Group IX - Tetranectin Family
The tetranectin group of CTLD-containing secreted
proteins has three members in both human and mouse: tetranectin,
cartilage-derived C-type lectin, and stem cell growth factor (SCGF). Each
polypeptide has an N-terminal tail rich in charged residues, a central
neck region, and a C-terminal CTLD. The neck region mediates
homotrimerization through the formation of a coiled-coil of
alpha-helices.
Tetranectin is found in serum, and is present in the extracellular matrix during development, tissue regeneration and cancer, but not in normal adult tissue. Lower serum tetranectin and higher matrix tetranectin both correlate with poor cancer prognosis. The charged tail of tetranectin binds sulphated carbohydrates such as glycosaminoglycans. The CTLD undergoes structural rearrangements upon calcium binding and in its calcium-free form binds to proteins with kringle domains, such as plasminogen. By stimulating plasminogen activation, tetranectin may regulate proteolysis of extracellular matrix components in development, tissue remodelling and cancer, and influence the proteolytic activation of proteases and growth factors. Tetranectin may affect coagulation and angiogenesis through interaction with fibrin and angiostatin (a plasminogen fragment), respectively. During development, tetranectin stimulates muscle cell differentiation and fibre formation, and promotes bone mineralization. Tetranectin-deficient mice develop a spinal deformity. Cartilage-derived C-type lectin is expressed in cartilage, where it may have a role in organizing the extracellular matrix. SCGF is expressed in skeletal and connective tissues, where it stimulates proliferation and differentiation of haematopoietic precursor cells.
It is not known if carbohydrate recognition plays a role in the function of tetranectin group proteins. The CTLDs in these proteins resemble CTLDs of the galactose-binding subtype, but attempts to demonstrate sugar-binding activity have been unsuccessful.
Ca2+ ions are shown in dark blue. Protein Data Bank structure ID: 1HTN.
