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Integrin alpha-6 (CD49 antigen-like family member F) (VLA-6) (CD antigen CD49f) [Cleaved into: Integrin alpha-6 heavy chain; Integrin alpha-6 light chain]

 ITA6_MOUSE              Reviewed;        1091 AA.
Q61739; A2AU04;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
27-JUL-2011, sequence version 3.
23-MAY-2018, entry version 162.
RecName: Full=Integrin alpha-6;
AltName: Full=CD49 antigen-like family member F;
AltName: Full=VLA-6;
AltName: CD_antigen=CD49f;
Contains:
RecName: Full=Integrin alpha-6 heavy chain;
Contains:
RecName: Full=Integrin alpha-6 light chain;
Flags: Precursor;
Name=Itga6;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-6X1A AND ALPHA-6X1B).
STRAIN=BALB/cJ; TISSUE=Mammary gland;
PubMed=8081870;
Hierck B.P., Thorsteinsdottir S., Niessen C.M., Freund E.,
van Iperen L., Feyen A., Hogervorst F., Poelmann R.E., Mummery C.L.,
Sonnenberg A.;
"Variants of the alpha 6 beta 1 laminin receptor in early murine
development: distribution, molecular cloning and chromosomal
localization of the mouse integrin alpha 6 subunit.";
Cell Adhes. Commun. 1:33-53(1993).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=C57BL/6J;
PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S.,
She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
Lindblad-Toh K., Eichler E.E., Ponting C.P.;
"Lineage-specific biology revealed by a finished genome assembly of
the mouse.";
PLoS Biol. 7:E1000112-E1000112(2009).
[3]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=8673141; DOI=10.1038/ng0796-370;
Georges-Labouesse E., Messaddeq N., Yehia G., Cadalbert L.,
Dierich A., Le Meur M.;
"Absence of integrin alpha 6 leads to epidermolysis bullosa and
neonatal death in mice.";
Nat. Genet. 13:370-373(1996).
[4]
INTERACTION WITH ADAM9.
PubMed=10825303;
Nath D., Slocombe P.M., Webster A., Stephens P.E., Docherty A.J.,
Murphy G.;
"Meltrin gamma(ADAM-9) mediates cellular adhesion through
alpha(6)beta(1)integrin, leading to a marked induction of fibroblast
cell motility.";
J. Cell Sci. 113:2319-2328(2000).
[5]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-284; ASN-927 AND ASN-958.
PubMed=19349973; DOI=10.1038/nbt.1532;
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
Schiess R., Aebersold R., Watts J.D.;
"Mass-spectrometric identification and relative quantification of N-
linked cell surface glycoproteins.";
Nat. Biotechnol. 27:378-386(2009).
[6]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
Pancreas, Spleen, and Testis;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
-!- FUNCTION: Integrin alpha-6/beta-1 is a receptor for laminin on
platelets. Integrin alpha-6/beta-4 is a receptor for laminin in
epithelial cells and it plays a critical structural role in the
hemidesmosome (PubMed:8673141). ITGA6:ITGB4 binds to NRG1 (via EGF
domain) and this binding is essential for NRG1-ERBB signaling.
ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1
signaling (By similarity). ITGA6:ITGB4 binds to IGF2 and this
binding is essential for IGF2 signaling (By similarity).
{ECO:0000250|UniProtKB:P23229, ECO:0000269|PubMed:8673141}.
-!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The alpha
subunit is composed of a heavy and a light chain linked by a
disulfide bond. Alpha-6 associates with either beta-1 or beta-4.
Interacts with RAB21. ITGA6:ITGB4 is found in a ternary complex
with NRG1 and ERBB3. ITGA6:ITGB4 is found in a ternary complex
with IGF1 and IGF1R (By similarity). ITGA6:ITGB4 interacts with
IGF2 (By similarity). Interacts with ADAM9 (PubMed:10825303).
{ECO:0000250|UniProtKB:P23229, ECO:0000269|PubMed:10825303}.
-!- SUBCELLULAR LOCATION: Cell membrane
{ECO:0000250|UniProtKB:P23229}; Single-pass type I membrane
protein {ECO:0000255}. Cell membrane
{ECO:0000250|UniProtKB:P23229}; Lipid-anchor
{ECO:0000250|UniProtKB:P23229}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=Alpha-6X1B;
IsoId=Q61739-1; Sequence=Displayed;
Name=Alpha-6X1A;
IsoId=Q61739-2; Sequence=VSP_002726;
Note=Contains a phosphoserine at position 1064.
{ECO:0000250|UniProtKB:P23229};
-!- PTM: Isoforms containing segment A, but not segment B, are the
major targets for PMA-induced phosphorylation. Phosphorylation
occurs on 'Ser-1064' of isoform alpha-6X1A. Phosphorylation is not
required for the induction of integrin alpha-6A/beta-1 high
affinity but may reduce the affinity for ligand (By similarity).
{ECO:0000250|UniProtKB:P23229}.
-!- PTM: Palmitoylation by DHHC3 enhances stability and cell surface
expression. {ECO:0000250|UniProtKB:P23229}.
-!- DISRUPTION PHENOTYPE: Mice expressing a null mutation of the
alpha-6 subunit gene die soon after birth and develop severe
blistering. The blisters are due to separation of the basal
epithelial cells from a normally formed basement membrane.
{ECO:0000269|PubMed:8673141}.
-!- SIMILARITY: Belongs to the integrin alpha chain family.
{ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; X69902; CAA49527.1; -; mRNA.
EMBL; AL928963; -; NOT_ANNOTATED_CDS; Genomic_DNA.
CCDS; CCDS16118.1; -. [Q61739-2]
CCDS; CCDS71074.1; -. [Q61739-1]
PIR; A40463; A40463.
RefSeq; NP_001264899.1; NM_001277970.1. [Q61739-1]
RefSeq; XP_011237610.1; XM_011239308.1. [Q61739-1]
UniGene; Mm.225096; -.
ProteinModelPortal; Q61739; -.
BioGrid; 200819; 3.
IntAct; Q61739; 1.
MINT; Q61739; -.
STRING; 10090.ENSMUSP00000028522; -.
iPTMnet; Q61739; -.
PhosphoSitePlus; Q61739; -.
SwissPalm; Q61739; -.
PaxDb; Q61739; -.
PeptideAtlas; Q61739; -.
PRIDE; Q61739; -.
Ensembl; ENSMUST00000028522; ENSMUSP00000028522; ENSMUSG00000027111. [Q61739-2]
Ensembl; ENSMUST00000112101; ENSMUSP00000107729; ENSMUSG00000027111. [Q61739-1]
GeneID; 16403; -.
KEGG; mmu:16403; -.
UCSC; uc008kbd.2; mouse. [Q61739-1]
CTD; 3655; -.
MGI; MGI:96605; Itga6.
eggNOG; KOG3637; Eukaryota.
eggNOG; ENOG410XPVZ; LUCA.
GeneTree; ENSGT00760000118782; -.
HOGENOM; HOG000015786; -.
HOVERGEN; HBG108011; -.
InParanoid; Q61739; -.
KO; K06485; -.
OMA; YVYINQQ; -.
OrthoDB; EOG091G012D; -.
TreeFam; TF105391; -.
Reactome; R-MMU-2022090; Assembly of collagen fibrils and other multimeric structures.
Reactome; R-MMU-210991; Basigin interactions.
Reactome; R-MMU-216083; Integrin cell surface interactions.
Reactome; R-MMU-3000157; Laminin interactions.
Reactome; R-MMU-3000170; Syndecan interactions.
Reactome; R-MMU-446107; Type I hemidesmosome assembly.
PRO; PR:Q61739; -.
Proteomes; UP000000589; Chromosome 2.
Bgee; ENSMUSG00000027111; -.
CleanEx; MM_ITGA6; -.
ExpressionAtlas; Q61739; baseline and differential.
Genevisible; Q61739; MM.
GO; GO:0045178; C:basal part of cell; IDA:MGI.
GO; GO:0009925; C:basal plasma membrane; IDA:MGI.
GO; GO:0005604; C:basement membrane; IDA:MGI.
GO; GO:0016323; C:basolateral plasma membrane; IDA:MGI.
GO; GO:0009986; C:cell surface; IDA:MGI.
GO; GO:0005913; C:cell-cell adherens junction; IEA:Ensembl.
GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
GO; GO:0030175; C:filopodium; IEA:Ensembl.
GO; GO:0030056; C:hemidesmosome; IDA:MGI.
GO; GO:0034676; C:integrin alpha6-beta4 complex; IEA:Ensembl.
GO; GO:0008305; C:integrin complex; IDA:MGI.
GO; GO:0005886; C:plasma membrane; IDA:MGI.
GO; GO:0045296; F:cadherin binding; ISO:MGI.
GO; GO:0031994; F:insulin-like growth factor I binding; ISS:UniProtKB.
GO; GO:0005178; F:integrin binding; IPI:MGI.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0038132; F:neuregulin binding; ISS:UniProtKB.
GO; GO:0097186; P:amelogenesis; ISO:MGI.
GO; GO:0050873; P:brown fat cell differentiation; IDA:MGI.
GO; GO:0033627; P:cell adhesion mediated by integrin; IDA:MGI.
GO; GO:0098609; P:cell-cell adhesion; IEA:Ensembl.
GO; GO:0007160; P:cell-matrix adhesion; IMP:MGI.
GO; GO:0031589; P:cell-substrate adhesion; ISO:MGI.
GO; GO:0031668; P:cellular response to extracellular stimulus; IDA:MGI.
GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
GO; GO:0048565; P:digestive tract development; ISO:MGI.
GO; GO:0010668; P:ectodermal cell differentiation; IEA:Ensembl.
GO; GO:0046847; P:filopodium assembly; IMP:MGI.
GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:UniProtKB-KW.
GO; GO:0050900; P:leukocyte migration; IMP:MGI.
GO; GO:0035878; P:nail development; ISO:MGI.
GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISO:MGI.
GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IMP:MGI.
GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
GO; GO:0022409; P:positive regulation of cell-cell adhesion; IDA:MGI.
GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IEA:Ensembl.
GO; GO:0043547; P:positive regulation of GTPase activity; ISO:MGI.
GO; GO:0042327; P:positive regulation of phosphorylation; ISO:MGI.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
GO; GO:0072001; P:renal system development; ISO:MGI.
GO; GO:0043588; P:skin development; ISO:MGI.
Gene3D; 2.130.10.130; -; 1.
InterPro; IPR013519; Int_alpha_beta-p.
InterPro; IPR000413; Integrin_alpha.
InterPro; IPR013649; Integrin_alpha-2.
InterPro; IPR018184; Integrin_alpha_C_CS.
InterPro; IPR028994; Integrin_alpha_N.
InterPro; IPR032695; Integrin_dom_sf.
Pfam; PF08441; Integrin_alpha2; 1.
PRINTS; PR01185; INTEGRINA.
SMART; SM00191; Int_alpha; 5.
SUPFAM; SSF69179; SSF69179; 3.
PROSITE; PS51470; FG_GAP; 7.
PROSITE; PS00242; INTEGRIN_ALPHA; 1.
1: Evidence at protein level;
Alternative splicing; Calcium; Cell adhesion; Cell membrane;
Cleavage on pair of basic residues; Complete proteome; Disulfide bond;
Glycoprotein; Integrin; Lipoprotein; Membrane; Metal-binding;
Palmitate; Phosphoprotein; Receptor; Reference proteome; Repeat;
Signal; Transmembrane; Transmembrane helix.
SIGNAL 1 23 {ECO:0000250}.
CHAIN 24 1091 Integrin alpha-6.
/FTId=PRO_0000016261.
CHAIN 24 899 Integrin alpha-6 heavy chain.
{ECO:0000255}.
/FTId=PRO_0000016262.
CHAIN 903 1091 Integrin alpha-6 light chain.
{ECO:0000255}.
/FTId=PRO_0000016263.
TOPO_DOM 24 1011 Extracellular. {ECO:0000255}.
TRANSMEM 1012 1037 Helical. {ECO:0000255}.
TOPO_DOM 1038 1091 Cytoplasmic. {ECO:0000255}.
REPEAT 30 95 FG-GAP 1. {ECO:0000255|PROSITE-
ProRule:PRU00803}.
REPEAT 101 166 FG-GAP 2. {ECO:0000255|PROSITE-
ProRule:PRU00803}.
REPEAT 176 229 FG-GAP 3. {ECO:0000255|PROSITE-
ProRule:PRU00803}.
REPEAT 244 300 FG-GAP 4. {ECO:0000255|PROSITE-
ProRule:PRU00803}.
REPEAT 301 363 FG-GAP 5. {ECO:0000255|PROSITE-
ProRule:PRU00803}.
REPEAT 364 419 FG-GAP 6. {ECO:0000255|PROSITE-
ProRule:PRU00803}.
REPEAT 420 479 FG-GAP 7. {ECO:0000255|PROSITE-
ProRule:PRU00803}.
CA_BIND 324 332 {ECO:0000255}.
CA_BIND 386 394 {ECO:0000255}.
CA_BIND 441 449 {ECO:0000255}.
MOTIF 1040 1044 GFFKR motif.
LIPID 1039 1039 S-palmitoyl cysteine; by DHHC3.
{ECO:0000250}.
CARBOHYD 78 78 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 223 223 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 284 284 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:19349973}.
CARBOHYD 370 370 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 731 731 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 746 746 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 927 927 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:19349973}.
CARBOHYD 958 958 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:19349973}.
DISULFID 86 94 {ECO:0000250}.
DISULFID 131 154 {ECO:0000250}.
DISULFID 175 188 {ECO:0000250}.
DISULFID 489 496 {ECO:0000250}.
DISULFID 502 562 {ECO:0000250}.
DISULFID 626 632 {ECO:0000250}.
DISULFID 726 737 {ECO:0000250}.
DISULFID 881 928 Interchain (between heavy and light
chains). {ECO:0000250}.
DISULFID 934 939 {ECO:0000250}.
VAR_SEQ 1045 1091 SRYDDSIPRYHAVRIRKEEREIKDEKHMDNLEKKQWITKWN
ENESYS -> NKKDHYDATYHKAEIHTQPSDKERLTSDA
(in isoform Alpha-6X1A).
{ECO:0000303|PubMed:8081870}.
/FTId=VSP_002726.
CONFLICT 592 592 S -> T (in Ref. 1; CAA49527).
{ECO:0000305}.
CONFLICT 781 781 N -> K (in Ref. 1; CAA49527).
{ECO:0000305}.
CONFLICT 799 799 V -> L (in Ref. 1; CAA49527).
{ECO:0000305}.
CONFLICT 946 946 S -> T (in Ref. 1; CAA49527).
{ECO:0000305}.
CONFLICT 953 953 R -> C (in Ref. 1; CAA49527).
{ECO:0000305}.
CONFLICT 975 975 L -> V (in Ref. 1; CAA49527).
{ECO:0000305}.
SEQUENCE 1091 AA; 122159 MW; F33B055C2E8BAFAD CRC64;
MAVAGQLCLL YLSAGLLARL GTAFNLDTRE DNVIRKSGDP GSLFGFSLAM HWQLQPEDKR
LLLVGAPRAE ALPLQRANRT GGLYSCDITS RGPCTRIEFD NDADPMSESK EDQWMGVTVQ
SQGPGGKVVT CAHRYEKRQH VNTKQESRDI FGRCYVLSQN LRIEDDMDGG DWSFCDGRLR
GHEKFGSCQQ GVAATFTKDF HYIVFGAPGT YNWKGIVRVE QKNNTFFDMN IFEDGPYEVG
GETDHDESLV PVPANSYLGF SLDSGKGIVS KDDITFVSGA PRANHSGAVV LLKRDMKSAH
LLPEYIFDGE GLASSFGYDV AVVDLNADGW QDIVIGAPQY FDRDGEVGGA VYVYINQQGK
WSNVKPIRLN GTKDSMFGIS VKNIGDINQD GYPDIAVGAP YDDLGKVFIY HGSPTGIITK
PTQVLEGTSP YFGYSIAGNM DLDRNSYPDL AVGSLSDSVT IFRSRPVINI LKTITVTPNR
IDLRQKSMCG SPSGICLKVK ACFEYTAKPS GYNPPISILG ILEAEKERRK SGLSSRVQFR
NQGSEPKYTQ ELTLNRQKQR ACMEETLWLQ ENIRDKLRPI PITASVEIQE PSSRRRVNSL
PEVLPILNSN EAKTVQTDVH FLKEGCGDDN VCNSNLKLEY KFGTREGNQD KFSYLPIQKG
IPELVLKDQK DIALEITVTN SPSDPRNPRK DGDDAHEAKL IATFPDTLTY SAYRELRAFP
EKQLSCVANQ NGSQADCELG NPFKRNSSVT FYLILSTTEV TFDTTDLDIN LKLETTSNQD
NLAPITAKAK VVIELLLSVS GVAKPSQVYF GGTVVGEQAM KSEDEVGSLI EYEFRVINLG
KPLKNLGTAT LNIQWPKEIS NGKWLLYLMK VESKGLEQIV CEPHNEINYL KLKESHNSRK
KRELPEKQID DSRKFSLFPE RKYQTLNCSV NVRCVNIRCP LRGLDSKASL VLRSRLWNST
FLEEYSKLNY LDILLRASID VTAAAQNIKL PHAGTQVRVT VFPSKTVAQY SGVAWWIILL
AVLAGILMLA LLVFLLWKCG FFKRSRYDDS IPRYHAVRIR KEEREIKDEK HMDNLEKKQW
ITKWNENESY S


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