RTL6

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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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

File:RTL6 gene neighborhood.gif
Gene neighborhood of RTL6 on chromosome 22.[1]

The gene is on Chromosome 22 (human) at 22q13.31 on the minus strand from 44492570-44498125 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 170-310 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]

File:LDOC1L.jpg
I-TASSER predicted secondary and tertiary structures for the RTL6 protein.[6][7][8]
File:LDOC1L Stain.png
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]

File:LDOC1L Protein Annotation.png
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 lucious Northern Pike Bony Fishes XP_019899574.1 [49] 31 55 31
Nothobranchius furzeri Black Rockcod Bony Fishes XP_010767110 [50] 37 35 39

References

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  49. "PREDICTED: protein LDOC1L-like [Esox lucius] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
  50. "PREDICTED: uncharacterized protein LOC104943421 [Notothenia coriiceps] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.