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Gene Review

CPB2  -  carboxypeptidase B2 (plasma)

Homo sapiens

Synonyms: CPU, Carboxypeptidase B2, Carboxypeptidase U, PCPB, Plasma carboxypeptidase B, ...
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Disease relevance of CPB2


Psychiatry related information on CPB2

  • We estimated the service time for each queue of the CPU, database, and network, and measured the response time and possible bottlenecks of the model [6].

High impact information on CPB2

  • Purified carboxypeptidase N, which is constitutively active, and plasma carboxypeptidase B, which circulates as a zymogen, were both capable of significantly reducing plasminogen binding to cells [7].
  • To get a better insight into the identification of QTNs, a transethnic haplotype analysis contrasting 2 populations of African and European subjects was performed using 13 CPB2 polymorphisms [8].
  • However, the strong linkage disequilibrium (LD) between CPB2 polymorphisms in European whites did not allow one to distinguish which polymorphisms could be the putative QTNs [8].
  • A phylogenetic study suggested that these 3 polymorphisms occurred before the period of migration "out of Africa." Although this transethnic comparison contributed to better map the putative CPB2 QTNs, further studies are required to clarify the role of the promoter region [8].
  • We prospectively followed up 600 patients with a first VTE and evaluated the thrombin-activatable fibrinolysis inhibitor (TAFI) as a risk factor for recurrence [9].

Chemical compound and disease context of CPB2


Biological context of CPB2


Anatomical context of CPB2


Associations of CPB2 with chemical compounds

  • The tandemly arranged CPB genes of Leishmania mexicana are polycistronically transcribed and encode cysteine proteases that are differentially stage-specific; CPB1 and CPB2 are expressed predominantly in metacyclics, whereas CPB3-CPB18 are expressed mainly in amastigotes [14].
  • In addition, TAFIa has been shown to be capable of removing the carboxyl-terminal arginine residues from the anaphylatoxins and bradykinin, thus implying a role for the TAFI pathway in the vascular responses to inflammation [1].
  • Treatment with the synthetic glucocorticoid dexamethasone resulted in a 2-fold increase of both TAFI mRNA levels and promoter activity [1].
  • CPU removes C-terminal lysine residues that act as plasminogen binding sites from partially degraded fibrin, thereby down-regulating plasminogen activation and fibrinolysis [20].
  • Thrombin-activatable fibrinolysis inhibitor (TAFI), also known as procarboxypeptidase U or plasma procarboxypeptidase B, is a relatively recently described plasma glycoprotein synthesised in the liver [3].
  • When other positively charged surface residues of TAFI (Lys-133, Lys-211, Lys-212, Arg-220, Lys-240, or Arg-275) were mutated to alanine, the catalytic efficiencies for TAFI activation with TM decreased by 1.7-2.7-fold [21].

Physical interactions of CPB2


Regulatory relationships of CPB2

  • A newly developed functional assay demonstrated that HUVECs potentiate the thrombin-catalyzed, TM-dependent formation of activated TAFI [17].
  • Plasminogen-binding sites (C-terminal lysines) on the surface of a plasmin-treated fibrin clot were eliminated within 1-3 min by plasma with maximally activated pCPB, as studied in a recently described model involving fluorescence microscopy [23].
  • Thrombus lysis by uPA, scuPA and tPA is regulated by plasma TAFI [4].
  • Thrombin-activable fibrinolysis inhibitor (TAFI) is a recently described plasma zymogen that can be activated by thrombin to an enzyme with carboxypeptidase B-like activity [17].
  • Provided that thrombomodulin EGF-like domain 3 was present, TAFI competitively inhibited protein C activation catalyzed by the thrombin-thrombomodulin complex [24].

Other interactions of CPB2

  • In this work, the effects of both soluble and cellular forms of TM on TAFI activation-dependent suppression of fibrinolysis were investigated [17].
  • In the presence of TM (and a concomitant pro-pCPB activation), lysis was slow and was not accompanied by accumulation of plasminogen on the fibers [23].
  • A significant negative correlation was found between TAFI levels and APCR (r = -0.478, p <0.001), APCRV (r = -0.598; p <0.001), PS (r = -0.490, P <0.001) and PC (r = -0.198, p = 0.02) [25].
  • Our threshold-based hypothesis indicates that the time course of proCPU activation, the stability of CPU and the t-PA concentration all play a crucial role in determining the result of the in vitro clot lysis experiment [26].
  • The CPB2 gene encoding TAFI is a candidate gene for blood pressure [16].

Analytical, diagnostic and therapeutic context of CPB2


  1. Acute phase mediators modulate thrombin-activable fibrinolysis inhibitor (TAFI) gene expression in HepG2 cells. Boffa, M.B., Hamill, J.D., Maret, D., Brown, D., Scott, M.L., Nesheim, M.E., Koschinsky, M.L. J. Biol. Chem. (2003) [Pubmed]
  2. Characterization of the gene encoding human TAFI (thrombin-activable fibrinolysis inhibitor; plasma procarboxypeptidase B). Boffa, M.B., Reid, T.S., Joo, E., Nesheim, M.E., Koschinsky, M.L. Biochemistry (1999) [Pubmed]
  3. Thrombin-activatable fibrinolysis inhibitor antigen and TAFI activity in patients with APC resistance caused by factor V Leiden mutation. Antovic, J.P., Blombäck, M. Thromb. Res. (2002) [Pubmed]
  4. Thrombus lysis by uPA, scuPA and tPA is regulated by plasma TAFI. Mutch, N.J., Moore, N.R., Wang, E., Booth, N.A. J. Thromb. Haemost. (2003) [Pubmed]
  5. Dyslipidemias and fibrinolysis. Puccetti, L., Bruni, F., Pasqui, A.L., Pastorelli, M., Bova, G., Cercignani, M., Palazzuoli, A., Auteri, A. Italian heart journal : official journal of the Italian Federation of Cardiology. (2002) [Pubmed]
  6. Performance analysis of a medical record exchanges model. Huang, E.W., Liou, D.M. IEEE transactions on information technology in biomedicine : a publication of the IEEE Engineering in Medicine and Biology Society (2007) [Pubmed]
  7. Plasma carboxypeptidases as regulators of the plasminogen system. Redlitz, A., Tan, A.K., Eaton, D.L., Plow, E.F. J. Clin. Invest. (1995) [Pubmed]
  8. Fine mapping of quantitative trait nucleotides underlying thrombin-activatable fibrinolysis inhibitor antigen levels by a transethnic study. Frère, C., Tregouet, D.A., Morange, P.E., Saut, N., Kouassi, D., Juhan-Vague, I., Tiret, L., Alessi, M.C. Blood (2006) [Pubmed]
  9. Thrombin-activatable fibrinolysis inhibitor and the risk for recurrent venous thromboembolism. Eichinger, S., Schönauer, V., Weltermann, A., Minar, E., Bialonczyk, C., Hirschl, M., Schneider, B., Quehenberger, P., Kyrle, P.A. Blood (2004) [Pubmed]
  10. Thrombin activatable fibrinolysis inhibitor, a potential regulator of vascular inflammation. Myles, T., Nishimura, T., Yun, T.H., Nagashima, M., Morser, J., Patterson, A.J., Pearl, R.G., Leung, L.L. J. Biol. Chem. (2003) [Pubmed]
  11. The effects of short-term raloxifene therapy on fibrinolysis markers: TAFI, tPA, and PAI-1. Ozeren, M., Karahan, S.C., Ozgur, M., Eminagaoglu, S., Unsal, M., Baytan, S., Bozkaya, H. Acta obstetricia et gynecologica Scandinavica. (2005) [Pubmed]
  12. The effect of anthracycline-based (epirubicin) adjuvant chemotherapy on plasma TAFI and PAI-1 levels in operable breast cancer. Demirkan, B., Ozcan, M.A., Glu, A.A., Yüksel, F., Undar, B., Alakavuklar, M. Clin. Appl. Thromb. Hemost. (2006) [Pubmed]
  13. Elevated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Overt and Subclinical Hypothyroid Patients Were Reduced by Levothyroxine Replacement. Akinci, B., Comlekci, A., Ali Ozcan, M., Demir, T., Yener, S., Demirkan, F., Yuksel, F., Yesil, S. Endocr. J. (2007) [Pubmed]
  14. The stage-regulated expression of Leishmania mexicana CPB cysteine proteases is mediated by an intercistronic sequence element. Brooks, D.R., Denise, H., Westrop, G.D., Coombs, G.H., Mottram, J.C. J. Biol. Chem. (2001) [Pubmed]
  15. The gene encoding human plasma carboxypeptidase B (CPB2) resides on chromosome 13. Tsai, S.P., Drayna, D. Genomics (1992) [Pubmed]
  16. Association of a single nucleotide polymorphism in CPB2 encoding the thrombin-activable fibrinolysis inhibitor (TAF1) with blood pressure. Koschinsky, M.L., Boffa, M.B., Nesheim, M.E., Zinman, B., Hanley, A.J., Harris, S.B., Cao, H., Hegele, R.A. Clin. Genet. (2001) [Pubmed]
  17. Both cellular and soluble forms of thrombomodulin inhibit fibrinolysis by potentiating the activation of thrombin-activable fibrinolysis inhibitor. Bajzar, L., Nesheim, M., Morser, J., Tracy, P.B. J. Biol. Chem. (1998) [Pubmed]
  18. Thrombin-activatable fibrinolysis inhibitor (TAFI): a novel predictor of angiographic coronary restenosis. Lau, H.K., Segev, A., Hegele, R.A., Sparkes, J.D., Teitel, J.M., Chisholm, R.J., Strauss, B.H. Thromb. Haemost. (2003) [Pubmed]
  19. Weak and non-independent association between plasma TAFI antigen levels and the insulin resistance syndrome. Aubert, H., Frère, C., Aillaud, M.F., Morange, P.E., Juhan-Vague, I., Alessi, M.C. J. Thromb. Haemost. (2003) [Pubmed]
  20. Plasma procarboxypeptidase U in men with symptomatic coronary artery disease. Silveira, A., Schatteman, K., Goossens, F., Moor, E., Scharpé, S., Strömqvist, M., Hendriks, D., Hamsten, A. Thromb. Haemost. (2000) [Pubmed]
  21. The roles of selected arginine and lysine residues of TAFI (Pro-CPU) in its activation to TAFIa by the thrombin-thrombomodulin complex. Wu, C., Kim, P.Y., Manuel, R., Seto, M., Whitlow, M., Nagashima, M., Morser, J., Gils, A., Declerck, P., Nesheim, M.E. J. Biol. Chem. (2009) [Pubmed]
  22. Protein C inhibitor regulates the thrombin-thrombomodulin complex in the up- and down regulation of TAFI activation. Mosnier, L.O., Elisen, M.G., Bouma, B.N., Meijers, J.C. Thromb. Haemost. (2001) [Pubmed]
  23. On the mechanism of the antifibrinolytic activity of plasma carboxypeptidase B. Sakharov, D.V., Plow, E.F., Rijken, D.C. J. Biol. Chem. (1997) [Pubmed]
  24. Activation of thrombin-activable fibrinolysis inhibitor requires epidermal growth factor-like domain 3 of thrombomodulin and is inhibited competitively by protein C. Kokame, K., Zheng, X., Sadler, J.E. J. Biol. Chem. (1998) [Pubmed]
  25. Thrombin activatable fibrinolysis inhibitor and its fibrinolytic effect in normal pregnancy. Mousa, H.A., Downey, C., Alfirevic, Z., Toh, C.H. Thromb. Haemost. (2004) [Pubmed]
  26. Carboxypeptidase U (TAFIa) prevents lysis from proceeding into the propagation phase through a threshold-dependent mechanism. Leurs, J., Nerme, V., Sim, Y., Hendriks, D. J. Thromb. Haemost. (2004) [Pubmed]
  27. Low degree of activation of circulating neutrophils determined by flow cytometry during cardiac surgery with cardiopulmonary bypass. Tárnok, A., Bocsi, J., Rössler, H., Schlykow, V., Schneider, P., Hambsch, J. Cytometry. (2001) [Pubmed]
  28. Inactivation of active thrombin-activable fibrinolysis inhibitor takes place by a process that involves conformational instability rather than proteolytic cleavage. Marx, P.F., Hackeng, T.M., Dawson, P.E., Griffin, J.H., Meijers, J.C., Bouma, B.N. J. Biol. Chem. (2000) [Pubmed]
  29. Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis. Colucci, M., Binetti, B.M., Branca, M.G., Clerici, C., Morelli, A., Semeraro, N., Gresele, P. Hepatology (2003) [Pubmed]
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