Species: Hu
Applications: Bioactivity
Species: Mu
Applications: Bioactivity
Description
Integrin alpha 6 beta 4 is an epithelial and Schwann cell laminin-binding integrin. While alpha 6 can also pair with beta 1, beta 4 pairs only with alpha 6 (1-3). Expression of the non-covalent heterodimer composed of a ~150 kDa alpha 6/CD49f and 150-200 kDa beta 4/CD104 type I transmembrane glycoprotein subunit is required for hemidesmosome formation (2, 4). The alpha 6 subunit contains an I (inhibitory) domain and a cleavage site that creates extracellular heavy and transmembrane light chains. Alternative splicing in the alpha 6 extracellular domain (ECD) at amino acid (aa) 216 creates X1 (ubiquitous), X2 and X1X2 isoforms, while splicing at a cytoplasmic site creates A and B isoforms (5, 6). The cytoplasmic domain of beta 4 is unusually long (~1000 aa) and contains four type III fibronectin repeats that bind intracellular hemidesmosomal components (2, 4, 7). Alternative splicing between repeats # 2 and 3 creates A, B, C and (truncated) D isoforms (7). All ECD variants share similar ligand binding characteristics, while cytoplasmic variants differ in tissue distribution and signaling pathways (5-7). The 683 aa human alpha 6X1 heavy chain shares 94-95% aa identity with mouse, rat, bovine, and canine a6, and the 683 aa human beta 4 ECD shares 87-92% aa identity with mouse, rat, bovine, and equine beta 4. Mutation of alpha 6 beta 4 can cause EB-PA, or epidermolysis bullosa (detachment of epidermis from basement membrane) with pyloric atresia, that is neonatally lethal if severe (8). On Schwann cells, alpha 6 beta 4 cooperates with dystroglycan to stabilize the myelin sheath, and mediates attachment to the basal lamina (9, 10). High alpha 6 beta 4 expression correlates with invasiveness of carcinomas (2). EGF R-induced phosphorylation of beta 4 disrupts hemidesmosomes and allows tumor cell migration (11, 12). alpha 6 beta 4 signaling can also amplify tumor production of VEGF and ErbB proteins (13, 14).
Bioinformatics
| Uniprot |
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| Product By Gene ID |
3655 |
| Alternate Names |
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