ID ITA6_HUMAN STANDARD; PRT; 1130 AA. AC P23229; Q14646; Q16508; Q08443; Q9UN03; DT 01-NOV-1991 (Rel. 20, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 15-JUN-2002 (Rel. 41, Last annotation update) DE Integrin alpha-6 precursor (VLA-6) (CD49f). GN ITGA6. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM ALPHA-6X1A). RC TISSUE=Pancreas; RX MEDLINE=91009492; PubMed=1976638; 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 REVISIONS TO 78 AND 362. RA Quaranta V.; RL Submitted (JUN-1991) to the EMBL/GenBank/DDBJ databases. RN [3] RP SEQUENCE FROM N.A. (ISOFORM ALPHA-6X1A). RA Pulkkinen L., Uitto J.; RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP PARTIAL SEQUENCE FROM N.A. (ISOFORM ALPHA-6X1A). RC TISSUE=Keratinocytes; 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 SEQUENCE OF 748-849 FROM N.A. 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 SEQUENCE FROM N.A. (ISOFORMS ALPHA-6X1A AND 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 SEQUENCE FROM N.A. (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 SEQUENCE FROM N.A. (ISOFORMS ALPHA-6X1 AND 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 [9] RP 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 [10] RP 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 [11] RP CHARACTERIZATION, AND TISSUE SPECIFICITY. RX MEDLINE=93209985; PubMed=7681434; 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 [12] 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). 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 -!- SUBCELLULAR LOCATION: Type I membrane protein. CC -!- ALTERNATIVE PRODUCTS: AT LEAST 6 ISOFORMS; ALPHA-6X1A, ALPHA-6X1B, CC ALPHA-6X2A, ALPHA-6X2B, ALPHA-6X1X2A AND ALPHA-6X1X2B (SHOWN CC HERE); MAY BE PRODUCED BY ALTERNATIVE SPLICING. THERE IS A CC COMBINATION OF AT LEAST FOUR ALTERNATIVE SPLICED DOMAINS, TWO CC EXTRACELLULAR (X1 AND X2) AND TWO CYTOPLASMIC (A AND B). SO FAR CC DETECTED ARE ISOFORMS ALPHA-6X1A, ALPHA-6X1B AND ALPHA-6X1X2A CC (MINOR). 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 THE ALPHA-6X1X2A ISOFORM. 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 LETALIS WITH PYLORIC ATRESIA (EB-PA), ALSO KNOWN AS JUNCTIONAL CC EPIDERMOLYSIS BULLOSA WITH PYLORIC ATRESIA (PA-JEB) OR APLASIA CC CUTIS CONGENITA WITH GASTROINTESTINAL ATRESIA. IT IS CHARACTERIZED CC BY MUCOCUTANEOUS FRAGILITY AND GASTROINTESTINAL ATRESIA, WHICH CC MOST COMMONLY AFFECTS THE PYLORUS. CC -!- SIMILARITY: BELONGS TO THE INTEGRIN ALPHA CHAIN FAMILY. CC -!- SIMILARITY: CONTAINS 7 FG-GAP REPEATS. CC -!- DATABASE: NAME=PROW; NOTE=CD guide CD49f entry; CC WWW="http://www.ncbi.nlm.nih.gov/prow/cd/cd49f.htm". 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; -. DR EMBL; AF166343; AAD48469.1; -. DR EMBL; AF166335; AAD48469.1; JOINED. DR EMBL; AF166336; AAD48469.1; JOINED. DR EMBL; AF166337; AAD48469.1; JOINED. DR EMBL; AF166338; AAD48469.1; JOINED. DR EMBL; AF166339; AAD48469.1; JOINED. DR EMBL; AF166340; AAD48469.1; JOINED. DR EMBL; AF166341; AAD48469.1; JOINED. DR EMBL; AF166342; AAD48469.1; JOINED. DR EMBL; X59512; CAA42099.1; -. DR EMBL; S52135; AAB24829.1; -. DR EMBL; S66213; AAB20355.1; -. DR EMBL; S66196; AAB20354.1; -. DR EMBL; L40385; -; NOT_ANNOTATED_CDS. DR PIR; B36429; B36429. DR PIR; S06962; S06962. DR HSSP; P11215; 1A8X. DR MIM; 147556; -. DR MIM; 226730; -. DR InterPro; IPR000413; Integrin_alpha. DR Pfam; PF00357; integrin_A; 1. DR Pfam; PF01839; FG-GAP; 5. DR PRINTS; PR01185; INTEGRINA. DR SMART; SM00191; Int_alpha; 5. DR PROSITE; PS00242; INTEGRIN_ALPHA; 1. KW Integrin; Cell adhesion; Receptor; Glycoprotein; Transmembrane; KW Signal; Phosphorylation; Repeat; Alternative splicing; Calcium; KW Epidermolysis bullosa. FT SIGNAL 1 23 FT CHAIN 24 1130 INTEGRIN ALPHA-6. FT CHAIN 24 938 INTEGRIN ALPHA-6 HEAVY CHAIN (POTENTIAL). FT CHAIN 942 1130 INTEGRIN ALPHA-6 LIGHT CHAIN (POTENTIAL). FT DOMAIN 24 1050 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 1051 1076 POTENTIAL. FT DOMAIN 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 SITE 1079 1083 GFFKR MOTIF. 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 (BY SIMILARITY). FT DISULFID 973 978 BY SIMILARITY. FT CARBOHYD 78 78 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 223 223 N-LINKED (GLCNAC...) (POTENTIAL). FT CARBOHYD 323 323 N-LINKED (GLCNAC...) (POTENTIAL). 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 VARSPLIC 215 258 MISSING (IN ISOFORM ALPHA-6X2A AND FT ISOFORM ALPHA-6X2B). FT VARSPLIC 259 297 MISSING (IN ISOFORM ALPHA-6X1A AND FT ISOFORM ALPHA-6X1B). FT VARSPLIC 1084 1130 SRYDDSVPRYHAVRIRKEEREIKDEKYIDNLEKKQWITKWN FT RNESYS -> NKKDHYDATYHKAEIHAQPSDKERLTSDA FT (IN ISOFORM ALPHA-6X1A, ISOFORM ALPHA- FT 6X2A AND ISOFORM ALPHA-6X1X2A). FT CONFLICT 69 69 G -> A (IN REF. 3). FT CONFLICT 289 289 P -> G (IN REF. 7). FT CONFLICT 501 501 F -> L (IN REF. 4). FT CONFLICT 805 805 D -> Y (IN REF. 1 AND 3). SQ SEQUENCE 1130 AA; 126618 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 //