TMEM247

The TMEM247 gene is located on chromosome 2 at c2p21, nucleotide: 46,479,565-46,484,425. It has three exons and two introns. TMEM247 is 4,861 nucleotides (nt) long pre-mRNA processing, reduced to 661 nt after mRNA processing and its protein product is 219 amino acids (aa) long.[6] The gene does not include a stop codon as most genes do, but instead has a stop codon created by the process of polyadenylation during mRNA processing. Due to this, TMEM247 has no 3' UTR (untranslated region). TMEM247 codes only for one variant.

The promoter region of TMEM247 has a huge variety of predicted binding sites in the promoter region associated with the gene. Twenty potential interactions of interest have been collected below, though many more exist. Anchor base positions are based on distance from the start of the gene's promoter region, which itself is 1302 base pairs long.

There are a number of notable predicted binding sites on the TMEM247 promoter, as well as a notable omission. The promoter lacks a traditional TATA box, the typical binding site for proteins that recruit RNA Polymerase and begin the process of transcription. Instead, TMEM247 contains several predicted binding sites which are core promoter elements for TATA-less promoters.

TMEM247 has a promoter region that also contains a significant number of predicted development-related binding sites, such as pluripotent stem cell related factors (Oct4, Sox2, Nanog), sex-determining HMG box factors, and various homeobox/homeodomain binding sites.[7]

Tail end of the promoter region of the TMEM247 gene with notable predicted binding sites highlighted. The start of transcription is marked by an arrow.

Transmembrane protein 247 has two transmembrane domains. The three regions of the protein that remain are predicted to be outside of the membrane it resides in on the N- and C-terminus of the protein, while the segment between the protein's two transmembrane regions is predicted to reside inside of the membrane.[12][13]

Analysis of TMEM247 predicts that it localizes in the cell at the endoplasmic reticulum. In this case, inner predicted domains would be inside the ER and outer predicted domains would reside in the cytoplasm.

A domain-level view of TMEM247 with points of interest at predicted post-translational modification sites.

Transmembrane protein 247 has a variety of predicted post-translational modifications that may affect protein function. Predicted modifications include O-beta-GlcNAc attachment, Glycation, and O-glycosylation.[14][15][16]

A conceptual translation of TMEM247 and predicted modifications to its protein product

Protein kinases may modify transmembrane protein 247, and a variety of sites along the translated protein have been predicted to be kinase binding sites. These are represented by red squares surrounding the potential bound amino acids in the conceptual translation and listed in the table below. Predicted kinase interactions are listed in the order of the score of their prediction (higher, lower).[17]

Transmembrane protein 247 has a predicted secondary structure which includes two major features in the form of beta sheets that reside near its determined transmembrane regions. This is slightly unusual for transmembrane proteins, whose transmembrane regions are often alpha helices.[18][19]

A Chou-Fasman method prediction of TMEM247's secondary protein structure.

A 3D prediction of the TMEM247 secondary protein structure.

TMEM247 has several hundred orthologs, with its most distant fully sequenced available ortholog being Anolis carolinensis.[20][21] These orthologs are exclusive to land-based animals, as clades with an evolutionary origin before reptiles are not represented. The fact that TMEM247 has no relatives before the green anole makes it likely that the gene was novel when it appeared in an ancestor of the species, and was nonexistent before the evolution of reptiles. Classes represented in the orthologs include mammalia, aves, and reptilia.

Most orthologs within mammalia are strongly conserved across the entire gene, including a very highly conserved region near the center of the translated protein. The highest evolutionary conservation is centered around the transmembrane regions of the protein, which are highly conserved in all orthologous species.[22]

In humans, TMEM247 has a single paralog (hCG17037) that has a sequence which theoretically would translate into a protein which is identical to that produced by TMEM247 aside from seven positions constituting a 96.8% similarity, including two deletions that reduce the total amino acid count from 219 to 217.[23] The extreme similarity of the TMEM247 gene and its paralog make it a likely result of gene duplication.