Integrin alpha 4

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
Gene location (Human)
Chr.	Chromosome 2 (human)
End	181,538,940 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	79,333,123 bp
RNA expression pattern
	Top expressed in
	lung; ; spleen; ; lymph node; ; bone marrow; ; appendix; ; kidney; ; stomach; ; thymus;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	GO:0001948 protein binding; protein antigen binding; metal ion binding; GO:0003823 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; neuronal cell body; 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
	3676
	16401
	ENSG00000115232
	ENSMUSG00000027009
	P13612
	Q00651
	NM_000885; NM_001316312
	NM_010576
	NP_000876; NP_001303241
	NP_034706
	Wikidata
View/Edit Human	View/Edit Mouse

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.^[5]

Interactions[]

CD49d has been shown to interact with LGALS8^[6] and Paxillin.^[7]^[8]

References[]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000115232 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027009 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: ITGA4 integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)".
^ 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.
^ 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.
^ 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. Novartis Foundation Symposia. 189: 177–91, discussion 191–9. doi:10.1002/9780470514719.ch13. ISBN 9780470514719. 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. 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. 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
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.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000115232 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000027009 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] "Entrez Gene: ITGA4 integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)".

[pmid10852818-6] 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.

[pmid11533025-7] 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.

[pmid11919182-8] 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.

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v t Proteins: clusters of differentiation (see also list of human clusters of differentiation)
1–50	CD1 a-c 1A 1B 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51–100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101–150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151–200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201–250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249
251–300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301–350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350