Summary for peptidase M14.011: metallocarboxypeptidase D peptidase unit 1

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

 

Names
MEROPS Namemetallocarboxypeptidase D peptidase unit 1
Other namesmetallocarboxypeptidase D domain A
Domain architecture
MEROPS Classification
Parent M14.011 is one peptidase unit of the compound peptidase XM14-001. Other units of XM14-001 are M14.016, M14.950
Classification Clan MC >> Subclan (none) >> Family M14 >> Subfamily B >> M14.011
Holotypemetallocarboxypeptidase D peptidase unit 1 (Anas platyrhynchos) (peptidase unit: 38-489), MERNUM MER0004961
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeMetallo
PeplistIncluded in the Peplist with identifier PL00215
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.17 (Metallocarboxypeptidases) >> Peptidase 3.4.17.22
EnzymologyBRENDA database
Activity statushuman: active (Fricker, 2004)
mouse: putative
SpecificityCleaves C-terminal basic residues (Lys, Arg) from peptides and proteins (Song & Fricker, 1995).
pH optimum6-8 (Novikova et al., 1999)
Substrate commentsDansyl-Phe-Ala-Arg (Song & Fricker, 1995)
Inhibitor commentsZinc chelators such as 1,10-phenanthroline, and more selective compounds like guandinoethylmercaptosuccinic acid (Song & Fricker, 1995).
StructureIn Drosophila, carboxypeptidase D-domain 1 exists as a separate protein (due to RNA splicing; Sidyelyeva et al., 2010) but in humans and other mammals, domain 1 appears to be only present in the full-length carboxypeptidase D, containing domains 2 and 3.
LocationSecretory pathway, primarily in trans Golgi network. Also cycles to cell surface (active domain facing the extracellular space) and back to the Golgi (Varlamov & Fricker, 1998).
PhysiologyProposed role in processing of numerous proteins in secretory pathway.
Biological aspectsPresent in all cells (Song & Fricker, 1996). Functions after endopeptidases such as furin (S08.071) and related proprotein convertases cleave proteins at basic residues; carboxypeptidase D removes the basic residues from the C-terminus (Varlamov et al., 1999).
RNA splicingIn Drosophila, there is extensive RNA splicing that gives rise to a number of forms of carboxypeptidase D, some containing just a single carboxypeptidase domain, while others include multiple domains (Settle et al., 1995). No clear evidence of multiple splicing in mammalian system.
KnockoutMice lacking CPD have not been successfully generated, despite multiple attempts. Drosophila with mutations that eliminate the production of all forms of CPD are embryonic lethal (Sidyelyeva et al., 2006). However, domain 2 of carboxypeptidase D can partially rescue this lethality, suggesting that domain 1 does not play an essential role (Sidyelyeva et al., 2010).
Distinguishing featuresVertebrate carboxypeptidase D contains three carboxypeptidase domains (two are active, the third is not) (Kuroki et al., 1995).
Contributing authorsLloyd D. Fricker, Departments of Molecular Pharmacology and Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
CPD 17p11.1-q11.2 ENSG00000108582 1362 CPD 603102
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Cpd 11:B5 ENSMUSG00000020841 12874 MGI:107265