Tissue factor pathway inhibitor-like (IPR008296)

Short name: TFPI-like

Overlapping homologous superfamilies


Family relationships


Tissue factor pathway inhibitor (TFPI or TFPI1), also called lipoprotein-associated coagulation inhibitor (LACI) or extrinsic pathway inhibitor, is an anti-coagulation plasma protein that acts as a Kunitz-type serine protease inhibitor. Though TFPI lacks a membrane attachment signal, it remains associated with the endothelial surface through its association with a GPI-anchored co-receptor, which acts as a molecular chaperone to move TFPI to the cell surface [PMID: 16689766]. TFPI is a dual inhibitor, binding directly to factor Xa (FXa), and to tissue factor/factor VIIa (TF/FVIIa) in a FXa-dependent way, presumably by forming a quaternary FXa/TFPI/FVIIa/TF complex, thereby blocking the continuation of the coagulation pathway. TFPI is thought to be important in modulating tissue factor-induced thrombogenesis [PMID: 16261634].

The sequence of TFPI contains three Kunitz/Bovine pancreatic trypsin inhibitor domains. Inhibitor domains 1 and 2 belong to MEROPS protease inhibitor family I2 (aprotinin, clan IB). Domains 1 and 2 are required for the inhibition of TF/FVIIa activity, while domain 2 is required for binding and inhibition of FXa. Alteration of the inhibitory-site residue of the third domain has no significant effect on either function.

The homologous tissue factor pathway inhibitor 2 (TFPI-2) has a similar structure and is thought to play a role in the regulation of extracellular matrix digestion and remodelling [PMID: 16411383]. This entry also includes SmCI from Sabellastarte magnifica. SmCI is a bifunctional inhibitor of metallo carboxypeptidase and serine proteinase [PMID: 23746805].

GO terms

Biological Process

GO:0010466 negative regulation of peptidase activity

Molecular Function

GO:0030414 peptidase inhibitor activity

Cellular Component

GO:0005576 extracellular region

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.