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FLASH GENE
Symbol RNF139 contributors: mct/npt - updated : 29-12-2016
HGNC name ring finger 139
HGNC id 17023
EXPRESSION
Type widely
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunethymus   highly
Nervousnerve   highly
Reproductivemale systemtestis  highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • ten membrane spanning segments
  • two regions of homology with PTCH (patched)
  • a RING zinc finger (RING-H2) domain essential for ubiquitin ligase activity
  • also contains a predicted sterol-sensing domain (SSD)
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum ,rough,smooth
    basic FUNCTION
  • mediating through RING finger ubiquitin-conjugating enzyme (E2)-dependent ubiquitination, among diverse functions
  • playing a role in mediating ubiquitination
  • may function as a signaling receptor
  • modulating signalosome levels or compartmentalization
  • suppressing kidney cells growth (inhibition is manifested by G2/M arrest, decreased DNA synthesis and increased apoptosis and is dependent upon the Ub ligase activity of the RING domain) (Brauweiler 2007)
  • involved in the modulation of SREBP activity comprising a novel regulatory link between growth control and the cholesterol/lipid homeostasis pathway (Brauweiler 2007)
  • is a novel sterol-sensing endoplasmic reticulum membrane protein that hinders SREBPF2 processing through interaction with SREBPF2 and SCAP, regulating its own turnover rate by means of its E3 ubiquitin ligase activity
  • RNF139 E3 ligase is required for MHC I dislocation from the ER
  • inhibits growth in a RING- and ubiquitylation-dependent manner
  • its function may provide a regulatory link between the lipid and protein biosynthetic pathways
  • endoplasmic reticulum-resident E3 ligase, that exhibits a tumor-suppressive effect through its E3-ligase activity
  • tumorigenic role of HMOX1 and the importance of RNF139-mediated HMOX1 degradation in the control of cancer growth
  • AMFR and RNF139 are implicated in the sterol-regulated degradation of HMG-CoA reductase and INSIG1 through ER-associated degradation (ERAD)
  • INSIG-associated ubiquitin ligases AMFR and RNF139, is obligatory for extraction of reductase from lipid droplet-associated ER membranes into the cytosol for proteasome-mediated, ER-associated degradation (ERAD)
  • MARCH6 and RNF139 facilitate the quality control of cytosolic and tail-anchored proteins
  • CELLULAR PROCESS cell cycle
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component forms an integral part of a novel multiprotein ER complex that contains MHC I, cytomegalovirus US2, and signal peptide peptidase
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • binding SHH by the second extracellular loop
  • interacts with VHL
  • may interact with COPS5/JAB1, a protein responsible for the degradation of tumor suppressor CDKN1B/P27KIP (growth suppression is dependent upon COPS5)
  • is a target of Translin (TSN), a posttranscriptional regulator of genes transcribed by the transcription factor CREM-tau in postmeiotic male germ cells
  • its overexpression hinders sterol regulatory element-binding protein-2 (SREBPF2) processing, thereby reducing SREBPF2 target gene expression
  • binds and stimulates ubiquitylation of the endoplasmic reticulum anchor protein INSIG
  • sterol-induced ubiquitination and proteasomal degradation of reductase is dictated by the complex interplay of at least four proteins: INSIG1, INSIG2, AMFR, and RNF139
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) RCC3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    in translocation t(3;8)(p14.2;q24.1),associated with renal cell carcinoma and fused with FHIT with conserved structure and expression
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS