Vitronectin

Vitronectin also known as VTN is a is_associated_with::protein that in humans is encoded by the VTN is_associated_with::gene.

The protein encoded by this gene is a member of the is_associated_with::pexin family. Vitronectin is an abundant is_associated_with::glycoprotein found in serum, the is_associated_with::extracellular matrix and is_associated_with::bone and promotes is_associated_with::cell adhesion and spreading, inhibits the membrane-damaging effect of the terminal cytolytic complement pathway, and binds to several is_associated_with::serpins (serine protease inhibitors). It is a secreted protein and exists in either a single chain form or a clipped, two chain form held together by a disulfide bond. Vitronectin has been speculated to be involved in is_associated_with::hemostasis and is_associated_with::tumor is_associated_with::malignancy.

Structure
Vitronectin is a 75 kDa glycoprotein, consisting of 459 is_associated_with::amino acid residues. About one-third of the protein's is_associated_with::molecular mass is composed of is_associated_with::carbohydrates. On occasion, the protein is cleaved after is_associated_with::arginine 379, to produce two-chain vitronectin, where the two parts are linked by a is_associated_with::disulfide bond. No high resolution structure has been determined experimentally yet, except for the N-terminal domain.

The protein consists of three domains:
 * The N-terminal is_associated_with::Somatomedin B domain (1-39)
 * A central domains with is_associated_with::hemopexin homology (131-342)
 * A C-terminal domain (residues 347-459) also with hemopexin homology.

Several structures has been reported for the Somatomedin B domain. The protein was initially crystallized in complex with one of its physiological binding partners: the is_associated_with::Plasminogen activator inhibitor-1 (PAI-1) and the structure solved for this complex. Subsequently two groups reported NMR structures of the domain.

The Somatomedin B domain is a close-knit disulfide knot, with 4 disulfide bonds within 35 residues. Different disulfide configurations had been reported for this domain  but this ambiguity has been resolved by the crystal structure.

Homology models have been built for the central and C-terminal domains.

Function
The somatomedin B domain of vitronectin binds to is_associated_with::plasminogen activator inhibitor-1 (PAI-1), and stabilizes it. Thus vitronectin serves to regulate proteolysis initiated by is_associated_with::plasminogen activation. In addition, vitronectin is a component of is_associated_with::platelets and is, thus, involved in hemostasis. Vitronectin contains an RGD (45-47) sequence, which is a binding site for membrane-bound is_associated_with::integrins, e.g., the is_associated_with::vitronectin receptor, which serve to anchor cells to the extracellular matrix. The Somatomedin B domain interacts with the is_associated_with::urokinase receptor, and this interaction has been implicated in cell migration and signal transduction. High plasma levels of both PAI-1 and the urokinase receptor have been shown to correlate with a negative prognosis for cancer patients. Cell adhesion and migration are directly involved in cancer is_associated_with::metastasis, which provides a probable mechanistic explanation for this observation.