RAD18

RAD18 E3 ubiquitin protein ligase
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols RAD18 ; RNF73
External IDs OMIM: 605256 MGI: 1890476 HomoloGene: 48572 GeneCards: RAD18 Gene
Orthologs
Species Human Mouse
Entrez 56852 58186
Ensembl ENSG00000070950 ENSMUSG00000030254
UniProt Q9NS91 Q9QXK2
RefSeq (mRNA) NM_020165 NM_001167730
RefSeq (protein) NP_064550 NP_001161202
Location (UCSC) Chr 3:
8.78 – 8.96 Mb
Chr 6:
112.62 – 112.7 Mb
PubMed search

E3 ubiquitin-protein ligase RAD18 is an enzyme that in humans is encoded by the RAD18 gene.[1][2][3]

The protein encoded by this gene is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through its interaction with Rad6, which is a ubiquitin-conjugating enzyme required for post-replication repair of damaged DNA. Similar to its yeast counterpart, this protein is able to interact with the human homolog of yeast Rad6 protein through a conserved ring finger motif. Mutation of this motif results in defective replication of UV-damaged DNA and hypersensitivity to multiple mutagens.[3]

Animal models

Model organisms have been used in the study of RAD18 function. A conditional knockout mouse line, called Rad18tm1a(EUCOMM)Wtsi,[4] was generated as part of the EUCOMM program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[5][6][7][8][9] Mice lacking Rad18 had no significant defects in viability or fertility,[10][11] therefore male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[6][12][13]

Twenty five tests were carried out and four significant phenotypes were reported:[13]

Interactions

RAD18 has been shown to interact with HLTF,[21] UBE2B[1][2] and UBE2A.[1][2]

References

  1. 1 2 3 Tateishi S, Sakuraba Y, Masuyama S, Inoue H, Yamaizumi M (Aug 2000). "Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens". Proc Natl Acad Sci U S A 97 (14): 7927–32. doi:10.1073/pnas.97.14.7927. PMC 16647. PMID 10884424.
  2. 1 2 3 Xin H, Lin W, Sumanasekera W, Zhang Y, Wu X, Wang Z (Sep 2000). "The human RAD18 gene product interacts with HHR6A and HHR6B". Nucleic Acids Res 28 (14): 2847–54. doi:10.1093/nar/28.14.2847. PMC 102657. PMID 10908344.
  3. 1 2 "Entrez Gene: RAD18 RAD18 homolog (S. cerevisiae)".
  4. EUCOMM. "Rad18tm1a(EUCOMM)Wtsi". www.knockoutmouse.org. External link in |publisher= (help)
  5. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  6. 1 2 Van der Weyden L, White JK, Adams, DA, 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.
  7. Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474: 262–263. doi:10.1038/474262a. PMID 21677718.
  8. 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.
  9. Auwerx J, Avner P, Baldock R, et al. (September 2004). "The European dimension for the mouse genome mutagenesis program". Nat. Genet. 36 (9): 925–7. doi:10.1038/ng0904-925. PMC 2716028. PMID 15340424.
  10. Wellcome Trust Sanger Institute. "Viability at Weaning Data for Rad18". Mouse Resources Portal. www.sanger.ac.uk. External link in |publisher= (help)
  11. Wellcome Trust Sanger Institute. "Fertility Data for Rad18". Mouse Resources Portal. www.sanger.ac.uk. External link in |publisher= (help)
  12. 1 2 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.
  13. 1 2 Wellcome Trust Sanger Institute. "MGP Phenotyping of Rad18tm1a(EUCOMM)Wtsi". Mouse Resources Portal. www.sanger.ac.uk. External link in |publisher= (help)
  14. "Body weight data for Rad18". Wellcome Trust Sanger Institute.
  15. "Dysmorphology data for Rad18". Wellcome Trust Sanger Institute.
  16. "Indirect calorimetry data for Rad18". Wellcome Trust Sanger Institute.
  17. "DEXA data for Rad18". Wellcome Trust Sanger Institute.
  18. "Salmonella infection data for Rad18". Wellcome Trust Sanger Institute.
  19. "Citrobacter infection data for Rad18". Wellcome Trust Sanger Institute.
  20. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  21. Unk, Ildiko; Hajdú Ildikó; Fátyol Károly; Hurwitz Jerard; Yoon Jung-Hoon; Prakash Louise; Prakash Satya; Haracska Lajos (Mar 2008). "Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination". Proc. Natl. Acad. Sci. U.S.A. (United States) 105 (10): 3768–73. doi:10.1073/pnas.0800563105. PMC 2268824. PMID 18316726.

Further reading

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