Carboxypeptidase B2 Explained

Carboxypeptidase B2 (CPB2), also known as carboxypeptidase U (CPU), plasma carboxypeptidase B (pCPB) or thrombin-activatable fibrinolysis inhibitor (TAFI), is an enzyme that, in humans, is encoded by the gene CPB2.^{[1] [2]}

Function

CPB2 is synthesized by the liver^[3] and circulates in the plasma as a plasminogen-bound zymogen. When it is activated by proteolysis at residue Arg92 by the thrombin/thrombomodulin complex, CPB2 exhibits carboxypeptidase activity. Activated CPB2 reduces fibrinolysis by removing the fibrin C-terminal residues that are important for the binding and activation of plasminogen.^{[4] [5]}

Carboxypeptidases are enzymes that hydrolyze C-terminal peptide bonds. The carboxypeptidase family includes metallo-, serine, and cysteine carboxypeptidases. According to their substrate specificity, these enzymes are referred to as carboxypeptidase A (cleaving aliphatic residues) or carboxypeptidase B (cleaving basic amino residues). The protein encoded by this gene is activated by thrombin and acts on carboxypeptidase B substrates. After thrombin activation, the mature protein downregulates fibrinolysis.^[6]

Isozymes

Polymorphisms have been described for this gene and its promoter region. Available sequence data analyses indicate splice variants that encode different isoforms.^[6]

See also

• Carboxypeptidase B

Further reading

• Bouma BN, Mosnier LO . Thrombin activatable fibrinolysis inhibitor (TAFI) at the interface between coagulation and fibrinolysis. . Pathophysiol. Haemost. Thromb. . 33 . 5–6 . 375–81 . 2005 . 15692247 . 10.1159/000083832 . free .
• Marinkovic DV, Marinkovic JN, Erdös EG, Robinson CJ . Purification of carboxypeptidase B from human pancreas . Biochem. J. . 163 . 2 . 253–60 . 1977 . 10.1042/bj1630253 . 17398 . 1164691 .
• Pascual R, Burgos FJ, Salva M . Purification and properties of five different forms of human procarboxypeptidases . Eur. J. Biochem. . 179 . 3 . 609–16 . 1989 . 2920728 . 10.1111/j.1432-1033.1989.tb14590.x . etal. free .
• Valnickova Z, Thogersen IB, Christensen S . Activated human plasma carboxypeptidase B is retained in the blood by binding to alpha2-macroglobulin and pregnancy zone protein . J. Biol. Chem. . 271 . 22 . 12937–43 . 1996 . 8662763 . 10.1074/jbc.271.22.12937 . etal. free .
• Bajzar L, Morser J, Nesheim M . TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex . J. Biol. Chem. . 271 . 28 . 16603–8 . 1996 . 8663147 . 10.1074/jbc.271.28.16603 . free .
• Vanhoof G, Wauters J, Schatteman K . The gene for human carboxypeptidase U (CPU)--a proposed novel regulator of plasminogen activation--maps to 13q14.11 . Genomics . 38 . 3 . 454–5 . 1997 . 8975730 . 10.1006/geno.1996.0656 . etal.
• Matsumoto A, Itoh K, Matsumoto R . A novel carboxypeptidase B that processes native beta-amyloid precursor protein is present in human hippocampus . Eur. J. Neurosci. . 12 . 1 . 227–38 . 2000 . 10651877 . 10.1046/j.1460-9568.2000.00908.x . 26058321 .
• Marx PF, Hackeng TM, Dawson PE . Inactivation of active thrombin-activable fibrinolysis inhibitor takes place by a process that involves conformational instability rather than proteolytic cleavage . J. Biol. Chem. . 275 . 17 . 12410–5 . 2000 . 10777524 . 10.1074/jbc.275.17.12410 . etal. free .
• Mosnier LO, Lisman T, van den Berg HM . The defective down regulation of fibrinolysis in haemophilia A can be restored by increasing the TAFI plasma concentration . Thromb. Haemost. . 86 . 4 . 1035–9 . 2002 . 10.1055/s-0037-1616530 . 11686321 . 4080586 . etal.
• Mosnier LO, Meijers JC, Bouma BN . The role of protein S in the activation of thrombin activatable fibrinolysis inhibitor (TAFI) and regulation of fibrinolysis . Thromb. Haemost. . 86 . 4 . 1040–6 . 2002 . 10.1055/s-0037-1616531 . 11686322 . 21500722 .
• Mosnier LO, Elisen MG, Bouma BN, Meijers JC . Protein C inhibitor regulates the thrombin-thrombomodulin complex in the up- and down regulation of TAFI activation . Thromb. Haemost. . 86 . 4 . 1057–64 . 2002 . 10.1055/s-0037-1616533 . 11686324 . 32258311 .
• Morange PE, Aillaud MF, Nicaud V . Ala147Thr and C+1542G polymorphisms in the TAFI gene are not associated with a higher risk of venous thrombosis in FV Leiden carriers . Thromb. Haemost. . 86 . 6 . 1583–4 . 2002 . 10.1055/s-0037-1616769 . 11776333 . 30051401 . etal.
• Schneider M, Nagashima M, Knappe S . Amino acid residues in the P6-P'3 region of thrombin-activable fibrinolysis inhibitor (TAFI) do not determine the thrombomodulin dependence of TAFI activation . J. Biol. Chem. . 277 . 12 . 9944–51 . 2002 . 11786552 . 10.1074/jbc.M111685200 . etal. free .
• Koschinsky ML, Boffa MB, Nesheim ME . Association of a single nucleotide polymorphism in CPB2 encoding the thrombin-activable fibrinolysis inhibitor (TAF1) with blood pressure . Clin. Genet. . 60 . 5 . 345–9 . 2002 . 11903334 . 10.1034/j.1399-0004.2001.600504.x . 86724521 . etal.
• Yano Y, Gabazza EC, Hori Y . Association between plasma thrombin-activatable fibrinolysis inhibitor levels and activated protein C in normotensive type 2 diabetic patients . Diabetes Care . 25 . 7 . 1245–6 . 2002 . 12087030 . 10.2337/diacare.25.7.1245 . etal. free .
• Antovic JP, Blombäck M . Thrombin-activatable fibrinolysis inhibitor antigen and TAFI activity in patients with APC resistance caused by factor V Leiden mutation . Thromb. Res. . 106 . 1 . 59–62 . 2003 . 12165290 . 10.1016/S0049-3848(02)00072-5 .

Notes and References

1. Eaton DL, Malloy BE, Tsai SP, Henzel W, Drayna D . Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma . J Biol Chem . 266 . 32 . 21833–8 . Dec 1991 . 10.1016/S0021-9258(18)54713-X . 1939207 . free .
2. Tsai SP, Drayna D . The gene encoding human plasma carboxypeptidase B (CPB2) resides on chromosome 13 . Genomics . 14 . 2 . 549–50 . Dec 1992 . 1427879 . 10.1016/S0888-7543(05)80268-X.
3. Kaushansky K, Lichtman M, Beutler E, Kipps T, Prchal J, Seligsohn U. (2010; edition 8: pages 1833-1834 and 2040-2041) Williams Hematology. McGraw-Hill.
4. Zhao L, Morser J, Bajzar L, Nesheim M, Nagashima M . Identification and characterization of two thrombin-activatable fibrinolysis inhibitor isoforms . Thromb. Haemost. . 80 . 6 . 949–55 . December 1998 . 10.1055/s-0037-1615394 . 9869166 . 1803078 .
5. Boffa MB, Reid TS, Joo E, Nesheim ME, Koschinsky ML . Characterization of the gene encoding human TAFI (thrombin-activable fibrinolysis inhibitor; plasma procarboxypeptidase B) . Biochemistry . 38 . 20 . 6547–58 . May 1999 . 10350473 . 10.1021/bi990229v .
6. Web site: Entrez Gene: CPB2 carboxypeptidase B2 (plasma).