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Function

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.¹

Interactions

CD49d has been shown to interact with LGALS8² and Paxillin.³⁴

See also

• Carotegrast methyl, an integrin alpha 4 antagonist used for the treatment of ulcerative colitis

Further reading

• 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". Ciba Foundation Symposium 189 - Cell Adhesion and Human Disease. Novartis Foundation Symposia. Vol. 189. pp. 177–91, discussion 191–9. doi:10.1002/9780470514719.ch13. ISBN 978-0-470-51471-9. PMID 7587632. {{cite book}}: |journal= ignored (help)
• Oostendorp RA, Dörmer P (1997). "VLA-4-mediated interactions between normal human hematopoietic progenitors and stromal cells". Leuk. Lymphoma. 24 (5–6): 423–35. doi:10.3109/10428199709055581. PMID 9086434.
• Porter JC, Hogg N (1999). "Integrins take partners: cross-talk between integrins and other membrane receptors". Trends Cell Biol. 8 (10): 390–6. doi:10.1016/S0962-8924(98)01344-0. PMID 9789327.
• Rose DM, Han J, Ginsberg MH (2003). "Alpha4 integrins and the immune response". Immunol. Rev. 186 (1): 118–24. doi:10.1034/j.1600-065X.2002.18611.x. PMID 12234367. S2CID 37850994.
• O'Connor P (2007). "Natalizumab and the role of alpha 4-integrin antagonism in the treatment of multiple sclerosis". Expert Opinion on Biological Therapy. 7 (1): 123–36. doi:10.1517/14712598.7.1.123. PMID 17150024. S2CID 73319319.
• Chan BM, Elices MJ, Murphy E, Hemler ME (1992). "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". J. Biol. Chem. 267 (12): 8366–70. doi:10.1016/S0021-9258(18)42453-2. PMID 1373725.
• 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". Eur. J. Immunol. 22 (2): 587–90. doi:10.1002/eji.1830220243. PMID 1537388. S2CID 86449765.
• 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". Eur. J. Immunol. 22 (4): 1099–102. doi:10.1002/eji.1830220434. PMID 1551405. S2CID 83613615.
• Sonnenberg A, Linders CJ, Modderman PW, Damsky CH, Aumailley M, Timpl R (1990). "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". J. Cell Biol. 110 (6): 2145–55. doi:10.1083/jcb.110.6.2145. PMC 2116116. PMID 1693624.
• Teixidó J, Parker CM, Kassner PD, Hemler ME (1992). "Functional and structural analysis of VLA-4 integrin alpha 4 subunit cleavage". J. Biol. Chem. 267 (3): 1786–91. doi:10.1016/S0021-9258(18)46014-0. PMID 1730718.
• Rosemblatt M, Vuillet-Gaugler MH, Leroy C, Coulombel L (1991). "Coexpression of two fibronectin receptors, VLA-4 and VLA-5, by immature human erythroblastic precursor cells". J. Clin. Invest. 87 (1): 6–11. doi:10.1172/JCI115002. PMC 294977. PMID 1824634.
• Rosen GD, Birkenmeier TM, Dean DC (1991). "Characterization of the alpha 4 integrin gene promoter". Proc. Natl. Acad. Sci. U.S.A. 88 (10): 4094–8. Bibcode:1991PNAS...88.4094R. doi:10.1073/pnas.88.10.4094. PMC 51604. PMID 2034655.
• Takada Y, Elices MJ, Crouse C, Hemler ME (1989). "The primary structure of the alpha 4 subunit of VLA-4: homology to other integrins and a possible cell-cell adhesion function". EMBO J. 8 (5): 1361–8. doi:10.1002/j.1460-2075.1989.tb03516.x. PMC 400962. PMID 2788572.
• Takada Y, Strominger JL, Hemler ME (1987). "The very late antigen family of heterodimers is part of a superfamily of molecules involved in adhesion and embryogenesis". Proc. Natl. Acad. Sci. U.S.A. 84 (10): 3239–43. Bibcode:1987PNAS...84.3239T. doi:10.1073/pnas.84.10.3239. PMC 304844. PMID 3033641.
• Hemler ME, Huang C, Schwarz L (1987). "The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight beta subunit". J. Biol. Chem. 262 (7): 3300–9. doi:10.1016/S0021-9258(18)61504-2. PMID 3546305.
• Gailit J, Pierschbacher M, Clark RA (1993). "Expression of functional alpha 4 beta 1 integrin by human dermal fibroblasts". J. Invest. Dermatol. 100 (3): 323–8. doi:10.1111/1523-1747.ep12470011. PMID 8440915.
• Pujades C, Teixidó J, Bazzoni G, Hemler ME (1996). "Integrin alpha 4 cysteines 278 and 717 modulate VLA-4 ligand binding and also contribute to alpha 4/180 formation". Biochem. J. 313. ( Pt 3) (3): 899–908. doi:10.1042/bj3130899. PMC 1216996. PMID 8611173.
• Szabo M, McIntyre BW (1996). "Identification of two variants of the human integrin alpha 4 subunit". Mol. Immunol. 32 (17–18): 1453–4. doi:10.1016/0161-5890(96)00001-6. PMID 8643114.
• Mannion BA, Berditchevski F, Kraeft SK, Chen LB, Hemler ME (1996). "Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29)". J. Immunol. 157 (5): 2039–47. doi:10.4049/jimmunol.157.5.2039. PMID 8757325. S2CID 1977096.

External links

• CD49d+antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• ITGA4 Info with links in the Cell Migration Gateway Archived 2014-12-11 at the Wayback Machine
• Human ITGA4 genome location and ITGA4 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: P13612 (Human Integrin alpha-4) at the PDBe-KB.

References

1. "Entrez Gene: ITGA4 integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3676 ↩

2. 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. /wiki/Doi_(identifier) ↩

3. 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. https://doi.org/10.1074%2Fjbc.M102665200 ↩

4. 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. https://doi.org/10.1074%2Fjbc.M110928200 ↩