Chromosome 16 open reading frame 46 is a protein of yet to be determined function in Homo sapiens. It is encoded by the C16orf46 gene with NCBI accession number of NM_001100873. It is a protein-coding gene with an overlapping locus^[2].

Gene[edit | edit source]

An alternative name for this gene is FLJ32702, however it is most commonly referred to as C16orf46^[3].

Location[edit | edit source]

The C16orf26 gene is found on chromosome 16q23.2 negative strand^[4]. The promoter region is 1152 base pairs long^[5]. It has three exons, one from 1-380 bp, the second from 381-1254 bp, and the third from 1255-1982 bp^[2].

Expression[edit | edit source]

C16orf46 is broadly expressed in the testis and thyroid as well as 18 other tissues^[4]. These tissue expression patterns are found to be low to moderate (25-50%)^[6]. When looking at tissue profiles, the highest expression is in the adult mammalian kidney, liver, prefrontal cortex, cerebellum, heart, and brain^[7].

Protein[edit | edit source]

Protein Analysis[edit | edit source]

The full C16orf46 protein is 417 amino acids long^[9]. It has no isoforms, and its most distant ortholog, Rhincodon typus (whale shark), also has no known isoforms^[10]. The molecular weight was found to be 45.8 kdal^[11]. The isoelectric point is 7.4, average for all proteins, and C16orf46 is electrically neutral^[12].

C16orf46 is predicted to be found in the nucleus by all orthologs^[13].

The secondary structure of C16orf46 has alternating alpha helices and beta sheets^[14].

Protein Level Regulation[edit | edit source]

In C16orf46, there is N-linked glycosylation, O-linked glycosylation, and SUMOylation^[15][16].

There are phosphorylation sites found with the kinases CKII, CKI, PKC, and cdc2^[17].

A coronavirus cleavage site is predicted at the 235 amino acid position^[18]. There are also tyrosine motif locations between amino acids 42-45 and 251-252^[19].

Transcript Level Regulation[edit | edit source]

mRNA folding on the 5' UTR predicts a stem loop twice in the area between base pairs 47-90^[20].

Homologs[edit | edit source]

Orthologs[edit | edit source]

C16orf46 has over 50 orthologs ranging from primate to chordate^[21]. The table below shows a representation of the diversity of C16orf46 by listing a selection of orthologs found using NCBI. When C16orf46 Homo sapiens was run through a multiple alignment sequence program, Clustal Omega, against 20 true orthologs and 16 distant orthologs, Trp74 and Pro212 were found to be conserved in all^[22].

Paralogs[edit | edit source]

C16orf46 has no known paralogs^[21].

Mutations[edit | edit source]

C16orf46 has been compared against Fibrinogen, a protein which mutates rapidly, and Cytochrome C, a protein which mutates slowly.

As can be seen below, when multiple species of the three proteins were plotted, C16orf46 more closely resembled that of Fibrinogen than Cytochrome C, suggesting a possible rapid mutation^[21].

Interacting Proteins[edit | edit source]

C16orf46 interacts with FAT3 which has been linked to neurite interactions during development^[23]. C16orf46 is thought to have coexpression with the PLAC8L1 and CFAP43 gene, both of unknown function^[24].

Clinical Significance[edit | edit source]

There are higher levels of C16orf46 expression in pancreatic adenocarcinoma tumor epithelia tissue compared to the control^[25]. There is also higher gene expression in patients with small-cell carcinoma compared to the control^[26].

References[edit | edit source]