RAD18

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RAD18 homolog (S. cerevisiae)
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols RAD18 ; RNF73
External IDs OMIM605256 MGI1890476 HomoloGene48572 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:
8.82 – 9.01 Mb
Chr 6:
112.62 – 112.7 Mb
PubMed search [1] [2]

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[edit]

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[edit]

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

References[edit]

  1. ^ a b c 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. ^ a b c 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. ^ a b "Entrez Gene: RAD18 RAD18 homolog (S. cerevisiae)". 
  4. ^ EUCOMM. "Rad18tm1a(EUCOMM)Wtsi". www.knockoutmouse.org. 
  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.  edit
  6. ^ a b 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. 
  11. ^ Wellcome Trust Sanger Institute. "Fertility Data for Rad18". Mouse Resources Portal. www.sanger.ac.uk. 
  12. ^ a b 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. ^ a b Wellcome Trust Sanger Institute. "MGP Phenotyping of Rad18tm1a(EUCOMM)Wtsi". Mouse Resources Portal. www.sanger.ac.uk. 
  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[edit]