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C9orf3

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C9orf3

chromosome 9 open reading frame 3
Identifiers
Symbol C9orf3
Alt. symbols C90RF3, FLJ14675, APO
Entrez HUGO RefSeq UniProt EC number Locus q22

Chromosome 9 open reading frame 3 (C9ORF3) also known as aminopeptidase O (APO) is an enyzme which in humans is encoded by the C9ORF3 gene.[1] The protein encoded by this gene is an aminopeptidase which is most closely related in sequence to leukotriene A4 hydrolase (LTA4H).[2] APO is a member of the M1 metalloproteinase family.[3][4]

Structure

The C9ORF3 aminopeptidase enzyme contains the following domains:[2]

Function

The C9ORF3 aminopeptidase cleaves the N-terminal amino acid from polypeptides and shows a strong preference for peptides in which the N-terminus is arginine and to a lesser extent asparagine. Furthermore the activity of the enzyme is inhibited by o-phenanthroline, a metalloprotease inhibitor and by arphamenine A, a potent inhibitor of aminopeptidases such as LTA4H. Also able to cleave angiotensin III to generate angiotensin IV, a bioactive peptide of the renin-angiotensin pathway.[2]

Due to its aminopeptidase activity this enzyme may play a role in the proteolytic processing of bioactive peptides in those tissues where it is expressed.

Tissue distribution

C9ORF3 Messenger RNA has been detected in human pancreas, placenta, liver, testis, and heart. The expression in the heart suggests this enzyme may also play a role in the regulating the physiology of cardiac muscle.[2] Several ApO isoforms are expressed predominantly in blood vessels suggesting that ApO plays a role in vascular cell biology.[3]

Clinical significance

High expression levels of C9ORF3 is positively correlated with maximal oxygen uptake (VO2 max) and the amount of "slow-twitch" type 1 muscle fibers.[5]

References


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