Transmembrane protein 217

Transmembrane Protein 217 is a protein encoded by the gene TMEM217. TMEM217 has been found to have expression correlated with the lymphatic system and endothelial tissues, and has been predicted to have a function linked to the cytoskeleton.^[1][2][3]

TMEM217 is located on the chromosome 6 minus strand at 6p21.2.^[4] The gene consists of 46,857 base pairs and is flanked by TBC1D22B (TBC1 Domain Family Member 22B) and PIM1.^[4][5] It was previously known as C6orf128 (Chromosome 6 open reading frame 128).^[4]

TMEM217 has three common isoforms formed from the alternative splicing of three exons. Isoform 1 translates for the longest polypeptide, consisting of 1590 nucleotides.^[6] The 5’ un-translated region of isoform 1 is relatively short and is predicted to fold into several stem loop domains within conserved areas of the un-translated region.^[7]

The longest polypeptide of transmembrane protein 217 consists of 229 amino acids.^[8] This protein isoform has a predicted weight of 26.6 kDa and isoelectric point at a pH of 9.3.^[9][10] It is notably rich in isoleucine and phenylalanine, and deficient in alanine, aspartate, and proline compared to other proteins.^[11] Transmembrane protein 217 contains the domain of unknown function, DUF4534, between amino acids 11-171.^[12]

Transmembrane protein 217 is predicted to have four transmembrane domains.^[8][13] These transmembrane domains consist primarily of uncharged amino acids in predicted alpha helices.^[11][14] The N-terminus and C-terminus of the protein are predicted to be facing the cytosol with the C-terminus containing a long predicted coiled tail extending from the final transmembrane domain.^[13]

There are several predicted phosphorylation and glycosylation sites on transmembrane protein 217 in highly conserved parts of the protein, where the phosphorylation sites are located primarily on the C-terminal tail.^[15][16][17] There are also two highly conserved cysteine residues, which have the potential to form a disulfide bond in the extracellular space between the first and second transmembrane domains.

TMEM217 is not ubiquitously expressed. The gene tends to have expression correlated to lymphatic system, vascular/arterial endothelial tissue, and notable expression in the bladder based on expression profiles and microarray analysis.^[1][2] Other tissues that have been shown to express TMEM217 include: connective tissues, the liver, mammary glands, the testis, and the cervix.^[1] Co-expression analyses have found that TMEM217 was up-regulated in response to mechanical stretch in dermal fibroblast cells and in response to the resveratrol derivative, DMU-212, in vascular endothelial tissues.^[3][18]

No known function has been attributed to TMEM217, however a co-expression analysis in dermal fibroblasts has predicted the protein to have a potential association with the cytoskeleton.^[3]

Single nucleotide polymorphisms in TMEM217 have been linked to Alzheimer’s disease and diabetic retinopathy.^[19][20] TMEM217 was also found to have similar expression patterns as TRPM2, a biomarker linked to breast carcinoma.^[21] Expression profiles have also linked elevated TMEM217 expression to bladder cancer and lymphoma.^[1]

TMEM217 was found to have orthologs in organisms as early as the scaled fish, which diverged 420 million years ago.^[22] Although found in organisms as early as fish and reptiles, TMEM217 has no known orthologs in any bird species.^[23][24]

TMEM217 has no known paralogs.