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Symbol RAD18 contributors: mct/shn/pgu - updated : 24-07-2015
HGNC name RAD18 homolog (S. cerevisiae)
HGNC id 18278
Location 3p25.3      Physical location : 8.918.881 - 9.005.159
Synonym name
  • postreplication repair protein hRAD18p
  • postreplication repair protein RAD18
  • RAD18, S. cerevisiae, homolog
  • RING finger protein 73
  • E3 ubiquitin-protein ligase RAD18
  • Synonym symbol(s) RNF73, hHR18, hRAD18
    TYPE functioning gene
    STRUCTURE 86.28 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D3S4545 - D3S3691 - RAD18 - D3S1597 - D3S3611 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 5739 - 495 - 2009 19228710
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Lymphoid/Immunethymus   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    at STAGE
  • conserved RING finger motif and zinc finger motif in the N-terminal half
  • a SAP domain (residues 248-282), required for the efficient mono-ubiquitination of PCNA, and crucial for binding of RAD18 complexed with UBE2B to DNA substrates
    interspecies homolog to yeast S.cerevisiae Rad18
    ortholog to Rad18, Mus musculus
    ortholog to Rad18, Rattus norvegicus
    ortholog to rad18, Danio rerio
    ortholog to RAD18, Pan troglodytes
  • RAD18 family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • plays a crucial role in post-replication repair (PRR)
  • with UBE2B is recruited to stalled replication forks via interactions with forked DNA or long ssDNA structures, a process that is required for initiating post-replication repair
  • accumulates at blocked forks and initiates the signal to recruit translesion DNA synthesis polymerases
  • functions as an adaptor to facilitate homologous recombinaison through direct interaction with the recombinase RAD51C
  • promotes TP53BP1-directed DSB repair by enhancing retention of TP53BP1, possibly through an interaction between RAD18 and TP53BP1 and the modification of TP53BP1
  • having a rolein the cellular response to DSBs
  • RAD18-mediated PCNA monoubiquitination is a central hub for the mobilization of the FA pathway by promoting FANCL-mediated FANCD2 monoubiquitylation
  • key role for the E3 ligase activity of RAD18 in the recruitment of FANCD2 and FANCI to chromatin and the events leading to their ubiquitylation during S phase
  • at the XY body, RAD18 mediates the chromatin association of its interaction partners, the ubiquitin-conjugating enzymes UBE2A, UBE2B
  • RAD18 and UBE2B have a role in the efficient repair of a small subset of meiotic DSBs
  • ubiquitin ligase involved in replicative damage bypass and DNA double-strand break (DSB) repair processes
  • required for recruitment of RAD9A, one of the components of the 9-1-1 checkpoint complex
  • interacts with ubiquitylated chromatin components and facilitates RAD9A recruitment to DNA double strand breaks
  • is necessary for damage tolerance during S-phase
  • RAD18 and RNF8 operate in the same pathway in the promotion of homologous recombination (HR)
  • involved in post replication repair pathways via its recruitment to stalled replication forks, and its role in the ubiquitylation of proliferating cell nuclear antigen (PCNA)
  • can function as a mediator for DNA damage response signals to activate the G2/M checkpoint in order to maintain genome integrity and cell survival after IR exposure
  • functions at the cross-roads of three different DNA damage response (DDR) pathways involved in protecting stressed replication forks: homologous recombination repair, DNA inter-strand cross-link repair and DNA damage tolerance
  • having hematopoietic functions and confering DNA damage tolerance and tumor-suppression in a physiological setting
  • CELLULAR PROCESS nucleotide, repair, recombination
    nucleotide, transcription
    text maybe an important role in lexin bypass mechanisms
    RAD18-PCNA-DLCRE1A activation pathway appears to be independent of another DNA crosslink repair pathway, the FA (Fanconi anemia) pathway
    a component
  • complexed with UBE2B preferentially binds to forked and single-stranded DNA (ssDNA) structures, which are known to be localized at stalled replication forks
    small molecule
  • HHR6A and HHR6B (
  • RAD51C (
  • WRNIP1 (
  • FANCD2 (
  • DNA Polymerase eta (
  • ubiquitylated H2A (
  • binds to RAD18 after UV irradiation and mediates the recruitment of RAD18 to sites of DNA damage
  • BRCTx (
  • RAD18 phosphorylation by MAPK8 represents a novel mechanism for promoting translesion synthesis (TLS) and DNA damage tolerance
  • is targeted to PCNA by DNA polymerase eta (POLH) (pMID: 23345618)
  • SIVA1 interacts with RAD18 and serves as a molecular bridge between RAD18 and PCNA, thus targeting the E3 ligase activity of RAD18 onto PCNA
  • RAD18 E3 ligase requires an accessory protein for binding to its substrate PCNA
  • de-ubiquitylating enzyme USP7 is a critical regulator of RAD18 protein levels
  • NBN initiates POLH-dependent translesion DNA synthesis by recruiting RAD18 through its binding at the NBS1 C-terminus after UV exposure, and it also functions after the generation of interstrand crosslink DNA damage
  • cell & other
    Other regulation by direct phosphorylation
    corresponding disease(s)
    Susceptibility to colorectal cancer risk (CRC) and non-small-cell lung cancer
    Variant & Polymorphism SNP association between the RAD18 Arg302Gln polymorphism and CRC and non-small-cell lung cancer risk
    Candidate gene
    Therapy target
  • Cells from Rad18(-/-) transgenic mice show defective recovery from BPDE-induced S-phase checkpoints (