RTL6

RTL6
Identifiers
Aliases	RTL6, Mar6, Mart6, dJ1033E15.2, LDOC1L, leucine zipper, down-regulated in cancer 1-like, leucine zipper, down-regulated in cancer 1 like, LDOC1 like, SIRH3, retrotransposon Gag like 6
External IDs	MGI: 2675858; HomoloGene: 18594; GeneCards: RTL6; OMA:RTL6 - orthologs
Gene location (Human)
Chr.	Chromosome 22 (human)
End	44,498,233 bp
Gene location (Mouse)
Chr.	Chromosome 15 (mouse)
End	84,442,024 bp
RNA expression pattern
	Top expressed in
	endothelial cell; ; tibialis anterior muscle; ; mucosa of ileum; ; pancreatic epithelial cell; ; myocardium of left ventricle; ; ganglionic eminence; ; pancreatic ductal cell; ; cardiac muscle tissue of right atrium; ; middle temporal gyrus; ; ventricular zone;
	Top expressed in
	saccule; ; otic vesicle; ; perirhinal cortex; ; entorhinal cortex; ; ganglionic eminence; ; CA3 field; ; medial ganglionic eminence; ; habenula; ; visual cortex; ; olfactory epithelium;
	More reference expression data
	n/a
Orthologs
	84247
	223732
	ENSG00000188636
	ENSMUSG00000055745
	Q6ICC9
	Q505G4
	NM_032287
	NM_177630
	NP_115663
	NP_808298
	Wikidata
View/Edit Human	View/Edit Mouse

RTL6
Identifiers
Aliases	RTL6, Mar6, Mart6, dJ1033E15.2, LDOC1L, leucine zipper, down-regulated in cancer 1-like, leucine zipper, down-regulated in cancer 1 like, LDOC1 like, SIRH3, retrotransposon Gag like 6
External IDs	MGI: 2675858; HomoloGene: 18594; GeneCards: RTL6; OMA:RTL6 - orthologs
Gene location (Human)
Chr.	Chromosome 22 (human)
End	44,498,233 bp
Gene location (Mouse)
Chr.	Chromosome 15 (mouse)
End	84,442,024 bp
RNA expression pattern
	Top expressed in
	endothelial cell; ; tibialis anterior muscle; ; mucosa of ileum; ; pancreatic epithelial cell; ; myocardium of left ventricle; ; ganglionic eminence; ; pancreatic ductal cell; ; cardiac muscle tissue of right atrium; ; middle temporal gyrus; ; ventricular zone;
	Top expressed in
	saccule; ; otic vesicle; ; perirhinal cortex; ; entorhinal cortex; ; ganglionic eminence; ; CA3 field; ; medial ganglionic eminence; ; habenula; ; visual cortex; ; olfactory epithelium;
	More reference expression data
	n/a
Orthologs
	84247
	223732
	ENSG00000188636
	ENSMUSG00000055745
	Q6ICC9
	Q505G4
	NM_032287
	NM_177630
	NP_115663
	NP_808298
	Wikidata
View/Edit Human	View/Edit Mouse

From Wikipedia, the free encyclopedia

Retrotransposon Gag Like 6 is a protein encoded by the RTL6 gene in humans.^[5] RTL6 is a member of the Mart family of genes, which are related to Sushi-like retrotransposons and were derived from fish and amphibians.^[6] 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

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 .^[7]

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.^[6] Between 170 and 310 MYA, MART genes lost their ability to retrotranspose and concomitantly gained new, beneficial function for its host organism.^[8]

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.^[7]

Protein

Primary information

The primary amino acid sequence for RTL6 is made up of 239 residues.^[5] 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.^[9] RTL6 is a proline and arginine rich protein.^[9]

I-TASSER predicted secondary and tertiary structures for the RTL6 protein.^[10]^[11]^[12]
Immunohistochemical staining of human stomach shows strong nuclear and cytoplasmic positivity in glandular cells.^[13]

Domains and motifs

RTL6 contains a predicted leucine zipper motif known to participate in nucleic acid binding in other proteins.^[9] 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.^[14]

Secondary structure

The secondary structure of RTL6 is made up of largely alpha helices.^[15] One region of RTL6 is also predicted to participate in a coiled-coil structure from amino acid residues 29–63.^[14]

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.^[16]^[17] There is also a predicted ubiquitination site with medium-confidence at amino acid residue 8.^[18]

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.^[19]^[20]^[21]

Expression

RTL6 has been shown to be expressed at high levels during all stages of development and in a wide variety of tissues.^[22]^[23]^[13]

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.^[24]^[25]

Interacting proteins

RTL6 has been shown to interact with the following proteins:

DDIT3	DNA damage-inducible transcript 3 protein ^[26]
NXF1	Nuclear RNA export factor 1 ^[27]
STX18	Syntaxin 18 ^[28]
MAFF	MAF bZIP transcription factor F ^[28]
GOPC	Golgi-associated PDZ and coiled-coil motif-containing protein ^[28]
BATF3	Basic leucine zipper transcriptional factor ATF-like 3 ^[28]
TERF2	Telomeric repeat-binding factor 2 ^[29]
UXAC	Uronate isomerase (Yersinia pestis) ^[30]

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.^[30]

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 ^[31]	NP_001128360.1	1358	100	7.6
PEG10 (RTL2) ^[32]	NP_055883.2	359	35	35
RTL3 ^[33]	NP_689907.1	2648	100	2.2
RTL4 ^[34]	NP_001004308.2	310	100	19
RTL5 ^[35]	NP_001019626.1	569	37	53
RTL6 ^[5]	NP_115663.2	239	NA	NA
LDOC1 (RTL7) ^[36]	NP_036449.1	146	33	41
RTL8A ^[37]	NP_001071640.1	113	33	44
RTL8B ^[38]	NP_001071641.1	113	33	43
RTL8C ^[39]	NP_001071639.1	113	33	44
RTL9 ^[40]	NP_065820.1	1388	22	39
RTL10 ^[41]	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:^[6]

Organism	Common name	Classification	Accession number	Percent identity	Query Cover	Percent Similarity
Homo sapiens	Humans	Primate	NP_115663.2 ^[5]	NA	NA	NA
Macaca mulatta	Rhesus Monkey	Primate	NP_001181372.1 ^[42]	98	100	99
Felis catus	House Cat	Carnivore	XP_003989415.1 ^[43]	97	100	98
Mus muscalus	Common Mouse	Rodent	NP_808298.2 ^[44]	92	100	96
Pteropus alecto	Black Flying Fox	Bat	XP_006917396.1 ^[45]	96	100	98
Equus caballus	Horse	Odd-Toed Ungulates	XP_005606827.1 ^[46]	95	100	98
Bos Taurus	Cattle	Even-Toed Ungulates	XP_015326927.1 ^[47]	94	100	97
Orcinus orca	Killer Whale	Whales/Dolphins	XP_004279624.1 ^[48]	95	100	98
Trichechus manatus latirostirs	Florida Manatee	Placentals	XP_004380056.1 ^[49]	95	100	96
Erinaceus europaeus	European Hedgehog	Rabbits/Hares	XP_016043235.1 ^[50]	93	100	96
Ochotona princeps	American Pika	Insectivoires	XP_004589491.1 ^[51]	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 ^[5]	100	100	100
Cyprinus carpio	Common Carp	Bony Fishes	XP_018946777 ^[52]	30	41	34
Esox lucius	Northern Pike	Bony Fishes	XP_019899574.1 ^[53]	31	55	31
Nothobranchius furzeri	Black Rockcod	Bony Fishes	XP_010767110 ^[54]	37	35	39

References

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^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000055745 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c ^d ^e ^f "RTL6 retrotransposon Gag like 6 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-02.
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^ ^a ^b "LDOC1L LDOC1 like [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-02-05.
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^ ^a ^b "Cell atlas - LDOC1L - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-05-02.
^ ^a ^b "LDOC1L - Protein LDOC1L - Homo sapiens (Human) - LDOC1L gene & protein". www.uniprot.org. Retrieved 2017-05-07.
^ Garnier, Gibrat, and Robson, Meth. Enzymol., R.F. Doolittle ed. (1996) 266:97-120
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^ Radivojac P, Vacic V, Haynes C, Cocklin RR, Mohan A, Heyen JW, Goebl MG, Iakoucheva LM (February 2010). "Identification, analysis, and prediction of protein ubiquitination sites". Proteins. 78 (2): 365–80. doi:10.1002/prot.22555. PMC 3006176. PMID 19722269.
^ "PSORT: Protein Subcellular Localization Prediction Tool". www.genscript.com. Retrieved 2017-05-02.
^ Lin WZ, Fang JA, Xiao X, Chou KC (April 2013). "iLoc-Animal: a multi-label learning classifier for predicting subcellular localization of animal proteins". Molecular BioSystems. 9 (4): 634–44. doi:10.1039/c3mb25466f. PMID 23370050.
^ "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2017-02-19.
^ "Gene Detail :: Allen Brain Atlas: Mouse Brain". mouse.brain-map.org. Retrieved 2017-05-02.
^ "Leucine zipper, down-regulated in cancer 1-like (Ldoc1l)". www.ncbi.nlm.nih.gov. Retrieved 2017-05-02.^{[dead link]}
^ Serment-Guerrero J, Cano-Sanchez P, Reyes-Perez E, Velazquez-Garcia F, Bravo-Gomez ME, Ruiz-Azuara L (October 2011). "Genotoxicity of the copper antineoplastic coordination complexes casiopeinas". Toxicology in Vitro. 25 (7): 1376–84. doi:10.1016/j.tiv.2011.05.008. PMID 21601632.
^ Capranico G, Binaschi M (October 1998). "DNA sequence selectivity of topoisomerases and topoisomerase poisons". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1400 (1–3): 185–94. doi:10.1016/S0167-4781(98)00135-3. PMID 9748568.
^ Behrends C, Sowa ME, Gygi SP, Harper JW (July 2010). "Network organization of the human autophagy system". Nature. 466 (7302): 68–76. Bibcode:2010Natur.466...68B. doi:10.1038/nature09204. PMC 2901998. PMID 20562859.
^ Castello A, Fischer B, Eichelbaum K, Horos R, Beckmann BM, Strein C, Davey NE, Humphreys DT, Preiss T, Steinmetz LM, Krijgsveld J, Hentze MW (June 2012). "Insights into RNA biology from an atlas of mammalian mRNA-binding proteins". Cell. 149 (6): 1393–406. doi:10.1016/j.cell.2012.04.031. PMID 22658674.
^ ^a ^b ^c ^d Huttlin EL, Ting L, Bruckner RJ, Gebreab F, Gygi MP, Szpyt J, Tam S, Zarraga G, Colby G, Baltier K, Dong R, Guarani V, Vaites LP, Ordureau A, Rad R, Erickson BK, Wühr M, Chick J, Zhai B, Kolippakkam D, Mintseris J, Obar RA, Harris T, Artavanis-Tsakonas S, Sowa ME, De Camilli P, Paulo JA, Harper JW, Gygi SP (July 2015). "The BioPlex Network: A Systematic Exploration of the Human Interactome". Cell. 162 (2): 425–440. doi:10.1016/j.cell.2015.06.043. PMC 4617211. PMID 26186194.
^ Giannone RJ, McDonald HW, Hurst GB, Shen RF, Wang Y, Liu Y (August 2010). "The protein network surrounding the human telomere repeat binding factors TRF1, TRF2, and POT1". PLOS ONE. 5 (8) e12407. Bibcode:2010PLoSO...512407G. doi:10.1371/journal.pone.0012407. PMC 2928292. PMID 20811636.
^ ^a ^b Dyer MD, Neff C, Dufford M, Rivera CG, Shattuck D, Bassaganya-Riera J, Murali TM, Sobral BW (August 2010). "The human-bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestis". PLOS ONE. 5 (8) e12089. Bibcode:2010PLoSO...512089D. doi:10.1371/journal.pone.0012089. PMC 2918508. PMID 20711500.
^ "RTL1 retrotransposon Gag like 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "PEG10 paternally expressed 10 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL3 retrotransposon Gag like 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL4 retrotransposon Gag like 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL5 retrotransposon Gag like 5 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "LDOC1 LDOC1, regulator of NFKB signaling [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL8A retrotransposon Gag like 8A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL8B retrotransposon Gag like 8B [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL8C retrotransposon Gag like 8C [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL9 retrotransposon Gag like 9 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL10 retrotransposon Gag like 10 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL6 retrotransposon Gag like 6 [Macaca mulatta (Rhesus monkey)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL6 retrotransposon Gag like 6 [Felis catus (domestic cat)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "Ldoc1l leucine zipper, down-regulated in cancer 1-like [Mus musculus (house mouse)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL6 retrotransposon Gag like 6 [Pteropus alecto (black flying fox)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL6 retrotransposon Gag like 6 [Equus caballus (horse)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL6 retrotransposon Gag like 6 [Bos taurus (cattle)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL6 retrotransposon Gag like 6 [Orcinus orca (killer whale)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "LOC101345980 retrotransposon Gag like 6 [Trichechus manatus latirostris (Florida manatee)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL6 retrotransposon Gag like 6 [Erinaceus europaeus (western European hedgehog)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "RTL6 retrotransposon Gag like 6 [Ochotona princeps (American pika)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
^ "PREDICTED: protein LDOC1-like [Cyprinus carpio] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
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^ "PREDICTED: uncharacterized protein LOC104943421 [Notothenia coriiceps] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.

Retrotransposon Gag Like 6 is a protein encoded by the RTL6 gene in humans.^[5] RTL6 is a member of the Mart family of genes, which are related to Sushi-like retrotransposons and were derived from fish and amphibians.^[6] 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

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 .^[7]

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.^[6] Between 170 and 310 MYA, MART genes lost their ability to retrotranspose and concomitantly gained new, beneficial function for its host organism.^[8]

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.^[7]

Protein