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FLASH GENE
Symbol RNF168 contributors: mct/ - updated : 04-02-2015
HGNC name ring finger protein 168
HGNC id 26661
Corresponding disease
RIDIS RIDDLE syndrome
Location 3q29      Physical location : 196.195.662 - 196.230.639
Synonym name E3 ubiquitin-protein ligase RNF168
Synonym symbol(s) FLJ35794
EC.number 6.3.2.-
DNA
TYPE functioning gene
STRUCTURE 31.96 kb     6 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 - 5365 65 571 - 2009 19203579
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunetonsils   highly
Reproductivemale systemtestis  highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • RING-type zinc finger
  • two ubiquitin binding domains (UBDs) named MIU (motif interacting with ubiquitin), and UMI (UIM- and MIU-related UBD)(integrity of the UMI, in addition to the MIUs, is necessary for the proper localization of RNF168 and for ubiquitination of nuclear proteins, including histone H2A)
  • a coiled-coil is predicted in RNF168 C-terminal to the RING domain around AAs 170200 and is likely the main interface required if dimerization of RNF168 in fact occurs
  • mono polymer trimer
    HOMOLOGY
    intraspecies paralog to RNF169
    Homologene
    FAMILY
  • RNF168 family
  • CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • recruited to sites of DNA damage by binding to ubiquitylated histone H2A
  • chromatin-associated RING finger protein which targets histones HIST2H2AC and H2AFX)
  • acting with UBE2N to amplify the RNF8-dependent histone ubiquitylation by targeting H2A-type histones and by promoting the formation of lysine 63-linked ubiquitin conjugates
  • E3 ubiquitin ligase that acts in concert with UBE2N to catalyze the formation of lysine 63 (K63)-linked ubiquitin conjugates and promotes the ubiquitylation of H2A-type histones surrounding the damage
  • chromatin-associated ubiquitin ligase with an ability to bind ubiquitin
  • ubiquitin-dependent DNA-damage signaling cascade involving the E34 ubiquitin ligases RNF8 and RNF168 plays key roles in coordinating cell cycle progression and DNA repair
  • combines E3 ubiquitin ligase activity with an ability to bind conjugated ubiquitin on damaged chromosomes and mechanistically defines a molecular pathway involved in the DNA damage-induced chromatin response
  • chromatin-associated RING finger protein, targeting histones HIST2H2AC and H2AFX
  • facilitate recruitment of TP53BP1 to sites of DNA damage and the ubiquitination pathway mediated by RNF8 and RNF168 plays an integral part in class switch recombination
  • with others ATM signalling mediator proteins, RNF8, MDC1 and TP53BP1 are also required for heterochromatic DSB repair
  • RNF8 and RNF168 effect the formation of lysine 63-linked polyubiquitin (K63Ub) chains on damaged chromatin, including on histones HIST2H2AC and H2AFX, in an ATM-dependent manner
  • contributes to this emerging pathway of several E3 ubiquitin ligases that perform sequential ubiquitylations on damaged chromosomes, chromatin modifications essential for aggregation of repair complexes at the DSB sites
  • E3 ubiquitin ligases RNF8 and RNF168 may participate in cellular responses upon replication stress
  • HERC2 and RNF168 are novel DNA damage-dependent SUMOylation targets in human cells
  • RNF8 and RNF168 are essential RING-E3 ubiquitin ligases that catalyze the formation of Lys-63 ubiquitin chains in the DNA damage response
  • histone ubiquitination during the DSB pathway is initiated by RNF168 on HIST2H2AC and H2AFX, whereas RNF8 is inactive toward them
  • RNF168 and TP53BP1 have a similar influence on homologous recombination (HR) and also indicate that these factors may function in the same pathway to inhibit HR
  • RNF168 is important for HR deficiency in cells with BRCA1 silencing
  • RNF8 and RNF168 operate in different modes with their cognate E2 UBE2N at DSBs
  • RNF168, in complex with UBE2A or UBE2B, is activated in the DNA-damage-induced protein ubiquitination cascade
  • plays a central role in the regulation of TP53BP1 functions
  • multistep roles of RNF168 in signaling DNA damage
  • nucleosome acidic patch plays a critical role in RNF168-dependent ubiquitination of histone H2A
  • RNF8 is less abundant than RNF168, and RNF8 is a rate-limiting determinant of focal repair complex assembly
  • promotes noncanonical K27-linked ubiquitination
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • RNF8/RNF168 pathway that might be an important conduit for ATM-dependent DNA damage signaling
  • RNF8-RNF168-BRCA1 cascade emerges as a target for mutations in genome instability disorders
  • a component
  • part of MRE11A-ATM-RNF168 signaling complex, implicated in a signaling cascade that directly promotes a PI3K-independent pathway of AKT1 phosphorylation
  • RNF168, in complex with UBE2A or UBE2BB, is activated in the DNA-damage-induced protein ubiquitination cascade
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • interacts with ubiquitylated HIST2H2AC
  • interacting with HIST2H2AC(RNF168 modifies chromatin structure by modulating ubiquitination of histone HIST2H2AC)
  • RNF8 and RNF168 promote VCP-mediated displacement of L3MBTL1 to unmask TP53BP1 chromatin binding sites
  • both HERC2 and RNF168 were specifically modified with SUMO1 at DSB sites in a manner dependent on the SUMO E3 ligase PIAS4
  • RNF169 antagonizes potentially RNF168 functions at DSBs
  • TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage
  • is required for recruitment of several DNA damage response factors to double strand breaks (DSBs), including TP53BP1 and BRCA1
  • RNF168, in complex with UBE2A or UBE2B, is activated in the DNA-damage-induced protein ubiquitination cascade
  • USP44 implicated in negative regulation of the RNF8/RNF168 pathway
  • ATM-dependent phosphorylation of BCL10 promotes its interaction with and presentation of UBE2N to RNF8, and RNF8-mediated ubiquitination of BCL10 enhances binding of BCL10 and UBE2N to RNF168
  • interacting with TP53BP1 whose ensuing degradation is regulated by RNF8 and RNF168
  • KDM1A, RNF168 and TP53BP1 interacted with each other directly
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) RIDIS
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    may be a therapeutic target to restore HR in cells with BRCA1 loss
    ANIMAL & CELL MODELS