View source for C9orf3

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''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]].<ref name="pmid12477932">{{cite journal | vauthors = Strausberg RL, Feingold EA, Grouse LH | title = Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 26 | pages = 16899–903 |date=December 2002 | pmid = 12477932 | pmc = 139241 | doi = 10.1073/pnas.242603899 | bibcode = 2002PNAS...9916899M |display-authors=etal| doi-access = free }}</ref> The [[protein]] encoded by this gene is an [[aminopeptidase]] which is most closely related in [[homology (biology)|sequence]] to [[leukotriene A4 hydrolase]] (LTA4H). APO is a member of the M1 [[metalloproteinase]] family.<ref name="pmid17803194">{{cite journal | vauthors = Axton R, Wallis JA, Taylor H, Hanks M, Forrester LM | title = Aminopeptidase O contains a functional nucleolar localization signal and is implicated in vascular biology | journal = J. Cell. Biochem. | volume = 103 | issue = 4 | pages = 1171–82 |date=March 2008 | pmid = 17803194 | doi = 10.1002/jcb.21497 | s2cid = 11365605 }}</ref><ref name="pmid15544570">{{cite journal | vauthors = Albiston AL, Ye S, Chai SY | title = Membrane bound members of the M1 family: more than aminopeptidases | journal = Protein Pept. Lett. | volume = 11 | issue = 5 | pages = 491–500 |date=October 2004 | pmid = 15544570 | doi = 10.2174/0929866043406643}}</ref>

==Structure==
The C9ORF3 aminopeptidase enzyme contains the following [[protein domain|domains]]:{{needs source|date=December 2024}}
* LTA4H-like [[N-terminus|N-terminal]] domain
* gluzincin aminopeptidase domain
* [[SH3 domain|SH3]]-like motif
* [[Armadillo repeats|ARM]] [[C-terminus|C-terminal]] domain

==Function==
The C9ORF3 aminopeptidase cleaves the [[N-terminus|N-terminal]] amino acid from [[polypeptide]]s 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#Angiotensin III|angiotensin III]] to generate [[Angiotensin#Angiotensin IV|angiotensin IV]], a bioactive peptide of the [[renin–angiotensin system|renin–angiotensin pathway]].{{needs source|date=December 2024}}

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.{{needs source|date=December 2024}}  Several ApO isoforms are expressed predominantly in blood vessels suggesting that ApO plays a role in vascular cell biology.<ref name="pmid17803194"/>

==Clinical significance==
High expression levels of C9ORF3 is positively correlated with maximal oxygen uptake ([[VO2 max|VO<sub>2</sub> max]]) and the amount of "slow-twitch" [[Muscle fiber#Skeletal muscle fiber types|type 1 muscle fibers]].<ref name="pmid18445752">{{cite journal | vauthors = Parikh H, Nilsson E, Ling C, Poulsen P, Almgren P, Nittby H, Eriksson KF, Vaag A, Groop LC | title = Molecular correlates for maximal oxygen uptake and type 1 fibers | journal = Am. J. Physiol. Endocrinol. Metab. | volume = 294 | issue = 6 | pages = E1152–9 |date=June 2008 | pmid = 18445752 | doi = 10.1152/ajpendo.90255.2008 }}</ref>

==References==
{{Reflist|2}}

==External links==
* {{UCSC gene info|C9orf3}}

{{Proteases}}
{{Enzymes}}
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[[Category:EC 3.4.11]]


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