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FLASH GENE
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.-
    DNA
    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
    RNA
    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
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text abundantly in various tissues
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
    HOMOLOGY
    Homologene
    FAMILY
  • RING (really interesting new gene) finger protein family
  • SUMO-Targeted Ubiquitin Ligase (STUbL) family
    • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    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
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component component in PML bodies
    INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
    zinc Zn2+
    protein
  • 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
    REGULATION
    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)
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS