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Symbol RNF4 contributors: mct/ - updated : 05-04-2016
HGNC name ring finger protein 4
HGNC id 10067
Location 4p16.3      Physical location : 2.470.794 - 2.517.585
Synonym name
  • small nuclear ring finger protein
  • E3 ubiquitin ligase RNF4
  • protein SNURF
  • Synonym symbol(s) RING4, RES4.26, SNURF, SLX5
    EC.number 6.3.2.-
    TYPE functioning gene
    STRUCTURE 46.80 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Map cen - D4S180 - HDAC1 - GRK4 - D4S127 - C4orf10 - C4orf9 - D4S95 - ADD1 - SH3BP2 - RNF4 - D4S183 - C4orf8 - D4S182 - pter
    Physical map
    CPLX1 4p16.3 complexin 1 GAK 4p16 cyclin G associated kinase MGC4618 4p16.3 hypothetical protein MGC4618 DGKQ 4p16.3 diacylglycerol kinase, theta 110kDa SLC26A1 4p16.3 solute carrier family 26 (sulfate transporter), member 1 IDUA 4p16.3 iduronidase, alpha-L- FGFRL1 4p16 fibroblast growth factor receptor-like 1 LOC285498 4p16.3 hypothetical protein LOC285498 LOC132969 4p16.3 similar to hornerin SPON2 4p16.3 spondin 2, extracellular matrix protein CTBP1 4p16 C-terminal binding protein 1 MGC21675 4p16.3 hypothetical protein MGC21675 MAEA 4p16.3 macrophage erythroblast attacher KIAA1530 4p16.3 KIAA1530 protein FLJ34443 4p16.3 hypothetical protein FLJ34443 HSPX153 4p16.3 HPX-153 homeobox LOC345375 4p16.3 similar to CG32656-PA LOC152877 4p16.3 similar to RIKEN cDNA 5430419M09 SLBP 4p16 stem-loop (histone) binding protein LOC92305 4p16.3 hypothetical protein BC009331 TACC3 4p16.3 transforming, acidic coiled-coil containing protein 3 FGFR3 4p16.3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) LETM1 4p16.3 leucine zipper-EF-hand containing transmembrane protein 1 WHSC1 4p16.3 Wolf-Hirschhorn syndrome candidate 1 WHSC2 4p16.3 Wolf-Hirschhorn syndrome candidate 2 LOC389195 4 hypothetical gene supported by BC038466; BC047038 FLJ37478 4p16.3 hypothetical protein FLJ37478 POLN 4p16.3 polymerase (DNA directed) nu MGC4701 4p16.3 hypothetical protein MGC4701 MXD4 4p16.3 MAX dimerization protein 4 KIAA1643 4p16.3 KIAA1643 protein LOC339985 4p16.3 hypothetical gene supported by BC010180 RNF4 4p16.3 ring finger protein 4 C4orf8 4p16.3 chromosome 4 open reading frame 8 TNIP2 4p16.3 TNFAIP3 interacting protein 2 LOC389196 4 LOC389196 SH3BP2 4p16.3 SH3-domain binding protein 2 ADD1 4p16.3 adducin 1 (alpha) TETRAN 4p16.3 tetracycline transporter-like protein C4orf9 4p16.3 chromosome 4 open reading frame 9 GPRK2L 4p16.3 G protein-coupled receptor kinase 2-like (Drosophila) HD 4p16.3 huntingtin (Huntington disease) LOC345222 4p16.3 hypothetical gene supported by BC043530 RGS12 4p16.3 regulator of G-protein signalling 12 HGFAC 4p16.3 HGF activator FLJ33718 4p16.3 hypothetical protein FLJ33718 LOC391612 4 similar to hypothetical protein MGC45871 LRPAP1 4p16.3 low density lipoprotein receptor-related protein associated protein 1 FLJ35424 4p16.3 hypothetical protein FLJ35424 ADRA2C 4p16.3-p15 adrenergic, alpha-2C-, receptor LOC391613 4 similar to mannosyltransferase LOC196483 LOC391614 4 similar to Alkaline sphingomyelinase
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 2811 - 113 - 1998 9710597
    8 - 2971 21.3 190 - 1998 9710597
    9 - 3493 21.3 190 - 1998 9710597
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis  highly
    cell lineage
    cell lines
    at STAGE
    physiological period fetal, pregnancy
    Text abundantly in various tissues
  • SUMO interaction motifs (SIMs) in the N-terminal part of RNF4 tightly bind to SUMO polymers
  • the RING finger domain C3HC4 type, which forms a stable dimer, dimerization required for ubiquitin transfer , and a nucleosome-targeting motif within the RNF4 RING domain that can bind DNA and thereby enables RNF4 to selectively ubiquitinate nucleosomal histones
  • two putative nuclear localization signals (NLS), and stretches of acidic Aas
  • arginine-rich motif (ARM) in RNF4 acting as a novel recognition motif for selective target recruitment
  • conjugated MetalloP
  • RING (really interesting new gene) finger protein family
  • SUMO-Targeted Ubiquitin Ligase (STUbL) family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • involved in the protein and DNA association in the nucleus of the cell
  • functions as an E3 ligase and this activity is closely linked to its transcription regulatory functions
  • involved in transcriptional and cell growth regulation
  • poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation
  • coregulator of seroid receptor-mediated gene transcription
  • SUMO-targeted ubiquitin ligase that mediates heat-shock-inducible ubiquitination of PARP1, regulates the stability of PARP1, and, like PIAS4, is a positive regulator of HSPA1A gene activity
  • with VHL regulate the proteasomal degradation of SUMO-conjugated HIF2A
  • finely balanced activities of SENP6 and RNF4 control vertebrate kinetochore assembly through SUMO-targeted destabilization of inner plate components
  • RING E3 ligase that regulate the homoeostasis of SUMOylated proteins by promoting their ubiquitylation
  • SUMO-dependent ubiquitin E3-ligase implicated in maintaining genome stability, and playing a key role in active DNA demethylation
  • may serve as a direct link between epigenetic DNA demethylation and DNA repair in mammalian cells
  • gene essential for mammalian embryonic development, playing a critical role in active DNA demethylation through mechanisms that involve the BER (base excision repair) pathway
  • RING E3 ligase that regulate the homoeostasis of SUMOylated proteins by promoting their ubiquitylation
  • is a dimeric RING ubiquitin E3 ligase that ubiquitylates poly-SUMOylated proteins
  • operates as a DSB response factor at the crossroads between the SUMO and ubiquitin systems
  • is a novel DNA damage-responsive protein that plays a role in homologous recombination and integrates SUMO modification and ubiquitin signaling in the cellular response to genotoxic stress
  • is a critical component of the DDR ( DNA damage response)and RNF4 controls potentially protein localization at DNA damage sites by integrating SUMOylation and ubiquitylation events
  • ARM is required for RNF4 to efficiently target Ser(P)-824-SUMO-KAP1, conferring ubiquitin Lys-48-mediated proteasomal degradation in the context of double strand breaks
  • manipulates the conformation of the SUMO chain, thereby facilitating optimal delivery of the distal SUMO domain for ubiquitin transfer
  • plays a novel role in preventing the loss of intact chromosomes and ensures the maintenance of chromosome integrity 0)
  • is an E3 ubiquitin ligase originally identified as a transcription co-activator
  • antagonizes transcriptional repression mediated by DNA methylation
  • is a SUMO-targeted ubiquitin E3 ligase with a pivotal function in the DNA damage response (DDR)
  • USP11 and RNF4 as a balanced SUMO-targeted ubiquitin ligase/protease pair with a role in the DDR
  • RNF4 and TRIM28 play critical roles in the response to DNA double-strand breaks (DSBs)
  • combined effect of dynamic recruitment of RNF4 to TRIM28 regulates likely the relative occupancy of TP53BP1 and BRCA1 at DSB sites to direct DSB repair in a cell cycle-dependent manner
  • CELLULAR PROCESS nucleotide, transcription, regulation
    a component component in PML bodies
    DNA binding
    small molecule metal binding,
    zinc Zn2+
  • androgen receptor (AR)
  • TATA binding protein (TBP)
  • GSC2/RNF4 interactions (in addition to acting as a modulator of transcriptional activity, RNF4 may function, as do other RING proteins, to promote the formation of intracytoplasmic complexes involved in shuttling information between the cytoplasm and the nucleus)
  • targets poly-SUMO-modified proteins for degradation mediated by ubiquitin
  • RNF4, a SUMO-targeted ubiquitin E3 ligase that synthesizes hybrid SUMO-ubiquitin chains, localized to DSBs and was critical for the recruitment of UIMC1 and BRCA1 to sites of DNA damage
  • KDM5B is modulated by RNF4, an E3 ubiquitin ligase that targets SUMO-modified proteins to proteasomal degradation
  • ubiquitin E3 ligase activity of RNF4 is directly linked to the availability of its polySUMO substrates
  • RNF4 nucleosome-targeting is crucially required for the repair of TERF2-depleted dysfunctional telomeres by TP53BP1-mediated non-homologous end joining
  • RNF4 does not promote DNA demethylation, but mediates the ubiquitination of MECP2, a methyl-CpG-binding domain (MBD) protein
  • RNF4-mediated polyubiquitination regulates the FANCA/BRCA pathway
  • in addition to drive cell cycle progression, CDK2 also targets RNF4, which is involved in the regulatory network of DSBs repair
  • USP11 is a functional interactor of RNF4, and USP11 can deubiquitinate hybrid SUMO-ubiquitin chains to counteract RNF4
  • RNF4 interacts with the NR2C2-TAB2-TAB3 complex, but not TAB1
  • RNF4 specifically down-regulated TAB2 through a lysosomal pathway
  • cell & other
    Other regulated by SUMO1 (promotes association of RNF4 with PML nuclear bodies, and SUMO1-facilitated sequestration into these nuclear domains regulates the transcriptional activity of RNF4)