Description
Integrin alpha 6 beta 1, also called platelet glycoprotein GPIc-IIa, is a laminin binding integrin that is expressed on T cells, monocytes, endothelial cells, stem cells, and platelets (1-9). The non-covalent heterodimer is composed of ~150 kDa alpha 6/CD49f and 130 kDa beta 1/CD29 type I transmembrane glycoprotein subunits (2). While alpha 6 pairs only with beta 1 or beta 4, twelve integrins share the beta 1 subunit (1‑5). The alpha 6 subunit is cleaved into extracellular heavy and transmembrane light chains (3). Alternative splicing in the human alpha 6 extracellular domain (ECD) at amino acid (aa) 216 creates X1 (ubiquitous), X2 and X1X2 isoforms, while splicing at a mouse or human cytoplasmic site creates A and B isoforms (10, 11). These forms do not appear to alter the binding specificity (4, 10, 11). The beta 1 ECD contains a vWFA domain, which participates in binding. Each subunit then has a transmembrane sequence and a short cytoplasmic tail. The dimer is folded when it is least active. Divalent cations and intracellular (inside‑out) signaling convert it to its most active, extended and open conformation (1, 2). The mouse alpha 6 heavy chain shares 98% aa identity with rat and 92‑93% with human (X1), bovine, and canine alpha 6, and the mouse beta 1 ECD shares 98% aa identity with rat and 93‑94% with human, bovine, porcine, ovine, canine and feline beta 1. alpha 6 beta 1 shows broad specificity for adhesion to laminin isoforms (4, 10). Its expression on human and mouse pluripotent stem cells is important for attachment, expansion, and self-renewal on LN‑511 (laminin alpha
5 beta
1 gamma
1) (6, 7). The secreted protein Netrin‑4 and the laminin gamma
1 subunit form an adhesion‑activating complex with alpha 6 beta 1 on mouse neural stem cells and human lymphatic endothelial cells that promotes lymphangiogenesis (8, 9). alpha 6 beta 1 up‑regulation on cancers such as prostate, glioma, and hepatoma is reported to enhance tumorigenicity, motility, invasion and metastasis (12‑14). alpha 6 beta 1 cleavage via uPA (urokinase‑type plasminogen activator) facilitates tumorigenicity in prostate cancers, and interaction of hepatoma alpha 6 beta 1 with EMMPRIN/CD147 may also enhance tumorigenicity by inducing uPA and other metalloproteinases (12, 13).
Bioinformatics
| Uniprot |
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| Product By Gene ID |
3655 |
| Alternate Names |
- CD49f
- Integrin alpha 6 beta 1
- ITGA6B
- VLA-6
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