CD49d

Integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3V4P​, 3V4V​, 4HKC​
Identifiers
Symbols	ITGA4 ; CD49D; IA4
External IDs	OMIM: 192975 MGI: 96603 HomoloGene: 37364 ChEMBL: 278 GeneCards: ITGA4 Gene
Gene ontology Molecular function • fibronectin binding • protein binding • metal ion binding • cell adhesion molecule binding • protein antigen binding Cellular component • plasma membrane • cell-cell junction • focal adhesion • external side of plasma membrane • cell surface • membrane • integrin alpha4-beta7 complex • extracellular exosome Biological process • blood vessel remodeling • cell-matrix adhesion involved in ameboidal cell migration • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules • leukocyte cell-cell adhesion • cell-matrix adhesion • integrin-mediated signaling pathway • heart development • blood coagulation • B cell differentiation • extracellular matrix organization • heterotypic cell-cell adhesion • substrate adhesion-dependent cell spreading • endodermal cell differentiation • receptor clustering • regulation of immune response • leukocyte migration • leukocyte tethering or rolling • diapedesis • face development • chorio-allantoic fusion • cellular response to cytokine stimulus • T cell migration • negative regulation of protein homodimerization activity • import into cell • positive regulation of leukocyte tethering or rolling • positive regulation of T cell migration Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3676	16401
Ensembl	ENSG00000115232	ENSMUSG00000027009
UniProt	P13612	Q00651
RefSeq (mRNA)	NM_000885	NM_010576
RefSeq (protein)	NP_000876	NP_034706
Location (UCSC)	Chr 2: 181.46 – 181.54 Mb	Chr 2: 79.26 – 79.33 Mb
PubMed search

CD49d is an integrin alpha subunit. It makes up half of the α4β1 lymphocyte homing receptor.

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 LGALS8^[2] and Paxillin.^[3][4]

References

1. "Entrez Gene: ITGA4 integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)".
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. PMID 10852818.
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.
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.

Further reading

• Humphries MJ, Sheridan J, Mould AP, Newham P (1995). "Mechanisms of VCAM-1 and fibronectin binding to integrin alpha 4 beta 1: implications for integrin function and rational drug design.". Ciba Found. Symp. 189: 177–91; discussion 191–9. PMID 7587632.
• 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.
• 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.
• 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. 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.
• 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.
• 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. 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. 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. 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. 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. 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): 899–908. 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. PMID 8757325.

External links

• CD49d antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
• ITGA4 Info with links in the Cell Migration Gateway