ITGA4
Description
The ITGA4 (integrin subunit alpha 4) is a protein-coding gene located on chromosome 2.
CD49d is an integrin alpha subunit, forming half of the α4β1 lymphocyte homing receptor. It belongs to the integrin alpha chain family, but unlike other members, it lacks an I-domain and doesn't undergo disulfide-linked cleavage. CD49d associates with either beta 1 or beta 7 chains. It interacts with LGALS8 and Paxillin. CD49d is targeted by Carotegrast methyl, an integrin alpha 4 antagonist used to treat ulcerative colitis.
ITGA4, also known as CD49d, forms heterodimers with either ITGB1 or ITGB7, resulting in the integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7, respectively. These integrins serve as receptors for fibronectin, recognizing specific domains within its CS-1 and CS-5 regions. They also act as receptors for VCAM1 and MADCAM1, with VLA-4 specifically recognizing the Q-I-D-S sequence in VCAM1 and alpha-4/beta-7 recognizing the L-D-T sequence in MADCAM1. On activated endothelial cells, VLA-4 triggers homotypic aggregation of VLA-4-positive leukocyte cell lines. VLA-4 may also participate in cytolytic T-cell interactions with target cells. The ITGA4:ITGB1 heterodimer binds to fractalkine (CX3CL1), potentially acting as its coreceptor in CX3CR1-dependent fractalkine signaling. It also binds to PLA2G2A via a site distinct from the classical ligand-binding site, inducing integrin conformational changes and enhancing ligand binding. ITGA4:ITGB1 interacts with SVEP1 to repress PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells, ultimately inhibiting vasocontraction.
ITGA4 is also known as CD49D, IA4.
