RAD18

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]

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 cells 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
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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]