RAD18

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RAD18
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRAD18, RNF73, E3 ubiquitin protein ligase, RAD18 E3 ubiquitin protein ligase
External IDsOMIM: 605256 MGI: 1890476 HomoloGene: 48572 GeneCards: RAD18
Gene location (Human)
Chromosome 3 (human)
Chr.Chromosome 3 (human)[1]
Chromosome 3 (human)
Genomic location for RAD18
Genomic location for RAD18
Band3p25.3Start8,775,402 bp[1]
End8,963,773 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_020165

NM_001167730
NM_021385

RefSeq (protein)

NP_064550

NP_001161202
NP_067360

Location (UCSC)Chr 3: 8.78 – 8.96 MbChr 6: 112.62 – 112.7 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

E3 ubiquitin-protein ligase RAD18 is an enzyme that in humans is encoded by the RAD18 gene.[5][6][7]

Function[edit]

The protein encoded by this ne is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through 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.[7]

Animal models[edit]

Model organisms have been used in the study of RAD18 function. A conditional knockout mouse line, called Rad18tm1a(EUCOMM)Wtsi,[8] 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.[9][10][11][12][13] Mice lacking Rad18 had no significant defects in viability or fertility,[14][15] therefore male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[10][16][17]

Twenty five tests were carried out and four significant phenotypes were reported:[17]

A knockout in a human colorectal cancer cell line, HCT116, has also been created.[25]

Interactions[edit]

RAD18 has been shown to interact with HLTF,[26] UBE2B[5][6] and UBE2A.[5][6]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000070950 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030254 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c Tateishi S, Sakuraba Y, Masuyama S, Inoue H, Yamaizumi M (July 2000). "Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens". Proceedings of the National Academy of Sciences of the United States of America. 97 (14): 7927–32. Bibcode:2000PNAS...97.7927T. doi:10.1073/pnas.97.14.7927. PMC 16647. PMID 10884424.
  6. ^ a b c Xin H, Lin W, Sumanasekera W, Zhang Y, Wu X, Wang Z (July 2000). "The human RAD18 gene product interacts with HHR6A and HHR6B". Nucleic Acids Research. 28 (14): 2847–54. doi:10.1093/nar/28.14.2847. PMC 102657. PMID 10908344.
  7. ^ a b "Entrez Gene: RAD18 RAD18 homolog (S. cerevisiae)".
  8. ^ EUCOMM. "Rad18tm1a(EUCOMM)Wtsi". www.knockoutmouse.org.
  9. ^ 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.
  10. ^ a b 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.
  11. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  12. ^ 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.
  13. ^ Auwerx J, Avner P, Baldock R, Ballabio A, Balling R, Barbacid M, Berns A, Bradley A, Brown S, Carmeliet P, Chambon P, Cox R, Davidson D, Davies K, Duboule D, Forejt J, Granucci F, Hastie N, de Angelis MH, Jackson I, Kioussis D, Kollias G, Lathrop M, Lendahl U, Malumbres M, von Melchner H, Müller W, Partanen J, Ricciardi-Castagnoli P, Rigby P, Rosen B, Rosenthal N, Skarnes B, Stewart AF, Thornton J, Tocchini-Valentini G, Wagner E, Wahli W, Wurst W (September 2004). "The European dimension for the mouse genome mutagenesis program". Nature Genetics. 36 (9): 925–7. doi:10.1038/ng0904-925. PMC 2716028. PMID 15340424.
  14. ^ Wellcome Trust Sanger Institute. "Viability at Weaning Data for Rad18". Mouse Resources Portal. www.sanger.ac.uk.
  15. ^ Wellcome Trust Sanger Institute. "Fertility Data for Rad18". Mouse Resources Portal. www.sanger.ac.uk.
  16. ^ 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.
  17. ^ a b Wellcome Trust Sanger Institute. "MGP Phenotyping of Rad18tm1a(EUCOMM)Wtsi". Mouse Resources Portal. www.sanger.ac.uk.
  18. ^ "Body weight data for Rad18". Wellcome Trust Sanger Institute.
  19. ^ "Dysmorphology data for Rad18". Wellcome Trust Sanger Institute.
  20. ^ "Indirect calorimetry data for Rad18". Wellcome Trust Sanger Institute.
  21. ^ "DEXA data for Rad18". Wellcome Trust Sanger Institute.
  22. ^ "Salmonella infection data for Rad18". Wellcome Trust Sanger Institute.
  23. ^ "Citrobacter infection data for Rad18". Wellcome Trust Sanger Institute.
  24. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  25. ^ Shiomi N, Mori M, Tsuji H, Imai T, Inoue H, Tateishi S, Yamaizumi M, Shiomi T (2007-01-01). "Human RAD18 is involved in S phase-specific single-strand break repair without PCNA monoubiquitination". Nucleic Acids Research. 35 (2): e9. doi:10.1093/nar/gkl979. PMC 1802632. PMID 17158148.
  26. ^ Unk I, Hajdú I, Fátyol K, Hurwitz J, Yoon JH, Prakash L, Prakash S, Haracska L (March 2008). "Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination". Proceedings of the National Academy of Sciences of the United States of America. 105 (10): 3768–73. Bibcode:2008PNAS..105.3768U. doi:10.1073/pnas.0800563105. PMC 2268824. PMID 18316726.

Further reading[edit]