释义 |
- Function
- Isozymes
- See also
- References
- Further reading
{{redirect|TAFI||TAFI (disambiguation)}}{{Infobox_gene}}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]FunctionCPB2 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]IsozymesPolymorphisms have been described for this gene and its promoter region. Available sequence data analyses indicate splice variants that encode different isoforms.[6] See alsoReferences1. ^{{cite journal |vauthors=Eaton DL, Malloy BE, Tsai SP, Henzel W, Drayna D |title=Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma |journal=J Biol Chem |volume=266 |issue=32 |pages=21833–8 |date=Dec 1991 |pmid=1939207 |pmc= |doi=}} 2. ^{{cite journal |vauthors=Tsai SP, Drayna D |title=The gene encoding human plasma carboxypeptidase B (CPB2) resides on chromosome 13 |journal=Genomics |volume=14 |issue=2 |pages=549–50 |date=Dec 1992 |pmid=1427879 |pmc= |doi=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. {{ISBN|978-0071621519}} 4. ^{{cite journal |vauthors=Zhao L, Morser J, Bajzar L, Nesheim M, Nagashima M | title = Identification and characterization of two thrombin-activatable fibrinolysis inhibitor isoforms | journal = Thromb. Haemost. | volume = 80 | issue = 6 | pages = 949–55 |date=December 1998 | pmid = 9869166 | doi = | url = }} 5. ^{{cite journal |vauthors=Boffa MB, Reid TS, Joo E, Nesheim ME, Koschinsky ML | title = Characterization of the gene encoding human TAFI (thrombin-activable fibrinolysis inhibitor; plasma procarboxypeptidase B) | journal = Biochemistry | volume = 38 | issue = 20 | pages = 6547–58 |date=May 1999 | pmid = 10350473 | doi = 10.1021/bi990229v | url = }} 6. ^1 {{cite web | title = Entrez Gene: CPB2 carboxypeptidase B2 (plasma)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1361| accessdate = }}
Further reading{{refbegin | 2}}- {{cite journal |vauthors=Bouma BN, Mosnier LO |title=Thrombin activatable fibrinolysis inhibitor (TAFI) at the interface between coagulation and fibrinolysis. |journal=Pathophysiol. Haemost. Thromb. |volume=33 |issue= 5–6 |pages= 375–81 |year= 2005 |pmid= 15692247 |doi= 10.1159/000083832 }}
- {{cite journal |vauthors=Marinkovic DV, Marinkovic JN, Erdös EG, Robinson CJ |title=Purification of carboxypeptidase B from human pancreas |journal=Biochem. J. |volume=163 |issue= 2 |pages= 253–60 |year= 1977 |pmid= 17398 |doi= | pmc=1164691 }}
- {{cite journal |vauthors=Pascual R, Burgos FJ, Salva M |title=Purification and properties of five different forms of human procarboxypeptidases |journal=Eur. J. Biochem. |volume=179 |issue= 3 |pages= 609–16 |year= 1989 |pmid= 2920728 |doi=10.1111/j.1432-1033.1989.tb14590.x |display-authors=etal}}
- {{cite journal |vauthors=Valnickova Z, Thogersen IB, Christensen S |title=Activated human plasma carboxypeptidase B is retained in the blood by binding to alpha2-macroglobulin and pregnancy zone protein |journal=J. Biol. Chem. |volume=271 |issue= 22 |pages= 12937–43 |year= 1996 |pmid= 8662763 |doi=10.1074/jbc.271.22.12937 |display-authors=etal}}
- {{cite journal |vauthors=Bajzar L, Morser J, Nesheim M |title=TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex |journal=J. Biol. Chem. |volume=271 |issue= 28 |pages= 16603–8 |year= 1996 |pmid= 8663147 |doi=10.1074/jbc.271.28.16603 }}
- {{cite journal |vauthors=Vanhoof G, Wauters J, Schatteman K |title=The gene for human carboxypeptidase U (CPU)--a proposed novel regulator of plasminogen activation--maps to 13q14.11 |journal=Genomics |volume=38 |issue= 3 |pages= 454–5 |year= 1997 |pmid= 8975730 |doi= 10.1006/geno.1996.0656 |display-authors=etal}}
- {{cite journal |vauthors=Matsumoto A, Itoh K, Matsumoto R |title=A novel carboxypeptidase B that processes native beta-amyloid precursor protein is present in human hippocampus |journal=Eur. J. Neurosci. |volume=12 |issue= 1 |pages= 227–38 |year= 2000 |pmid= 10651877 |doi=10.1046/j.1460-9568.2000.00908.x }}
- {{cite journal |vauthors=Marx PF, Hackeng TM, Dawson PE |title=Inactivation of active thrombin-activable fibrinolysis inhibitor takes place by a process that involves conformational instability rather than proteolytic cleavage |journal=J. Biol. Chem. |volume=275 |issue= 17 |pages= 12410–5 |year= 2000 |pmid= 10777524 |doi=10.1074/jbc.275.17.12410 |display-authors=etal}}
- {{cite journal |vauthors=Mosnier LO, Lisman T, van den Berg HM |title=The defective down regulation of fibrinolysis in haemophilia A can be restored by increasing the TAFI plasma concentration |journal=Thromb. Haemost. |volume=86 |issue= 4 |pages= 1035–9 |year= 2002 |pmid= 11686321 |doi= |display-authors=etal}}
- {{cite journal |vauthors=Mosnier LO, Meijers JC, Bouma BN |title=The role of protein S in the activation of thrombin activatable fibrinolysis inhibitor (TAFI) and regulation of fibrinolysis |journal=Thromb. Haemost. |volume=86 |issue= 4 |pages= 1040–6 |year= 2002 |pmid= 11686322 |doi= }}
- {{cite journal |vauthors=Mosnier LO, Elisen MG, Bouma BN, Meijers JC |title=Protein C inhibitor regulates the thrombin-thrombomodulin complex in the up- and down regulation of TAFI activation |journal=Thromb. Haemost. |volume=86 |issue= 4 |pages= 1057–64 |year= 2002 |pmid= 11686324 |doi= }}
- {{cite journal |vauthors=Morange PE, Aillaud MF, Nicaud V |title=Ala147Thr and C+1542G polymorphisms in the TAFI gene are not associated with a higher risk of venous thrombosis in FV Leiden carriers |journal=Thromb. Haemost. |volume=86 |issue= 6 |pages= 1583–4 |year= 2002 |pmid= 11776333 |doi= |display-authors=etal}}
- {{cite journal |vauthors=Schneider M, Nagashima M, Knappe S |title=Amino acid residues in the P6-P'3 region of thrombin-activable fibrinolysis inhibitor (TAFI) do not determine the thrombomodulin dependence of TAFI activation |journal=J. Biol. Chem. |volume=277 |issue= 12 |pages= 9944–51 |year= 2002 |pmid= 11786552 |doi= 10.1074/jbc.M111685200 |display-authors=etal}}
- {{cite journal |vauthors=Koschinsky ML, Boffa MB, Nesheim ME |title=Association of a single nucleotide polymorphism in CPB2 encoding the thrombin-activable fibrinolysis inhibitor (TAF1) with blood pressure |journal=Clin. Genet. |volume=60 |issue= 5 |pages= 345–9 |year= 2002 |pmid= 11903334 |doi=10.1034/j.1399-0004.2001.600504.x |display-authors=etal}}
- {{cite journal |vauthors=Yano Y, Gabazza EC, Hori Y |title=Association between plasma thrombin-activatable fibrinolysis inhibitor levels and activated protein C in normotensive type 2 diabetic patients |journal=Diabetes Care |volume=25 |issue= 7 |pages= 1245–6 |year= 2002 |pmid= 12087030 |doi=10.2337/diacare.25.7.1245 |display-authors=etal}}
- {{cite journal |vauthors=Antovic JP, Blombäck M |title=Thrombin-activatable fibrinolysis inhibitor antigen and TAFI activity in patients with APC resistance caused by factor V Leiden mutation |journal=Thromb. Res. |volume=106 |issue= 1 |pages= 59–62 |year= 2003 |pmid= 12165290 |doi=10.1016/S0049-3848(02)00072-5 }}
{{refend}}{{NLM content}}{{Proteases}}{{Coagulation}}{{DEFAULTSORT:Thrombin-Activatable Fibrinolysis Inhibitor}}{{Hydrolase-stub}} 1 : Fibrinolytic system |