TMEM275 (Transmembrane protein 275) is a protein that in humans is encoded by the TMEM275 gene. TMEM275 has two, highly-conserved, helical trans-membrane regions. It is predicted to reside within the plasma membrane or the endoplasmic reticulum's membrane.
Gene
Locus
In humans, the gene is located on chromosomal band 1p33 on the minus strand. It specifically resides on chromosome 1 at chr1:46,532,166-46,543,969. TMEM275 is 11,804bp long.
Gene neighborhood
Upstream, on the minus strand, of TMEM275 is another gene; KNCN.
Transcripts
The TMEM275 gene encodes four exons, only three of which are included within the final mRNA transcript. Two of those three are within the 5’ UTR and the coding sequence codes for 177 amino acids. TMEM275 is found two have two potential isoforms outside of its reference transcript. The reference isoform does not include exon 1, while isoform X1 has a shortened 5' UTR and isoform X2 has a shortened 3' UTR. However, all versions of mRNA transcripts yield the same 177 amino acid sequence.
Protein
General properties
The TMEM275 protein contains 177 amino acids with a predicted molecular mass of 17.2 kDa and a pI of 8.13. TMEM275 was found to have a higher presence of alanine and proline amino acid residues than most proteins. When looking at orthologous proteins sequences within other species, the alanine presence was conserved throughout, but the same could not be said of the proline presence.
Primary sequence
TMEM275's protein consists of 177 amino acids. The protein, or polypeptide chain, that is encoded by the coding sequence is made through the process of translation and is shown below among other regions of interest. There is also a poly-A, or polyadenylation signal, towards the end of the 3'UTR.
Domains
TMEM275 has two, highly-conserved, helical trans-membrane regions. The regions can be seem within the amino acid sequence above within the conceptual translation in purple. Evolutionary analysis showed that these trans-membrane domains are highly conserved across all ortholog taxa.
Secondary structure
Many programs were used to analyze the predicted secondary structure for TMEM275. It was found to have a highly varied structure. However, prediction data supports the alpha helical structure of the two transmembrane domains.
Regulation
Gene level regulation
Promoter
The predicted promoter region is 1116 bp long and located on chromosome 1 on the minus strand and extends from 46535401- 46536515.
Transcription factor binding sites
ElDorado through Genomatix was used to analyze the top 20 transcription factor binding sites within the promoter.
Expression pattern
TMEM275's RNA levels are very high at around 11 weeks of gestation within the intestines. Some other notable peaks include the lungs, kidneys, and adrenal tissues at 10, 16, and 20 weeks, respectively. It has also been found that of the 20 human tissues tested, RNA was notably present within fetal brain tissue. Further testing on tissue types lead to the discovery that TMEM275 may have tissue-specificity with the testis, the brain, and the prostate. Along with the thyroid and ovaries.
Protein level regulation
Subcellular Localization
TMEM275 is predicted to be within the plasma membrane or the endoplasmic reticulum's membrane.
Post-translational modifications
Various PTMs were analyzed for association with TMEM275. This includes looking for the presence of a SUMO-motif, acetylation sites, the presence of signal peptides, and any O-GlcNAc site and N-myristylation predictions.
Cleavage site
Homology
Paralogs
There are no known paralogs for TMEM275.
Homologs
No homologs or homologous domains exist within TMEM275.
Orthologs
A total of 105 organisms are found to have orthologs with the human TMEM275 genes, all of which are a part of the Teleostomi, or jawed vertebrates, clade. Of the 105 organisms that have an orthologous TMEM275: 49 are mammals, 27 are birds, 3 are turtles, 3 are lizards, 3 are amphibians, 19 are bony fishes, and 1 is an alligator.
The group with the most similar sequences by percent identity was unsurprisingly Mammalia. The percent identities of those orthologous proteins in relation to humans ranged from 52.1% to 70.9%. The group that had the orthologous TMEM275, but was the least similar was Actinopterygii or Bony Fishes. Their percent similarities ranged from 38.5% to 47.6%. Percent similarities were found by conducting a pairwise analysis of each orthologous protein within each species against the human protein.
Phylogeny
Gene appearance
TMEM275 seems to have appeared 435 MYA within the Bony fishes or Actinopterygii.
Interacting proteins
There were no known protein interactions for TMEM275.
Clinical significance
TMEM275 has no known link to medical disease.
