Transmembrane protein 217 explained

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.

Gene

TMEM217 is located on the chromosome 6 minus strand at 6p21.2.[1] The gene consists of 46,857 base pairs and is flanked by TBC1D22B (TBC1 Domain Family Member 22B) and PIM1.[2] It was previously known as C6orf128 (Chromosome 6 open reading frame 128).

mRNA

TMEM217 has three common isoforms formed from the alternative splicing of three exons. Isoform 1 translates for the longest polypeptide, consisting of 1590 nucleotides.[3] 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.[4]

Protein

Primary Protein Sequence

The longest polypeptide of transmembrane protein 217 consists of 229 amino acids.[5] This protein isoform has a predicted weight of 26.6 kDa and isoelectric point at a pH of 9.3.[6] [7] It is notably rich in isoleucine and phenylalanine, and deficient in alanine, aspartate, and proline compared to other proteins.[8] Transmembrane protein 217 contains the domain of unknown function, DUF4534, between amino acids 11-171.[9]

Secondary Structure

Transmembrane protein 217 is predicted to have four transmembrane domains.[10] These transmembrane domains consist primarily of uncharged amino acids in predicted alpha helices.[11] 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.

Post-Translational Modifications

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.[12] [13] [14] 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.

Expression

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.[15] [16] Other tissues that have been shown to express TMEM217 include: connective tissues, the liver, mammary glands, the testis, and the cervix. 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.[17] [18]

Function

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.

Clinical Significance

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.

Homology

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.

Notes and References

  1. Web site: TMEM217 Gene. GeneCards.
  2. Web site: TMEM217 Transmembrane Protein 217 [Homo Sapiens (human)]-Gene-NCBI]. National Center for Biotechnology Information. NCBI.
  3. Homo Sapiens Transmembrane Protein 217 (TMEM217), Transcript Variant 1, mRNA. National Center for Biotechnology Information. 17 September 2018. NCBI.
  4. Zuker. M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Research. 2003. 13. 31. 3406–3415. 10.1093/nar/gkg595. 12824337. 169194.
  5. Web site: Transmembrane Protein 217 Isoform 1 [Homo Sapiens] - Protein - NCBI]. National Center for Biotechnology Information. NCBI.
  6. Web site: Kramer. Jack. AASTATS. Biology Workbench. San Diego Supercomputer Center.
  7. Web site: Toldo. Luca. Isoelectric Point Determination. Biology Workbench. San Diego Supercomputer Center.
  8. Brendel. V.. Bucher. P.. Nourbakhsh. I.R.. Blaisdell. B.E.. Karlin. S.. Methods and algorithms for statistical analysis of protein sequences. Proceedings of the National Academy of Sciences. 1992. 89. 6. 2002–2006. 10.1073/pnas.89.6.2002. 1549558. 48584. 1992PNAS...89.2002B. free.
  9. Bo. Y.. Han. L.. He. J. Lanczycki. C.J.. 2017. CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.. Nucleic Acids Research. 45. D1. D200–D203. Marchler-Baur. A.. 10.1093/nar/gkw1129. 27899674. 5210587. free.
  10. Web site: Predict Location of Transmembrane Helices and Location of Intervening Loop Regions. Biology Workbench. San Diego Supercomputer Center.
  11. Fasman. G. D.. 1978. Prediction of the secondary structure of proteins from their amino acid sequence. Advances in Enzymology. 47. 45–148. Chou. P. Y..
  12. Blom. N.. Sicheritz. T.. Gupta. R.. Gammeltoft. S.. Brunak. S.. Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics. 2004. 4. 6. 1633–1649. 10.1002/pmic.200300771. 15174133. 18810164.
  13. Web site: Motif Scan. MyHits. ExPasy.
  14. Web site: Gupta. R.. Jung. E.. Brunak. S.. Prediction of N-glycosylation sites in human proteins. NetNGlyc 1.0 Server. Center for Biological Sequence Analysis.
  15. Web site: EST Profile-TMEM217-Transmembrane Protein 217. National Center for Biotechnology Information. NCBI.
  16. Web site: GEO Profiles-TMEM217. National Center for Biotechnology Information. NCBI.
  17. Reichenbach. M.. Reimann. K.. Reuter. H.. Gene expression in response to cyclic mechanical stretch in primary human dermal fibroblasts. Genomics Data. 2014. 2. 335–9. 10.1016/j.gdata.2014.09.010. 26484124. 4535970.
  18. Miao. Y.. Cui. L.. Chen. Z.. Zhang. L. Gene expression profiling of DMU-212-induced apoptosis and anti-angiogenesis in vascular endothelial cells. Pharmaceutical Biology. 2016. 54. 4. 660–666. 10.3109/13880209.2015.1071414. 26428916. free.
  19. Floudas. C. S.. Um. N.. Kamboh. M. I.. Barmada. M. M.. Visweswaran. S.. Identifying genetic interactions associated with late-onset Alzheimer's disease. BioData Mining. 2014. 7. 1. 35. 10.1186/s13040-014-0035-z. 25649863. 4300162 . free .
  20. Lin. H.. Huang. Y.. Lin. J.. Wu. J.. Association of Genes on Chromosome 6, GRIK2, TMEM217 and TMEM63B (Linked to MRPL14) with Diabetic Retinopathy. Ophthalmologica. 2013. 229. 1. 54–60. 10.1159/000342616. 23037145. 20024729.
  21. Sumoza-Toledo. A.. Espinoza-Gabriel. M.. Montiel-Condado. D.. Evaluation of the TRPM2 channel as a biomarker in breast cancer using public databases analysis. Boletín Médico del Hospital Infantil de México. 2016. 73. 6. 397–404. 10.1016/j.bmhime.2017.11.038. 29421284. free.
  22. Web site: TimeTree.
  23. Altschul. S.F.. Gish. W.. Miller. W.. Meyers. E.W.. Lipman. D.J.. Basic local alignment search tool. Molecular Biology. 1990. 215. 3. 403–410. 10.1006/jmbi.1990.9999. 2231712.
  24. Kent. W.J.. BLAT- the BLAST-like alignment tool. Genome Research. 2002. 12. 4. 656–664. 10.1101/gr.229202. 11932250. 187518.

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