Transmembrane protein 255A

Transmembrane protein 255A^[5] is a protein that is encoded by the TMEM255A gene.^[6] TMEM255A is often referred to as family with sequence similarity 70, member A (FAM70A).^[7] The TMEM255A protein is transmembrane and is predicted to be located the nuclear envelope of eukaryote organisms.^[8]

The TMEM25A gene (often referred to as Family with Sequence Similarity 70 Member A; FAM70A) is located on Xq24, spanning 60,555 base pairs.^[10] TMEM255A is flanked by the genes ATPase Na+/K+ transporting family member beta 4 (ATP1B4) and NF_KB activating protein pseudogene 1 (NKAPP1).^[11]

There are three variants of the transcript seen, where isoform 1 is the longest. The 5’- and 3’- UTRs of the mRNA spans 227 and 2207 base pairs, respectively, and are predicted to contain several stem-loops.^[12] The mRNA is 3512 base pairs long and the gene consists of 9 exons.^[13]

The longest protein encoded for is isoform 1, which spans 349 amino acids, and is predicted to have a molecular weight at 38 kDa and isoelectric point at pH 7.89.^[15][16][17] Compared to the average vertebrate protein, TMEM255A is rich in aspartic acid, isoleucine, proline and tyrosine, and relatively poor in glutamic acid and lysine.^[18] No charge clusters have been found in this protein.

The protein is predicted to be post-translationally modified by phosphorylation and glycosylation.^[19] The protein is predicted to have four transmembrane domains in the nuclear membrane. The structure of the protein is predicted to be helical in the transmembrane domains.^[20][21][22] Disulfide bonds are predicted to be found in the region in between transmembrane domains 3 and 4, which indicates that this particular region is located in the nucleoplasm.^{[23][24][25][26]}

TMEM255A is predicted to be most abundantly expressed in nerve, brain, testis, ovary, thymus and kidney. The protein is expressed in a variety of tissues, but at relatively moderate levels.^[27][28][29]

Both the 5' and 3' Untranslated Regions (UTRs) are predicted to consist of several stem-loops.^[30] The 3' UTR also contain a conserved miRNA target site (amino acids 22-29).^[31] Phosphorylation and glycosylation sites have also been predicted in TMEM255A.^[32][33]

Affinity Capture MS experimentally predicts that TMEM255A interacts with ten different proteins; Ankyrin repeat domain 13D (ANKRD13D), Collagen beta (1-O) galactosyltransferase 2 (COLGALT2), Grancalcin (GCA), Itchy E3 ubiquitin protein ligase (ITCH), Potassium channel tetramerization domain containing 2 (KCTD2), Neural precursor cell expressed developmentally down-regulated 4 (NEDD4), SEC24 family member B (SEC24D), Ubiquitin associated and SH3 domain containing B (UBASH3D), WW domain containing E3 ubiquitin protein ligase 1 and 2 (WWP1, WWP2) - most of these are included in ubiquitination processes, transcription regulation and protein degradation.^[34]

TMEM255A is predicted to be highly expressed in peroxisome proliferator-activated receptor γ coactivator 1α-upregulated glioblastoma multiforme cells (specific gene function not yet fully established).^[35] Ongoing research is investigating the possibility of TMEM255A to be used in personalized immunotherapy.^[36]

There is one known paralog for TMEM255A, called TMEM255B, which is found on chromosome 13 (position 13q34).^[37] TMEM255A is only found in the kingdom of animalia, and its most distant homolog is found in invertebrata (i.e. Saccoglossus kowalenskii).