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FLASH GENE
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
    DNA
    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
    Physical map
    LOC389092 3 LOC389092 LMCD1 3p26-p24 LIM and cysteine-rich domains 1 LOH3CR2A 3 loss of heterozygosity, 3, chromosomal region 2, gene A LOC51066 3p25.3 fls485 LOC391507 3 similar to seven transmembrane helix receptor CAV3 3p25 caveolin 3 OXTR 3p25 oxytocin receptor RAD18 3p25-p24 RAD18 homolog (S. cerevisiae) SRGAP2 3p25.3 SLIT-ROBO Rho GTPase activating protein 2 LOC391508 3 similar to Phosphoglycerate mutase 1 (Phosphoglycerate mutase isozyme B) (PGAM-B) (BPG-dependent PGAM 1) DKFZP434F091 3p25.3 DKFZP434F091 protein FLJ10707 3p25.3 hypothetical protein FLJ10707 LOC375323 3p25.3 lipoma HMGIC fusion partner-like protein 4 FLJ22405 3p26 hypothetical protein FLJ22405 LOC151835 3p25.3 copine family member BRPF1 3p26-p25 bromodomain and PHD finger containing, 1 OGG1 3p26.2 8-oxoguanine DNA glycosylase CAMK1 3p25.2 calcium/calmodulin-dependent protein kinase I TADA3L 3p25.3 transcriptional adaptor 3 (NGG1 homolog, yeast)-like ARPC4 3p25.3-p24.1 actin related protein 2/3 complex, subunit 4, 20kDa LOC389093 3 similar to RIKEN cDNA 4833441J24 DKFZP434B103 MGC29784 3p25.3 hypothetical protein MGC29784 CIDE-3 3p25.3 cell death activator CIDE-3
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 5739 - 495 - 2009 19228710
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Lymphoid/Immunethymus   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
  • HOMOLOGY
    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
    Homologene
    FAMILY
  • RAD18 family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    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
    PHYSIOLOGICAL PROCESS
    text maybe an important role in lexin bypass mechanisms
    PATHWAY
    metabolism
    signaling
    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
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
    REGULATION
    Other regulation by direct phosphorylation
    ASSOCIATED DISORDERS
    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
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Cells from Rad18(-/-) transgenic mice show defective recovery from BPDE-induced S-phase checkpoints (