C9orf3

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; OMA:AOPEP - orthologs
Gene location (Human)
Chr.	Chromosome 9 (human)
End	95,087,218 bp
Gene location (Mouse)
Chr.	Chromosome 13 (mouse)
End	63,473,910 bp
RNA expression pattern
	Top expressed in
	apex of heart; ; right coronary artery; ; ascending aorta; ; Descending thoracic aorta; ; body of uterus; ; popliteal artery; ; tibial arteries; ; left uterine tube; ; sural nerve; ; left coronary artery;
	Top expressed in
	lip; ; ascending aorta; ; genital tubercle; ; right kidney; ; aortic valve; ; muscle of thigh; ; tail of embryo; ; superior frontal gyrus; ; interventricular septum; ; primary visual cortex;
	More reference expression data
	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
	84909
	72061
	ENSG00000148120
	ENSMUSG00000021458
	Q8N6M6
	Q8BXQ6
	NM_001193329; NM_001193330; NM_001193331; NM_032823
	NM_001289924; NM_001289926; NM_028079
	NP_001180258; NP_001180260; NP_116212
	NP_001276853; NP_001276855
	Wikidata
View/Edit Human	View/Edit Mouse

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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000148120 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021458 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Strausberg RL, Feingold EA, Grouse LH, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
^ ^a ^b ^c ^d Díaz-Perales A, Quesada V, Sánchez LM, Ugalde AP, Suárez MF, Fueyo A, López-Otín C (April 2005). "Identification of human aminopeptidase O, a novel metalloprotease with structural similarity to aminopeptidase B and leukotriene A4 hydrolase". J. Biol. Chem. 280 (14): 14310–7. doi:10.1074/jbc.M413222200. PMID 15687497. (Retracted, see doi:10.1074/jbc.W118.007327, PMID 30808004, Retraction Watch. If this is an intentional citation to a retracted paper, please replace {{retracted|...}} with {{retracted|...|intentional=yes}}.)
^ ^a ^b Axton R, Wallis JA, Taylor H, Hanks M, Forrester LM (March 2008). "Aminopeptidase O contains a functional nucleolar localization signal and is implicated in vascular biology". J. Cell. Biochem. 103 (4): 1171–82. doi:10.1002/jcb.21497. PMID 17803194. S2CID 11365605.
^ Albiston AL, Ye S, Chai SY (October 2004). "Membrane bound members of the M1 family: more than aminopeptidases". Protein Pept. Lett. 11 (5): 491–500. doi:10.2174/0929866043406643. PMID 15544570.
^ Parikh H, Nilsson E, Ling C, Poulsen P, Almgren P, Nittby H, Eriksson KF, Vaag A, Groop LC (June 2008). "Molecular correlates for maximal oxygen uptake and type 1 fibers". Am. J. Physiol. Endocrinol. Metab. 294 (6): E1152–9. doi:10.1152/ajpendo.90255.2008. PMID 18445752.

External links

Human C9orf3 genome location and C9orf3 gene details page in the UCSC Genome Browser.

This article on a gene on human chromosome 9 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000148120 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021458 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid12477932-5] Strausberg RL, Feingold EA, Grouse LH, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.

[pmid15687497-6] Díaz-Perales A, Quesada V, Sánchez LM, Ugalde AP, Suárez MF, Fueyo A, López-Otín C (April 2005). "Identification of human aminopeptidase O, a novel metalloprotease with structural similarity to aminopeptidase B and leukotriene A4 hydrolase". J. Biol. Chem. 280 (14): 14310–7. doi:10.1074/jbc.M413222200. PMID 15687497. (Retracted, see doi:10.1074/jbc.W118.007327, PMID 30808004, Retraction Watch. If this is an intentional citation to a retracted paper, please replace {{retracted|...}} with {{retracted|...|intentional=yes}}.)

[pmid17803194-7] Axton R, Wallis JA, Taylor H, Hanks M, Forrester LM (March 2008). "Aminopeptidase O contains a functional nucleolar localization signal and is implicated in vascular biology". J. Cell. Biochem. 103 (4): 1171–82. doi:10.1002/jcb.21497. PMID 17803194. S2CID 11365605.

[pmid15544570-8] Albiston AL, Ye S, Chai SY (October 2004). "Membrane bound members of the M1 family: more than aminopeptidases". Protein Pept. Lett. 11 (5): 491–500. doi:10.2174/0929866043406643. PMID 15544570.

[pmid18445752-9] Parikh H, Nilsson E, Ling C, Poulsen P, Almgren P, Nittby H, Eriksson KF, Vaag A, Groop LC (June 2008). "Molecular correlates for maximal oxygen uptake and type 1 fibers". Am. J. Physiol. Endocrinol. Metab. 294 (6): E1152–9. doi:10.1152/ajpendo.90255.2008. PMID 18445752.

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v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)