ITGA4

The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 4 subunit. This subunit associates with a beta 1 or beta 7 subunit to form an integrin that may play a role in cell motility and migration. This integrin is a therapeutic target for the treatment of multiple sclerosis, Crohn's disease and inflammatory bowel disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

Full Name

Integrin Subunit Alpha 4

Function

Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415).
ITGA4:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877).

Biological Process

Axonogenesis involved in innervationIEA:Ensembl
B cell differentiation1 PublicationIC:BHF-UCL
Cell-cell adhesion in response to extracellular stimulusManual Assertion Based On ExperimentIGI:ARUK-UCL
Cell-cell adhesion mediated by integrinManual Assertion Based On ExperimentIGI:ARUK-UCL
Cell-matrix adhesionManual Assertion Based On ExperimentIMP:UniProtKB
Cell-matrix adhesion involved in ameboidal cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Cellular response to amyloid-betaManual Assertion Based On ExperimentIGI:ARUK-UCL
Cellular response to cytokine stimulusIEA:Ensembl
Clathrin-dependent extracellular exosome endocytosisIEA:Ensembl
DiapedesisIEA:Ensembl
Endodermal cell differentiationManual Assertion Based On ExperimentIEP:UniProtKB
Heterotypic cell-cell adhesionManual Assertion Based On ExperimentIMP:UniProtKB
Import into cellIEA:Ensembl
Integrin-mediated signaling pathwayIEA:UniProtKB-KW
Leukocyte cell-cell adhesionManual Assertion Based On ExperimentIDA:BHF-UCL
Leukocyte tethering or rollingManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of protein homodimerization activityManual Assertion Based On ExperimentIDA:UniProtKB
Neuron projection extensionIEA:Ensembl
Positive regulation of endothelial cell apoptotic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of leukocyte tethering or rollingIEA:Ensembl
Positive regulation of T cell migrationIEA:Ensembl
Positive regulation of vascular endothelial cell proliferationManual Assertion Based On ExperimentIMP:BHF-UCL
Receptor clusteringManual Assertion Based On ExperimentIMP:UniProtKB
Substrate adhesion-dependent cell spreadingManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Membrane

Topology

Extracellular: 35-977
Helical: 978-1001
Cytoplasmic: 1002-1032

PTM

Phosphorylation on Ser-1027 inhibits PXN binding.

ITGA4

Anti-ITGA4 antibodies