SETMAR

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SETMAR
Protein SETMAR PDB 3BO5.png
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]

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.[5][6]

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 a D610N mutation, but the domain itself can still recognize the mariner repeat elements and introduce nicks in the DNA.[7]

Model organisms[]

Model organisms have been used in the study of SETMAR function. A conditional knockout mouse line, called Setmartm1a(EUCOMM)Wtsi[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18] Note that the mouse ortholog is does not have the Tc1/mariner ("MAR") fusion; such a fusion is found only in anthropoid primates. Therefore, the knockout mouse is not for SETMAR but only the SET domain of this chimeric fusion protein.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.[12] Homozygous mutant animals of both sex had abnormal retinal pigmentation and morphology, while males also had atypical peripheral blood lymphocyte parameters.[12]

References[]

  1. ^ a b c 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): 203–17. doi:10.1016/S0378-1119(97)00472-1. PMID 9461395.
  4. ^ "Entrez Gene: SETMAR SET domain and mariner transposase fusion gene".
  5. ^ Lee SH, Oshige M, Durant ST, Rasila KK, Williamson EA, Ramsey H, Kwan L, Nickoloff JA, Hromas R (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): 18075–80. Bibcode:2005PNAS..10218075L. doi:10.1073/pnas.0503676102. PMC 1312370. PMID 16332963.
  6. ^ Fnu S, Williamson EA, De Haro LP, Brenneman M, Wray J, Shaheen M, Radhakrishnan K, Lee SH, Nickoloff JA, Hromas R (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): 540–5. Bibcode:2011PNAS..108..540F. doi:10.1073/pnas.1013571108. PMC 3021059. PMID 21187428.
  7. ^ 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): 4589–600. doi:10.1128/MCB.02027-06. PMC 1900042. PMID 17403897.
  8. ^ "Eye morphology data for Setmar". Wellcome Trust Sanger Institute.
  9. ^ "Peripheral blood lymphocytes data for Setmar". Wellcome Trust Sanger Institute.
  10. ^ "Salmonella infection data for Setmar". Wellcome Trust Sanger Institute.
  11. ^ "Citrobacter infection data for Setmar". Wellcome Trust Sanger Institute.
  12. ^ a b c d Gerdin, AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  13. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  14. ^ "International Knockout Mouse Consortium".
  15. ^ "Mouse Genome Informatics".
  16. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  17. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  18. ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  19. ^ van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading[]

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