RAD18, RNF73, E3 ubiquitin protein ligase, RAD18 E3 ubiquitin protein ligase
External IDs
MGI: 1890476 HomoloGene: 48572 GeneCards: RAD18
Gene location (Human)
Chr.
Chromosome 3 (human)[1]
Band
3p25.3
Start
8,775,402 bp[1]
End
8,963,773 bp[1]
Gene location (Mouse)
Chr.
Chromosome 6 (mouse)[2]
Band
6|6 E3
Start
112,619,850 bp[2]
End
112,696,686 bp[2]
Gene ontology
Molecular function
• metal ion binding • polyubiquitin modification-dependent protein binding • Y-form DNA binding • ubiquitin protein ligase activity • damaged DNA binding • DNA binding • ubiquitin protein ligase binding • single-stranded DNA-dependent ATPase activity • protein binding • identical protein binding • transferase activity • macromolecular complex binding • single-stranded DNA binding
Cellular component
• cytoplasm • site of double-strand break • microtubule organizing center • cell nucleus • replication fork • centrosome • Rad6-Rad18 complex • nuclear inclusion body • cytoskeleton • nucleoplasm • nuclear body
Biological process
• protein monoubiquitination • response to UV • negative regulation of cell death • positive regulation of chromosome segregation • DNA damage response, detection of DNA damage • cellular response to DNA damage stimulus • postreplication repair • protein autoubiquitination • DNA repair • protein ubiquitination
Sources:Amigo / QuickGO
Orthologs
Species
Human
Mouse
Entrez
56852
58186
Ensembl
ENSG00000070950
ENSMUSG00000030254
UniProt
Q9NS91
Q9QXK2
RefSeq (mRNA)
NM_020165
NM_001167730 NM_021385
RefSeq (protein)
NP_064550
NP_001161202 NP_067360
Location (UCSC)
Chr 3: 8.78 – 8.96 Mb
Chr 6: 112.62 – 112.7 Mb
PubMed search
[3]
[4]
Wikidata
View/Edit Human
View/Edit Mouse
E3 ubiquitin-protein ligase RAD18 is an enzyme that in humans is encoded by the RAD18 gene.[5][6][7]
Contents
1Function
2Animal models
3Interactions
4References
5Further reading
Function
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
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]
Rad18 knockout mouse phenotype
Characteristic
Phenotype
Homozygote viability
Normal
Fertility
Normal
Body weight
Abnormal[18]
Anxiety
Normal
Neurological assessment
Normal
Grip strength
Normal
Hot plate
Normal
Dysmorphology
Normal[19]
Indirect calorimetry
Abnormal[20]
Glucose tolerance test
Normal
Auditory brainstem response
Normal
DEXA
Abnormal[21]
Radiography
Normal
Body temperature
Normal
Eye morphology
Normal
Clinical chemistry
Normal
Plasma immunoglobulins
Normal
Haematology
Normal
Peripheral blood lymphocytes
Normal
Micronucleus test
Abnormal
Heart weight
Normal
Tail epidermis wholemount
Normal
Skin Histopathology
Normal
Salmonella infection
Normal[22]
Citrobacter infection
Normal[23]
All tests and analysis from[16][24]
Twenty five tests were carried out and four significant phenotypes were reported:[17]
Mutant male mice had a decreased body weight compared to wildtype control mice.
Mutant male mice showed increased activity, VO2 and energy expenditure, determined by indirect calorimetry.
Dual-energy X-ray absorptiometry (DEXA) showed mutant male mice had a decrease in fat mass.
A micronucleus test found a potential increase in DNA damage in mutant mice.
A knockout in a human colorectal cancer cell line, HCT116, has also been created.[25]
Interactions
RAD18 has been shown to interact with HLTF,[26]UBE2B[5][6] and UBE2A.[5][6]
References
^ abcGRCh38: Ensembl release 89: ENSG00000070950 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000030254 - Ensembl, May 2017
^ abcTateishi 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. doi:10.1073/pnas.97.14.7927. PMC 16647. PMID 10884424.
^ abcXin 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.
^ ab"Entrez Gene: RAD18 RAD18 homolog (S. cerevisiae)".
^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.
^ abvan 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.
^Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
^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.
^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.
^Wellcome Trust Sanger Institute. "Viability at Weaning Data for Rad18". Mouse Resources Portal. www.sanger.ac.uk.
^Wellcome Trust Sanger Institute. "Fertility Data for Rad18". Mouse Resources Portal. www.sanger.ac.uk.
^ abGerdin, 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.
^ abWellcome Trust Sanger Institute. "MGP Phenotyping of Rad18tm1a(EUCOMM)Wtsi". Mouse Resources Portal. www.sanger.ac.uk.
^"Body weight data for Rad18". Wellcome Trust Sanger Institute.
^"Dysmorphology data for Rad18". Wellcome Trust Sanger Institute.
^"Indirect calorimetry data for Rad18". Wellcome Trust Sanger Institute.
^"DEXA data for Rad18". Wellcome Trust Sanger Institute.
^"Salmonella infection data for Rad18". Wellcome Trust Sanger Institute.
^"Citrobacter infection data for Rad18". Wellcome Trust Sanger Institute.
^Mouse Resources Portal, Wellcome Trust Sanger Institute.
^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. PMID 17158148.
^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. doi:10.1073/pnas.0800563105. PMC 2268824. PMID 18316726.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Mulder LC, Chakrabarti LA, Muesing MA (July 2002). "Interaction of HIV-1 integrase with DNA repair protein hRad18". The Journal of Biological Chemistry. 277 (30): 27489–93. doi:10.1074/jbc.M203061200. PMID 12016221.
Nikiforov AA, Sasina LK, Svetlova MP, Solovjeva LV, Oei SL, Bradbury EM, Tomilin NV (2004). "Early immobilization of nuclease FEN1 and accumulation of hRAD18 protein at stalled DNA replication forks in mammalian cells". Doklady Biochemistry and Biophysics. 389: 122–5. doi:10.1023/A:1023696425171. PMID 12856420.
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
Watanabe K, Tateishi S, Kawasuji M, Tsurimoto T, Inoue H, Yamaizumi M (October 2004). "Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination". The EMBO Journal. 23 (19): 3886–96. doi:10.1038/sj.emboj.7600383. PMC 522788. PMID 15359278.
Nikiforov A, Svetlova M, Solovjeva L, Sasina L, Siino J, Nazarov I, Bradbury M, Tomilin N (October 2004). "DNA damage-induced accumulation of Rad18 protein at stalled replication forks in mammalian cells involves upstream protein phosphorylation". Biochemical and Biophysical Research Communications. 323 (3): 831–7. doi:10.1016/j.bbrc.2004.08.165. PMID 15381075.
Miyase S, Tateishi S, Watanabe K, Tomita K, Suzuki K, Inoue H, Yamaizumi M (January 2005). "Differential regulation of Rad18 through Rad6-dependent mono- and polyubiquitination". The Journal of Biological Chemistry. 280 (1): 515–24. doi:10.1074/jbc.M409219200. PMID 15509568.
Masuyama S, Tateishi S, Yomogida K, Nishimune Y, Suzuki K, Sakuraba Y, Inoue H, Ogawa M, Yamaizumi M (August 2005). "Regulated expression and dynamic changes in subnuclear localization of mammalian Rad18 under normal and genotoxic conditions". Genes to Cells. 10 (8): 753–62. doi:10.1111/j.1365-2443.2005.00874.x. PMID 16098139.
Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R (April 2006). "Phosphoproteome analysis of the human mitotic spindle". Proceedings of the National Academy of Sciences of the United States of America. 103 (14): 5391–6. doi:10.1073/pnas.0507066103. PMC 1459365. PMID 16565220.
Bi X, Barkley LR, Slater DM, Tateishi S, Yamaizumi M, Ohmori H, Vaziri C (May 2006). "Rad18 regulates DNA polymerase kappa and is required for recovery from S-phase checkpoint-mediated arrest". Molecular and Cellular Biology. 26 (9): 3527–40. doi:10.1128/MCB.26.9.3527-3540.2006. PMC 1447421. PMID 16611994.
Lloyd AG, Tateishi S, Bieniasz PD, Muesing MA, Yamaizumi M, Mulder LC (May 2006). "Effect of DNA repair protein Rad18 on viral infection". PLoS Pathogens. 2 (5): e40. doi:10.1371/journal.ppat.0020040. PMC 1463017. PMID 16710452.
Yuasa MS, Masutani C, Hirano A, Cohn MA, Yamaizumi M, Nakatani Y, Hanaoka F (July 2006). "A human DNA polymerase eta complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest". Genes to Cells. 11 (7): 731–44. doi:10.1111/j.1365-2443.2006.00974.x. PMID 16824193.
Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (October 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
Indian Forest Service Service Overview Preceding service Imperial Forest Service (1864 to 1935) Year of Constitution 1966 Country India Staff College Indira Gandhi National Forest Academy (IGNFA), Dehradun, Uttarakhand Cadre Controlling Authority Ministry of Environment, Forests and Climate Change Legal personality Governmental: Government service General nature Administration of Forest and Wildlife resources Cadre strength 3131 (2182 Direct Recruits and 949 Promotion Posts) Website ifs.nic.in Service Chief Director General of Forests Siddhanth Das, IFS (1982 Batch, Odisha Cadre) [1] Head of the All India Civil Services Cabinet Secretary Pradeep Kumar Sinha, IAS Indian Forest Service (भारतीय वन सेवा) [2] is one of the three All India Services of the Government of India. The other two All India Services being the Indian Administrative Service (IAS) and the Indian Police Service (IPS). [3] [4] [5] It was constituted in
