ITA4_HUMAN
ID ITA4_HUMAN Reviewed; 1032 AA.
AC P13612; D3DPG4; Q7Z4L6;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Integrin alpha-4;
DE AltName: Full=CD49 antigen-like family member D;
DE AltName: Full=Integrin alpha-IV;
DE AltName: Full=VLA-4 subunit alpha;
DE AltName: CD_antigen=CD49d;
DE Flags: Precursor;
GN Name=ITGA4; Synonyms=CD49D;
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).
RX PubMed=2788572; DOI=10.1002/j.1460-2075.1989.tb03516.x;
RA Takada Y., Elices M.J., Crouse C., Hemler M.E.;
RT "The primary structure of the alpha 4 subunit of VLA-4: homology to other
RT integrins and a possible cell-cell adhesion function.";
RL EMBO J. 8:1361-1368(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1551405; DOI=10.1002/eji.1830220434;
RA Rubio M., Nueda A., Vara A., Corbi-Lopez A.L.;
RT "A single mRNA encodes the alpha 150 and alpha 80/70 forms of the alpha
RT subunit of VLA4.";
RL Eur. J. Immunol. 22:1099-1102(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-878.
RX PubMed=8643114; DOI=10.1016/0161-5890(96)00001-6;
RA Szabo M.C., McIntyre B.W.;
RT "Identification of two variants of the human integrin alpha 4 subunit.";
RL Mol. Immunol. 32:1453-1454(1995).
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], AND VARIANT GLN-878.
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 2).
RC TISSUE=Prostate;
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 [MRNA] OF 1-87 (ISOFORM 1).
RX PubMed=2034655; DOI=10.1073/pnas.88.10.4094;
RA Rosen G.D., Birkenmeier T.M., Dean D.C.;
RT "Characterization of the alpha 4 integrin gene promoter.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:4094-4098(1991).
RN [8]
RP PROTEIN SEQUENCE OF 34-47.
RX PubMed=3033641; DOI=10.1073/pnas.84.10.3239;
RA Takada Y., Strominger J.L., Hemler M.E.;
RT "The very late antigen family of heterodimers is part of a superfamily of
RT molecules involved in adhesion and embryogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:3239-3243(1987).
RN [9]
RP PROTEIN SEQUENCE OF 592-601, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF
RP LYS-590 AND ARG-591.
RX PubMed=1730718; DOI=10.1016/s0021-9258(18)46014-0;
RA Teixido J., Parker C.M., Kassner P.D., Hemler M.E.;
RT "Functional and structural analysis of VLA-4 integrin alpha 4 subunit
RT cleavage.";
RL J. Biol. Chem. 267:1786-1791(1992).
RN [10]
RP DOMAIN, AND INTERACTION WITH CSPG4.
RX PubMed=9488735; DOI=10.1074/jbc.273.10.5955;
RA Iida J., Meijne A.M.L., Oegema T.R. Jr., Yednock T.A., Kovach N.L.,
RA Furcht L.T., McCarthy J.B.;
RT "A role of chondroitin sulfate glycosaminoglycan binding site in
RT alpha4beta1 integrin-mediated melanoma cell adhesion.";
RL J. Biol. Chem. 273:5955-5962(1998).
RN [11]
RP INTERACTION WITH PXN; LPXN AND TGFB1I1, AND MUTAGENESIS OF TYR-1024.
RX PubMed=10604475; DOI=10.1038/45264;
RA Liu S., Thomas S.M., Woodside D.G., Rose D.M., Kiosses W.B., Pfaff M.,
RA Ginsberg M.H.;
RT "Binding of paxillin to alpha4 integrins modifies integrin-dependent
RT biological responses.";
RL Nature 402:676-681(1999).
RN [12]
RP PHOSPHORYLATION AT SER-1021, AND MUTAGENESIS OF SER-1021.
RX PubMed=11533025; DOI=10.1074/jbc.m102665200;
RA Han J., Liu S., Rose D.M., Schlaepfer D.D., McDonald H., Ginsberg M.H.;
RT "Phosphorylation of the integrin alpha 4 cytoplasmic domain regulates
RT paxillin binding.";
RL J. Biol. Chem. 276:40903-40909(2001).
RN [13]
RP INTERACTION WITH MDK.
RX PubMed=15466886; DOI=10.1242/jcs.01423;
RA Muramatsu H., Zou P., Suzuki H., Oda Y., Chen G.Y., Sakaguchi N.,
RA Sakuma S., Maeda N., Noda M., Takada Y., Muramatsu T.;
RT "alpha4beta1- and alpha6beta1-integrins are functional receptors for
RT midkine, a heparin-binding growth factor.";
RL J. Cell Sci. 117:5405-5415(2004).
RN [14]
RP FUNCTION, AND MUTAGENESIS OF THR-222 AND GLY-223.
RX PubMed=18635536; DOI=10.1074/jbc.m804835200;
RA Saegusa J., Akakura N., Wu C.Y., Hoogland C., Ma Z., Lam K.S., Liu F.T.,
RA Takada Y.K., Takada Y.;
RT "Pro-inflammatory secretory phospholipase A2 type IIA binds to integrins
RT alphavbeta3 and alpha4beta1 and induces proliferation of monocytic cells in
RT an integrin-dependent manner.";
RL J. Biol. Chem. 283:26107-26115(2008).
RN [15]
RP FUNCTION IN LEUKOCYTE TO ENDOTHELIAL CELLS ADHESION, AND INTERACTION WITH
RP JAML.
RX PubMed=19064666; DOI=10.1083/jcb.200805061;
RA Luissint A.C., Lutz P.G., Calderwood D.A., Couraud P.O., Bourdoulous S.;
RT "JAM-L-mediated leukocyte adhesion to endothelial cells is regulated in cis
RT by alpha4beta1 integrin activation.";
RL J. Cell Biol. 183:1159-1173(2008).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-480; ASN-518; ASN-538 AND
RP ASN-645.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1021, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP FUNCTION, BINDING TO CX3CL1, AND IDENTIFICATION IN A COMPLEX WITH CX3CR1
RP AND CX3CL1.
RX PubMed=23125415; DOI=10.4049/jimmunol.1200889;
RA Fujita M., Takada Y.K., Takada Y.;
RT "Integrins alphavbeta3 and alpha4beta1 act as coreceptors for fractalkine,
RT and the integrin-binding defective mutant of fractalkine is an antagonist
RT of CX3CR1.";
RL J. Immunol. 189:5809-5819(2012).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1021, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP FUNCTION.
RX PubMed=25398877; DOI=10.1074/jbc.m114.579946;
RA Fujita M., Zhu K., Fujita C.K., Zhao M., Lam K.S., Kurth M.J., Takada Y.K.,
RA Takada Y.;
RT "Proinflammatory secreted phospholipase A2 type IIA (sPLA-IIA) induces
RT integrin activation through direct binding to a newly identified binding
RT site (site 2) in integrins alphavbeta3, alpha4beta1, and alpha5beta1.";
RL J. Biol. Chem. 290:259-271(2015).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are
CC receptors for fibronectin. They recognize one or more domains within
CC the alternatively spliced CS-1 and CS-5 regions of fibronectin. They
CC are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the
CC sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor
CC for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated
CC endothelial cells integrin VLA-4 triggers homotypic aggregation for
CC most VLA-4-positive leukocyte cell lines. It may also participate in
CC cytolytic T-cell interactions with target cells. ITGA4:ITGB1 binds to
CC fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent
CC fractalkine signaling (PubMed:23125415). ITGA4:ITGB1 binds to PLA2G2A
CC via a site (site 2) which is distinct from the classical ligand-binding
CC site (site 1) and this induces integrin conformational changes and
CC enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877).
CC {ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:19064666,
CC ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:25398877}.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The alpha subunit
CC can sometimes be cleaved into two non-covalently associated fragments.
CC Alpha-4 associates with either beta-1 or beta-7. Alpha-4 interacts with
CC PXN, LPXN, and TGFB1I1/HIC5. Interacts with CSPG4 through CSPG4
CC chondroitin sulfate glycosaminoglycan. Interacts with JAML; integrin
CC alpha-4/beta-1 may regulate leukocyte to endothelial cells adhesion by
CC controlling JAML homodimerization. ITGA4:ITGB1 is found in a ternary
CC complex with CX3CR1 and CX3CL1 (PubMed:23125415). Interacts with MDK
CC (PubMed:15466886). ITGA4:ITGB1 interacts with MDK; this interaction
CC mediates MDK-induced osteoblast cells migration through PXN
CC phosphorylation (PubMed:15466886). {ECO:0000269|PubMed:10604475,
CC ECO:0000269|PubMed:15466886, ECO:0000269|PubMed:19064666,
CC ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:9488735}.
CC -!- INTERACTION:
CC P13612; Q8IZP0-2: ABI1; NbExp=2; IntAct=EBI-703044, EBI-7358775;
CC P13612; P05556: ITGB1; NbExp=4; IntAct=EBI-703044, EBI-703066;
CC P13612; P26010: ITGB7; NbExp=6; IntAct=EBI-703044, EBI-702932;
CC P13612; P49023: PXN; NbExp=4; IntAct=EBI-703044, EBI-702209;
CC P13612; O43294: TGFB1I1; NbExp=2; IntAct=EBI-703044, EBI-1051449;
CC P13612; P84092: Ap2m1; Xeno; NbExp=2; IntAct=EBI-703044, EBI-297693;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P13612-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P13612-2; Sequence=VSP_056612, VSP_056613;
CC -!- DOMAIN: The SG1 motif is involved in binding to chondroitin sulfate
CC glycosaminoglycan and cell adhesion. {ECO:0000269|PubMed:9488735}.
CC -!- PTM: Phosphorylation on Ser-1027 inhibits PXN binding.
CC {ECO:0000269|PubMed:11533025}.
CC -!- SIMILARITY: Belongs to the integrin alpha chain family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB59613.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA34852.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X16983; CAA34852.1; ALT_FRAME; mRNA.
DR EMBL; L12002; AAB59613.1; ALT_FRAME; mRNA.
DR EMBL; AC020595; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471058; EAX10985.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX10987.1; -; Genomic_DNA.
DR EMBL; BC055419; AAH55419.1; -; mRNA.
DR CCDS; CCDS42788.1; -. [P13612-1]
DR CCDS; CCDS82540.1; -. [P13612-2]
DR PIR; S06046; S06046.
DR RefSeq; NP_000876.3; NM_000885.5. [P13612-1]
DR RefSeq; NP_001303241.1; NM_001316312.1. [P13612-2]
DR PDB; 3V4P; X-ray; 3.15 A; A/C=34-620.
DR PDB; 3V4V; X-ray; 3.10 A; A/C=34-620.
DR PDB; 4HKC; X-ray; 2.20 A; B=1003-1032.
DR PDB; 5C7Z; X-ray; 2.77 A; B=1008-1015.
DR PDB; 5FPI; X-ray; 2.77 A; B=1008-1015.
DR PDBsum; 3V4P; -.
DR PDBsum; 3V4V; -.
DR PDBsum; 4HKC; -.
DR PDBsum; 5C7Z; -.
DR PDBsum; 5FPI; -.
DR AlphaFoldDB; P13612; -.
DR BMRB; P13612; -.
DR SMR; P13612; -.
DR BioGRID; 109883; 532.
DR ComplexPortal; CPX-1802; Integrin alpha4-beta1 complex.
DR ComplexPortal; CPX-1823; Integrin alpha4-beta7 complex.
DR CORUM; P13612; -.
DR DIP; DIP-34971N; -.
DR IntAct; P13612; 30.
DR STRING; 9606.ENSP00000380227; -.
DR BindingDB; P13612; -.
DR ChEMBL; CHEMBL278; -.
DR DrugBank; DB04997; ATL1102.
DR DrugBank; DB05092; CDP323.
DR DrugBank; DB15791; MK-0668.
DR DrugBank; DB00108; Natalizumab.
DR DrugBank; DB05122; R1295.
DR DrugBank; DB05468; R411.
DR DrugBank; DB06822; Tinzaparin.
DR DrugBank; DB09033; Vedolizumab.
DR DrugCentral; P13612; -.
DR GuidetoPHARMACOLOGY; 2443; -.
DR GlyGen; P13612; 12 sites.
DR iPTMnet; P13612; -.
DR PhosphoSitePlus; P13612; -.
DR BioMuta; ITGA4; -.
DR DMDM; 311033436; -.
DR EPD; P13612; -.
DR jPOST; P13612; -.
DR MassIVE; P13612; -.
DR MaxQB; P13612; -.
DR PaxDb; P13612; -.
DR PeptideAtlas; P13612; -.
DR PRIDE; P13612; -.
DR ProteomicsDB; 52943; -. [P13612-1]
DR ProteomicsDB; 69208; -.
DR ABCD; P13612; 23 sequenced antibodies.
DR Antibodypedia; 10886; 2041 antibodies from 52 providers.
DR DNASU; 3676; -.
DR Ensembl; ENST00000339307.8; ENSP00000340149.4; ENSG00000115232.14. [P13612-2]
DR Ensembl; ENST00000397033.7; ENSP00000380227.2; ENSG00000115232.14. [P13612-1]
DR GeneID; 3676; -.
DR KEGG; hsa:3676; -.
DR MANE-Select; ENST00000397033.7; ENSP00000380227.2; NM_000885.6; NP_000876.3.
DR UCSC; uc002unu.4; human. [P13612-1]
DR CTD; 3676; -.
DR DisGeNET; 3676; -.
DR GeneCards; ITGA4; -.
DR HGNC; HGNC:6140; ITGA4.
DR HPA; ENSG00000115232; Group enriched (bone marrow, lymphoid tissue).
DR MalaCards; ITGA4; -.
DR MIM; 192975; gene.
DR neXtProt; NX_P13612; -.
DR OpenTargets; ENSG00000115232; -.
DR PharmGKB; PA29940; -.
DR VEuPathDB; HostDB:ENSG00000115232; -.
DR eggNOG; KOG3637; Eukaryota.
DR GeneTree; ENSGT00940000158443; -.
DR HOGENOM; CLU_1639373_0_0_1; -.
DR InParanoid; P13612; -.
DR OMA; HNQVKFG; -.
DR OrthoDB; 189377at2759; -.
DR PhylomeDB; P13612; -.
DR TreeFam; TF105391; -.
DR PathwayCommons; P13612; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-HSA-216083; Integrin cell surface interactions.
DR Reactome; R-HSA-8949275; RUNX3 Regulates Immune Response and Cell Migration.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR SignaLink; P13612; -.
DR SIGNOR; P13612; -.
DR BioGRID-ORCS; 3676; 27 hits in 1075 CRISPR screens.
DR ChiTaRS; ITGA4; human.
DR GeneWiki; CD49d; -.
DR GenomeRNAi; 3676; -.
DR Pharos; P13612; Tclin.
DR PRO; PR:P13612; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P13612; protein.
DR Bgee; ENSG00000115232; Expressed in monocyte and 141 other tissues.
DR ExpressionAtlas; P13612; baseline and differential.
DR Genevisible; P13612; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR GO; GO:0034668; C:integrin alpha4-beta1 complex; TAS:ARUK-UCL.
DR GO; GO:0034669; C:integrin alpha4-beta7 complex; IDA:UniProtKB.
DR GO; GO:0008305; C:integrin complex; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0050839; F:cell adhesion molecule binding; IMP:UniProtKB.
DR GO; GO:0015026; F:coreceptor activity; TAS:UniProtKB.
DR GO; GO:0001968; F:fibronectin binding; IEA:Ensembl.
DR GO; GO:0005178; F:integrin binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1990405; F:protein antigen binding; IEA:Ensembl.
DR GO; GO:0060385; P:axonogenesis involved in innervation; IEA:Ensembl.
DR GO; GO:0030183; P:B cell differentiation; IC:BHF-UCL.
DR GO; GO:0033627; P:cell adhesion mediated by integrin; IBA:GO_Central.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0140039; P:cell-cell adhesion in response to extracellular stimulus; IGI:ARUK-UCL.
DR GO; GO:0033631; P:cell-cell adhesion mediated by integrin; IGI:ARUK-UCL.
DR GO; GO:0007160; P:cell-matrix adhesion; IMP:UniProtKB.
DR GO; GO:0003366; P:cell-matrix adhesion involved in ameboidal cell migration; IMP:UniProtKB.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IEA:Ensembl.
DR GO; GO:1990771; P:clathrin-dependent extracellular exosome endocytosis; IEA:Ensembl.
DR GO; GO:0050904; P:diapedesis; IEA:Ensembl.
DR GO; GO:0035987; P:endodermal cell differentiation; IEP:UniProtKB.
DR GO; GO:0034113; P:heterotypic cell-cell adhesion; IMP:UniProtKB.
DR GO; GO:0098657; P:import into cell; IEA:Ensembl.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0050900; P:leukocyte migration; IBA:GO_Central.
DR GO; GO:0050901; P:leukocyte tethering or rolling; IMP:UniProtKB.
DR GO; GO:0090074; P:negative regulation of protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:1990138; P:neuron projection extension; IEA:Ensembl.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IMP:BHF-UCL.
DR GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; IEA:Ensembl.
DR GO; GO:2000406; P:positive regulation of T cell migration; IEA:Ensembl.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IMP:BHF-UCL.
DR GO; GO:0043113; P:receptor clustering; IMP:UniProtKB.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IMP:UniProtKB.
DR Gene3D; 2.130.10.130; -; 1.
DR IDEAL; IID00615; -.
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; IPR018184; Integrin_alpha_C_CS.
DR InterPro; IPR028994; Integrin_alpha_N.
DR InterPro; IPR032695; Integrin_dom_sf.
DR Pfam; PF01839; FG-GAP; 2.
DR Pfam; PF08441; Integrin_alpha2; 1.
DR PRINTS; PR01185; INTEGRINA.
DR SMART; SM00191; Int_alpha; 5.
DR SUPFAM; SSF69179; SSF69179; 3.
DR SUPFAM; SSF69318; SSF69318; 1.
DR PROSITE; PS51470; FG_GAP; 7.
DR PROSITE; PS00242; INTEGRIN_ALPHA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell adhesion;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Integrin;
KW Membrane; Metal-binding; Phosphoprotein; Receptor; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..33
FT /evidence="ECO:0000269|PubMed:3033641"
FT CHAIN 34..1032
FT /note="Integrin alpha-4"
FT /id="PRO_0000016244"
FT TOPO_DOM 35..977
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 978..1001
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1002..1032
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 35..100
FT /note="FG-GAP 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 110..177
FT /note="FG-GAP 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 185..237
FT /note="FG-GAP 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 238..291
FT /note="FG-GAP 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 292..351
FT /note="FG-GAP 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 355..412
FT /note="FG-GAP 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT REPEAT 416..478
FT /note="FG-GAP 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00803"
FT MOTIF 606..616
FT /note="SG1"
FT MOTIF 1003..1007
FT /note="GFFKR motif"
FT BINDING 314
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 316
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 318
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 322
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 377
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 379
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 381
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 385
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 439
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 441
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 443
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 445
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT BINDING 447
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P08648"
FT SITE 591..592
FT /note="Cleavage"
FT MOD_RES 1021
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11533025,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 518
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 538
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 626
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 645
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 660
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 806
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 821
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 91..101
FT /evidence="ECO:0000250"
FT DISULFID 144..165
FT /evidence="ECO:0000250"
FT DISULFID 183..198
FT /evidence="ECO:0000250"
FT DISULFID 486..495
FT /evidence="ECO:0000250"
FT DISULFID 501..557
FT /evidence="ECO:0000250"
FT DISULFID 622..627
FT /evidence="ECO:0000250"
FT DISULFID 698..711
FT /evidence="ECO:0000250"
FT DISULFID 852..890
FT /evidence="ECO:0000250"
FT DISULFID 897..902
FT /evidence="ECO:0000250"
FT VAR_SEQ 186..195
FT /note="DYVKKFGENF -> GSISKYRART (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056612"
FT VAR_SEQ 196..1032
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056613"
FT VARIANT 634
FT /note="S -> T (in dbSNP:rs35322532)"
FT /id="VAR_047423"
FT VARIANT 824
FT /note="V -> A (in dbSNP:rs1143675)"
FT /id="VAR_047424"
FT VARIANT 878
FT /note="R -> Q (in dbSNP:rs1143676)"
FT /evidence="ECO:0000269|PubMed:8643114, ECO:0000269|Ref.5"
FT /id="VAR_003978"
FT MUTAGEN 222
FT /note="T->A: Blocks binding to PLA2G2A."
FT /evidence="ECO:0000269|PubMed:18635536"
FT MUTAGEN 223
FT /note="G->A: Blocks binding to PLA2G2A."
FT /evidence="ECO:0000269|PubMed:18635536"
FT MUTAGEN 590
FT /note="K->Q: Abolishes almost completely cleavage."
FT /evidence="ECO:0000269|PubMed:1730718"
FT MUTAGEN 591
FT /note="R->L: Abolishes completely cleavage."
FT /evidence="ECO:0000269|PubMed:1730718"
FT MUTAGEN 1021
FT /note="S->A: Abolishes phosphorylation."
FT /evidence="ECO:0000269|PubMed:11533025"
FT MUTAGEN 1021
FT /note="S->D: Reduces PXN binding."
FT /evidence="ECO:0000269|PubMed:11533025"
FT MUTAGEN 1024
FT /note="Y->A: Disrupts PXN binding."
FT /evidence="ECO:0000269|PubMed:10604475"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 54..61
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 64..71
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 87..95
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:3V4V"
FT TURN 152..156
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 165..168
FT /evidence="ECO:0007829|PDB:3V4V"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:3V4V"
FT TURN 193..197
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 202..206
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 208..215
FT /evidence="ECO:0007829|PDB:3V4V"
FT HELIX 218..221
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 223..229
FT /evidence="ECO:0007829|PDB:3V4V"
FT TURN 230..233
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 234..237
FT /evidence="ECO:0007829|PDB:3V4P"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 267..272
FT /evidence="ECO:0007829|PDB:3V4V"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 280..286
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 288..298
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 308..313
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 322..327
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 338..344
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 346..349
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:3V4P"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 386..390
FT /evidence="ECO:0007829|PDB:3V4V"
FT HELIX 393..396
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 398..403
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 415..419
FT /evidence="ECO:0007829|PDB:3V4V"
FT HELIX 420..422
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 429..438
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 440..445
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 447..452
FT /evidence="ECO:0007829|PDB:3V4V"
FT HELIX 453..455
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 457..461
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 466..474
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 495..505
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 511..522
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 532..534
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 536..538
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 542..554
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 556..564
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 575..583
FT /evidence="ECO:0007829|PDB:3V4V"
FT STRAND 610..617
FT /evidence="ECO:0007829|PDB:3V4V"
SQ SEQUENCE 1032 AA; 114900 MW; 73EC1204DE78CD35 CRC64;
MAWEARREPG PRRAAVRETV MLLLCLGVPT GRPYNVDTES ALLYQGPHNT LFGYSVVLHS
HGANRWLLVG APTANWLANA SVINPGAIYR CRIGKNPGQT CEQLQLGSPN GEPCGKTCLE
ERDNQWLGVT LSRQPGENGS IVTCGHRWKN IFYIKNENKL PTGGCYGVPP DLRTELSKRI
APCYQDYVKK FGENFASCQA GISSFYTKDL IVMGAPGSSY WTGSLFVYNI TTNKYKAFLD
KQNQVKFGSY LGYSVGAGHF RSQHTTEVVG GAPQHEQIGK AYIFSIDEKE LNILHEMKGK
KLGSYFGASV CAVDLNADGF SDLLVGAPMQ STIREEGRVF VYINSGSGAV MNAMETNLVG
SDKYAARFGE SIVNLGDIDN DGFEDVAIGA PQEDDLQGAI YIYNGRADGI SSTFSQRIEG
LQISKSLSMF GQSISGQIDA DNNGYVDVAV GAFRSDSAVL LRTRPVVIVD ASLSHPESVN
RTKFDCVENG WPSVCIDLTL CFSYKGKEVP GYIVLFYNMS LDVNRKAESP PRFYFSSNGT
SDVITGSIQV SSREANCRTH QAFMRKDVRD ILTPIQIEAA YHLGPHVISK RSTEEFPPLQ
PILQQKKEKD IMKKTINFAR FCAHENCSAD LQVSAKIGFL KPHENKTYLA VGSMKTLMLN
VSLFNAGDDA YETTLHVKLP VGLYFIKILE LEEKQINCEV TDNSGVVQLD CSIGYIYVDH
LSRIDISFLL DVSSLSRAEE DLSITVHATC ENEEEMDNLK HSRVTVAIPL KYEVKLTVHG
FVNPTSFVYG SNDENEPETC MVEKMNLTFH VINTGNSMAP NVSVEIMVPN SFSPQTDKLF
NILDVQTTTG ECHFENYQRV CALEQQKSAM QTLKGIVRFL SKTDKRLLYC IKADPHCLNF
LCNFGKMESG KEASVHIQLE GRPSILEMDE TSALKFEIRA TGFPEPNPRV IELNKDENVA
HVLLEGLHHQ RPKRYFTIVI ISSSLLLGLI VLLLISYVMW KAGFFKRQYK SILQEENRRD
SWSYINSKSN DD
