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FLASH GENE
Symbol RNF139 contributors: mct/npt - updated : 29-12-2016
HGNC name ring finger 139
HGNC id 17023
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
2 - 3312 75.9 664 - 2007 17016439
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