Biology:RTL6

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

Retrotransposon Gag Like 6 is a protein encoded by the RTL6 gene in humans.[1] RTL6 is a member of the Mart family of genes, which are related to Sushi-like retrotransposons and were derived from fish and amphibians.[2] The RTL6 protein is localized to the nucleus and has a predicted leucine zipper motif that is known to bind nucleic acids in similar proteins, such as LDOC1.

Gene

Locus

Gene neighborhood of RTL6 on chromosome 22.[1]

The gene is on Chromosome 22 (human) at 22q13.31 on the minus strand from 44492570 to 44498125 nt on the GRCh38.p7 assembly of the human genome. Aliases for the gene include LDOC1L, MAR6, MART6, and SIRH3. RTL6 is made up of 2 exons and is encoded by 5556 base pairs of DNA .[3]

Origin

RTL6 is a retrotransposon GAG related gene. It is one of eleven MART (Mammalian Retrotransposon Derived) genes in humans related to Sushi-like retrotransposons with long terminal repeats from fish and amphibians.[2] Between 170 and 310 MYA, MART genes lost their ability to retrotranspose and concomitantly gained new, beneficial function for its host organism.[4]

mRNA

RTL6 has an alternate start of transcription 140 base pairs upstream of the normal transcribed region. The lengths of the primary mRNA and that with the upstream start of transcription are 5355 and 5495 base pairs respectively.[3]

Protein

Primary information

The primary amino acid sequence for RTL6 is made up of 239 residues.[1] There are no known alternative splice variants of the protein. The molecular weight of the protein is 26.2 kDa and the isoelectric point is 11.58.[5] RTL6 is a proline and arginine rich protein.[5]

Immunohistochemical staining of human stomach shows strong nuclear and cytoplasmic positivity in glandular cells.[9]

Domains and motifs

RTL6 contains a predicted leucine zipper motif known to participate in nucleic acid binding in other proteins.[5] RTL6 also contains a domain of unknown function from amino acid residues 98-177 . RTL6 is one of a number of genes belonging to the DUF4939 (domain of unknown function) superfamily.[10]

Secondary structure

The secondary structure of RTL6 is made up of largely alpha helices.[11] One region of RTL6 is also predicted to participate in a coiled-coil structure from amino acid residues 29–63.[10]

Post-translational modifications

There are also two predicted phosphorylation sites for Protein Kinase C with high confidence scores at amino acid residues 6 and 45.[12][13] There is also a predicted ubiquitination site with medium-confidence at amino acid residue 8.[14]

An annotated schematic of the RTL6 protein showing motifs and predicted phosphorylation and ubiquitination sites.

Cellular sublocation

RTL6 is expected to be localized to the nucleus and cytosol based on the presence of a leucine zipper domain, the absence of signals indicating secretion or transmembrane domains, and immunohistochemical staining.[15][16][17]

Expression

RTL6 has been shown to be expressed at high levels during all stages of development and in a wide variety of tissues.[18][19][9]

RTL6 expression has been shown to fall in HeLa cervical cancer cells upon treatment with chemotherapeutic Casiopeinas and in A549 lung cancer cells upon treatment with Actinomycin D.[20][21]

Interacting proteins

RTL6 has been shown to interact with the following proteins:

DDIT3 DNA damage-inducible transcript 3 protein [22]
NXF1 Nuclear RNA export factor 1 [23]
STX18 Syntaxin 18 [24]
MAFF MAF bZIP transcription factor F [24]
GOPC Golgi-associated PDZ and coiled-coil motif-containing protein [24]
BATF3 Basic leucine zipper transcriptional factor ATF-like 3 [24]
TERF2 Telomeric repeat-binding factor 2 [25]
UXAC Uronate isomerase (Yersinia pestis) [26]

Clinical significance

The RTL6 protein has been shown to interact with the UXAC protein from Yersinia pestis, the gram-negative bacterium responsible for the bubonic plague.[26]

Homology/evolution

Paralogs

Eleven paralogs were identified for RTL6 in humans. The paralogs have diverse functions and expression patterns, although many are known to have zinc finger domains and bind nucleic acids:

MART Family Name Accession Number Sequence Length Query Cover Percent Similarity
RTL1 [27] NP_001128360.1 1358 100 7.6
PEG10 (RTL2) [28] NP_055883.2 359 35 35
RTL3 [29] NP_689907.1 2648 100 2.2
RTL4 [30] NP_001004308.2 310 100 19
RTL5 [31] NP_001019626.1 569 37 53
RTL6 [1] NP_115663.2 239 NA NA
LDOC1 (RTL7) [32] NP_036449.1 146 33 41
RTL8A [33] NP_001071640.1 113 33 44
RTL8B [34] NP_001071641.1 113 33 43
RTL8C [35] NP_001071639.1 113 33 44
RTL9 [36] NP_065820.1 1388 22 39
RTL10 [37] NP_078903.3 364 34 35

Orthologs

RTL6 is highly conserved across mammals, including the leucine zipper motif and DUF4939. The gene is also conserved in marsupials such as the opossum but not in birds such as the chicken, suggesting the gene was likely formed after the divergence of mammals and birds but before the divergence of marsupials and mammals (170-310 MYA:[2]

Organism Common Name Classification Accession Number Percent Identity Query Cover Percent Similarity
Homo sapiens Humans Primate NP_115663.2 [1] NA NA NA
Macaca mulatta Rhesus Monkey Primate NP_001181372.1 [38] 98 100 99
Felis catus House Cat Carnivore XP_003989415.1 [39] 97 100 98
Mus muscalus Common Mouse Rodent NP_808298.2 [40] 92 100 96
Pteropus alecto Black Flying Fox Bat XP_006917396.1 [41] 96 100 98
Equus caballus Horse Odd-Toed Ungulates XP_005606827.1 [42] 95 100 98
Bos Taurus Cattle Even-Toed Ungulates XP_015326927.1 [43] 94 100 97
Orcinus orca Killer Whale Whales/Dolphins XP_004279624.1 [44] 95 100 98
Trichechus manatus latirostirs Florida Manatee Placentals XP_004380056.1 [45] 95 100 96
Erinaceus europaeus European Hedgehog Rabbits/Hares XP_016043235.1 [46] 93 100 96
Ochotona princeps American Pika Insectivoires XP_004589491.1 [47] 92 100 97

The most distantly detectable organisms with homology in the gene are bony fishes including salmon and the common carp, but similarity to the human protein sequence is markedly less than that of mammals. No traces of the gene can be seen in intermediates between mammals and bony fishes such as reptiles or amphibians:

Organism Common Name Classification Accession Number Percent Identity Query Cover Percent Similarity
Homo sapiens Humans Primate NP_115663.2 [1] 100 100 100
Cyprinus carpio Common Carp Bony Fishes XP_018946777 [48] 30 41 34
Esox lucius Northern Pike Bony Fishes XP_019899574.1 [49] 31 55 31
Nothobranchius furzeri Black Rockcod Bony Fishes XP_010767110 [50] 37 35 39

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "RTL6 retrotransposon Gag like 6 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/84247. 
  2. ↑ 2.0 2.1 2.2 "Transposable elements as a source of genetic innovation: expression and evolution of a family of retrotransposon-derived neogenes in mammals". Gene 345 (1): 101–11. January 2005. doi:10.1016/j.gene.2004.11.022. PMID 15716091. 
  3. ↑ 3.0 3.1 "LDOC1L LDOC1 like [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/84247. 
  4. ↑ "A family of neofunctionalized Ty3/gypsy retrotransposon genes in mammalian genomes". Cytogenetic and Genome Research 110 (1–4): 307–17. 2005-01-01. doi:10.1159/000084963. PMID 16093683. 
  5. ↑ 5.0 5.1 5.2 Brendel, V., Bucher, P., Nourbakhsh, I.R., Blaisdell, B.E. & Karlin, S. (1992) "Methods and algorithms for statistical analysis of protein sequences" Proc. Natl. Acad. Sci. U.S.A. 89, 2002-2006.
  6. ↑ J Yang, R Yan, A Roy, D Xu, J Poisson, Y Zhang. The I-TASSER Suite: Protein structure and function prediction. Nature Methods, 12: 7-8, 2015.
  7. ↑ A Roy, A Kucukural, Y Zhang. I-TASSER: a unified platform for automated protein structure and function prediction. Nature Protocols, 5: 725-738, 2010.
  8. ↑ Y Zhang. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics, 9: 40, 2008.
  9. ↑ 9.0 9.1 "Cell atlas - LDOC1L - The Human Protein Atlas". http://www.proteinatlas.org/ENSG00000188636-LDOC1L/cell. 
  10. ↑ 10.0 10.1 "LDOC1L - Protein LDOC1L - Homo sapiens (Human) - LDOC1L gene & protein" (in en). https://www.uniprot.org/uniprot/Q6ICC9. 
  11. ↑ Garnier, Gibrat, and Robson, Meth. Enzymol., R.F. Doolittle ed. (1996) 266:97-120
  12. ↑ "Motif Scan" (in en). http://myhits.isb-sib.ch/cgi-bin/motif_scan. 
  13. ↑ "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. 
  14. ↑ "Identification, analysis, and prediction of protein ubiquitination sites". Proteins 78 (2): 365–80. February 2010. doi:10.1002/prot.22555. PMID 19722269. 
  15. ↑ "PSORT: Protein Subcellular Localization Prediction Tool". http://www.genscript.com/psort.html. 
  16. ↑ "iLoc-Animal: a multi-label learning classifier for predicting subcellular localization of animal proteins" (in en). Molecular BioSystems 9 (4): 634–44. April 2013. doi:10.1039/c3mb25466f. PMID 23370050. 
  17. ↑ "BLAST: Basic Local Alignment Search Tool". https://blast.ncbi.nlm.nih.gov/Blast.cgi. 
  18. ↑ "Gene Detail :: Allen Brain Atlas: Mouse Brain". http://mouse.brain-map.org/gene/show/85967. 
  19. ↑ "Leucine zipper, down-regulated in cancer 1-like (Ldoc1l)". https://www.ncbi.nlm.nih.gov/UniGene/clust.cgi?UGID=258347&TAXID=10090&SEARCH=LDOC1L. 
  20. ↑ "Genotoxicity of the copper antineoplastic coordination complexes casiopeinas". Toxicology in Vitro 25 (7): 1376–84. October 2011. doi:10.1016/j.tiv.2011.05.008. PMID 21601632. 
  21. ↑ "DNA sequence selectivity of topoisomerases and topoisomerase poisons". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1400 (1–3): 185–94. October 1998. doi:10.1016/S0167-4781(98)00135-3. PMID 9748568. 
  22. ↑ "Network organization of the human autophagy system". Nature 466 (7302): 68–76. July 2010. doi:10.1038/nature09204. PMID 20562859. Bibcode: 2010Natur.466...68B. 
  23. ↑ "Insights into RNA biology from an atlas of mammalian mRNA-binding proteins". Cell 149 (6): 1393–406. June 2012. doi:10.1016/j.cell.2012.04.031. PMID 22658674. 
  24. ↑ 24.0 24.1 24.2 24.3 "The BioPlex Network: A Systematic Exploration of the Human Interactome". Cell 162 (2): 425–440. July 2015. doi:10.1016/j.cell.2015.06.043. PMID 26186194. 
  25. ↑ "The protein network surrounding the human telomere repeat binding factors TRF1, TRF2, and POT1". PLOS ONE 5 (8): e12407. August 2010. doi:10.1371/journal.pone.0012407. PMID 20811636. Bibcode: 2010PLoSO...512407G. 
  26. ↑ 26.0 26.1 "The human-bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestis". PLOS ONE 5 (8): e12089. August 2010. doi:10.1371/journal.pone.0012089. PMID 20711500. Bibcode: 2010PLoSO...512089D. 
  27. ↑ "RTL1 retrotransposon Gag like 1 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/388015. 
  28. ↑ "PEG10 paternally expressed 10 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/23089. 
  29. ↑ "RTL3 retrotransposon Gag like 3 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/?term=rtl3+homo+sapiens. 
  30. ↑ "RTL4 retrotransposon Gag like 4 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/340595. 
  31. ↑ "RTL5 retrotransposon Gag like 5 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/340526. 
  32. ↑ "LDOC1 LDOC1, regulator of NFKB signaling [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/?term=rtl7. 
  33. ↑ "RTL8A retrotransposon Gag like 8A [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/?term=FAM127B+homo+sapiens. 
  34. ↑ "RTL8B retrotransposon Gag like 8B [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/?term=FAM127C+homo+sapiens. 
  35. ↑ "RTL8C retrotransposon Gag like 8C [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/?term=FAM127A+homo+sapiens. 
  36. ↑ "RTL9 retrotransposon Gag like 9 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/57529. 
  37. ↑ "RTL10 retrotransposon Gag like 10 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/79680. 
  38. ↑ "RTL6 retrotransposon Gag like 6 [Macaca mulatta (Rhesus monkey) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/712760. 
  39. ↑ "RTL6 retrotransposon Gag like 6 [Felis catus (domestic cat) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/101088345. 
  40. ↑ "Ldoc1l leucine zipper, down-regulated in cancer 1-like [Mus musculus (house mouse) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/223732. 
  41. ↑ "RTL6 retrotransposon Gag like 6 [Pteropus alecto (black flying fox) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/102880687. 
  42. ↑ "RTL6 retrotransposon Gag like 6 [Equus caballus (horse) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/100051281. 
  43. ↑ "RTL6 retrotransposon Gag like 6 [Bos taurus (cattle) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/786696. 
  44. ↑ "RTL6 retrotransposon Gag like 6 [Orcinus orca (killer whale) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/101279333. 
  45. ↑ "LOC101345980 retrotransposon Gag like 6 [Trichechus manatus latirostris (Florida manatee) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/101345980. 
  46. ↑ "RTL6 retrotransposon Gag like 6 [Erinaceus europaeus (western European hedgehog) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/103112730. 
  47. ↑ "RTL6 retrotransposon Gag like 6 [Ochotona princeps (American pika) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/101529959. 
  48. ↑ "PREDICTED: protein LDOC1-like [Cyprinus carpio - Protein - NCBI"]. https://www.ncbi.nlm.nih.gov/protein/1101561525/. 
  49. ↑ "PREDICTED: protein LDOC1L-like [Esox lucius - Protein - NCBI"]. https://www.ncbi.nlm.nih.gov/protein/XP_019899574.1. 
  50. ↑ "PREDICTED: uncharacterized protein LOC104943421 [Notothenia coriiceps - Protein - NCBI"]. https://www.ncbi.nlm.nih.gov/protein/XP_010767110. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:RTL6&oldid=3503123"