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). 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)
Heterodimer of an alpha and a beta subunit. The alpha subunit can sometimes be cleaved into two non-covalently associated fragments. Alpha-4 associates with either beta-1 or beta-7.
Alpha-4 interacts with PXN, LPXN, and TGFB1I1/HIC5. Interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan. Interacts with JAML; integrin alpha-4/beta-1 may regulate leukocyte to endothelial cells adhesion by controlling JAML homodimerization.
ITGA4:ITGB1 is found in a ternary complex with CX3CR1 and CX3CL1 (PubMed:23125415). Interacts with MDK (PubMed:15466886). ITGA4:ITGB1 interacts with MDK; this interaction mediates MDK-induced osteoblast cells migration through PXN phosphorylation (PubMed:15466886).
Integrin ITGA4:ITGB1 interacts with SVEP1 (via Sushi domain 21); thereby inhibits Ca(2+) intracellular signaling and as a result represses vasocontraction (PubMed:35802072). ITGA4:ITGB1 interacts with SELP (PubMed:37184585). ITGA4:ITGB1 interacts with BCAM (PubMed:17158232)
Expressed in vascular smooth muscle cells (at protein level)
The SG1 motif is involved in binding to chondroitin sulfate glycosaminoglycan and cell adhesion
Click a pathway to open the interactive Reactome viewer.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to ITGA4, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 2
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT06366516 | Precancerous Cervical Lesion | Role of Methylation Test Triage in HPV Positive Women | NA | UNKNOWN |
| NCT05371392 | Chronic Lymphocytic Leukemia | Polymorphism of ITGA4 Gene in Chronic Lymphocytic Leukemia | N/A | NOT_YET_RECRUITING |