AOPEP
Identifiers
Aliases	AOPEP, chromosome 9 open reading frame 3, AP-O, APO, C90RF3, ONPEP, aminopeptidase O (putative), C9orf3
External IDs	MGI: 1919311 HomoloGene: 66273 GeneCards: AOPEP
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q22.32 Start 94,726,701 bp[1] End 95,087,218 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 B3 Start 63,112,707 bp[2] End 63,473,910 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right coronary artery ascending aorta popliteal artery left uterine tube sural nerve left coronary artery right lobe of liver body of pancreas smooth muscle tissue skin of abdomen Top expressed in lip ascending aorta aortic valve superior frontal gyrus interventricular septum spermatid spermatocyte esophagus cerebellar cortex proximal tubule More reference expression data BioGPS n/a
Gene ontology Molecular function peptide binding zinc ion binding peptidase activity metallopeptidase activity hydrolase activity metal ion binding metalloaminopeptidase activity aminopeptidase activity Cellular component cytoplasm nucleolus cytosol nucleus Biological process proteolysis peptide catabolic process angiotensin maturation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 84909 72061 Ensembl ENSG00000148120 ENSMUSG00000021458 UniProt Q8N6M6 Q8BXQ6 RefSeq (mRNA) NM_001193329 NM_001193330 NM_001193331 NM_032823 NM_001289924 NM_001289926 NM_028079 RefSeq (protein) NP_001180258 NP_001180260 NP_116212 NP_001276853 NP_001276855 Location (UCSC) Chr 9: 94.73 – 95.09 Mb Chr 13: 63.11 – 63.47 Mb PubMed search [3] [4]
Wikidata
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Chromosome 9 open reading frame 3 (C9ORF3) also known as aminopeptidase O (APO) is an enzyme which in humans is encoded by the C9ORF3 gene.^[5] The protein encoded by this gene is an aminopeptidase which is most closely related in sequence to leukotriene A4 hydrolase (LTA4H).^[6] APO is a member of the M1 metalloproteinase family.^[7][8]

Structure

The C9ORF3 aminopeptidase enzyme contains the following domains:^[6]

• 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 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.^[6]

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.^[6] Several ApO isoforms are expressed predominantly in blood vessels suggesting that ApO plays a role in vascular cell biology.^[7]

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.^[9]