C9orf3

protein
Name = chromosome 9 open reading frame 3
caption =


width =
HGNCid = 1361
Symbol = C9orf3
AltSymbols = C90RF3, FLJ14675, APO
EntrezGene = 84909
OMIM =
RefSeq = NM_032823
UniProt = Q8N6M6
PDB =
ECnumber = 3.4.11.-
Chromosome = 9
Arm = q
Band = 22
LocusSupplementaryData =

Chromosome 9 open reading frame 3 also known as C9ORF3 is a human gene.cite journal | author = Strausberg RL, Feingold EA, Grouse LH, "et al" | 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 | year = 2002 | month = December | pmid = 12477932 | pmc = 139241 | doi = 10.1073/pnas.242603899 | url = | issn = ] The protein encoded by this gene is an aminopeptidase which is most closely related in sequence to leukotriene A4 hydrolase (LTA4H).cite journal | author = Díaz-Perales A, Quesada V, Sánchez LM, Ugalde AP, Suárez MF, Fueyo A, López-Otín C | title = Identification of human aminopeptidase O, a novel metalloprotease with structural similarity to aminopeptidase B and leukotriene A4 hydrolase | journal = J. Biol. Chem. | volume = 280 | issue = 14 | pages = 14310–7 | year = 2005 | month = April | pmid = 15687497 | doi = 10.1074/jbc.M413222200 | url = | issn = ]

tructure

The C9ORF3 aminopeptidase enzyme contains the following domains:
* 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.

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. Role of C9ORF3 is under investigation.

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 play a role in the regulating the physiology of cardiac muscle.

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.cite journal | author = 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 | year = 2008 | month = June | pmid = 18445752 | doi = 10.1152/ajpendo.90255.2008 | url = | issn = ]

References