Carboxypeptidase B2

"TAFI" redirects here. For other uses, see TAFI (disambiguation).

CPB2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3D66, 3D67, 3D68, 3LMS, 4P10, 5HVG, 5HVH, 5HVF
Identifiers
Aliases	CPB2, CPU, PCPB, TAFI, carboxypeptidase B2
External IDs	OMIM: 603101; MGI: 1891837; HomoloGene: 55610; GeneCards: CPB2; OMA:CPB2 - orthologs
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q14.13 Start 46,053,186 bp[1] End 46,105,033 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 D3 Start 75,479,727 bp[2] End 75,520,995 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver lower lobe of lung corpus epididymis tail of epididymis right lung testicle gallbladder upper lobe of lung upper lobe of left lung visceral pleura Top expressed in left lobe of liver primary oocyte zygote secondary oocyte human fetus fetal liver hematopoietic progenitor cell urethra sexually immature organism morula embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function metal ion binding peptidase activity hydrolase activity zinc ion binding carboxypeptidase activity metallopeptidase activity metallocarboxypeptidase activity Cellular component extracellular exosome extracellular space extracellular region Biological process blood coagulation negative regulation of hepatocyte proliferation positive regulation of extracellular matrix constituent secretion liver regeneration cellular response to glucose stimulus negative regulation of plasminogen activation negative regulation of fibrinolysis response to heat hemostasis proteolysis fibrinolysis regulation of complement activation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1361 56373 Ensembl ENSG00000080618 ENSMUSG00000021999 UniProt Q96IY4 Q9JHH6 RefSeq (mRNA) NM_016413 NM_001278541 NM_001872 NM_019775 RefSeq (protein) NP_001265470 NP_001863 NP_062749 Location (UCSC) Chr 13: 46.05 – 46.11 Mb Chr 14: 75.48 – 75.52 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[5][6]

Function

CPB2 is synthesized by the liver^[7] 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.^[8][9]

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.^[10]

Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

Isozymes

Polymorphisms have been described for this gene and its promoter region. Available sequence data analyses indicate splice variants that encode different isoforms.^[10]

See also

• Carboxypeptidase B

References

1. GRCh38: Ensembl release 89: ENSG00000080618 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021999 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Eaton DL, Malloy BE, Tsai SP, Henzel W, Drayna D (Dec 1991). "Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma". J Biol Chem. 266 (32): 21833–8. doi:10.1016/S0021-9258(18)54713-X. PMID 1939207.
6. Tsai SP, Drayna D (Dec 1992). "The gene encoding human plasma carboxypeptidase B (CPB2) resides on chromosome 13". Genomics. 14 (2): 549–50. doi:10.1016/S0888-7543(05)80268-X. PMID 1427879.
7. 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. ISBN 978-0071621519
8. Zhao L, Morser J, Bajzar L, Nesheim M, Nagashima M (December 1998). "Identification and characterization of two thrombin-activatable fibrinolysis inhibitor isoforms". Thromb. Haemost. 80 (6): 949–55. doi:10.1055/s-0037-1615394. PMID 9869166. S2CID 1803078.
9. Boffa MB, Reid TS, Joo E, Nesheim ME, Koschinsky ML (May 1999). "Characterization of the gene encoding human TAFI (thrombin-activable fibrinolysis inhibitor; plasma procarboxypeptidase B)". Biochemistry. 38 (20): 6547–58. doi:10.1021/bi990229v. PMID 10350473.
10. "Entrez Gene: CPB2 carboxypeptidase B2 (plasma)".

Further reading

• Bouma BN, Mosnier LO (2005). "Thrombin activatable fibrinolysis inhibitor (TAFI) at the interface between coagulation and fibrinolysis". Pathophysiol. Haemost. Thromb. 33 (5–6): 375–81. doi:10.1159/000083832. PMID 15692247.
• Marinkovic DV, Marinkovic JN, Erdös EG, Robinson CJ (1977). "Purification of carboxypeptidase B from human pancreas". Biochem. J. 163 (2): 253–60. doi:10.1042/bj1630253. PMC 1164691. PMID 17398.
• Pascual R, Burgos FJ, Salva M, et al. (1989). "Purification and properties of five different forms of human procarboxypeptidases". Eur. J. Biochem. 179 (3): 609–16. doi:10.1111/j.1432-1033.1989.tb14590.x. PMID 2920728.
• Valnickova Z, Thogersen IB, Christensen S, et al. (1996). "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. doi:10.1074/jbc.271.22.12937. PMID 8662763.
• Bajzar L, Morser J, Nesheim M (1996). "TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex". J. Biol. Chem. 271 (28): 16603–8. doi:10.1074/jbc.271.28.16603. PMID 8663147.
• Vanhoof G, Wauters J, Schatteman K, et al. (1997). "The gene for human carboxypeptidase U (CPU)--a proposed novel regulator of plasminogen activation--maps to 13q14.11". Genomics. 38 (3): 454–5. doi:10.1006/geno.1996.0656. PMID 8975730.
• Matsumoto A, Itoh K, Matsumoto R (2000). "A novel carboxypeptidase B that processes native beta-amyloid precursor protein is present in human hippocampus". Eur. J. Neurosci. 12 (1): 227–38. doi:10.1046/j.1460-9568.2000.00908.x. PMID 10651877. S2CID 26058321.
• Marx PF, Hackeng TM, Dawson PE, et al. (2000). "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. doi:10.1074/jbc.275.17.12410. PMID 10777524.
• Mosnier LO, Lisman T, van den Berg HM, et al. (2002). "The defective down regulation of fibrinolysis in haemophilia A can be restored by increasing the TAFI plasma concentration". Thromb. Haemost. 86 (4): 1035–9. doi:10.1055/s-0037-1616530. PMID 11686321. S2CID 4080586.
• Mosnier LO, Meijers JC, Bouma BN (2002). "The role of protein S in the activation of thrombin activatable fibrinolysis inhibitor (TAFI) and regulation of fibrinolysis". Thromb. Haemost. 86 (4): 1040–6. doi:10.1055/s-0037-1616531. PMID 11686322. S2CID 21500722.
• Mosnier LO, Elisen MG, Bouma BN, Meijers JC (2002). "Protein C inhibitor regulates the thrombin-thrombomodulin complex in the up- and down regulation of TAFI activation". Thromb. Haemost. 86 (4): 1057–64. doi:10.1055/s-0037-1616533. PMID 11686324. S2CID 32258311.
• Morange PE, Aillaud MF, Nicaud V, et al. (2002). "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. doi:10.1055/s-0037-1616769. PMID 11776333. S2CID 30051401.
• Schneider M, Nagashima M, Knappe S, et al. (2002). "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. doi:10.1074/jbc.M111685200. PMID 11786552.
• Koschinsky ML, Boffa MB, Nesheim ME, et al. (2002). "Association of a single nucleotide polymorphism in CPB2 encoding the thrombin-activable fibrinolysis inhibitor (TAF1) with blood pressure". Clin. Genet. 60 (5): 345–9. doi:10.1034/j.1399-0004.2001.600504.x. PMID 11903334. S2CID 86724521.
• Yano Y, Gabazza EC, Hori Y, et al. (2002). "Association between plasma thrombin-activatable fibrinolysis inhibitor levels and activated protein C in normotensive type 2 diabetic patients". Diabetes Care. 25 (7): 1245–6. doi:10.2337/diacare.25.7.1245. PMID 12087030.
• Antovic JP, Blombäck M (2003). "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. doi:10.1016/S0049-3848(02)00072-5. PMID 12165290.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.