C10orf67

There are 23 alternatively spliced exons, which encode 13 transcript variants. The primary transcript, only 2943 bp, is not well conserved among orthologs, rather, the X2 variant, 3417 bp, has far greater identity with orthologous proteins. This X2 transcript variant contains 15 exons which yield a polypeptide of 551 amino acids.[9][10]

*depending on post-translational modifications (PTMs)

**From no PTMs - all possible PTMs

The isoelectric point is significantly greater than average for human proteins (6.81).[11]

Predicted tertiary structure of C10orf67 generated by software.[12] Based on a protein template covering 74% of the protein sequence with 96% identity.

Shown to the right is a predicted tertiary structure of the protein. It is marked by long alpha-helices with several coil regions and beta strands localized to the end of the protein opposite the N- and C- terminal ends.

Expression of C10orf67 in various tissues.[13]

C10orf67 is moderately expressed (50-75%) in most tissues in the body.[13] However, a study on NCBI GEO discussing the influence of interleukin-13 (IL-13) on gene expression[14] found that protein expression dropped to zero in the presence of IL-13 in airway epithelia.

The protein contains a mitochondrial signal peptide localizing it to the mitochondrial matrix.[15] Analysis with subcellular localization software[16][17] confirmed this finding. However, some orthologs were also predicted to localize in the nucleus. Though the high isoelectric point of the Human protein provides further evidence for the mitochondrial localization due to the high pH of the mitochondrial matrix.

The protein is initially cleaved to remove the 36 amino acid N-terminal signal peptide after it is localized to the mitochondrion.[18]

The possible phosphorylation sites of C10orf67. The concentration of possible phosphorylation sites is far greater near the C-terminus of the protein and far lower near the N-terminus, which contains the signal peptide.

There are a number of predicted phosphorylation sites, however there is one experimentally-confirmed phosphorylation site at threonine 69.[19] The other phosphorylation sites are summarized in the protein diagram below.

There are five predicted sumoylation sites within C10orf67. These are summarized by the following table:

Post translational modifications of C10orf67. The N-terminus is on the left with the 36 amino acid signal peptide and the C-terminus is on the right.

C10orf67 has no known paralogs but has many orthologs within eukaryotes and retains significant identity with species as distantly related as invertebrates. Several select orthologs are listed below with some identifying information.

The rate of evolution of C10orf67 relative to Fibrinogen and Cytochrome c.

The rate of evolution of C10orf67 was compared to that of fibrinogen and cytochrome c, which represent fast and slow rates of evolution, respectively. The bolded species in the table were selected to represent the fibrinogen and cytochrome c orthologs to determine the rate of evolution of the respective proteins.

The rate of evolution of C10orf67 is very curious in that it follows a logarithmic trend rather than a linear trend, like most proteins.

While the function of C10orf67 is unknown, its interactions with IL-13 further suggest a role of C10orf67 in sarcoidosis as the disease is known to involve various interleukins.

While several NCBI GEO profiles examining various factors on gene expression show that C10orf67 is expressed in varying levels in different cancer tissues,[20][21] the mitochondrial localization may yield some insight as to a clinical function. Mitochondria have been shown to have some influence in cell proliferation. Given the high energy demand from cell proliferation, there have been several hypotheses that the mitochondria may play a role in the cell cycle and that C10orf67, being localized to the mitochondria, may have a hand in this as well.