TFPI Kunitz-1, Human, mAb CLB/TFPI Kunitz-1

Antibody CLB/TFPI Kunitz-1 recognizes the Kunitz domain 1 (aa 12 – 88) of TFPI. TFPI (tissue factor pathway inhibitor) is a single-chain polypeptide serine protease inhibitor that regulates the tissue factor (TF)-dependent pathway of blood coagulation.

The coagulation process initiates with the formation of a factor VIIa-TF complex, which proteolytically activates additional proteases (factors IX and X) and ultimately leads to the formation of a fibrin clot. TFPI is known to interact and inhibit the activated factor X and VIIa-TF proteases in an autoregulatory loop.

TFPI is a dual inhibitor, binding to the TF/FVIIa complex to prevent it from acting on its FIX and FX substrates, and by directly inhibiting FXa. Inadequate down-regulation of FXa function by TFPI deficiency leads to thrombosis. Besides coagulation, TFPI may play additional roles in innate immunity, microbial defense, inflammation, angiogenesis, lipid metabolism, and cellular signaling, proliferation, migration and apoptosis.

Tissue factor pathway inhibitor (TFPI) Kunitz-1 is a multivalent, Kunitz-type proteinase inhibitor, which, due to alternative mRNA splicing, is transcribed in three isoforms: TFPIalpha, TFPIdelta, and glycosyl phosphatidyl inositol (GPI)-anchored TFPIbeta. The microvascular endothelium is thought to be the principal source of TFPI and TFPIalpha is the predominant isoform expressed in humans.

TFPI consists of an acidic aminoterminal polypeptide, followed by 3 tandem Kunitz-type domains (Kunitz domains 1, 2, and 3) and a basic carboxyterminal tail. The Kunitz domains are the active protease inhibiting domains of TFPI. The domains are relatively small with a length of about 50 to 60 amino acids and a molecular weight of 6 kDa. The Kunitz-1 domain is responsible for factor Xa-dependent inhibition of the factor VIIa/tissue factor catalytic complex.