Itga4

Domain

The SG1 motif is involved in binding to chondroitin sulfate glycosaminoglycan and cell adhesion.

Function

Integrins alpha-4/beta-1 (VLA-4 or LPAM-2) and alpha-4/beta-7 (LPAM-1) 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. 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. Integrin ITGA4:ITGB1 represses PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells via its interaction with SVEP1, thereby inhibiting vasocontraction (PubMed:35802072).

Post-translational modifications

Phosphorylation on Ser-1028 inhibits PXN binding.

Sequence Similarities

Belongs to the integrin alpha chain family.

Tissue Specificity

Expressed in the media layer of the arterial wall (at protein level) (PubMed:35802072). Weakly expression in the thymus, spleen and mesenteric lymph nodes (PubMed:1840602).

Cellular localization

• Membrane
• Single-pass type I membrane protein

Alternative names

CD49d, Integrin alpha-4, CD49 antigen-like family member D, Integrin alpha-IV, Lymphocyte Peyer patch adhesion molecules subunit alpha, VLA-4 subunit alpha, LPAM subunit alpha, Itga4

Database links

swissprot:Q00651 entrezGene:16421 entrezGene:16401 swissprot:P26011