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
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 Top expressed in lung Achilles tendon heart stomach kidney corpus callosum More reference expression data BioGPS n/a
Gene ontology Molecular function metal ion binding polyubiquitin modification-dependent protein binding Y-form DNA binding GO:1904264, GO:1904822, GO:0090622, GO:0090302 ubiquitin protein ligase activity damaged DNA binding DNA binding ubiquitin protein ligase binding GO:0043142 single-stranded DNA helicase activity GO:0001948 protein binding identical protein binding transferase activity GO:0032403 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]

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]

Animal models[]

Model organisms have been used in the study of RAD18 function. A conditional knockout mouse line, called Rad18^{tm1a(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]

• 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[]

Further reading[]