Carboxypeptidase B2

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.[5][6]

CPB2
Protein CPB2 PDB 3D66.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCPB2, CPU, PCPB, TAFI, carboxypeptidase B2
External IDsOMIM: 603101 MGI: 1891837 HomoloGene: 55610 GeneCards: CPB2
Gene location (Human)
Chromosome 13 (human)
Chr.Chromosome 13 (human)[1]
Chromosome 13 (human)
Genomic location for CPB2
Genomic location for CPB2
Band13q14.13Start46,053,186 bp[1]
End46,105,033 bp[1]
RNA expression pattern
PBB GE CPB2 206651 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_016413
NM_001278541
NM_001872

NM_019775

RefSeq (protein)

NP_001265470
NP_001863

NP_062749

Location (UCSC)Chr 13: 46.05 – 46.11 MbChr 14: 75.24 – 75.28 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

FunctionEdit

CPB2 is synthesized by the liver[7] 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.[8][9]

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.[10]

 
Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

IsozymesEdit

Polymorphisms have been described for this gene and its promoter region. Available sequence data analyses indicate splice variants that encode different isoforms.[10]

See alsoEdit

ReferencesEdit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000080618 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021999 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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
  8. ^ 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.
  9. ^ 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.
  10. ^ a b "Entrez Gene: CPB2 carboxypeptidase B2 (plasma)".

Further readingEdit

This article incorporates text from the United States National Library of Medicine, which is in the public domain.