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Integrin alpha 4
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<h2 id="function">Function</h2> <p>The product of this gene belongs to the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This gene encodes an alpha 4 chain. Unlike other integrin alpha chains, alpha 4 neither contains an I-domain, nor undergoes disulfide-linked cleavage. Alpha 4 chain associates with either beta 1 chain or beta 7 chain.<a class="footnote-ref" id="fnref:1" href="#fn:1"><sup>1</sup></a> </p> <h2 id="interactions">Interactions</h2> <p>CD49d has been shown to <a href="/facts/Protein-protein_interaction/etvm9Wmg">interact</a> with <a href="/facts/LGALS8/v5FBlyuo">LGALS8</a><a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> and <a href="/facts/Paxillin/f8bBseWR">Paxillin</a>.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a><a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li>Carotegrast methyl, an integrin alpha 4 antagonist used for the treatment of ulcerative colitis</li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Humphries MJ, Sheridan J, Mould AP, Newham P (1995). "Mechanisms of VCAM-1 and Fibronectin Binding to Integrin α 4 β 1 : Implications for Integrin Function and Rational Drug Design". <i>Ciba Foundation Symposium 189 - Cell Adhesion and Human Disease</i>. Novartis Foundation Symposia. Vol. 189. pp. 177–91, discussion 191–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2F9780470514719.ch13">10.1002/9780470514719.ch13</a>. <a href="/facts/ISBN_(identifier)/15AdSPa9">ISBN</a> 978-0-470-51471-9. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7587632">7587632</a>. {{cite book}}: |journal= ignored (help)</li> <li>Oostendorp RA, Dörmer P (1997). "VLA-4-mediated interactions between normal human hematopoietic progenitors and stromal cells". <i>Leuk. Lymphoma</i>. 24 (5–6): 423–35. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.3109%2F10428199709055581">10.3109/10428199709055581</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9086434">9086434</a>.</li> <li>Porter JC, Hogg N (1999). "Integrins take partners: cross-talk between integrins and other membrane receptors". <i>Trends Cell Biol</i>. 8 (10): 390–6. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0962-8924%2898%2901344-0">10.1016/S0962-8924(98)01344-0</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9789327">9789327</a>.</li> <li>Rose DM, Han J, Ginsberg MH (2003). "Alpha4 integrins and the immune response". <i>Immunol. Rev</i>. 186 (1): 118–24. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1034%2Fj.1600-065X.2002.18611.x">10.1034/j.1600-065X.2002.18611.x</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12234367">12234367</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:37850994">37850994</a>.</li> <li>O'Connor P (2007). "Natalizumab and the role of alpha 4-integrin antagonism in the treatment of multiple sclerosis". <i>Expert Opinion on Biological Therapy</i>. 7 (1): 123–36. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1517%2F14712598.7.1.123">10.1517/14712598.7.1.123</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17150024">17150024</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:73319319">73319319</a>.</li> <li>Chan BM, Elices MJ, Murphy E, Hemler ME (1992). <a href="https://doi.org/10.1016%2FS0021-9258%2818%2942453-2">"Adhesion to vascular cell adhesion molecule 1 and fibronectin. Comparison of alpha 4 beta 1 (VLA-4) and alpha 4 beta 7 on the human B cell line JY"</a>. <i>J. Biol. Chem</i>. 267 (12): 8366–70. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0021-9258%2818%2942453-2">10.1016/S0021-9258(18)42453-2</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1373725">1373725</a>.</li> <li>Fernández-Ruiz E, Pardo-Manuel de Villena F, Rubio MA, Corbí AL, Rodriguez de Córdoba S, Sánchez-Madrid F (1992). "Mapping of the human VLA-alpha 4 gene to chromosome 2q31-q32". <i>Eur. J. Immunol</i>. 22 (2): 587–90. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2Feji.1830220243">10.1002/eji.1830220243</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1537388">1537388</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:86449765">86449765</a>.</li> <li>Rubio M, Nueda A, Vara A, Corbí Lopez AL (1992). "A single mRNA encodes the alpha 150 and alpha 80/70 forms of the alpha subunit of VLA4". <i>Eur. J. Immunol</i>. 22 (4): 1099–102. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2Feji.1830220434">10.1002/eji.1830220434</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1551405">1551405</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:83613615">83613615</a>.</li> <li>Sonnenberg A, Linders CJ, Modderman PW, Damsky CH, Aumailley M, Timpl R (1990). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2116116">"Integrin recognition of different cell-binding fragments of laminin (P1, E3, E8) and evidence that alpha 6 beta 1 but not alpha 6 beta 4 functions as a major receptor for fragment E8"</a>. <i>J. Cell Biol</i>. 110 (6): 2145–55. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1083%2Fjcb.110.6.2145">10.1083/jcb.110.6.2145</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2116116">2116116</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1693624">1693624</a>.</li> <li>Teixidó J, Parker CM, Kassner PD, Hemler ME (1992). <a href="https://doi.org/10.1016%2FS0021-9258%2818%2946014-0">"Functional and structural analysis of VLA-4 integrin alpha 4 subunit cleavage"</a>. <i>J. Biol. Chem</i>. 267 (3): 1786–91. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0021-9258%2818%2946014-0">10.1016/S0021-9258(18)46014-0</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1730718">1730718</a>.</li> <li>Rosemblatt M, Vuillet-Gaugler MH, Leroy C, Coulombel L (1991). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC294977">"Coexpression of two fibronectin receptors, VLA-4 and VLA-5, by immature human erythroblastic precursor cells"</a>. <i>J. Clin. Invest</i>. 87 (1): 6–11. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1172%2FJCI115002">10.1172/JCI115002</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC294977">294977</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1824634">1824634</a>.</li> <li>Rosen GD, Birkenmeier TM, Dean DC (1991). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC51604">"Characterization of the alpha 4 integrin gene promoter"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. 88 (10): 4094–8. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1991PNAS...88.4094R">1991PNAS...88.4094R</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.88.10.4094">10.1073/pnas.88.10.4094</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC51604">51604</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/2034655">2034655</a>.</li> <li>Takada Y, Elices MJ, Crouse C, Hemler ME (1989). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC400962">"The primary structure of the alpha 4 subunit of VLA-4: homology to other integrins and a possible cell-cell adhesion function"</a>. <i>EMBO J</i>. 8 (5): 1361–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2Fj.1460-2075.1989.tb03516.x">10.1002/j.1460-2075.1989.tb03516.x</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC400962">400962</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/2788572">2788572</a>.</li> <li>Takada Y, Strominger JL, Hemler ME (1987). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC304844">"The very late antigen family of heterodimers is part of a superfamily of molecules involved in adhesion and embryogenesis"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. 84 (10): 3239–43. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1987PNAS...84.3239T">1987PNAS...84.3239T</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.84.10.3239">10.1073/pnas.84.10.3239</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC304844">304844</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/3033641">3033641</a>.</li> <li>Hemler ME, Huang C, Schwarz L (1987). <a href="https://doi.org/10.1016%2FS0021-9258%2818%2961504-2">"The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight beta subunit"</a>. <i>J. Biol. Chem</i>. 262 (7): 3300–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0021-9258%2818%2961504-2">10.1016/S0021-9258(18)61504-2</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/3546305">3546305</a>.</li> <li>Gailit J, Pierschbacher M, Clark RA (1993). "Expression of functional alpha 4 beta 1 integrin by human dermal fibroblasts". <i>J. Invest. Dermatol</i>. 100 (3): 323–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1111%2F1523-1747.ep12470011">10.1111/1523-1747.ep12470011</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8440915">8440915</a>.</li> <li>Pujades C, Teixidó J, Bazzoni G, Hemler ME (1996). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1216996">"Integrin alpha 4 cysteines 278 and 717 modulate VLA-4 ligand binding and also contribute to alpha 4/180 formation"</a>. <i>Biochem. J</i>. 313. ( Pt 3) (3): 899–908. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1042%2Fbj3130899">10.1042/bj3130899</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1216996">1216996</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8611173">8611173</a>.</li> <li>Szabo M, McIntyre BW (1996). "Identification of two variants of the human integrin alpha 4 subunit". <i>Mol. Immunol</i>. 32 (17–18): 1453–4. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0161-5890%2896%2900001-6">10.1016/0161-5890(96)00001-6</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8643114">8643114</a>.</li> <li>Mannion BA, Berditchevski F, Kraeft SK, Chen LB, Hemler ME (1996). <a href="https://doi.org/10.4049%2Fjimmunol.157.5.2039">"Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29)"</a>. <i>J. Immunol</i>. 157 (5): 2039–47. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.4049%2Fjimmunol.157.5.2039">10.4049/jimmunol.157.5.2039</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8757325">8757325</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:1977096">1977096</a>.</li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="https://meshb.nlm.nih.gov/record/ui?name=CD49d+antigen">CD49d+antigen</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li> <li><a href="https://archive.today/20130414110522/http://cmkb.cellmigration.org/report.cgi?report=orth_overview&gene_id=3676">ITGA4</a> Info with links in the <a href="http://www.cellmigration.org/index.shtml">Cell Migration Gateway</a> <a href="https://web.archive.org/web/20141211173306/http://www.cellmigration.org/index.shtml">Archived</a> 2014-12-11 at the <a href="/facts/Wayback_Machine/nmQ3a6JC">Wayback Machine</a></li> <li>Human <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&singleSearch=knownCanonical&position=ITGA4"><i>ITGA4</i></a> genome location and <a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_type=knownGene&hgg_gene=ITGA4"><i>ITGA4</i></a> gene details page in the <a href="/facts/UCSC_Genome_Browser/kwumPyLb">UCSC Genome Browser</a>.</li> <li>Overview of all the structural information available in the <a href="/facts/Protein_Data_Bank/oUhq4ABD">PDB</a> for <a href="/facts/UniProt/lfDDHjAl">UniProt</a>: <i><a href="https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P13612">P13612</a></i> (Human Integrin alpha-4) at the <a href="/facts/PDBe-KB/p1WX7lPH">PDBe-KB</a>.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>"Entrez Gene: ITGA4 integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3676" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3676</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Hadari YR, Arbel-Goren R, Levy Y, Amsterdam A, Alon R, Zakut R, Zick Y (2000). "Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis". J. Cell Sci. 113 (Pt 13): 2385–97. doi:10.1242/jcs.113.13.2385. PMID 10852818. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Han J, Liu S, Rose DM, Schlaepfer DD, McDonald H, Ginsberg MH (November 2001). "Phosphorylation of the integrin alpha 4 cytoplasmic domain regulates paxillin binding". J. Biol. Chem. 276 (44): 40903–9. doi:10.1074/jbc.M102665200. PMID 11533025. <a href="https://doi.org/10.1074%2Fjbc.M102665200" target="_blank">https://doi.org/10.1074%2Fjbc.M102665200</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Liu S, Kiosses WB, Rose DM, Slepak M, Salgia R, Griffin JD, Turner CE, Schwartz MA, Ginsberg MH (June 2002). "A fragment of paxillin binds the alpha 4 integrin cytoplasmic domain (tail) and selectively inhibits alpha 4-mediated cell migration". J. Biol. Chem. 277 (23): 20887–94. doi:10.1074/jbc.M110928200. PMID 11919182. <a href="https://doi.org/10.1074%2Fjbc.M110928200" target="_blank">https://doi.org/10.1074%2Fjbc.M110928200</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> </ol>