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.
An alternative name for this gene is FLJ32702, however it is most commonly referred to as C16orf46.[1]
The C16orf26 gene is found on chromosome 16q23.2 negative strand. The promoter region is 1152 base pairs long.[2] It has three exons, one from 1-380 bp, the second from 381 to 1254 bp, and the third from 1255 to 1982 bp.[3]
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%).[5] When looking at tissue profiles, the highest expression is in the adult mammalian kidney, liver, prefrontal cortex, cerebellum, heart, and brain.[6]
The full C16orf46 protein is 417 amino acids long.[7] It has no isoforms, and its most distant ortholog, Rhincodon typus (whale shark), also has no known isoforms.[8] The molecular weight was found to be 45.8 kdal.[9] The isoelectric point is 7.4, average for all proteins, and C16orf46 is electrically neutral.[10]
C16orf46 is predicted to be found in the nucleus by all orthologs.[11]
The secondary structure of C16orf46 has alternating alpha helices and beta sheets.[12]
In C16orf46, there is N-linked glycosylation, O-linked glycosylation, and SUMOylation.[13] [14]
There are phosphorylation sites found with the kinases CKII, CKI, PKC, and cdc2.[15]
A coronavirus cleavage site is predicted at the 235 amino acid position.[16] There are also tyrosine motif locations between amino acids 42-45 and 251–252.[17]
mRNA folding on the 5' UTR predicts a stem loop twice in the area between base pairs 47–90.[18]
C16orf46 has over 50 orthologs ranging from primate to chordate.[19] 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.[20]
| Homo sapiens | Humans | --- | XP_016878405.1 | 100.0% | |
| Ochotona princeps | American Pika | 90 | XP_004584265.1 | 52.7% | |
| Octodon degus | Common Degu | 90 | XP_003434773.2 | 47.8% | |
| Ursus maritimus | Polar Bear | 96 | XP_008687958.1 | 67.5% | |
| Leptonychotes weddellii | Weddell Seal | 96 | XP_006748170.1 | 67.2% | |
| Canis lupus | Gray Wolf | 96 | XP_003434773.2 | 65.8% | |
| Pteropus vampyrus | Large Flying Fox | 96 | XP_011354946.1 | 63.5% | |
| Sus scrofa | Wild Boar | 96 | XP_020952705.1 | 61.5% | |
| Bos indicus | Zebu | 96 | XP_019835282.1 | 60.2% | |
| Erinaceus europaeus | European Hedgehog | 96 | XP_007516703.1 | 56.7% | |
| Loxodonta africana | African Bush Elephant | 105 | XP_010596137.1 | 60.9% | |
| Sarcophilus harrisii | Tasmanian Devil | 159 | XP_003757901.1 | 43.1% | |
| Apteryx australis | Southern Brown Kiwi | 312 | XP_013796688.1 | 18.5% | |
| Aptenodytes forsteri | Emperor Penguin | 312 | XP_019327074.1 | 17.4% | |
| Chelonia mydas | Green Sea Turtle | 312 | XP_007059324.1 | 29.7% | |
| Gekko japonicus | Gekko Japonicus | 312 | XP_015261305.1 | 25.3% | |
| Nanorana parkeri | High Himalaya Frog | 352 | XP_018410908.1 | 22.4% | |
| Pygocentrus nattereri | Red Bellied Piranha | 435 | XP_017578196.1 | 21.2% | |
| Lepisosteus oculatus | Spotted Gar | 435 | XP_015223705.1 | 20.6% | |
| Callorhinchus milii | Australian Ghost Shark | 473 | XP_007887408.1 | 22.7% |
C16orf46 has no known paralogs.
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.
C16orf46 interacts with FAT3 which has been linked to neurite interactions during development.[21] C16orf46 is thought to have coexpression with the PLAC8L1 and CFAP43 gene, both of unknown function.[22]
There are higher levels of C16orf46 expression in pancreatic adenocarcinoma tumor epithelia tissue compared to the control.[23] There is also higher gene expression in patients with small-cell carcinoma compared to the control.[24]