SETMAR
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesSETMAR, HsMar1, METNASE, Mar1, SET domain and mariner transposase fusion gene
External IDsOMIM: 609834 HomoloGene: 121979 GeneCards: SETMAR
Orthologs
SpeciesHumanMouse
Entrez

6419

n/a

Ensembl

ENSG00000170364

n/a

UniProt

Q53H47

n/a

RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

Location (UCSC)Chr 3: 4.3 – 4.32 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Histone-lysine N-methyltransferase SETMAR is an enzyme that in humans is encoded by the SETMAR gene.[3][4][5][6]

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.[7][8]

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,[9] including the D610N mutation.[10][11] However, the domesticated transposase domain retains its ability to bind to the mariner repeat elements in the genome.[12][13][14][15] 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.[12][13][15] Both the SET, via its methyltransferase activity,[7][8][16] and the mariner, with its DNA-binding [17] and nuclease activities,[18][19][20][21][16] domains of SETMAR have been shown to act in non-homologous end joining (NHEJ) to repair DNA double strand breaks.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000170364 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ Robertson HM, Zumpano KL (December 1997). "Molecular evolution of an ancient mariner transposon, Hsmar1, in the human genome". Gene. 205 (1–2): 203–217. doi:10.1016/S0378-1119(97)00472-1. PMID 9461395.
  4. ↑ "Entrez Gene: SETMAR SET domain and mariner transposase fusion gene".
  5. ↑ Tellier M (December 2021). "Structure, Activity, and Function of SETMAR Protein Lysine Methyltransferase". Life. 11 (12): 1342. Bibcode:2021Life...11.1342T. doi:10.3390/life11121342. PMC 8704517. PMID 34947873.
  6. ↑ Lié O, Renault S, Augé-Gouillou C (April 2022). "SETMAR, a case of primate co-opted genes: towards new perspectives". Mobile DNA. 13 (1): 9. doi:10.1186/s13100-022-00267-1. PMC 8994322. PMID 35395947.
  7. 1 2 Lee SH, Oshige M, Durant ST, Rasila KK, Williamson EA, Ramsey H, et al. (December 2005). "The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repair". Proceedings of the National Academy of Sciences of the United States of America. 102 (50): 18075–18080. Bibcode:2005PNAS..10218075L. doi:10.1073/pnas.0503676102. PMC 1312370. PMID 16332963.
  8. 1 2 Fnu S, Williamson EA, De Haro LP, Brenneman M, Wray J, Shaheen M, et al. (January 2011). "Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining". Proceedings of the National Academy of Sciences of the United States of America. 108 (2): 540–545. Bibcode:2011PNAS..108..540F. doi:10.1073/pnas.1013571108. PMC 3021059. PMID 21187428.
  9. ↑ Tellier M, Chalmers R (2020-01-10). "Compensating for over-production inhibition of the Hsmar1 transposon in Escherichia coli using a series of constitutive promoters". Mobile DNA. 11 (1): 5. doi:10.1186/s13100-020-0200-5. PMC 6954556. PMID 31938044.
  10. ↑ Miskey C, Papp B, Mátés L, Sinzelle L, Keller H, Izsvák Z, Ivics Z (June 2007). "The ancient mariner sails again: transposition of the human Hsmar1 element by a reconstructed transposase and activities of the SETMAR protein on transposon ends". Molecular and Cellular Biology. 27 (12): 4589–4600. doi:10.1128/MCB.02027-06. PMC 1900042. PMID 17403897.
  11. ↑ Liu D, Bischerour J, Siddique A, Buisine N, Bigot Y, Chalmers R (February 2007). "The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase". Molecular and Cellular Biology. 27 (3): 1125–1132. doi:10.1128/MCB.01899-06. PMC 1800679. PMID 17130240.
  12. 1 2 Tellier M, Chalmers R (January 2019). "Human SETMAR is a DNA sequence-specific histone-methylase with a broad effect on the transcriptome". Nucleic Acids Research. 47 (1): 122–133. doi:10.1093/nar/gky937. PMC 6326780. PMID 30329085.
  13. 1 2 Antoine-Lorquin A, Arensburger P, Arnaoty A, Asgari S, Batailler M, Beauclair L, et al. (May 2021). "Two repeated motifs enriched within some enhancers and origins of replication are bound by SETMAR isoforms in human colon cells". Genomics. 113 (3): 1589–1604. doi:10.1016/j.ygeno.2021.03.032. PMID 33812898. S2CID 233028866.
  14. ↑ Miskei M, Horváth A, Viola L, Varga L, Nagy É, Feró O, et al. (2021-01-01). "Genome-wide mapping of binding sites of the transposase-derived SETMAR protein in the human genome". Computational and Structural Biotechnology Journal. 19: 4032–4041. doi:10.1016/j.csbj.2021.07.010. PMC 8327481. PMID 34377368.
  15. 1 2 Chen Q, Bates AM, Hanquier JN, Simpson E, Rusch DB, Podicheti R, et al. (May 2022). "Structural and genome-wide analyses suggest that transposon-derived protein SETMAR alters transcription and splicing". The Journal of Biological Chemistry. 298 (5): 101894. doi:10.1016/j.jbc.2022.101894. PMC 9062482. PMID 35378129.
  16. 1 2 Tellier M, Chalmers R (August 2019). "The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair". DNA Repair. 80: 26–35. doi:10.1016/j.dnarep.2019.06.006. PMC 6715855. PMID 31238295.
  17. ↑ Beck BD, Park SJ, Lee YJ, Roman Y, Hromas RA, Lee SH (April 2008). "Human Pso4 is a metnase (SETMAR)-binding partner that regulates metnase function in DNA repair". The Journal of Biological Chemistry. 283 (14): 9023–9030. doi:10.1074/jbc.M800150200. PMC 2431028. PMID 18263876.
  18. ↑ Hromas R, Wray J, Lee SH, Martinez L, Farrington J, Corwin LK, et al. (December 2008). "The human set and transposase domain protein Metnase interacts with DNA Ligase IV and enhances the efficiency and accuracy of non-homologous end-joining". DNA Repair. 7 (12): 1927–1937. doi:10.1016/j.dnarep.2008.08.002. PMC 2644637. PMID 18773976.
  19. ↑ Beck BD, Lee SS, Williamson E, Hromas RA, Lee SH (May 2011). "Biochemical characterization of metnase's endonuclease activity and its role in NHEJ repair". Biochemistry. 50 (20): 4360–4370. doi:10.1021/bi200333k. PMC 3388547. PMID 21491884.
  20. ↑ Mohapatra S, Yannone SM, Lee SH, Hromas RA, Akopiants K, Menon V, et al. (June 2013). "Trimming of damaged 3' overhangs of DNA double-strand breaks by the Metnase and Artemis endonucleases". DNA Repair. 12 (6): 422–432. doi:10.1016/j.dnarep.2013.03.005. PMC 3660496. PMID 23602515.
  21. ↑ Kim HS, Chen Q, Kim SK, Nickoloff JA, Hromas R, Georgiadis MM, Lee SH (April 2014). "The DDN catalytic motif is required for Metnase functions in non-homologous end joining (NHEJ) repair and replication restart". The Journal of Biological Chemistry. 289 (15): 10930–10938. doi:10.1074/jbc.M113.533216. PMC 4036204. PMID 24573677.

Further reading

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