C9orf3
C9orf3 | |||||||||||||||||
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Identifiers | |||||||||||||||||
Aliases | C9orf3, chromosome 9 open reading frame 3, AOPEP, AP-O, APO, C90RF3, ONPEP | ||||||||||||||||
External IDs | MGI: 1919311 HomoloGene: 66273 GeneCards: C9orf3 | ||||||||||||||||
Genetically Related Diseases | |||||||||||||||||
polycystic ovary syndrome, prostate cancer, impotence[1] | |||||||||||||||||
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Orthologs | |||||||||||||||||
Species | Human | Mouse | |||||||||||||||
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RefSeq (mRNA) |
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RefSeq (protein) |
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Location (UCSC) | Chr 9: 94.73 – 95.09 Mb | Chr 13: 63.01 – 63.33 Mb | |||||||||||||||
PubMed search | [2] | [3] | |||||||||||||||
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.[4] The protein encoded by this gene is an aminopeptidase which is most closely related in sequence to leukotriene A4 hydrolase (LTA4H).[5] APO is a member of the M1 metalloproteinase family.[6][7]
Structure[edit]
The C9ORF3 aminopeptidase enzyme contains the following domains:[5]
- LTA4H-like N-terminal domain
- gluzincin aminopeptidase domain
- SH3-like motif
- ARM C-terminal domain
Function[edit]
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.[5]
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[edit]
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.[5] Several ApO isoforms are expressed predominantly in blood vessels suggesting that ApO plays a role in vascular cell biology.[6]
Clinical significance[edit]
High expression levels of C9ORF3 is positively correlated with maximal oxygen uptake (VO2 max) and the amount of "slow-twitch" type 1 muscle fibers.[8]
References[edit]
- ^ "Diseases that are genetically associated with C9orf3 view/edit references on wikidata".
- ^ "Human PubMed Reference:".
- ^ "Mouse PubMed Reference:".
- ^ 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. 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.
- ^ 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.
- ^ 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.
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