Biology:Transmembrane protein 179

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A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Transmembrane protein 179 is a protein that in humans is encoded by the TMEM179 gene.[1] The function of transmembrane protein 179 is not yet well understood, but it is believed to have a function in the nervous system.[2]

Gene

In humans, TMEM179 is located on the long arm of chromosome 14 on the reverse strand and maps to 14q32.33 with the genomic sequence starting at 104,592,993 bp and ending at 104,604,983 bp.[1][3] Alternative names for this gene are "C14orf90" and "FLJ42486"[4][5] TMEM179 contains four exons.[6]

mRNA

There are four isoforms of the TMEM179 protein due to alternative splicing of the pre mRNA transcript.[1]

Protein

Transmembrane protein 179 is 233 amino acids long.[4] Transmembrane protein 179 has a predicted molecular weight of 26 kDa and a predicted isoelectric point of 5.[7] Both the Homo sapiens and Xenopus laevis proteins contain a much higher than normal level of phenylalanine, a higher than normal level of leucine and tryptophan, and a lower than normal level of proline compared to other proteins from their respective organisms.[8] Both the human and frog proteins have the repetitive structure of “LAFL” appearing twice in their protein which suggests that this repetitive sequence may have some significance.[8]

Isoform Name Size (AA) Exons used Accession Number
Transmembrane protein 179 Isoform 1 233 1,2,3,& 4 NP_001273318.1
Transmembrane protein 179 Isoform 2 174 1,2,& 3 NP_001273319.1
Transmembrane protein 179 Isoform 3 102 1 XP_011535048.1
Transmembrane protein 179 Isoform 4 131 2,3,& 4 XP_011535052.1

Subcellular location

Transmembrane protein 179 is predicted to be localized to the endoplasmic reticulum(ER).[9]

Structure

Transmembrane protein 179 is predicted to have four transmembrane regions with the N-terminus located on the cytosol side of the membrane.[10] The secondary structure of transmembrane protein 179 is predicted to be made up of mostly alpha helix (52.36%) with some regions of random coil (31.33%) and beta sheets (12.02%).[11] transmembrane protein 179 is predicted to have two disulfide bridges, both located on the ER lumenal side of the membrane.[12]

Post-translational modifications

Transmembrane protein 179 is predicted to undergo various post-translational modifications such as S-palmitoylation, N-glycosylation, Glycation, Phosphorylation, and O-Linked β-N-acetylglucosamine.[13][14][15][16][17]

A cartoon of transmembrane protein 179 depicting the orientation and location of the post-translational modifications of the protein.[18] The gray flags indicate the location of predicted post-translational modifications.
An annotated conceptual translation depicting the predicted post-translational modifications of transmembrane protein 179.

Expression

Normal tissue expression

TMEM179 has been shown to be most highly expressed in brain and spinal cord tissue.[19][20] The gene is also relatively highly expressed in tissues in the lungs, adrenal gland, and testis.[1][21]

Abnormal tissue expression

TMEM179 has been shown to be relatively highly expressed in glioma cells.[21] TMEM179 has also been shown to be expressed highly in some other cancer cell lines.[22] It was most highly expressed in a small cell lung cancer cell line. It was also expressed in cancer cell lines originating from the brain, renal/urinary/male reproductive systems, and Breast/female reproductive system.

Regulation of Expression

The TMEM179 promoter was found to start at 104,604,641 bp and end at 104,606,647 bp on the reverse strand using Genomatix's Gene2Promoter tool.[23] Genomatix's MatInspector tool found 732 predicted transcription factor binding sites for this promoter. Some transcription factors that are predicted to bind to the TMEM179 promoter that are of particular interest are EGR1—of which there are four predicted binding sites—and Neuron-Restrictive Silencer Factor (NRSF), both of which are involved in the regulation of neuron growth.

Interacting Proteins

Transmembrane protein 179 has no known protein interactions.[24]

Homology

Paralogs

There are no known paralogs of the TMEM179 gene.[6][25]

Orthologs

Orthologs of TMEM179 have been found in animals as distantly related to humans as annelids and arthropods, but no orthologs have been found in more distantly related animals such as those in clades Porifera, Nematoda, and Cnidaria.[25] No orthologs have been found in any nonanimal organisms.

A multiple sequence alignment of orthologous transmembrane protein 179 sequences from various species. The sequences are named with the first letter of the organism's genus name followed by the first two letters of the species name (Homo sapiens is labelled Hsa_TMEM179). Amino acids that are shaded black are highly conserved. This multiple sequence alignment was made using Clustal Omega and Boxshade.[26][27]
Table of TMEM179 Orthologs
Species Taxonomic Group Median Time of Divergence From Homo sapiens (Millions of Years Ago)[28] Accession Number Sequence Identity to Homo sapiens (%)
Homo sapiens Mammalia 0 NP_001273318.1 100
Mus musculus Mammalia 88 NP_849246.2 94
Dromaius novaehollandiae Aves 320 XP_025968310.1 84
Python bivittatus Reptila 320 XP_007436683.1 83
Xenopus laevis Amphibia 353 XP_018087798.1 76
Danio rerio Actinopterygii 432 XP_003200427.1 66
Rhincodon typus Chondrichthyes 465 XP_020385663.1 70
Branchiostoma belcheri Chordata 699 XP_019647683.1 35
Biomphalaria glabrata Mollusca 794 XP_013064109.1 38
Onthophagus taurus Arthropoda 794 XP_022914672.1 33
Daphnia pulex Arthropoda 794 EFX83970.1 33
Capitella teleta Annelida 794 ELU12883.1 32

Function

The function of transmembrane protein 179 is not yet well understood. TMEM179 has been identified in a patent involving the production of neural regenerating cells (NRCs) from marrow adherent stem cells (MASCs).[2] According to this patent the methylation of CpG sequences in TMEM179 is decreased in NRCs compared to MASCs. This finding, coupled with the finding that TMEM179 is most highly expressed in the brain and spinal cord, provides strong evidence that transmembrane protein 179 plays a role in nervous system development. This function is also supported by the fact that no orthologs of TMEM179 have been found in nonanimal organisms or animals that lack a nervous system such as sea sponges.

References

  1. ↑ 1.0 1.1 1.2 1.3 "TMEM179 transmembrane protein 179 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/388021. 
  2. ↑ 2.0 2.1 Case, C. (2011). US20110136114A1. United States. Retrieved from https://patents.google.com/patent/US20110136114A1/en
  3. ↑ "The human genome browser at UCSC". Genome Research 12 (6): 996–1006. June 2002. doi:10.1101/gr.229102. PMID 12045153. 
  4. ↑ 4.0 4.1 "Genecards Entry on TMEM179". https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM179&keywords=TMEM179. 
  5. ↑ "TMEM179 (transmembrane protein 179)". http://atlasgeneticsoncology.org/Genes/GC_TMEM179.html. 
  6. ↑ 6.0 6.1 "BLAT--the BLAST-like alignment tool". Genome Research 12 (4): 656–64. April 2002. doi:10.1101/gr.229202. PMID 11932250. 
  7. ↑ Walker, John M., 1948- (2005). The proteomics protocols handbook. Humana Press. ISBN 978-1588293435. OCLC 55955457. https://archive.org/details/proteomicsprotoc00john. 
  8. ↑ 8.0 8.1 "Methods and algorithms for statistical analysis of protein sequences". Proceedings of the National Academy of Sciences of the United States of America 89 (6): 2002–6. March 1992. doi:10.1073/pnas.89.6.2002. PMID 1549558. Bibcode: 1992PNAS...89.2002B. 
  9. ↑ Nakai, Kenta; Horton, Paul (2007). "Computational Prediction of Subcellular Localization". Protein Targeting Protocols. Methods in Molecular Biology. 390. Humana Press. pp. 429–466. doi:10.1007/1-59745-466-4_29. ISBN 9781588297020. https://archive.org/details/proteintargeting00mark. 
  10. ↑ "SOSUI: classification and secondary structure prediction system for membrane proteins". Bioinformatics 14 (4): 378–9. 1998-05-01. doi:10.1093/bioinformatics/14.4.378. PMID 9632836. 
  11. ↑ "NPS@: network protein sequence analysis". Trends in Biochemical Sciences 25 (3): 147–50. March 2000. doi:10.1016/s0968-0004(99)01540-6. PMID 10694887. 
  12. ↑ "DISULFIND: a disulfide bonding state and cysteine connectivity prediction server". Nucleic Acids Research 34 (Web Server issue): W177-81. July 2006. doi:10.1093/nar/gkl266. PMID 16844986. 
  13. ↑ "CSS-Palm: palmitoylation site prediction with a clustering and scoring strategy (CSS)". Bioinformatics 22 (7): 894–6. April 2006. doi:10.1093/bioinformatics/btl013. PMID 16434441. 
  14. ↑ Julenius, Karin; Johansen, Morten B.; Zhang, Yu; Brunak, Sre n; Gupta, Ramneek (2009). "Prediction of Glycosylation Sites in Proteins". Bioinformatics for Glycobiology and Glycomics. John Wiley & Sons, Ltd. pp. 163–192. doi:10.1002/9780470029619.ch9. ISBN 9780470029619. 
  15. ↑ "Analysis and prediction of mammalian protein glycation". Glycobiology 16 (9): 844–53. September 2006. doi:10.1093/glycob/cwl009. PMID 16762979. 
  16. ↑ "Sequence and structure-based prediction of eukaryotic protein phosphorylation sites". Journal of Molecular Biology 294 (5): 1351–62. December 1999. doi:10.1006/jmbi.1999.3310. PMID 10600390. 
  17. ↑ "Prediction of glycosylation across the human proteome and the correlation to protein function". Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing (World Scientific): 310–22. 2002. doi:10.1142/9789812799623_0029. ISBN 9789810247775. PMID 11928486. https://archive.org/details/pacificsymposium00paci/page/310. 
  18. ↑ "The 20 years of PROSITE". Nucleic Acids Research 36 (Database issue): D245-9. January 2008. doi:10.1093/nar/gkm977. PMID 18003654. 
  19. ↑ "AceView: Gene:TMEM179, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView.". https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=TMEM179&submit=Go. 
  20. ↑ NCBI GEO Profile GDS3052 entry on TMEM179. [https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS3052:1436754_at]
  21. ↑ 21.0 21.1 "NCBI Unigene EST Profile Viewer entry on TMEM179". https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi. 
  22. ↑ "Cell atlas - TMEM179 - The Human Protein Atlas". https://www.proteinatlas.org/ENSG00000258986-TMEM179/cell. 
  23. ↑ "MatInspector and beyond: promoter analysis based on transcription factor binding sites". Bioinformatics 21 (13): 2933–42. July 2005. doi:10.1093/bioinformatics/bti473. PMID 15860560. 
  24. ↑ "PSICQUIC and PSISCORE: accessing and scoring molecular interactions". Nature Methods 8 (7): 528–9. June 2011. doi:10.1038/nmeth.1637. PMID 21716279. 
  25. ↑ 25.0 25.1 "Protein BLAST: search protein databases using a protein query". https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins. 
  26. ↑ "Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega". Molecular Systems Biology 7 (1): 539. October 2011. doi:10.1038/msb.2011.75. PMID 21988835. 
  27. ↑ "BoxShade Server". https://embnet.vital-it.ch/software/BOX_form.html. 
  28. ↑ "TimeTree :: The Timescale of Life". http://www.timetree.org/. 




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