C9orf3

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

Structure
The C9ORF3 aminopeptidase enzyme contains the following domains:
 * LTA4H-like N-terminal domain
 * gluzincin aminopeptidase domain
 * SH3-like motif
 * ARM C-terminal domain

Function
The C9ORF3 aminopeptidase cleaves the N-terminal amino acid from is_associated_with::polypeptides and shows a strong preference for peptides in which the N-terminus is is_associated_with::arginine and to a lesser extent is_associated_with::asparagine. Furthermore the activity of the enzyme is inhibited by o-is_associated_with::phenanthroline, a is_associated_with::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.

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 is_associated_with::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. Several ApO isoforms are expressed predominantly in blood vessels suggesting that ApO plays a role in vascular cell biology.

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.