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FLASH GENE
Symbol RNF2 contributors: mct/pgu - updated : 06-02-2019
HGNC name ring finger protein 2
HGNC id 10061
Location 1q25.3      Physical location : 185.014.550 - 185.071.740
Synonym name
  • DinG protein
  • E3 ubiquitin-protein ligase RING2
  • Huntingtin-interacting protein 2-interacting protein 3
  • RING finger protein 1B
  • Synonym symbol(s) DING, BAP1, HIPI3, RING1B, RING2, BAP-1,
    EC.number 6.3.2.-/ 2.3.2.27
    DNA
    TYPE functioning gene
    STRUCTURE 57.19 kb     7 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   HRE
    text structure
  • RNF2 response elements in kidney cells (
  • MAPPING cloned Y linked N status provisional
    Physical map
    RNASEL 1q25 ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent) RGS16 1q25-q31 regulator of G-protein signalling 16 RGS8 1q25-q31 regulator of G-protein signalling 8 NPL 1q25 N-acetylneuraminate pyruvate lyase (dihydrodipicolinate synthase) DHX9 1q25 DEAH (Asp-Glu-Ala-His) box polypeptide 9 C1orf14 1q25-q31 chromosome 1 open reading frame 14 LOC391143 1 similar to natural cytotoxicity triggering receptor 1; lymphocyte antigen 94 (mouse) homolog (activating NK-receptor; NK-p46); lymphocyte antigen 94 (mouse) homolog (activating NK-receptor ; NK-p46); lymphocyte antigen 94 homolog, a LOC343326 1q25.2 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LAMC1 1q31 laminin, gamma 1 (formerly LAMB2) LAMC2 1q25-q31 laminin, gamma 2 NMNAT2 1q25-q31 nicotinamide nucleotide adenylyltransferase 2 C1orf16 1q25-q31 chromosome 1 open reading frame 16 NCF2 1q25 neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) ARPC5 1q25.2 actin related protein 2/3 complex, subunit 5, 16kDa RGL 1q25.2 actin related protein 2/3 complex, subunit 5, 16kDa C1orf17 1q25-q31 chromosome 1 open reading frame 17 C1orf19 1q25-q31 chromosome 1 open reading frame 19 LOC391144 1 similar to Rho-GTPase-activating protein 8 C1orf21 1q25-q31 chromosome 1 open reading frame 21 C1orf22 1q24-q25 chromosome 1 open reading frame 22 C1orf24 1q25-q31 chromosome 1 open reading frame 24 RNF2 1q25.1 ring finger protein 2 C1orf25 1q25.2 chromosome 1 open reading frame 25 C1orf26 1q25 chromosome 1 open reading frame 26 IVNS1ABP 1q25.1-q31.1 influenza virus NS1A binding protein FIBL-6 1q25.3 hemicentin PRG4 1q25-q31 proteoglycan 4, (megakaryocyte stimulating factor, articular superficial zone protein, camptodactyly, arthropathy, coxa vara, pericarditis syndrome) TPR 1q25 translocated promoter region (to activated MET oncogene) C1orf27 1q25-q31 translocated promoter region (to activated MET oncogene) PDC 1q32-q41 phosducin LOC391145 1 similar to KIAA1871 protein PTGS2 1q25.2-q25.3 prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) PLA2G4A 1q25 phospholipase A2, group IVA (cytosolic, calcium-dependent)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 3551 37.6 336 - 2007 17379327
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Nervousbrain    
    Reproductivefemale systemplacenta  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    cell lineage
    cell lines
    fluid/secretion synovial fluid
    at STAGE
    physiological period embryo, fetal, pregnancy
    Text liver, primitive neurectoderm, placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a conserved N-terminal RING finger domain and functions as an E3 ligase
  • C-RNF2 region is required for cbox binding (N- and C-terminal halves of C-RNF2 can be separated and are able to interact, suggesting the presence of an intramolecular interaction within C-RNF2)
  • conjugated MetalloP
    HOMOLOGY
    interspecies homolog to murine Rnf2
    Homologene
    FAMILY
  • Polycomb group family of proteins
  • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nucleus,chromatin/chromosome
    text
  • RNF2 co&
  • 8209;localized with PLK1 at mitotic chromosomes in the prometaphase and metaphase
    basic FUNCTION
  • E3 ubiquitin ligase activity intrinsic to the RING domain, playing an autocrine growth-stimulatory role
  • might have a dual function : facilitating the ubiquitination of its target substrates and recruiting the substrates to the proteasome
  • its phosphorylation differentially modulates the expression of transcription factors and histone 2B acetylation
  • its ability to restore a compact chromatin state and to repress Hox gene expression is not dependent on its histone ubiquitination activity
  • ubiquitin ligase that modifies nucleosomal histone H2A, a modification which plays a critical role in regulation of gene expression
  • plays an important role in Polycomb-mediated gene silencing by monoubiquitinating histone H2A
  • represses a number of genes involved in development, differentiation, malignant transformation and cell cycle
  • can associate with nonmethylated chromatin suggesting an alternate mechanism for RING1B interaction with chromatin
  • BMI1 and RNF2 are critical components of PRC1 (Polycomb repressive complex 1) that heterodimerize via their N-terminal RING domains to form an active E3 ubiquitin ligase
  • RNF2, AURKB have essential roles in regulating transcriptionally active genes in quiescent lymphocytes
  • critical role for the polycomb group protein RNF2 in nonhomologous end-joining (NHEJ)-mediated end-to-end chromosome fusion
  • is the catalytic subunit of the polycomb repressive complex 1 (PRC1) a major epigenetic repressor essential for pluripotency maintenance and differentiation
  • RNF2 is an important upstream negative regulator of SIK1 and that restoration of SIK1 levels induced by loss of RNF2 inhibited HCC cell growth and promoted apoptosis
  • displays oncogenic functions in different types of cancers
  • RNF2 is required to support DNA replication, similar to MDM2
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • with Polycomb (Pc) are two components of a multiprotein complex called polycomb repression complex 1 (PRC1) that is essential for establishing and maintaining long-term repressed gene states
  • forms a functional complex with CDKN2A, but in the case of CDKN2A repression by BMI1, RNF2 was not involved and was therefore not necessary for BMI1-mediated regulation of CDKN2A )
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • with HIP2 (Huntingtin interacting protein 2), a ubiquitin conjugating enzyme
  • interacting with TFCP2 and PHB2 (RNF2 and PHB2 modulate the TFCP2-mediated transcriptional pathway)
  • interaction between the C-terminal region of RNF2(C-RING1B) and the Pc cbox domain
  • target for phosphorylation by MAPK14 and ERK signaling pathways
  • expanded regulatory role for RING1, RNF2 proteins in the epigenetic regulation of gene expression
  • USP7 is a deubiquitinating enzyme that regulates the ubiquitination state of RNF2 (RNF2 interacts with USP7, which is mediated in part by its RING domain)
  • binds methylated chromatin through its association with another PcG protein called Polycomb (Pc)
  • UBE2D3 interacts with RNF2, in a manner fairly typical of E2-E3 interactions
  • by binding to the RING domain of RNF2, CDKN2A disrupts RNF2 homodimerization, providing a potential mechanism for its effect on RNF2 self-ubiquitination
  • CDKN2A specifically directs RNF2 into the E6-AP-mediated ubiquitination pathway by preventing its self-ubiquitination
  • CBX7 is necessary for recruitment of RNF2 to chromatin, whereas RYBP enhances the Polycomb repressive complex 1 enzymatic activity
  • RNF2 is an E3 ligase for TP53 degradation in selective cells
  • RNF2 functionally interacts with BCOR and is required to prevent colobomata
  • SNAI1 recruits RNF2 to mediate transcriptional repression and cell migration in pancreatic cancer cells
  • RNF2 potentiates AMBRA1 degradation with the help of WASH1
  • OGT modifies and regulates an essential epigenetic tool, RNF2, which may contribute to embryonic stem cells (hESC) pluripotency maintenance and differentiation
  • RNF2 regulates distinct biologic processes in the genesis and progression of melanoma via different molecular mechanisms
  • RNF2 is an important upstream negative regulator of SIK1 and restoration of SIK1 levels induced by loss of RNF2 inhibited hepatocellular carcinoma (HCC)cell growth and promoted apoptosis
  • RYBP inhibits the polyubiquitination-mediated proteasomal degradation of RNF2 independently of its ubiquitin (Ub)-protein isopeptide ligase (E3) ligase activity
  • RYBP modulates stability and function of RNF2 through targeting UBE3A
  • cell & other
    REGULATION
    activated by ID1 (overexpression of ID1 enhanced RNF2 E3 ligase activity leading to accumulation of H2A ubiquitination and ubiquitin/proteasome-mediated degradation of geminin)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • RNF2 might serve as an independent biomarker indicative of poor prognosis in patients with ovarian carcinoma
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    loss of RNF2 inhibited HCC cell growth and promoted apoptosis, which may represent a promising therapeutic strategy for HCC treatment
    ANIMAL & CELL MODELS