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]
| AOPEP | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure
editThe C9ORF3 aminopeptidase enzyme contains the following domains:[6]
- LTA4H-like N-terminal domain
- gluzincin aminopeptidase domain
- SH3-like motif
- ARM C-terminal domain
Function
editThe 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
editC9ORF3 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
editHigh 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
edit- ^ 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)
- ^ 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
edit- Human C9orf3 genome location and C9orf3 gene details page in the UCSC Genome Browser.
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