Biology:Transmembrane protein 255A

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Short description: Mammalian protein found in Homo sapiens

Transmembrane protein 255A[1] is a protein that is encoded by the TMEM255A gene.[2] TMEM255A is often referred to as family with sequence similarity 70, member A (FAM70A).[3] The TMEM255A protein is transmembrane and is predicted to be located the nuclear envelope of eukaryote organisms.[4]

Gene

Human X chromosome with the location of TMEM255A marked at q24.[5]

The TMEM25A gene (often referred to as Family with Sequence Similarity 70 Member A; FAM70A) is located on Xq24, spanning 60,555 base pairs.[6] TMEM255A is flanked by the genes ATPase Na+/K+ transporting family member beta 4 (ATP1B4) and NFKB activating protein pseudogene 1 (NKAPP1).[7]

mRNA

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.[8] The mRNA is 3512 base pairs long and the gene consists of 9 exons.[9]

A prediction of TMEM255A's location in the nuclear membrane of Eukaryotic cells.[10]

Protein

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.[11][12][13] Compared to the average vertebrate protein, TMEM255A is rich in aspartic acid, isoleucine, proline and tyrosine, and relatively poor in glutamic acid and lysine.[14] No charge clusters have been found in this protein.

The protein is predicted to be post-translationally modified by phosphorylation and glycosylation.[15] 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.[16][17][18] 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.[19][20][21][22]

Isoform Accession number Description
1 NP_060408.3 The longest transcript and isoform
2 NP_001098014.1 Shorter protein product than isoform 1, lacks one in-frame alternative midsection exon
3 NP_001098015.1 Lacks three in-frame exons. Shorter than isoform 1 and 2.

Expression

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.[23][24][25]

Regulation of expression

Both the 5' and 3' Untranslated Regions (UTRs) are predicted to consist of several stem-loops.[26] The 3' UTR also contain a conserved miRNA target site (amino acids 22-29).[27] Phosphorylation and glycosylation sites have also been predicted in TMEM255A.[28][29]

Interacting proteins

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.[30]

Clinical significance

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).[31] Ongoing research is investigating the possibility of TMEM255A to be used in personalized immunotherapy.[32]

Homology

This time-calibrated phylogenetic tree shows the evolution of TMEM255A through its journey of human evolution. The distance on the tree correlates to years since divergence.

There is one known paralog for TMEM255A, called TMEM255B, which is found on chromosome 13 (position 13q34).[33] TMEM255A is only found in the kingdom of animalia, and its most distant homolog is found in invertebrata (i.e. Saccoglossus kowalenskii).

Species NCBI Accession # Divergence (MYA) Sequence Length (aa) Sequence ID (%) Sequence Similarity (%)
Homo sapiens (Human) NP_060408.3 - 349 100 100
Elephantulus edwardii (Cape Elephant Shrew) XP_006893850.1 105 351 97 98
Gallus gallus (Chicken) XP_015134112.1 312 323 79 84
Chrysemys picta bellii (Painted turtle) XP_008167250.1 312 323 79 84
Nanorana parkeri (High Himalaya frog) XP_018415588.1 352 327 69 77
Cyprinus carpio (Common carp) XP_018971120.1 435 342 58 67
Saccoglossus kowalevskii (Acorn worm) XP_006819139.1 684 351 23 45

References

  1. ↑ Homo sapiens transmembrane protein 255A (TMEM255A), transcript variant - Nucleotide - NCBI. 2018-06-24. https://www.ncbi.nlm.nih.gov/nuccore/NM_017938.3. 
  2. ↑ NCBI, National Center for Biotechnology Information. "TMEM255A Transmembrane Protein 255A [Homo sapiens"]. https://www.ncbi.nlm.nih.gov/gene/55026. 
  3. ↑ Database, GeneCards Human Gene. "TMEM255A Gene - GeneCards | T255A Protein | T255A Antibody". https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM255A. 
  4. ↑ "Search: TMEM255A - The Human Protein Atlas". http://www.proteinatlas.org/search/TMEM255A. 
  5. ↑ ] (2017-05-06). Image: GeneCards, 2017
  6. ↑ "TMEM255A". April 25, 2017. https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM255A. 
  7. ↑ "Gene neighbors for Gene (Select 55026) - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene?LinkName=gene_gene_neighbors&from_uid=55026. 
  8. ↑ "The Mfold Web Server" (in EN). http://unafold.rna.albany.edu/?q=mfold. 
  9. ↑ National Center for Biotechnology Information, NCBI. "TMEM255A transmembrane protein 255A [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/55026. 
  10. ↑ Image: Kristin H. Aaen, 2017.
  11. ↑ National Center for Biotechnology Information, NCBI Gene (2017-04-02). "Transmembrane Domain 255A, Homo sapiens". https://www.ncbi.nlm.nih.gov/gene/55026. 
  12. ↑ Subramaniam, S. (1998). "The Biology Workbench: a seamless database and analysis environment for the biologist". Proteins 2 (1): 1–2. doi:10.1002/(SICI)1097-0134(19980701)32:1<1::AID-PROT1>3.0.CO;2-Q. PMID 9672036. 
  13. ↑ Toldo, Luca (April 25, 2017). "Gateway to Isoelectric Point Service". http://www.embl-heidelberg.de/cgi/pi-wrapper.pl. 
  14. ↑ Dyer, K. F. (1971). "The quiet revolution: A new synthesis of biological knowledge". Journal of Biological Education 5: 15–24. doi:10.1080/00219266.1971.9653663. http://www.tiem.utk.edu/~gross/bioed/webmodules/aminoacid.htm. Retrieved 2017-05-06. 
  15. ↑ Blom, N. (Summer 2002). "Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence". Proteomics 6: 1633–49. 
  16. ↑ Yang, J. (2015). "The I-TASSER Suite: Protein structure and function prediction". Nature Methods 12 (1): 7–8. doi:10.1038/nmeth.3213. PMID 25549265. 
  17. ↑ Roy, A. (2010). "I-TASSER: a unified platform for automated protein structure and function prediction". Nature Protocols 5 (4): 725–738. doi:10.1038/nprot.2010.5. PMID 20360767. 
  18. ↑ Zhang, Y. (2008). "I-TASSER server for protein 3D structure prediction". BMC Bioinformatics 9: 40. doi:10.1186/1471-2105-9-40. PMID 18215316. 
  19. ↑ Ferre & Clote (2006). "DiANNA 1.1: an extension of the DiANNA web server for ternary cysteine classification". Nucleic Acids Research 34 (Web Server issue): W182-5. doi:10.1093/nar/gkl189. PMID 16844987. 
  20. ↑ Ferre & Clote (Summer 2005). "DiANNA: a web server for disulfide connectivity prediction". Nucleic Acids Res. 33 (Web Server issue): W230–2. doi:10.1093/nar/gki412. PMID 15980459. 
  21. ↑ Ferre & Clote (Summer 2005). "Disulfide connectivity prediction using secondary structure information and diresidue frequencies". Bioinformatics 21 (10): 2336–46. doi:10.1093/bioinformatics/bti328. PMID 15741247. 
  22. ↑ Go (2010). "Redox control systems in the nucleus: mechanisms and functions". Antioxidants & Redox Signaling 13 (4): 489–509. doi:10.1089/ars.2009.3021. PMID 20210649. 
  23. ↑ Input: TMEM255A. "EST Profile: Transmembrane Protein Domain 255A". https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.437563. 
  24. ↑ National Cancer Institute, Cancer Genome Anatomy Project. "Transmembrane protein 255A". https://cgap.nci.nih.gov/Genes/GeneInfo?ORG=Hs&CID=437563&LLNO=55026. 
  25. ↑ BioGPS, BioGPS. "TMEM255A". http://biogps.org/#goto=genereport&id=55026. 
  26. ↑ "SUNY Albany Research IT Group". 2017-04-02. http://unafold.rna.albany.edu/?q=mfold. 
  27. ↑ Argawal (2017-04-17). "TargetScan Human: Prediction of miRNA Targets". http://www.targetscan.org/vert_71/. 
  28. ↑ Gupta & Brunak (2002). "Prediction of glycosylation across the human proteome and the correlation to protein function". Pacific Symposium on Biocomputing 322: 310–22. PMID 11928486. 
  29. ↑ Blom (2004-06-04). "Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence". Proteomics 4 (6): 1633–49. doi:10.1002/pmic.200300771. PMID 15174133. 
  30. ↑ Chatr-Aryamontri (2016-12-14). "The BioGRID interaction database: 2017 update". Nucleic Acids Research 45 (D1): D369–D379. doi:10.1093/nar/gkw1102. PMID 27980099. PMC 5210573. https://thebiogrid.org/. 
  31. ↑ Cho (2017-01-13). "Expression of PGC1α in glioblastoma multiforme patients". Oncology Letters 13 (6): 4055–76. doi:10.3892/ol.2017.5972. PMID 28599408. 
  32. ↑ Weinschenk (2014). "Personalized immunotherapy against several neuronal and brain tumors". U.S. Patent Application No 14/531: 472. https://www.google.com/patents/CA2929445A1?cl=en&hl=no. 
  33. ↑ Human Gene Database, GeneCards. "TMEM255B Gene". GeneCards. https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM255B. 



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