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
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]
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]
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]
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.[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:
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:
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]
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:
^
abcBrandt J, Schrauth S, Veith AM, Froschauer A, Haneke T, Schultheis C, Gessler M, Leimeister C, Volff JN (January 2005). "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.
doi:
10.1016/j.gene.2004.11.022.
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^Brandt J, Veith AM, Volff JN (2005-01-01). "A family of neofunctionalized Ty3/gypsy retrotransposon genes in mammalian genomes". Cytogenetic and Genome Research. 110 (1–4): 307–17.
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PMID16093683.
S2CID38398479.
^
abcBrendel, 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.
^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.
^A Roy, A Kucukural, Y Zhang. I-TASSER: a unified platform for automated protein structure and function prediction. Nature Protocols, 5: 725-738, 2010.
^Y Zhang. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics, 9: 40, 2008.
^Blom N, Gammeltoft S, Brunak S (December 1999). "Sequence and structure-based prediction of eukaryotic protein phosphorylation sites". Journal of Molecular Biology. 294 (5): 1351–62.
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10.1006/jmbi.1999.3310.
PMID10600390.