel G.O., Kuikman I., Sonnenberg A.; RT "An alternatively spliced exon in the extracellular domain of the RT human alpha 6 integrin subunit -- functional analysis of the alpha 6 RT integrin variants."; RL Cell Adhes. Commun. 3:143-161(1995). RN [10] RP PROTEIN SEQUENCE OF 24-44. RX MEDLINE=89197963; PubMed=2649503; RA Hemler M.E., Crouse C., Sonnenberg A.; RT "Association of the VLA alpha 6 subunit with a novel protein. A RT possible alternative to the common VLA beta 1 subunit on certain cell RT lines."; RL J. Biol. Chem. 264:6529-6535(1989). RN [11] RP PROTEIN SEQUENCE OF 24-46. RX MEDLINE=89251596; PubMed=2542022; RA Kajiji S., Tamura R.N., Quaranta V.; RT "A novel integrin (alpha E beta 4) from human epithelial cells RT suggests a fourth family of integrin adhesion receptors."; RL EMBO J. 8:673-680(1989). RN [12] RP CHARACTERIZATION, AND TISSUE SPECIFICITY. RX MEDLINE=93209985; PubMed=7681434; DOI=10.1083/jcb.121.1.179; RA Hogervorst F., Admiraal L.G., Niessen C., Kuikman I., Janssen H., RA Daams H., Sonnenberg A.; RT "Biochemical characterization and tissue distribution of the A and B RT variants of the integrin alpha 6 subunit."; RL J. Cell Biol. 121:179-191(1993). RN [13] RP PHOSPHORYLATION. RX MEDLINE=93366736; PubMed=8360143; RA Hogervorst F., Kuikman I., Noteboom E., Sonnenberg A.; RT "The role of phosphorylation in activation of the alpha 6A beta 1 RT laminin receptor."; RL J. Biol. Chem. 268:18427-18430(1993). RN [14] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-323, AND MASS RP SPECTROMETRY. RC TISSUE=Platelet; RX PubMed=16263699; DOI=10.1074/mcp.M500324-MCP200; RA Lewandrowski U., Moebius J., Walter U., Sickmann A.; RT "Elucidation of N-glycosylation sites on human platelet proteins: a RT glycoproteomic approach."; RL Mol. Cell. Proteomics 5:226-233(2006). CC -!- FUNCTION: Integrin alpha-6/beta-1 is a receptor for laminin on CC platelets. Integrin alpha-6/beta-4 is a receptor for laminin in CC epithelial cells and it plays a critical structural role in the CC hemidesmosome. CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The alpha CC subunit is composed of an heavy and a light chain linked by a CC disulfide bond. Alpha-6 associates with either beta-1 or beta-4. CC Interacts with HPS5. CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Comment=Additional isoforms seem to exist. There is a CC combination of at least four alternatively spliced domains, two CC extracellular (X1 and X2) and two cytoplasmic (A and B). So far CC detected are isoform Alpha-6X1A, isoform Alpha-6X1B and isoform CC Alpha-6X1X2A (minor). Experimental confirmation may be lacking CC for some isoforms; CC Name=Alpha-6X1X2B; CC IsoId=P23229-1; Sequence=Displayed; CC Name=Alpha-6X1A; CC IsoId=P23229-2; Sequence=VSP_002724, VSP_002725; CC Name=Alpha-6X1B; CC IsoId=P23229-3; Sequence=VSP_002724; CC Name=Alpha-6X2A; CC IsoId=P23229-4; Sequence=VSP_002723, VSP_002725; CC Name=Alpha-6X2B; CC IsoId=P23229-5; Sequence=VSP_002723; CC Name=Alpha-6X1X2A; CC IsoId=P23229-6; Sequence=VSP_002725; CC -!- TISSUE SPECIFICITY: Integrin alpha-6/beta-4 is predominantly CC expressed by epithelia. Isoforms containing segment X1 are CC ubiquitously expressed. Isoforms containing segment X1X2 are CC expressed in heart, kidney, placenta, colon, duodenum, myoblasts CC and myotubes, and in a limited number of cell lines; they are CC always coexpressed with the ubiquitous isoform containing segment CC X1. In some tissues (e.g. Salivary gland), isoforms containing CC cytoplasmic segment A and isoforms containing segment B are CC detected while in others, only isoforms containing one cytoplasmic CC segment are found (segment A in epidermis and segment B in CC kidney). CC -!- PTM: Isoforms containing segment A, but not segment B, are the CC major targets for PMA-induced phosphorylation. Phosphorylation CC occurs on 'Ser-1103' of isoform alpha-6X1X2A. Phosphorylation is CC not required for the induction of integrin alpha-6A/beta-1 high CC affinity but may reduce the affinity for ligand. CC -!- DISEASE: Defects in ITGA6 are a cause of epidermolysis bullosa CC with pyloric atresia (EB-PA) [MIM:226730]; also known as aplasia CC cutis congenita with gastrointestinal atresia. EB-PA is an CC autosomal recessive disease characterized by mucocutaneous CC fragility and gastrointestinal atresia, which most commonly CC affects the pylorus. CC -!- SIMILARITY: Belongs to the integrin alpha chain family. CC -!- SIMILARITY: Contains 7 FG-GAP repeats. 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; X53586; CAA37655.1; -; mRNA. DR EMBL; AF166343; AAD48469.1; -; Genomic_DNA. DR EMBL; AF166335; AAD48469.1; JOINED; Genomic_DNA. DR EMBL; AF166336; AAD48469.1; JOINED; Genomic_DNA. DR EMBL; AF166337; AAD48469.1; JOINED; Genomic_DNA. DR EMBL; AF166338; AAD48469.1; JOINED; Genomic_DNA. DR EMBL; AF166339; AAD48469.1; JOINED; Genomic_DNA. DR EMBL; AF166340; AAD48469.1; JOINED; Genomic_DNA. DR EMBL; AF166341; AAD48469.1; JOINED; Genomic_DNA. DR EMBL; AF166342; AAD48469.1; JOINED; Genomic_DNA. DR EMBL; X59512; CAA42099.1; -; mRNA. DR EMBL; S52135; AAB24829.1; -; Genomic_DNA. DR EMBL; S66213; AAB20355.1; -; mRNA. DR EMBL; S66196; AAB20354.1; -; mRNA. DR EMBL; L40385; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; B36429; B36429. DR RefSeq; NP_000201.2; -. DR RefSeq; NP_001073286.1; -. DR UniGene; Hs.133397; -. DR HSSP; P11215; 1A8X. DR OGP; P23229; -. DR Ensembl; ENSG00000091409; Homo sapiens. DR GeneID; 3655; -. DR KEGG; hsa:3655; -. DR HGNC; HGNC:6142; ITGA6. DR HPA; CAB009009; -. DR MIM; 147556; gene. DR MIM; 226730; phenotype. DR Orphanet; 305; Epidermolysis bullosa, junctional. DR PharmGKB; PA29942; -. DR HOGENOM; P23229; -. DR HOVERGEN; P23229; -. DR ArrayExpress; P23229; -. DR CleanEx; HS_ITGA6; -. DR GermOnline; ENSG00000091409; Homo sapiens. DR GO; GO:0007044; P:cell-substrate junction assembly; TAS:ProtInc. DR InterPro; IPR013517; FG-GAP. DR InterPro; IPR013519; Int_alpha_beta-p. DR InterPro; IPR000413; Integrin_alpha. DR InterPro; IPR013649; Integrin_alpha-2. DR InterPro; IPR013513; Integrin_alpha_C. DR Pfam; PF01839; FG-GAP; 3. DR Pfam; PF08441; Integrin_alpha2; 1. DR PRINTS; PR01185; INTEGRINA. DR SMART; SM00191; Int_alpha; 5. DR PROSITE; PS00242; INTEGRIN_ALPHA; 1. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Cell adhesion; KW Cleavage on pair of basic residues; Direct protein sequencing; KW Epidermolysis bullosa; Glycoprotein; Integrin; Membrane; KW Phosphoprotein; Receptor; Repeat; Signal; Transmembrane. FT SIGNAL 1 23 FT CHAIN 24 1130 Integrin alpha-6. FT /FTId=PRO_0000016258. FT CHAIN 24 938 Integrin alpha-6 heavy chain (Potential). FT /FTId=PRO_0000016259. FT CHAIN 942 1130 Integrin alpha-6 light chain (Potential). FT /FTId=PRO_0000016260. FT TOPO_DOM 24 1050 Extracellular (Potential). FT TRANSMEM 1051 1076 Potential. FT TOPO_DOM 1077 1130 Cytoplasmic (Potential). FT REPEAT 42 79 FG-GAP 1. FT REPEAT 113 145 FG-GAP 2. FT REPEAT 185 217 FG-GAP 3. FT REPEAT 295 331 FG-GAP 4. FT REPEAT 353 391 FG-GAP 5. FT REPEAT 414 450 FG-GAP 6. FT REPEAT 469 509 FG-GAP 7. FT CA_BIND 363 371 Potential. FT CA_BIND 425 433 Potential. FT CA_BIND 480 488 Potential. FT REGION 1077 1083 Interaction with HPS5. FT MOTIF 1079 1083 GFFKR motif. FT CARBOHYD 78 78 N-linked (GlcNAc...) (Potential). FT CARBOHYD 223 223 N-linked (GlcNAc...) (Potential). FT CARBOHYD 323 323 N-linked (GlcNAc...). FT CARBOHYD 409 409 N-linked (GlcNAc...) (Potential). FT CARBOHYD 770 770 N-linked (GlcNAc...) (Potential). FT CARBOHYD 787 787 N-linked (GlcNAc...) (Potential). FT CARBOHYD 930 930 N-linked (GlcNAc...) (Potential). FT CARBOHYD 966 966 N-linked (GlcNAc...) (Potential). FT CARBOHYD 997 997 N-linked (GlcNAc...) (Potential). FT DISULFID 86 94 By similarity. FT DISULFID 131 154 By similarity. FT DISULFID 175 188 By similarity. FT DISULFID 528 535 By similarity. FT DISULFID 541 601 By similarity. FT DISULFID 665 671 By similarity. FT DISULFID 765 776 By similarity. FT DISULFID 920 967 Interchain (between heavy and light FT chains) (By similarity). FT DISULFID 973 978 By similarity. FT VAR_SEQ 215 258 Missing (in isoform Alpha-6X2A and FT isoform Alpha-6X2B). FT /FTId=VSP_002723. FT VAR_SEQ 259 297 Missing (in isoform Alpha-6X1A and FT isoform Alpha-6X1B). FT /FTId=VSP_002724. FT VAR_SEQ 1084 1130 SRYDDSVPRYHAVRIRKEEREIKDEKYIDNLEKKQWITKWN FT RNESYS -> NKKDHYDATYHKAEIHAQPSDKERLTSDA FT (in isoform Alpha-6X1A, isoform Alpha- FT 6X2A and isoform Alpha-6X1X2A). FT /FTId=VSP_002725. FT CONFLICT 69 69 G -> A (in Ref. 3; AAD48469). FT CONFLICT 289 289 P -> G (in Ref. 7). FT CONFLICT 501 501 F -> L (in Ref. 4; CAA42099). FT CONFLICT 805 805 D -> Y (in Ref. 1 and 3). FT CONFLICT 1125 1125 R -> E (in Ref. 8). SQ SEQUENCE 1130 AA; 126619 MW; AAC96D0EF560BF6C CRC64; MAAAGQLCLL YLSAGLLSRL GAAFNLDTRE DNVIRKYGDP GSLFGFSLAM HWQLQPEDKR LLLVGAPRGE ALPLQRANRT GGLYSCDITA RGPCTRIEFD NDADPTSESK EDQWMGVTVQ SQGPGGKVVT CAHRYEKRQH VNTKQESRDI FGRCYVLSQN LRIEDDMDGG DWSFCDGRLR GHEKFGSCQQ GVAATFTKDF HYIVFGAPGT YNWKGIVRVE QKNNTFFDMN IFEDGPYEVG GETEHDESLV PVPANSYLGL LFLTSVSYTD PDQFVYKTRP PREQPDTFPD VMMNSYLGFS LDSGKGIVSK DEITFVSGAP RANHSGAVVL LKRDMKSAHL LPEHIFDGEG LASSFGYDVA VVDLNKDGWQ DIVIGAPQYF DRDGEVGGAV YVYMNQQGRW NNVKPIRLNG TKDSMFGIAV KNIGDINQDG YPDIAVGAPY DDLGKVFIYH GSANGINTKP TQVLKGISPY FGYSIAGNMD LDRNSYPDVA VGSLSDSVTI FRSRPVINIQ KTITVTPNRI DLRQKTACGA PSGICLQVKS CFEYTANPAG YNPSISIVGT LEAEKERRKS GLSSRVQFRN QGSEPKYTQE LTLKRQKQKV CMEETLWLQD NIRDKLRPIP ITASVEIQEP SSRRRVNSLP EVLPILNSDE PKTAHIDVHF LKEGCGDDNV CNSNLKLEYK FCTREGNQDK FSYLPIQKGV PELVLKDQKD IALEITVTNS PSNPRNPTKD GDDAHEAKLI ATFPDTLTYS AYRELRAFPE KQLSCVANQN GSQADCELGN PFKRNSNVTF YLVLSTTEVT FDTPDLDINL KLETTSNQDN LAPITAKAKV VIELLLSVSG VAKPSQVYFG GTVVGEQAMK SEDEVGSLIE YEFRVINLGK PLTNLGTATL NIQWPKEISN GKWLLYLVKV ESKGLEKVTC EPQKEINSLN LTESHNSRKK REITEKQIDD NRKFSLFAER KYQTLNCSVN VNCVNIRCPL RGLDSKASLI LRSRLWNSTF LEEYSKLNYL DILMRAFIDV TAAAENIRLP NAGTQVRVTV FPSKTVAQYS GVPWWIILVA ILAGILMLAL LVFILWKCGF FKRSRYDDSV PRYHAVRIRK EEREIKDEKY IDNLEKKQWI TKWNRNESYS //