RTL6

Retrotransposon Gag Like 6 is a protein encoded by the RTL6 gene in humans. RTL6 is a member of the Mart family of genes, which are related to Sushi-like retrotransposons and were derived from fish and amphibians. 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. __FORCETOC__

Gene

Locus 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 .

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. Between 170 and 310 MYA, MART genes lost their ability to retrotranspose and concomitantly gained new, beneficial function for its host organism.

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.

Protein

Primary information The primary amino acid sequence for RTL6 is made up of 239 residues. 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.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. RTL6 is a proline and arginine rich protein.

Domains and motifs RTL6 contains a predicted leucine zipper motif known to participate in nucleic acid binding in other proteins. 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.

Secondary structure The secondary structure of RTL6 is made up of largely alpha helices.Garnier, Gibrat, and Robson, Meth. Enzymol., R.F. Doolittle ed. (1996) 266:97-120 One region of RTL6 is also predicted to participate in a coiled-coil structure from amino acid residues 29–63.

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. There is also a predicted ubiquitination site with medium-confidence at amino acid residue 8.

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.

Expression RTL6 has been shown to be expressed at high levels during all stages of development and in a wide variety of tissues.

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.

Interacting proteins RTL6 has been shown to interact with the following proteins: DDIT3DNA damage-inducible transcript 3 protein NXF1Nuclear RNA export factor 1 STX18Syntaxin 18 MAFFMAF bZIP transcription factor F GOPCGolgi-associated PDZ and coiled-coil motif-containing protein BATF3Basic leucine zipper transcriptional factor ATF-like 3 TERF2Telomeric repeat-binding factor 2 UXACUronate isomerase (Yersinia pestis)

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.

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 NameAccession numberSequence lengthQuery CoverPercent SimilarityRTL1 NP_001128360.1 13581007.6PEG10 (RTL2) NP_055883.23593535RTL3 NP_689907.126481002.2RTL4 NP_001004308.231010019RTL5 NP_001019626.1 5693753RTL6 NP_115663.2 239NANALDOC1 (RTL7) NP_036449.11463341RTL8A NP_001071640.11133344RTL8B NP_001071641.11133343RTL8C NP_001071639.11133344RTL9 NP_065820.1 13882239RTL10 NP_078903.33643435

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: OrganismCommon nameClassificationAccession numberPercent identityQuery CoverPercent SimilarityHomo sapiensHumansPrimateNP_115663.2 NANANAMacaca mulatta Rhesus MonkeyPrimateNP_001181372.1 9810099Felis catusHouse CatCarnivoreXP_003989415.1 9710098Mus muscalus Common MouseRodentNP_808298.2 9210096Pteropus alectoBlack Flying FoxBatXP_006917396.1 9610098Equus caballusHorseOdd-Toed UngulatesXP_005606827.1 9510098Bos TaurusCattleEven-Toed UngulatesXP_015326927.1 9410097Orcinus orcaKiller WhaleWhales/DolphinsXP_004279624.1 9510098Trichechus manatus latirostirsFlorida ManateePlacentalsXP_004380056.1 9510096Erinaceus europaeusEuropean HedgehogRabbits/HaresXP_016043235.1 9310096Ochotona princepsAmerican PikaInsectivoiresXP_004589491.1 9210097 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: OrganismCommon nameClassificationAccession numberPercent identityQuery CoverPercent SimilarityHomo sapiensHumansPrimateNP_115663.2 100100100Cyprinus carpioCommon CarpBony FishesXP_018946777 304134Esox luciusNorthern PikeBony FishesXP_019899574.1 315531Nothobranchius furzeriBlack RockcodBony FishesXP_010767110 373539

References