Carboxipeptidase B2

A carboxipeptidase B2 (CPB2) tamén chamada carboxipeptidase U (CPU), carboxipeptidase B do plasma (pCPB), ou inhibidor da fibrinólise activable pola trombina (TAFI)^[1] é un encima que intervén na coagulación do sangue, que nos humanos está codificado polo xene CPB2 situado no cromosoma 13.^[2][3]

Estrutura cristalina do TAFI (PDB 3D66).

Función

O CPB2 sintetízase no fígado^[4] e circula no plasma como un cimóxeno unido ao plasminóxeno (procarboxipeptidase B2)^[5]. Cando é activado por proteólise no residuo Arg92 polo complexo trombina/trombomodulina, adquire actividade de carboxipeptidase. O CPB2 activado reduce a fibrinólise ao eliminar os residuos C-terminais da fibrina que son importantes para a unión e activación do plasminóxeno.^[6][7]

As carboxipeptidases son encimas que hidrolizan enlaces peptídicos no extremo C-terminal. A familia das carboxipeptidases comprende metalocarboxipeptidases, serina carboxipeptidases e cisteina carboxipeptidases. Segundo a súa especificidade de substrato, estes encimas denomínanse carboxipeptidases A (que clivan residuos alifáticos) ou carboxipeptidases B (que clivan aminoácidos básicos). A CPB2 é unha metalocarboxipeptidase. A proteína codificada por este xene é activada pola trombina e actúa sobre os substratos típicos das carboxipeptidases B. Unha vez activada pola trombina, a proteína madura regula á baixa a fibrinólise.^[8]

Fibrinólise simplificada. As frechas azuis indican estimulación, e as vermellas inhibición.

Isocimas

Neste xene e na súa rexión promotora describíronse polimorfismos. As análises de datos de secuencia dispoñibles indican que hai variantes de splicing que codifican diferentes isoformas (ver isoencima).^[8]

Notas

1. OMIM
2. Eaton DL, Malloy BE, Tsai SP, Henzel W, Drayna D (1991). "Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma". J Biol Chem 266 (32): 21833–8. PMID 1939207.
3. Tsai SP, Drayna D (1992). "The gene encoding human plasma carboxypeptidase B (CPB2) resides on chromosome 13". Genomics 14 (2): 549–50. PMID 1427879. doi:10.1016/S0888-7543(05)80268-X.
4. 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 978-0-07-162151-9
5. Bouma BN, Marx PF, Mosnier LO, Meijers JC. Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U). Thromb Res. 2001 Mar 1;101(5):329-54. PMID 11297751
6. Zhao L, Morser J, Bajzar L, Nesheim M, Nagashima M (1998). "Identification and characterization of two thrombin-activatable fibrinolysis inhibitor isoforms". Thromb. Haemost. 80 (6): 949–55. PMID 9869166.
7. Boffa MB, Reid TS, Joo E, Nesheim ME, Koschinsky ML (1999). "Characterization of the gene encoding human TAFI (thrombin-activable fibrinolysis inhibitor; plasma procarboxypeptidase B)". Biochemistry 38 (20): 6547–58. PMID 10350473. doi:10.1021/bi990229v.
8. "Entrez Gene: CPB2 carboxypeptidase B2 (plasma)".

Véxase tamén

Outros artigos

• Carboxipeptidase B
• Fibrinólise

Bibliografía

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• 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. PMID 2920728. doi:10.1111/j.1432-1033.1989.tb14590.x.
• 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. PMID 8662763. doi:10.1074/jbc.271.22.12937.
• 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. PMID 8663147. doi:10.1074/jbc.271.28.16603.
• 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. PMID 8975730. doi:10.1006/geno.1996.0656.
• 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. PMID 10651877. doi:10.1046/j.1460-9568.2000.00908.x.
• 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. PMID 10777524. doi:10.1074/jbc.275.17.12410.
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• 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. PMID 11786552. doi:10.1074/jbc.M111685200.
• 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. PMID 11903334. doi:10.1034/j.1399-0004.2001.600504.x.
• 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. PMID 12087030. doi:10.2337/diacare.25.7.1245.
• 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. PMID 12165290. doi:10.1016/S0049-3848(02)00072-5.