RAD18

RAD18
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MRE, 2MRF, 2Y43, 2YBF
Identifiers
Aliases	RAD18 , RNF73, E3 ubiquitin protein ligase, RAD18 E3 ubiquitin protein ligase
External IDs	OMIM: 605256; MGI: 1890476; HomoloGene: 48572; GeneCards: RAD18; OMA:RAD18 - orthologs
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 112,596,811 bp [2] End 112,673,647 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle Achilles tendon ventricular zone gonad ganglionic eminence jejunal mucosa stromal cell of endometrium epithelium of colon islet of Langerhans bone marrow cell Top expressed in tail of embryo zygote spermatocyte genital tubercle spermatid secondary oocyte primary oocyte epiblast lumbar spinal ganglion inner renal medulla More reference expression data BioGPS n/a
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 helicase activity protein binding identical protein binding transferase activity protein-containing complex binding single-stranded DNA binding Cellular component cytoplasm site of double-strand break microtubule organizing center 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 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 NM_001381931 NM_001381932 NM_001381933 RefSeq (protein) NP_064550 NP_001161202 NP_067360 NP_001368860 NP_001368861 NP_001368862 Location (UCSC) Chr 3: 8.78 – 8.96 Mb Chr 6: 112.6 – 112.67 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]} A knockout in a human colorectal cancer cell line, HCT116, has also been created. ^[8]

Function

The protein encoded by this gene 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]

RAD18 is an E3 ubiquitin ligase that enables movement of ubiquitin from a ubiquitin carrier to another protein (the substrate). One activity of RAD18 is to prevent replication fork collapse by promoting DNA translesion synthesis and template switching. ^[9] RAD18 is also involved in directing repair of DNA double-strand breaks by homologous recombination in post replicative chromatin. ^[9] RAD18 appears to promote homologous recombinational repair by recruiting the SMC5,SMC6 (SMC5/6) complex to the DNA breaks. ^[9]

Interactions

RAD18 has been shown to interact with HLTF, ^[10] UBE2B ^{[5] [6]} and UBE2A. ^{[5] [6]}

References

1. GRCh38: Ensembl release 89: ENSG00000070950 – Ensembl, May 2017
2. 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. 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. 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. "Entrez Gene: RAD18 RAD18 homolog (S. cerevisiae)".
8. 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.
9. Palek M, Palkova N, Kleiblova P, Kleibl Z, Macurek L (July 2024). "RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin". Nucleic Acids Res. 52 (13): 7687–7703. doi:10.1093/nar/gkae499. PMC   11260465 . PMID   38884202.
10. 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

• 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 (1–6): 122–5. doi:10.1023/A:1023696425171. PMID   12856420. S2CID   2646911.
• 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. Bibcode:2004PNAS..10112130B. 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. Bibcode:2004BBRC..323..831N. 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. S2CID   41733250.
• 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. Bibcode:2006PNAS..103.5391N. 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. S2CID   32695133.
• 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. S2CID   14294292.
• 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. S2CID   7827573.