Recombinant Human Fibronectin Fragment 4 Protein, CF

Fibronectin (FN) is a large modular glycoprotein that is found in a polymeric fibrillar network in the extracellular matrix (ECM). It also forms a soluble disulfide-linked dimeric protomers in plasma and other body fluids (1,2). The protein subunit is made up of three types of homologous structural motifs termed FN type I, type II, and type III repeats (3-5). Alternative splicing generates multiple isoforms of fibronectin which may have insertions of extra type III domains (EDA and EDB) or alteration of the type III connecting segment (IIICS) (5). Fibronectin is a ligand for fibrin, heparin, chondroitin sulfate, collagen/gelatin, and integrins. It is involved in multiple cellular processes including cell adhesion/migration, blood clotting, morphogenesis, tissue repair, and cell signaling. Fibronectin functions are mediated by the insoluble polymeric fibrils in the ECM. Conversion of soluble fibronectin to fibronectin fibrils in the ECM is initiated by binding to cell surface integrins, resulting in exposure of cryptic epitopes necessary for polymerization (1). FN1.4 contains one type III domain, the IIICS domain, three type I domains, and the site of interchain disulfide linkage. Within FN1.4, human fibronectin shares 91% and 88% aa sequence identity with mouse and rat fibronectin, respectively. FN1.4 contains regions that enable association with heparin and fibrin. The IIICS domain contains two sites (CS1 and CS2) that interact with integrin alpha4 beta1 (6-8). The CS1 sequence is not accessible in full length fibronectin but is exposed by protease digestion, thereby enabling cell adhesion via integrin alpha4 beta1 (9). This is distinct from integrin alpha5 beta1-mediated adhesion through an RGD motif located N-terminal to FN1.4 (10). Differential splicing within the IIICS domain determines the presence of CS1 and CS2 sequences and the sensitivity to proteases (6,11).