Human Thrombospondin-4 Antibody

Thrombospondin-4 (TSP-4) is a 140 kDa calcium-binding protein that interacts with other extracellular matrix molecules and modulates the activity of various cell types. TSP‑1 and -2 constitute subgroup A and form disulfide-linked homotrimers, whereas TSP-3, -4, and -5/COMP constitute subgroup B and form pentamers (1, 2). The human TSP-4 cDNA encodes a 961 amino acid (aa) precursor that includes a 26 aa signal sequence followed by an N-terminal heparin-binding domain, a coiled-coil motif, four EGF-like repeats, seven TSP type-3 repeats (one with an RGD motif), and a TSP C-terminal domain (3). Human TSP-4 shares 93% aa sequence identity with mouse and rat TSP-4. Within the TSP type-3 repeats and the TSP C-terminal domain, human TSP-4 shares 79% aa sequence identity with TSP-3 and COMP, and 58% aa sequence identity with TSP-1 and -2. The coiled-coil motif mediates pentamer formation with COMP, either homotypically or heterotypically (3-6). TSP-4 binds a variety of matrix proteins including collagens I, II, III, V, laminin-1, fibronectin, and matrilin-2 (4). Interactions of TSP-4 with non-collagenous proteins are independent of divalent cations, while interactions with collagenous proteins are enhanced in the presence of zinc (4). TSP-4 is expressed in heart, skeletal muscle, vascular smooth muscle, and vascular endothelial cells (7-9). It accumulates at neuromuscular junctions and synapse-rich regions and is upregulated in muscle by experimental denervation (8). TSP-4 mediates the adhesion of motor and sensory neurons and promotes neurite outgrowth (8). A polymorphism of TSP-4 (A387P) is associated with early coronary artery disease (10-12). Unlike wild type TSP-4, the A387P variant does not support HUVEC attachment and spreading (9). Integrin alphaM/ beta2 enables activated neutrophil adhesion to both the variant A387P and wild type TSP-4, although the A387P variant induces a greater release of proinflammatory molecules (13).