Summary for peptidase M14.009: carboxypeptidase B2

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS Namecarboxypeptidase B2
Other namesarginine carboxypeptidase, brain-specific carboxypeptidase B, carboxypeptidase R, carboxypeptidase U, HBCPB, plasma carboxypeptidase B, thrombin-activatable fibrinolysis inhibitor, TAFI
Domain architecture
MEROPS Classification
Classification Clan MC >> Subclan (none) >> Family M14 >> Subfamily A >> M14.009
Holotypecarboxypeptidase B2 (Homo sapiens), Uniprot accession Q96IY4 (peptidase unit: 112-423), MERNUM MER0001193
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeMetallo
PeplistIncluded in the Peplist with identifier PL00213
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.17 (Metallocarboxypeptidases) >> Peptidase 3.4.17.20
EnzymologyBRENDA database
ActivityA carboxypeptidase.
Proteolytic eventsCutDB database (3 cleavages)
Activity statushuman: active (Hendriks, 2004)
mouse: active (Marx et al., 2000)
PhysiologyHas anti-fibrinolytic activity, removing C-terminal lysine residues of partially degraded fibrin that are important in plasmin formation mediated by t-plasminogen activator (S01.232) (Marx, 2004). May also degradate bioactive peptides in the circulation. A splice variant of carboxypeptidase U has been termed 'brain carboxypeptidase B' and attributed a physiological role in the degradation of beta-amyloid 1-42 (Matsumoto et al., 2000). It is reported that the Thr325Ile dimorphism in carboxypeptidase U affects the outcome of meningococcal disease (Kremer Hovinga et al., 2004). Genetic variation in carboxypeptidase U reported to be associated with the risk of splanchnic vein thrombosis (de Bruijne et al., 2007).
KnockoutMice deficient in carboxypeptidase U (termed carboxypeptidase R) showed increased sensitivity to a combined challenge with lipopolysaccharide and cobra venom factor that wild-type mice were able to survive (Asai et al., 2004).
Pharmaceutical relevanceInhibitors of carboxypeptidase U have been reported to enhance endogenous fibrinolysis and reduce thrombi in a tissue factor-induced microthrombosis model (Muto et al., 2003). Such inhibitors therefore have potential use in antithrombotic and thrombolytic therapy (Barrow et al., 2003).
Pathways KEGGComplement and coagulation cascades
KEGGPancreatic secretion
KEGGProtein digestion and absorption
Other databases TREEFAMhttp://www.treefam.org/family/TF317197
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/l/-Scissile bondKR/-/-/- (based on 19 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 0 1 2 4 0 0 0 0
Pro 0 0 1 0 0 0 0 0
Ala 1 1 0 3 0 0 0 0
Val 1 0 0 0 0 0 0 0
Leu 2 1 4 2 0 0 0 0
Ile 0 0 0 1 0 0 0 0
Met 1 0 0 0 0 0 0 0
Phe 1 0 0 1 0 0 0 0
Tyr 0 1 0 2 0 0 0 0
Trp 0 0 0 0 0 0 0 0
Ser 3 1 2 0 0 0 0 0
Thr 1 0 1 0 0 0 0 0
Cys 0 0 0 0 0 0 0 0
Asn 0 0 0 0 0 0 0 0
Gln 1 3 0 0 0 0 0 0
Asp 0 0 0 0 0 0 0 0
Glu 1 2 1 1 0 0 0 0
Lys 2 3 1 2 10 0 0 0
Arg 0 1 2 2 9 0 0 0
His 0 0 0 0 0 0 0 0
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
CPB2 13q14.11 ENSG00000080618 1361 CPB2 603101
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Cpb2 14:D2 ENSMUSG00000021999 56373 MGI:1891837