- Carboxypeptidase B2
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Carboxypeptidase B2 (plasma)
Rendering based on PDB 3D66.Available structures PDB 3D66, 3D67, 3D68, 3LMS Identifiers Symbols CPB2; CPU; PCPB; TAFI External IDs OMIM: 603101 MGI: 1891837 HomoloGene: 55610 GeneCards: CPB2 Gene EC number 3.4.17.20 Gene Ontology Molecular function • metallocarboxypeptidase activity
• peptidase activity
• metallopeptidase activity
• zinc ion binding
• metal ion bindingCellular component • extracellular region
• extracellular spaceBiological process • proteolysis
• blood coagulation
• response to heat
• response to drug
• negative regulation of fibrinolysisSources: Amigo / QuickGO RNA expression pattern More reference expression data Orthologs Species Human Mouse Entrez 1361 56373 Ensembl ENSG00000080618 ENSMUSG00000021999 UniProt Q96IY4 Q9JHH6 RefSeq (mRNA) NM_001872.3 NM_019775.3 RefSeq (protein) NP_001863.2 NP_062749.2 Location (UCSC) Chr 13:
46.63 – 46.68 MbChr 14:
75.64 – 75.68 MbPubMed search [1] [2] Carboxypeptidase B2 (CPB2) also known as carboxypeptidase U (CPU), plasma carboxypeptidase B (pCPB), or thrombin-activable fibrinolysis inhibitor (TAFI) is an enzyme that in humans is encoded by the CPB2 gene.[1][2]
Contents
Function
CPB2 is synthesized by the liver 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.[3][4]
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.[5]
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.[5]
See also
References
- ^ 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. PMID 1939207.
- ^ 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.
- ^ 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. PMID 9869166.
- ^ 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.
- ^ a b "Entrez Gene: CPB2 carboxypeptidase B2 (plasma)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1361.
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. PMC 1164691. PMID 17398. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1164691.
- 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.
- 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. PMID 11686321.
- 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. PMID 11686322.
- 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. PMID 11686324.
- 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. PMID 11776333.
- 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.
- 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.
Hydrolase: proteases (EC 3.4) 3.4.11-19: Exopeptidase Dipeptidyl peptidase (Cathepsin C, Dipeptidyl peptidase-4) · Tripeptidyl peptidase (Tripeptidyl peptidase I, Tripeptidyl peptidase II)Other/ungrouped3.4.21-24: Endopeptidase Serine proteases · Cysteine protease · Aspartic acid protease · Metalloendopeptidases
Other/ungrouped: Amyloid precursor protein secretase (Alpha secretase, Beta-secretase 1, Beta-secretase 2, Gamma secretase)3.4.99: Unknown Proteins: coagulation Coagulation factors Coagulation inhibitors Thrombolysis/fibrinolysis This hydrolase article is a stub. You can help Wikipedia by expanding it.