Integrin alpha 1 beta 1, also called VLA1 is the only alpha 1 integrin family adhesion receptor, one of twelve integrins that share the beta 1 subunit, and one of four collagen‑binding integrins (1‑5). It is the non‑covalent heterodimer of 190‑210 kDa alpha 1 (CD49a) and 130 kDa beta 1 (CD29) type I transmembrane glycoprotein subunits. It is found on cells including activated T cells, B cells, monocytes, vascular smooth muscle cells, osteoblasts and adipocytes (2, 6‑8). The alpha 1 extracellular domain (ECD) contains an I (inserted) domain which includes the ligand binding site (2, 4). The beta 1 ECD contains a vWFA domain, which participates in binding (3). Each subunit then has a transmembrane sequence and a short cytoplasmic tail. Divalent cations and intracellular (inside-out) signaling convert the dimer from the folded, inactive form to its most active, extended conformation (1, 2). The 1113 amino acid (aa) human alpha 1 extracellular domain (ECD) shares 88‑92% aa sequence identity with mouse, rat, canine, bovine and equine alpha 1, while the 708 aa human beta 1 ECD shares 92‑96% aa sequence identity with rat, bovine, mouse, and feline beta 1. Potential alpha 1 splice variants show two or four aa substitutions for aa 765‑1179. alpha 1 beta 1 preferentially binds collagens I, IV, VI, XIII and XVI, but also binds laminin (4‑10). alpha 1 beta 1 is reported to down‑regulate EGF R signaling, increase expression of caveolin-1, reduce production of reactive oxygen species, regulate collagen expression, control MMP collagenase and gelatinase activity, and mediate the renal basement membrane disorder Alport syndrome (10‑12). These effects may begin by alpha 1 beta 1 binding of caveolin-1, initiating signaling pathways that involve the phosphatase TC-PTP, kinases ERK and p38, and the transcription factor PPAR-gamma (10‑13). alpha 1 beta 1 down‑regulates MMP-mediated angiostatin formation, enhancing tumor vascularization (8). alpha 1 beta 1-null mice are deficient in fibroblast collagen IV and laminin-mediated cell spreading and migration, show defects in bone healing, and are resistant to Alport renal fibrosis (9‑11, 14). When expressed in the same epithelial cells, alpha 1 beta 1 negatively regulates integrin alpha 2 beta 1‑mediated cell adhesion and migration (15).
| Uniprot | |
| Product By Gene ID | 3672 |
| Alternate Names |
|
