Integrin alpha 4

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

ITGA4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4HKC, 3V4P, 3V4V, 5FPI, 5C7Z
Identifiers
Aliases	ITGA4, CD49D, IA4, integrin subunit alpha 4
External IDs	OMIM: 192975; MGI: 96603; HomoloGene: 37364; GeneCards: ITGA4; OMA:ITGA4 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2q31.3 Start 181,457,202 bp End 181,538,940 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2 C3|2 47.38 cM Start 79,085,770 bp End 79,163,467 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte bone marrow cells granulocyte appendix blood lymph node spleen trabecular bone secondary oocyte epithelium of colon Top expressed in blood spleen lumbar spinal ganglion mesenteric lymph nodes internal carotid artery external carotid artery muscle layer of urethra thymus granulocyte human fetus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding protein antigen binding metal ion binding antigen binding fibronectin binding cell adhesion molecule binding coreceptor activity C-X3-C chemokine binding protein heterodimerization activity Cellular component extracellular exosome integral component of membrane membrane focal adhesion cell surface integrin alpha4-beta7 complex integrin complex plasma membrane growth cone soma protein-containing complex Biological process endodermal cell differentiation B cell differentiation positive regulation of T cell migration extracellular matrix organization heterotypic cell-cell adhesion substrate adhesion-dependent cell spreading cellular response to cytokine stimulus cell-matrix adhesion involved in ameboidal cell migration cell-matrix adhesion leukocyte tethering or rolling diapedesis regulation of immune response integrin-mediated signaling pathway leukocyte migration positive regulation of leukocyte tethering or rolling positive regulation of leukocyte cell-cell adhesion positive regulation of leukocyte migration import into cell leukocyte cell-cell adhesion negative regulation of protein homodimerization activity clathrin-dependent extracellular exosome endocytosis cell adhesion receptor clustering cell-cell adhesion mediated by integrin axonogenesis involved in innervation cell-cell adhesion in response to extracellular stimulus cellular response to amyloid-beta positive regulation of vascular endothelial cell proliferation neuron projection extension positive regulation of endothelial cell apoptotic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3676 16401 Ensembl ENSG00000115232 ENSMUSG00000027009 UniProt P13612 Q00651 RefSeq (mRNA) NM_000885 NM_001316312 NM_010576 RefSeq (protein) NP_000876 NP_001303241 NP_034706 Location (UCSC) Chr 2: 181.46 – 181.54 Mb Chr 2: 79.09 – 79.16 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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.

Interactions

CD49d has been shown to interact with LGALS8 and Paxillin.

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.