Characterization of carboxypeptidase A6, an extracellular matrix peptidase.

Article Details

Citation

Copy to clipboard

Lyons PJ, Callaway MB, Fricker LD

Characterization of carboxypeptidase A6, an extracellular matrix peptidase.

J Biol Chem. 2008 Mar 14;283(11):7054-63. doi: 10.1074/jbc.M707680200. Epub 2008 Jan 4.

PubMed ID

18178555 [ View in PubMed

]

Abstract

Carboxypeptidase A6 (CPA6) is a member of the M14 metallocarboxypeptidase family that is highly expressed in the adult mouse olfactory bulb and broadly expressed in embryonic brain and other tissues. A disruption in the human CPA6 gene is linked to Duane syndrome, a defect in the abducens nerve/lateral rectus muscle connection. In this study the cellular distribution, processing, and substrate specificity of human CPA6 were investigated. The 50-kDa pro-CPA6 is routed through the constitutive secretory pathway, processed by furin or a furin-like enzyme into the 37-kDa active form, and secreted into the extracellular matrix. CPA6 cleaves the C-terminal residue from a range of substrates, including small synthetic substrates, larger peptides, and proteins. CPA6 has a preference for large hydrophobic C-terminal amino acids as well as histidine. Peptides with a penultimate glycine or proline are very poorly cleaved. Several neuropeptides were found to be processed by CPA6, including Met- and Leu-enkephalin, angiotensin I, and neurotensin. Whereas CPA6 converts enkephalin and neurotensin into forms known to be inactive toward their receptors, CPA6 converts inactive angiotensin I into the biologically active angiotensin II. Taken together, these data suggest a role for CPA6 in the regulation of neuropeptides in the extracellular environment within the olfactory bulb and other parts of the brain.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Metenkefalin	Carboxypeptidase A6	Protein	Humans	Unknown	Substrate	Details

Polypeptides

Name	UniProt ID
Carboxypeptidase A6	Q8N4T0	Details