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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2012/06/05 16:37:35」(JST)
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Carboxypeptidase B2 (plasma) |
Rendering based on PDB 3D66. |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
3D66, 3D67, 3D68, 3LMS
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Identifiers |
Symbols |
CPB2; CPU; PCPB; TAFI |
External IDs |
OMIM: 603101 MGI: 1891837 HomoloGene: 55610 ChEMBL: 3419 GeneCards: CPB2 Gene |
EC number |
3.4.17.20 |
Gene Ontology |
Molecular function |
• metallocarboxypeptidase activity
• peptidase activity
• metallopeptidase activity
• zinc ion binding
• metal ion binding
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Cellular component |
• extracellular region
• extracellular space
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Biological process |
• proteolysis
• blood coagulation
• metabolic process
• response to heat
• response to drug
• negative regulation of fibrinolysis
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Sources: Amigo / QuickGO |
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RNA expression pattern |
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More reference expression data |
Orthologs |
Species |
Human |
Mouse |
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Entrez |
1361 |
56373 |
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Ensembl |
ENSG00000080618 |
ENSMUSG00000021999 |
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UniProt |
Q96IY4 |
Q9JHH6 |
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RefSeq (mRNA) |
NM_001872.3 |
NM_019775.3 |
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RefSeq (protein) |
NP_001863.2 |
NP_062749.2 |
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Location (UCSC) |
Chr 13:
46.63 – 46.68 Mb |
Chr 14:
75.64 – 75.68 Mb |
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PubMed search |
[1] |
[2] |
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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 CPB2 gene.[1][2]
Contents
- 1 Function
- 2 Isozymes
- 3 See also
- 4 References
- 5 Further reading
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Function
CPB2 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]
Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.
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Isozymes
Polymorphisms have been described for this gene and its promoter region. Available sequence data analyses indicate splice variants that encode different isoforms.[6]
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.
- ^ 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
- ^ 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. //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)
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3.4.11-19: Exopeptidase |
3.4.11
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Aminopeptidase (Alanine, Arginyl, Aspartyl, Cystinyl, Leucyl, Glutamyl, Methionyl (1, 2), O)
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3.4.13
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Dipeptidase (1, 2, 3)
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3.4.14
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Dipeptidyl peptidase (Cathepsin C, Dipeptidyl peptidase-4) · Tripeptidyl peptidase (Tripeptidyl peptidase I, Tripeptidyl peptidase II)
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3.4.15
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Angiotensin-converting enzyme
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3.4.16
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Serine type carboxypeptidases: Cathepsin A · DD-transpeptidase
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3.4.17
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Metallocarboxypeptidases: Carboxypeptidase (A, A2, B, C, E, Glutamate II)
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Other/ungrouped
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Metalloexopeptidase
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3.4.21-24: 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)
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3.4.99: Unknown |
Staphylokinase
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- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 2.7.10
- 2.7.11-12
- 3.1
- 3.1.3.48
- 3.4.21
- 4.1
- 5.1
- 6.1-3
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Proteins: coagulation
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Coagulation factors |
Primary hemostasis
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vWF
platelet membrane glycoproteins: Ib (A, B, IX) · IIb/IIIa (IIb, IIIa) · VI
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Intrinsic pathway
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HMWK/Bradykinin · Prekallikrein/Kallikrein · XII "Hageman"
XI · IX · VIII
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Extrinsic pathway
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III "Tissue factor" · VII
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Common pathway
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X · V · II "(Pro)thrombin" · I "Fibrin" · Fibrinogen (FGA, FGG)
XIII
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Coagulation inhibitors |
Antithrombin (inhibits II, IX, X, XI, XII) · Protein C (inhibits V, VIII)/Protein S (cofactor for protein C) · Protein Z (inhibits X) · ZPI (inhibits X, XI) · TFPI (inhibits III)
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Thrombolysis/fibrinolysis |
Plasmin · tPA/urokinase · PAI-1/2 · α2-AP · α2-macroglobulin · TAFI
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cell/phys (coag, heme, immu, gran), csfs
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rbmg/mogr/tumr/hist, sysi/epon, btst
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drug (B1/2/3+5+6), btst, trns
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UpToDate Contents
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English Journal
- Number of metabolic syndrome risk parameters associated with TAFIa/ai antigen levels.
- Gunes F, Akbal E, Asik M, Sen H, Binnetoglu E, Kizilgun M, Ozbek M.SourceaDepartment of Internal Medicine bDepartment of Gastroenterology cDepartment of Endocrinology, Çanakkale Onsekiz Mart University, Çanakkale dDepartment of Medical Biochemistry eDepartment of Endocrinology, Dışkapı Yıldırım Beyazıt Education and Research Hospital, Ankara, Turkey.
- Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.Blood Coagul Fibrinolysis.2013 Dec;24(8):844-7. doi: 10.1097/MBC.0b013e328364668a.
- Thrombin activatable fibrinolysis inhibitor (TAFI) is an important procoagulant factor. Patients with metabolic syndrome (MetS) also have an elevated procoagulant status. However, TAFI and its association with MetS are still not well known. We aimed to investigate TAFI in type 2 diabetes mellitus pa
- PMID 23945058
- Improvement of fibrin clot structure after factor VIII injection in haemophilia.
- Antovic A, Mikovic D, Elezovic I, Zabczyk M, Hutenby K, Antovic JP.SourceAleksandra Antovic, Karolinska Institutet, Dept. of Clinical Sciences, Danderyd Hospital, 182 88 Stockholm, Sweden, Tel.: + 46734294448, E-mail: aleksandra.antovic@ki.se.
- Thrombosis and haemostasis.Thromb Haemost.2013 Nov 21;111(4). [Epub ahead of print]
- Patients with haemophilia A have seriously impaired thrombin generation due to an inherited deficiency of factor (F)VIII, making them form unstable fibrin clots that are unable to maintain haemostasis. Data on fibrin structure in haemophilia patients remain limited. Fibrin permeability, assessed by
- PMID 24258360
Japanese Journal
- TAFI阻害薬 (特集 血栓症診療update : 新規経口抗凝固薬を加えて広がる世界) -- (近未来に使用可能となるかもしれない抗血栓薬)
- 血中カルボキシペプチダーゼTAFIの新機能 : 線溶系とともに炎症の調節などにも深く関与
Related Links
- 値は,それぞれ0.5~2.1μMおよび1.4~2.4 μMと大差は見られない웋웒웗웋웓웗.したがって,血中 ではトロンビン-トロンボモジュリン複合体に よるTAFIとPCの活性化は,それぞれ同程度 であり,お互いに拮抗しているものと推測され
- TAFI(注)の受託測定 1)TAFI (= ProCPR ) のELISA による測定 1検体 ¥21,000 検体は血漿0.2ml を冷蔵または凍結保存したもの(抗凝固剤はEDTA、ヘパリン またはクエン酸ナトリウム) 2)TAFI (= ProCPR ) の総 ...
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