C3orf38

Chromosome 3 open reading frame 38 (C3orf38) is a protein which in humans is encoded by the C3orf38 gene.

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]

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]

There have been a number of potential promoters identified for the C3orf38 gene, which are described in the table below.^[13]

The C3orf38 gene exhibits ubiquitous expression in human tissues.^[14]

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 PKC phosphorylation 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]

Orthologs for the C3orf38 protein can be found in mammals, reptiles, birds, amphibians, fish, and invertebrates using BLAST searches.^[17] A selection of these orthologs can be found in the ortholog table below. There are no paralogs.^[17] Additionally, by comparing sequences of C3orf38 protein with cytochrome C and fibrinogen alpha proteins, a moderate rate of evolution was determined for the C3orf38 protein.

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]