{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''Histone-lysine N-methyltransferase SETMAR''' is an enzyme that in humans is encoded by the ''SETMAR'' gene.<ref name="pmid9461395">{{cite journal | vauthors = Robertson HM, Zumpano KL | title = Molecular evolution of an ancient mariner transposon, Hsmar1, in the human genome | journal = Gene | volume = 205 | issue = 1–2 | pages = 203–217 | date = December 1997 | pmid = 9461395 | doi = 10.1016/S0378-1119(97)00472-1 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SETMAR SET domain and mariner transposase fusion gene| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=6419}}</ref><ref>{{cite journal | vauthors = Tellier M | title = Structure, Activity, and Function of SETMAR Protein Lysine Methyltransferase | journal = Life | volume = 11 | issue = 12 | pages = 1342 | date = December 2021 | pmid = 34947873 | pmc = 8704517 | doi = 10.3390/life11121342 | bibcode = 2021Life...11.1342T | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lié O, Renault S, Augé-Gouillou C | title = SETMAR, a case of primate co-opted genes: towards new perspectives | journal = Mobile DNA | volume = 13 | issue = 1 | article-number = 9 | date = April 2022 | pmid = 35395947 | pmc = 8994322 | doi = 10.1186/s13100-022-00267-1 | doi-access = free }}</ref>
== Function == SETMAR contains a SET domain that confers its histone methyltransferase activity, on Lys-4 and Lys-36 of Histone H3, both of which are specific tags for epigenetic activation. It has been identified as a repair protein as it mediates dimethylation at Lys-36 at double-strand break locations, a signal enhancing NHEJ repair.<ref name=":0">{{cite journal | vauthors = Lee SH, Oshige M, Durant ST, Rasila KK, Williamson EA, Ramsey H, Kwan L, Nickoloff JA, Hromas R | display-authors = 6 | title = The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repair | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 50 | pages = 18075–18080 | date = December 2005 | pmid = 16332963 | pmc = 1312370 | doi = 10.1073/pnas.0503676102 | doi-access = free | bibcode = 2005PNAS..10218075L }}</ref><ref name=":1">{{cite journal | vauthors = Fnu S, Williamson EA, De Haro LP, Brenneman M, Wray J, Shaheen M, Radhakrishnan K, Lee SH, Nickoloff JA, Hromas R | display-authors = 6 | title = Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 2 | pages = 540–545 | date = January 2011 | pmid = 21187428 | pmc = 3021059 | doi = 10.1073/pnas.1013571108 | doi-access = free | bibcode = 2011PNAS..108..540F }}</ref>
Anthropoid primates, including humans, have a version of the protein fused to a Mariner/Tc1 transposase. This fusion region provides the DNA-binding abilities for the protein as well as some nuclease activity. The transposase activity is lost due to the presence of several inactivating mutations,<ref>{{cite journal | vauthors = Tellier M, Chalmers R | title = Compensating for over-production inhibition of the Hsmar1 transposon in ''Escherichia coli'' using a series of constitutive promoters | journal = Mobile DNA | volume = 11 | issue = 1 | article-number = 5 | date = 2020-01-10 | pmid = 31938044 | pmc = 6954556 | doi = 10.1186/s13100-020-0200-5 | doi-access = free }}</ref> including the D610N mutation.<ref>{{cite journal | vauthors = Miskey C, Papp B, Mátés L, Sinzelle L, Keller H, Izsvák Z, Ivics Z | title = The ancient mariner sails again: transposition of the human Hsmar1 element by a reconstructed transposase and activities of the SETMAR protein on transposon ends | journal = Molecular and Cellular Biology | volume = 27 | issue = 12 | pages = 4589–4600 | date = June 2007 | pmid = 17403897 | pmc = 1900042 | doi = 10.1128/MCB.02027-06 }}</ref><ref>{{cite journal | vauthors = Liu D, Bischerour J, Siddique A, Buisine N, Bigot Y, Chalmers R | title = The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase | journal = Molecular and Cellular Biology | volume = 27 | issue = 3 | pages = 1125–1132 | date = February 2007 | pmid = 17130240 | pmc = 1800679 | doi = 10.1128/MCB.01899-06 }}</ref> However, the domesticated transposase domain retains its ability to bind to the mariner repeat elements in the genome.<ref name=":2">{{cite journal | vauthors = Tellier M, Chalmers R | title = Human SETMAR is a DNA sequence-specific histone-methylase with a broad effect on the transcriptome | journal = Nucleic Acids Research | volume = 47 | issue = 1 | pages = 122–133 | date = January 2019 | pmid = 30329085 | doi = 10.1093/nar/gky937 | pmc = 6326780 }}</ref><ref name=":3">{{cite journal | vauthors = Antoine-Lorquin A, Arensburger P, Arnaoty A, Asgari S, Batailler M, Beauclair L, Belleannée C, Buisine N, Coustham V, Guyetant S, Helou L, Lecomte T, Pitard B, Stévant I, Bigot Y | display-authors = 6 | title = Two repeated motifs enriched within some enhancers and origins of replication are bound by SETMAR isoforms in human colon cells | journal = Genomics | volume = 113 | issue = 3 | pages = 1589–1604 | date = May 2021 | pmid = 33812898 | doi = 10.1016/j.ygeno.2021.03.032 | s2cid = 233028866 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Miskei M, Horváth A, Viola L, Varga L, Nagy É, Feró O, Karányi Z, Roszik J, Miskey C, Ivics Z, Székvölgyi L | display-authors = 6 | title = Genome-wide mapping of binding sites of the transposase-derived SETMAR protein in the human genome | journal = Computational and Structural Biotechnology Journal | volume = 19 | pages = 4032–4041 | date = 2021-01-01 | pmid = 34377368 | pmc = 8327481 | doi = 10.1016/j.csbj.2021.07.010 }}</ref><ref name=":4">{{cite journal | vauthors = Chen Q, Bates AM, Hanquier JN, Simpson E, Rusch DB, Podicheti R, Liu Y, Wek RC, Cornett EM, Georgiadis MM | display-authors = 6 | title = Structural and genome-wide analyses suggest that transposon-derived protein SETMAR alters transcription and splicing | language = English | journal = The Journal of Biological Chemistry | volume = 298 | issue = 5 | article-number = 101894 | date = May 2022 | pmid = 35378129 | pmc = 9062482 | doi = 10.1016/j.jbc.2022.101894 | doi-access = free }}</ref> SETMAR has been found to affect the expression and splicing of genes close to or containing mariner repeat elements via its functions in histone methylation.<ref name=":2" /><ref name=":3" /><ref name=":4" /> Both the SET, via its methyltransferase activity,<ref name=":0" /><ref name=":1" /><ref name=":5">{{cite journal | vauthors = Tellier M, Chalmers R | title = The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair | journal = DNA Repair | volume = 80 | pages = 26–35 | date = August 2019 | pmid = 31238295 | pmc = 6715855 | doi = 10.1016/j.dnarep.2019.06.006 }}</ref> and the mariner, with its DNA-binding <ref>{{cite journal | vauthors = Beck BD, Park SJ, Lee YJ, Roman Y, Hromas RA, Lee SH | title = Human Pso4 is a metnase (SETMAR)-binding partner that regulates metnase function in DNA repair | language = English | journal = The Journal of Biological Chemistry | volume = 283 | issue = 14 | pages = 9023–9030 | date = April 2008 | pmid = 18263876 | pmc = 2431028 | doi = 10.1074/jbc.M800150200 | doi-access = free }}</ref> and nuclease activities,<ref>{{cite journal | vauthors = Hromas R, Wray J, Lee SH, Martinez L, Farrington J, Corwin LK, Ramsey H, Nickoloff JA, Williamson EA | display-authors = 6 | title = The human set and transposase domain protein Metnase interacts with DNA Ligase IV and enhances the efficiency and accuracy of non-homologous end-joining | journal = DNA Repair | volume = 7 | issue = 12 | pages = 1927–1937 | date = December 2008 | pmid = 18773976 | pmc = 2644637 | doi = 10.1016/j.dnarep.2008.08.002 }}</ref><ref>{{cite journal | vauthors = Beck BD, Lee SS, Williamson E, Hromas RA, Lee SH | title = Biochemical characterization of metnase's endonuclease activity and its role in NHEJ repair | journal = Biochemistry | volume = 50 | issue = 20 | pages = 4360–4370 | date = May 2011 | pmid = 21491884 | pmc = 3388547 | doi = 10.1021/bi200333k }}</ref><ref>{{cite journal | vauthors = Mohapatra S, Yannone SM, Lee SH, Hromas RA, Akopiants K, Menon V, Ramsden DA, Povirk LF | display-authors = 6 | title = Trimming of damaged 3' overhangs of DNA double-strand breaks by the Metnase and Artemis endonucleases | journal = DNA Repair | volume = 12 | issue = 6 | pages = 422–432 | date = June 2013 | pmid = 23602515 | pmc = 3660496 | doi = 10.1016/j.dnarep.2013.03.005 }}</ref><ref>{{cite journal | vauthors = Kim HS, Chen Q, Kim SK, Nickoloff JA, Hromas R, Georgiadis MM, Lee SH | title = The DDN catalytic motif is required for Metnase functions in non-homologous end joining (NHEJ) repair and replication restart | language = English | journal = The Journal of Biological Chemistry | volume = 289 | issue = 15 | pages = 10930–10938 | date = April 2014 | pmid = 24573677 | pmc = 4036204 | doi = 10.1074/jbc.M113.533216 | doi-access = free }}</ref><ref name=":5" /> domains of SETMAR have been shown to act in non-homologous end joining (NHEJ) to repair DNA double strand breaks.
== References == {{reflist}}
== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Berry R, Stevens TJ, Walter NA, Wilcox AS, Rubano T, Hopkins JA, Weber J, Goold R, Soares MB, Sikela JM | display-authors = 6 | title = Gene-based sequence-tagged-sites (STSs) as the basis for a human gene map | journal = Nature Genetics | volume = 10 | issue = 4 | pages = 415–423 | date = August 1995 | pmid = 7670491 | doi = 10.1038/ng0895-415 | s2cid = 22277955 }} * {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–174 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }} * {{cite journal | vauthors = Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA | title = A "double adaptor" method for improved shotgun library construction | journal = Analytical Biochemistry | volume = 236 | issue = 1 | pages = 107–113 | date = April 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }} * {{cite journal | vauthors = Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA | display-authors = 6 | title = Large-scale concatenation cDNA sequencing | journal = Genome Research | volume = 7 | issue = 4 | pages = 353–358 | date = April 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }} * {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–156 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }} * {{cite journal | vauthors = Lee SH, Oshige M, Durant ST, Rasila KK, Williamson EA, Ramsey H, Kwan L, Nickoloff JA, Hromas R | display-authors = 6 | title = The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repair | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 50 | pages = 18075–18080 | date = December 2005 | pmid = 16332963 | pmc = 1312370 | doi = 10.1073/pnas.0503676102 | doi-access = free | bibcode = 2005PNAS..10218075L }} * {{cite journal | vauthors = Cordaux R, Udit S, Batzer MA, Feschotte C | title = Birth of a chimeric primate gene by capture of the transposase gene from a mobile element | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 21 | pages = 8101–8106 | date = May 2006 | pmid = 16672366 | pmc = 1472436 | doi = 10.1073/pnas.0601161103 | doi-access = free | bibcode = 2006PNAS..103.8101C }} * {{cite journal | vauthors = Keravala A, Liu D, Lechman ER, Wolfe D, Nash JA, Lampe DJ, Robbins PD | title = Hyperactive Himar1 transposase mediates transposition in cell culture and enhances gene expression in vivo | journal = Human Gene Therapy | volume = 17 | issue = 10 | pages = 1006–1018 | date = October 2006 | pmid = 16989604 | doi = 10.1089/hum.2006.17.1006 }} * {{cite journal | vauthors = Liu D, Bischerour J, Siddique A, Buisine N, Bigot Y, Chalmers R | title = The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase | journal = Molecular and Cellular Biology | volume = 27 | issue = 3 | pages = 1125–1132 | date = February 2007 | pmid = 17130240 | pmc = 1800679 | doi = 10.1128/MCB.01899-06 }} * {{cite journal | vauthors = Miskey C, Papp B, Mátés L, Sinzelle L, Keller H, Izsvák Z, Ivics Z | title = The ancient mariner sails again: transposition of the human Hsmar1 element by a reconstructed transposase and activities of the SETMAR protein on transposon ends | journal = Molecular and Cellular Biology | volume = 27 | issue = 12 | pages = 4589–4600 | date = June 2007 | pmid = 17403897 | pmc = 1900042 | doi = 10.1128/MCB.02027-06 }} * {{cite journal | vauthors = Roman Y, Oshige M, Lee YJ, Goodwin K, Georgiadis MM, Hromas RA, Lee SH | title = Biochemical characterization of a SET and transposase fusion protein, Metnase: its DNA binding and DNA cleavage activity | journal = Biochemistry | volume = 46 | issue = 40 | pages = 11369–11376 | date = October 2007 | pmid = 17877369 | pmc = 3374406 | doi = 10.1021/bi7005477 }} {{refend}}
Category:Genes mutated in mice