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RAD18
Identifiers
Aliases	RAD18, RNF73, E3 ubiquitin protein ligase, RAD18 E3 ubiquitin protein ligase
External IDs	OMIM: 605256; MGI: 1890476; GeneCards: RAD18
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2MRE, 2MRF, 2Y43, 2YBF
Enzyme activity
Gene location (Human)
Chr.	Chromosome 3 (human)
End	8,963,773 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	112,673,647 bp
RNA expression pattern
	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
	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
Databases	NCBI: entry; OMA: entry
	56852
	58186
	ENSG00000070950
	ENSMUSG00000030254
	Q9NS91
	Q9QXK2
	NM_020165
	NM_001167730; NM_021385; NM_001381931; NM_001381932; NM_001381933
	NP_064550
	NP_001161202; NP_067360; NP_001368860; NP_001368861; NP_001368862
	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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000070950 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030254 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^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.
^ ^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.
^ ^a ^b "Entrez Gene: RAD18 RAD18 homolog (S. cerevisiae)".
^ 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.
^ ^a ^b ^c 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.
^ 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.

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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000070950 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid10884424-5] 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.

[pmid10908344-6] 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.

[entrez-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.

[Palek2024-9] 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.

[pmid18316726-10] 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.

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RAD18

Function

Interactions

References

Further reading

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