lmmol · Proteins

Integrin alpha-4

UniProt P13612 Organism Homo sapiens Gene CD49D, ITGA4

Also known as: CD49D, ITGA4

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. 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.

Classification

Family (Pfam)
PF01839 FG-GAP, PF08441 Integrin_A_Ig_1, PF20805 Integrin_A_Ig_2, PF20806 Integrin_A_Ig_3
InterPro
FG-GAP, Int_alpha_beta-p, Integrin_alpha, Integrin_alpha_C_CS, Integrin_alpha_Ig-like_1, Integrin_alpha_Ig-like_2, Integrin_alpha_Ig-like_3, Integrin_alpha_N, Integrin_dom_sf
Functional cluster
Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 7

A predicted model is available from AlphaFold.

Gene Ontology · 40

Drugs targeting this protein · 2

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 23 cited papers

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