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Symbol RNF139 contributors: mct/npt - updated : 29-12-2016
HGNC name ring finger 139
HGNC id 17023
Corresponding disease
RCC3 hereditary renal cell carcinoma
Location 8q24.13      Physical location : 125.487.007 - 125.500.858
Synonym name
  • patched related protein translocated in renal cancer
  • patched related gene
  • multiple membrane spanning receptor TRC8
  • translocation in renal carcinoma on chromosome 8
  • Synonym symbol(s) RCA1, HRCA1, TRC8, MGC31961
    TYPE functioning gene
    STRUCTURE 13.85 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC389683 8 LOC389683 LOC392265 8 similar to Cell division protein kinase 5 (Tau protein kinase II catalytic subunit) (TPKII catalytic subunit) (Serine/threonine protein kinase PSSALRE) LOC389684 8 LOC389684 ZHX2 8q24.13 zinc fingers and homeoboxes 2 MGC3067 8q24.13 hypothetical protein MGC3067 MGC21654 8q24.13 unknown MGC21654 product MGC14128 8q24.13 hypothetical protein MGC14128 FLJ14825 8q24.13 hypothetical protein FLJ14825 ZHX1 8q zinc-fingers and homeoboxes 1 LOC392266 8 similar to Peroxisomal multifunctional enzyme type 2 (MFE-2) (D-bifunctional protein) (DBP) (17-beta-hydroxysteroid dehydrogenase 4) (17-beta-HSD 4) PRO2000 8p22 similar to Peroxisomal multifunctional enzyme type 2 (MFE-2) (D-bifunctional protein) (DBP) (17-beta-hydroxysteroid dehydrogenase 4) (17-beta-HSD 4) LOC392267 8 similar to inosine monophosphate dehydrogenase 1 isoform b; sWSS2608 FLJ10204 8q24.13 hypothetical protein FLJ10204 FBXO32 8q24.13 F-box only protein 32 LOC340359 8q24.13 similar to hypothetical protein 8230402K04 ANXA13 8q24.13-q24.2 annexin A13 FLJ23790 8q24.13 hypothetical protein FLJ23790 FLJ35721 8q24.13 hypothetical protein FLJ35721 FLJ32770 8q24.13 hypothetical protein FLJ32770 LOC392268 8 similar to neuropilin- and tolloid-like protein 2 precursor LOC157378 8q24.13 hypothetical protein BC017881 LOC392269 8 similar to Transcription factor SOX-2 FLJ20772 8q24.13 hypothetical protein FLJ20772 RNF139 8q24.1 ring finger 139 CDA11 8q24.13 CDA11 protein NDUFB9 8q24.21 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 9, 22kDa MTSS1 8q22.3-q24.13 metastasis suppressor 1 LOC392270 8 similar to MRS2-like, magnesium homeostasis factor FLJ38002 8q24.13 hypothetical protein FLJ38002 SQLE 8q24.1 squalene epoxidase KIAA0196 8q24.1-q24.3 Homo sapiens KIAA0196 gene product (KIAA0196), mRNA. FLJ32440 8q24.13 hypothetical protein FLJ32440 C8FW 8q24.13 phosphoprotein regulated by mitogenic pathways LOC389685 8 LOC389685 NSE2 8q24.13 breast cancer membrane protein 101
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 3312 75.9 664 - 2007 17016439
    Type widely
    constitutive of
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunethymus   highly
    Nervousnerve   highly
    Reproductivemale systemtestis  highly
    cell lineage
    cell lines
    at STAGE
  • 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)
    CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     plasma 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
    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
    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
    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
    Variant & Polymorphism
    Candidate gene
    Therapy target