Figure depicting human chromosome 3 and the 3p11.1 location at which the C3orf38 gene is found. Image derived from GeneCards.[5]
The C3orf38 gene is located on chromosome 3 (3p11.1) on the forward strand.[5] It spans 18,771 bases from chr3:88,149,959-88,168,729.[5] It contains 3 exons.[6] Common aliases for this gene are MGC26717, LOC285237, and FLJ54270.[7] Some of the genes neighboring C3orf38 include ZNF654, CGGBP1, and LOC105377202.[8]
Multiple sequence alignment of C3orf38 protein in humans and various orthologs showing DUF conservation. MSA created using BoxShade tools.
The C3orf38 protein is 329 amino acids in length.[9] A large domain of unknown function, DUF4518, encompasses majority of the C3orf38 protein.[9] This domain is a part of the protein family pfam15008, which is thought to be involved in apoptosis regulation.[10] This pfam15008 is the only member of the cl20886 superfamily.[10] While the C3orf38 protein does not have any abnormal amino acid abundance as a whole, the DUF4518 has a high abundance of histidines and a low abundance of serines, according to compositional analysis.[11] The predicted molecular weight of the entire C3orf38 protein is 37.0 kD and the isoelectric point is 6.01.[12] The DUF4518 contained inside the C3orf38 protein has a predicted molecular weight of 31 kD and an isoelectric point of 6.49.[12]
The C3orf38 protein is expected to be found with the highest confidence in the cytoplasm.[15] This finding is supported by examination of an array of C3orf38 orthologs.[15]
There are several well conserved post translation modification sites found amongst the human C3orf38 protein and its orthologs, which are depicted in the table below.[16] Majority of these PTMs are PKCphosphorylation sites.[16] Additionally, two confirmed active sites are located in the C3orf38 protein. The first is an aldehyde dehydrogenases glutamic acid active site located from amino acids 1-8.[16] The second site is a eukaryotic thiol (cysteine) proteases histidine active site located from amino acids 227-237.[16]
Predicted cellular localization of C3orf38 in humans and several orthologs. Localization predictions gathered from PSORT II Prediction tool.[15]
Figure showing an evolution rate graph comparing the C3orf38, cytochrome C, and fibrinogen alpha proteins. Noting the cytochrome C to be a relatively slow-evolving protein and the fibrinogen alpha to be a relatively fast-evolving protein, it is clear that C3orf38 protein evolves at a comparatively moderate rate.
Although investigation into the function of the C3orf38 gene is ongoing, a couple studies have granted valuable insights into its role. One study has identified C3orf38 as a candidate proapoptotic gene.[20] Another study identified C3orf38 as a top candidate tumor suppressor gene (TSG).[21]
Of the various proteins C3orf38 protein interacts with, two are particularly interesting seeing as C3orf38 is a candidate proapoptotic and tumor suppressor gene. First, BAG family molecular chaperone regulator 4 (BAG4) is an anti-apoptotic protein that is known to interact with a number of apoptosis and growth-related proteins.[22] Second, DnaJ Heat Shock Protein Family Member B4 (DNAJB4) is a member of the heat shock protein-40 family (Hsp40), a molecular chaperone, and a tumor suppressor (specifically for colorectal carcinoma).[23]
