The reference OMIM entry for this protein is 603101

Carboxypeptidase b2, plasma; cpb2
Carboxypeptidase u; cpu
Thrombin-activatable fibrinolysis inhibitor; tafi

DESCRIPTION

Plasma carboxypeptidase B2 (CPB2; EC 3.4.17.20), also known as carboxypeptidase U (CPU) and thrombin-activatable fibrinolysis inhibitor (TAFI), is synthesized by the liver and circulates in plasma as a plasminogen-bound zymogen. When it is activated by the thrombin/thrombomodulin complex, CPB2 exhibits carboxypeptidase B (CPB1; 114852)-like activity. CPB2 potently attenuates fibrinolysis by removing the fibrin C-terminal residues that are important for the binding and activation of plasminogen (PLG; 173350) (summary by Zhao et al., 1998 and Boffa et al., 1999).

CLONING

Eaton et al. (1991) purified a 60-kD plasminogen-binding protein from human plasma and determined the N-terminal sequence. By RT-PCR with degenerate primers based on the protein sequence, they isolated a partial liver cDNA. The partial cDNA was used to isolate liver cDNAs containing the complete coding region. Sequence analysis revealed that the predicted 423-amino acid protein was similar to tissue-type carboxypeptidases A and B; therefore, Eaton et al. (1991) designated the gene 'plasma carboxypeptidase B' (pCPB). This enzyme is distinct from carboxypeptidase N, which has frequently been called serum or plasma carboxypeptidase B; see CPN2 (603104). pCPB consists of a 22-amino acid signal peptide, 92-amino acid activation peptide, and a 309-amino acid catalytic domain. When activated by trypsin, it hydrolyzes carboxypeptidase B substrates, but not carboxypeptidase A substrates, and is inhibited by a specific carboxypeptidase B inhibitor. By SDS-PAGE, Wang et al. (1994) determined that the active CPU enzyme has an apparent molecular mass of 53 kD by SDS-PAGE. When active, the enzyme tends to be very unstable. Vanhoof et al. (1996) noted that pro-CPU exhibits affinity for plasminogen and can be converted to its active form through the action of thrombin (176930) and plasmin. They stated that the most likely physiologic activator of pro-CPU is the thrombin-thrombomodulin complex.

GENE FUNCTION

Wang et al. (1994) stated that during fibrinolysis, when plasminogen is converted to plasmin by the tissue plasminogen activator (PLAT; 173370), plasmin cleaves pro-CPU to form active CPU, which thus is released at the specific site of coagulation and fibrinolysis. They suggested that CPU may play a role in the control of the fibrinolytic system. Because bradykinin is one of the substrates of TAFI, the CPB2 gene encoding TAFI is a candidate gene for blood pressure. Boffa et al. (1999) identified a single-nucleotide polymorphism (SNP) in the CPB2 coding region, 1057C-T, predicting an ile325-to-thr substitution in the mature TAFI polypeptide. Koschinsky et al. (2001) found that the genotype based on this SNP was significantly associated with blood pressure in aboriginal Canadians. Homozygotes for CPB2 1057T had significantly lower diastolic blood pressure than subjects with other CPB2 genotypes. The CPB2 genotype accounted for approximately 3% of the total variation in diastolic blood pressure, consistent with the expected magnitude of a modest genetic effect in a complex trait such as blood pressure.

GENE STRUCTURE

Boffa et al. (1999) found that the TAFI gene consists of 11 exons spanning approximately 48 kb.

MAPPING

Tsai and Drayna (1992) used PCR to identify the presence of the plasma carboxypeptidase B gene in somatic hybrid cell lines and demonstrated that the CPB2 gene is located on human chromosome 13. To regional ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 603101 was added.

Feb. 22, 2019: Protein entry updated
Automatic update: comparative model was added.

Feb. 22, 2019: Protein entry updated
Automatic update: model status changed

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).