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FLASH GENE
Symbol RCHY1 contributors: mct - updated : 05-01-2013
HGNC name ring finger and CHY zinc finger domain containing 1
HGNC id 17479
Location 4q21.1      Physical location : 76.404.354 - 76.439.628
Synonym name
  • androgen-receptor N-terminal-interacting protein
  • zinc finger protein 363
  • CH-rich interacting match with PLAG1
  • P53 induced RING-H2 protein
  • Synonym symbol(s) ARNIP, CHIMP, PIRH2, ZNF363, PRO1996, RNF199, DKFZp586C1620, PRO1996
    EC.number 6.3.2.-
    DNA
    TYPE functioning gene
    STRUCTURE 35.28 kb     8 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 4336 - 261 - 2010 20452352
  • PYRH2D
  • has a RING-H2 (C3H2C3) finger domain, defined by a consensus sequence with six cysteines and two histidines that coordinate two zinc ions accounts for E3 ligase activity
  • 9 - 4334 - 200 expression in prostate, bladder, and lung cancer cell lines 2009 19483087
  • PIRH2C
  • having a RING domain deletion and the abrogation of ubiquitin ligase activity
  • negatively regulate TP53 protein stability possibly by facilitating the intracellular ubiquitination of TP53
  • 8 - 4309 - 252 - 2009 19483087
  • PIRH2A
  • nuclear and nucleolar subcellular localization of PIRH2A (full-length) is an important factor influencing PIRH2 function and stability
  • negatively regulate the transcriptional activation function of TP53
  • 8 splicing 1320 20.7 188 nuclear and cytoplasmic 2010 20452352
  • also called PIRH2B
  • having a RING domain deletion and the abrogation of ubiquitin ligase activity
  • has a 38-nucleotide deletion, and no ubiquitin ligase activity
  • capable of binding to PIRH2A, suggesting that the C-terminal region absent in PIRH2C is critical for PIRH2-PIRH2 interactions
  • negatively regulate TP53 protein stability possibly by facilitating the intracellular ubiquitination of TP53
  • - - - - - - 2012 22766706
  • additional isoform from human hepatocellular liver carcinoma cell line
  • lacks amino acids 235-261, but harbor the RING domain
  • - - - - - - 2012 22766706
  • additional isoform from human hepatocellular liver carcinoma cell line
  • missing C-terminal amino acids 227-261 but harbor the RING domain
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   moderately
    Endocrinepancreas   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text eye
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a RING-H2 (C3H2C3) finger domain, which is capable of coordinating zinc ions, RING domain that differs from the MDM2 RING domain in its oligomeric state, surface charge distribution, and zinc coordination scheme
  • N terminus harbors only weak TP53 binding potential
  • several putative phosphorylation sites
  • cysteine-rich protein comprising three modular domains
  • nine zinc binding sites, with six located at the N-terminal domain (NTD), two in the RING domain and one in the C-terminal domain (CTD)
  • conjugated PhosphoP
    HOMOLOGY
    Homologene
    FAMILY
  • zinc finger protein family, RING finger family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • involved in the negative regulation of TP53 functon through physical interaction and ubiquitin -mediated proteolysis
  • regulates protein turnover of the transcriptionally active form of TP53
  • enhancing androgen receptor signaling through inhibition of histone deacetylase 1 (HDAC1)
  • target for RING domain-dependent proteasomal degradation
  • ubiquitin-protein ligase that negatively regulates TP53 through activity by targeting it for degradation
  • having intrinsic E3 ubiquitin ligase
  • E3 enzyme involved in an auto-regulatory feedback loop with TP53, and promoting ubiquitination of TP53 in an MDM2-independent manner
  • functions as the ubiquitin ligase of GORAB and mediates its degradation
  • E3 ligase that negatively regulates TP53 through both direct physical interaction and ubiquitin-mediated proteolysis
  • roles in the regulation of TP53 and MYC stability and possible role as a tumor suppressor
  • implicated in either promoting or suppressing tumor progression in a tissue-dependent manner
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forms dimers through its N- and C-terminus in cells and RCHY1 dimers interact with PLAGL2
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with androgen receptor (AR)
  • interacting with HTATIP, to regulate RCHY1 stability
  • enhancing AR-mediated transcription with a dynamic pattern of recruitment to androgen response elements in the prostate-specific antigen (PSA) gene
  • interaction with GORAB that enhances or represses the ubiquitin-protein ligase activity of RCHY1
  • interacting with TP53 (interacts with both N- and C-terminal domains of RCHY1)
  • interacting with UBE2D2
  • interacting with MDM2 (capacity to negatively regulate TP53 through physical interaction and ubiquitin-mediated proteolysis independent of MDM2)
  • AIG1 is a novel RCHY1-interacting protein, that activates the NFAT signaling pathway
  • target of the TP53 tumor suppressor, monoubiquitinates POLH at one of multiple lysine residues
  • promotes the proteasomal turnover of TP73
  • ubiquitination of TP73 mediated by RCHY1 represents an important pathway for controlling the suppressive function of TP73
  • MYC is a novel interacting protein for RCHY1 and RCHY1 mediates its polyubiquitylation and proteolysis
  • RCHY1 interacts with CHEK2 and mediates its polyubiquitylation and proteasomal degradation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in lung cancer, prostatic carcinoma, head and neck cancer
    tumoral     --over  
    in lung tumorigenesis by reducing TP53 activity
    tumoral     --over  
    in hepatocellular liver carcinoma (HCC) cell line, and is correlated with poor survival and prognostic in patients with HCC
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker potential drug target and a prognostic biomarker of cancers
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    new direction for targeted therapy in aggressive human prostate cancer
    cancer  
    targeting RCHY1 to restore TP73-mediated growth suppression in TP53-deficient tumors may be developed as a novel anti-cancer strategy.
    ANIMAL & CELL MODELS
  • Pirh2 mutant mice display elevated levels of c-Myc and are predisposed for plasma cell hyperplasia and tumorigenesis