Recombinant Human Integrin alpha 5 beta 1 Fc Protein, CF

Integrin alpha5/ beta1, also known as VLA-5, is a widely expressed non-covalent heterodimer of a 160 kDa alpha5 and a 130 kDa beta1 Integrin subunit. alpha5/ beta1 functions in cell adhesion, migration, activation, and matrix fibrillogenesis (1, 2). The human Integrin alpha5/CD49e cDNA encodes a 1049 amino acid (aa) precursor that includes a 41 aa signal sequence, a 954 aa extracellular domain (ECD), a 26 aa transmembrane segment, and a 28 aa cytoplasmic domain. The ECD contains seven FG-GAP repeats and nine internal disulfide bonds (3). Within the ECD, human alpha5 shares 90% and 46% aa sequence identity with mouse alpha5 and human alpha8, respectively, and less than 30% aa sequence identitity with other human alpha chains. The human Integrin beta1/CD29 cDNA encodes a 798 aa precursor that includes a 20 aa signal sequence, a 708 aa ECD, a 23 aa transmembrane segment, and a 47 aa cytoplasmic domain. The ECD contains one vWF-A domain, four Cys-rich repeats, and 29 internal disulfide bonds (3). Five alternate splice forms of the cytoplasmic domain vary by 12 to 48 aa. Within the ECD, human beta1 shares 92-96% aa sequence identity with rat, bovine, mouse, and feline beta1. It shares 35-45% aa sequence identity with other beta chains. alpha5/ beta1 binds fibronectin in both RGD-dependent and -independent manners (4, 5). alpha5/ beta1 is up‑regulated on tumor vasculature and promotes angiogenesis (6, 7). This is accomplished in part by a constitutive association in cis of alpha5/ beta1 with VEGFR3 and Tie2, a requirement for optimal activation of those receptors (8, 9). alpha5/ beta1 interacts with a variety of other proteins, including HER2, uPAR, Galectin-1, CTGF, and thrombin-cleaved Osteopontin (5, 10-13). alpha5/ beta1 also functions on some hematopoietic and neuronal stem cells (14, 15).