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 Ξ±4Ξ²1 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.
