The protein encoded by this gene is a multi-membrane spanning protein containing a RING-H2 finger. This protein is located in the endoplasmic reticulum, and has been shown to possess ubiquitin ligase activity. This gene was found to be interrupted by a t(3:8) translocation in a family with hereditary renal and non-medulary thyroid cancer. Studies of the Drosophila counterpart s... See more...

Aliases for RNF139 Gene

Aliases for RNF139 Gene

  • Ring Finger Protein 139 2 3 5
  • TRC8 2 3 4
  • Translocation In Renal Carcinoma On Chromosome 8 Protein 3 4
  • Translocation In Renal Carcinoma, Chromosome 8 2 3
  • RING-Type E3 Ubiquitin Transferase RNF139 3 4
  • E3 Ubiquitin-Protein Ligase RNF139 3 4
  • HRCA1 2 3
  • RCA1 2 3
  • Patched Related Protein Translocated In Renal Cancer 3
  • Multiple Membrane Spanning Receptor TRC8 3
  • RING Finger Protein 139 4
  • EC 2.3.2.27 4
  • RNF139 5

External Ids for RNF139 Gene

Previous GeneCards Identifiers for RNF139 Gene

  • GC08P125155
  • GC08P125443
  • GC08P125556
  • GC08P125487
  • GC08P120812

Summaries for RNF139 Gene

Entrez Gene Summary for RNF139 Gene

  • The protein encoded by this gene is a multi-membrane spanning protein containing a RING-H2 finger. This protein is located in the endoplasmic reticulum, and has been shown to possess ubiquitin ligase activity. This gene was found to be interrupted by a t(3:8) translocation in a family with hereditary renal and non-medulary thyroid cancer. Studies of the Drosophila counterpart suggested that this protein may interact with tumor suppressor protein VHL, as well as with COPS5/JAB1, a protein responsible for the degradation of tumor suppressor CDKN1B/P27KIP. [provided by RefSeq, Jul 2008]

GeneCards Summary for RNF139 Gene

RNF139 (Ring Finger Protein 139) is a Protein Coding gene. Diseases associated with RNF139 include Renal Cell Carcinoma, Nonpapillary and Hereditary Renal Cell Carcinoma. Among its related pathways are Calnexin/calreticulin cycle and Sterol Regulatory Element-Binding Proteins (SREBP) signalling. Gene Ontology (GO) annotations related to this gene include ligase activity. An important paralog of this gene is RNF145.

UniProtKB/Swiss-Prot Summary for RNF139 Gene

  • E3-ubiquitin ligase; acts as a negative regulator of cell proliferation through mechanisms involving G2/M arrest and cell death (PubMed:10500182, PubMed:12032852, PubMed:17016439). Required for MHC class I ubiquitination in cells expressing the cytomegalovirus protein US2 before dislocation from the endoplasmic reticulum (ER) (PubMed:19720873). Affects SREBP processing by hindering the SREBP-SCAP complex translocation from the ER to the Golgi, thereby reducing SREBF2 target gene expression (PubMed:19706601, PubMed:20068067). Involved in the sterol-accelerated degradation of HMGCR (PubMed:22143767, PubMed:23223569). This is achieved through binding of RNF139 to INSIG1 and/or INSIG2 at the ER membrane (PubMed:22143767). In addition, interaction of RNF139 with AUP1 facilitates interaction of RNF139 with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR, leading to ubiquitination of HMGCR (PubMed:23223569). The ubiquitinated HMGCR is then released from the ER into the cytosol for subsequent destruction (PubMed:22143767, PubMed:23223569). Required for INSIG1 ubiquitination (PubMed:20068067). May be required for EIF3 complex ubiquitination (PubMed:20068067).

Gene Wiki entry for RNF139 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RNF139 Gene

Genomics for RNF139 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RNF139 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RNF139 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RNF139

Top Transcription factor binding sites by QIAGEN in the RNF139 gene promoter:
  • Evi-1
  • GATA-1
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v2
  • Nkx3-1 v3
  • Nkx3-1 v4
  • Pax-6
  • POU3F2
  • RORalpha1

Genomic Locations for RNF139 Gene

Latest Assembly
chr8:124,474,880-124,488,618
(GRCh38/hg38)
Size:
13,739 bases
Orientation:
Plus strand

Previous Assembly
chr8:125,487,121-125,500,859
(GRCh37/hg19 by Entrez Gene)
Size:
13,739 bases
Orientation:
Plus strand

chr8:125,486,979-125,500,155
(GRCh37/hg19 by Ensembl)
Size:
13,177 bases
Orientation:
Plus strand

Genomic View for RNF139 Gene

Genes around RNF139 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RNF139 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RNF139 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RNF139 Gene

Proteins for RNF139 Gene

  • Protein details for RNF139 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WU17-RN139_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase RNF139
    Protein Accession:
    Q8WU17
    Secondary Accessions:
    • B3KMD5
    • O75485
    • Q7LDL3

    Protein attributes for RNF139 Gene

    Size:
    664 amino acids
    Molecular mass:
    75994 Da
    Quaternary structure:
    • Interacts with MHC class I and HM13 (PubMed:19720873, PubMed:25239945). Interacts with VHL (PubMed:12032852). Component of SCAP-SREBP complex composed of SREBF2, SCAP and RNF139; the complex hampers the interaction between SCAP and SEC24B, thereby reducing SREBF2 proteolytic processing (PubMed:19706601). Interacts with SREBF2 (via C-terminal domain) (PubMed:19706601). Interacts with SCAP; the interaction inhibits the interaction of SCAP with SEC24B and hampering the ER to Golgi transport of the SCAP-SREBP complex (PubMed:19706601). Interacts with SEC24B (PubMed:19706601). Interacts with INSIG1 and INSIG2 (PubMed:20068067, PubMed:22143767). Interacts with EIF3F and EIF3H; the interaction leads to protein translation inhibitions in a ubiquitination-dependent manner (PubMed:20068067). Interacts with XBP1 isoform 1; the interaction induces ubiquitination and degradation of XBP1 isoform 1 (PubMed:25239945). Interacts with AUP1, AMFR and UBE2G2; interaction with AUP1 facilitates interaction of RNF139 with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR/gp78, leading to sterol-induced ubiquitination of HMGCR and its subsequent proteasomal degradation (PubMed:23223569).

neXtProt entry for RNF139 Gene

Post-translational modifications for RNF139 Gene

  • Autoubiquitinated. Ubiquitination is induced by sterol and leads to ist degradation via the ubiquitin-proteasome pathway.
  • Ubiquitination at Lys574
  • Modification sites at PhosphoSitePlus

Other Protein References for RNF139 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for RNF139 Gene

Domains & Families for RNF139 Gene

Gene Families for RNF139 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted membrane proteins

Protein Domains for RNF139 Gene

InterPro:
Blocks:
  • Zn-finger, RING

Suggested Antigen Peptide Sequences for RNF139 Gene

GenScript: Design optimal peptide antigens:
  • Translocation in renal carcinoma on chromosome 8 protein (RN139_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8WU17

UniProtKB/Swiss-Prot:

RN139_HUMAN :
  • The RING-type zinc finger domain mediates ubiquitin ligase activity.
Domain:
  • The RING-type zinc finger domain mediates ubiquitin ligase activity.
genes like me logo Genes that share domains with RNF139: view

Function for RNF139 Gene

Molecular function for RNF139 Gene

UniProtKB/Swiss-Prot Function:
E3-ubiquitin ligase; acts as a negative regulator of cell proliferation through mechanisms involving G2/M arrest and cell death (PubMed:10500182, PubMed:12032852, PubMed:17016439). Required for MHC class I ubiquitination in cells expressing the cytomegalovirus protein US2 before dislocation from the endoplasmic reticulum (ER) (PubMed:19720873). Affects SREBP processing by hindering the SREBP-SCAP complex translocation from the ER to the Golgi, thereby reducing SREBF2 target gene expression (PubMed:19706601, PubMed:20068067). Involved in the sterol-accelerated degradation of HMGCR (PubMed:22143767, PubMed:23223569). This is achieved through binding of RNF139 to INSIG1 and/or INSIG2 at the ER membrane (PubMed:22143767). In addition, interaction of RNF139 with AUP1 facilitates interaction of RNF139 with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR, leading to ubiquitination of HMGCR (PubMed:23223569). The ubiquitinated HMGCR is then released from the ER into the cytosol for subsequent destruction (PubMed:22143767, PubMed:23223569). Required for INSIG1 ubiquitination (PubMed:20068067). May be required for EIF3 complex ubiquitination (PubMed:20068067).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000269|PubMed:17016439};.
UniProtKB/Swiss-Prot Induction:
Down-regulated by sterols (at protein level).

Enzyme Numbers (IUBMB) for RNF139 Gene

Phenotypes From GWAS Catalog for RNF139 Gene

Gene Ontology (GO) - Molecular Function for RNF139 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 25239945
GO:0004842 ubiquitin-protein transferase activity TAS 10500182
GO:0005515 protein binding IPI 12032852
GO:0008270 zinc ion binding IEA --
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with RNF139: view
genes like me logo Genes that share phenotypes with RNF139: view

Human Phenotype Ontology for RNF139 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for RNF139 Gene

MGI Knock Outs for RNF139:
  • Rnf139 Rnf139<tm1(KOMP)Wtsi>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RNF139

No data available for Transcription Factor Targets and HOMER Transcription for RNF139 Gene

Localization for RNF139 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RNF139 Gene

Endoplasmic reticulum membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RNF139 gene
Compartment Confidence
endoplasmic reticulum 5
plasma membrane 3
cytosol 2
extracellular 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
nucleus 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for RNF139 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IBA,IDA 12032852
GO:0005789 endoplasmic reticulum membrane TAS --
GO:0012505 endomembrane system IBA 21873635
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane TAS 12032852
genes like me logo Genes that share ontologies with RNF139: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for RNF139 Gene

Pathways & Interactions for RNF139 Gene

genes like me logo Genes that share pathways with RNF139: view

UniProtKB/Swiss-Prot Q8WU17-RN139_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for RNF139 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008285 negative regulation of cell proliferation IDA 17016439
GO:0016567 protein ubiquitination IMP 19720873
GO:0017148 negative regulation of translation IDA 20068067
GO:0018215 protein phosphopantetheinylation IEA --
GO:0031648 protein destabilization IMP 25239945
genes like me logo Genes that share ontologies with RNF139: view

No data available for SIGNOR curated interactions for RNF139 Gene

Drugs & Compounds for RNF139 Gene

No Compound Related Data Available

Transcripts for RNF139 Gene

mRNA/cDNA for RNF139 Gene

1 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RNF139

Alternative Splicing Database (ASD) splice patterns (SP) for RNF139 Gene

No ASD Table

Relevant External Links for RNF139 Gene

GeneLoc Exon Structure for
RNF139

Expression for RNF139 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RNF139 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for RNF139 Gene

This gene is overexpressed in Adrenal (34.7), Lung (22.8), and Heart (7.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RNF139 Gene



Protein tissue co-expression partners for RNF139 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RNF139

SOURCE GeneReport for Unigene cluster for RNF139 Gene:

Hs.744151

mRNA Expression by UniProt/SwissProt for RNF139 Gene:

Q8WU17-RN139_HUMAN
Tissue specificity: Highly expressed in testis, placenta and adrenal gland. Moderate expression in heart, brain, liver, skeletal muscle and pancreas, and low expression in lung and kidney.

Evidence on tissue expression from TISSUES for RNF139 Gene

  • Liver(4.4)
  • Nervous system(3.3)
  • Kidney(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for RNF139 Gene

Germ Layers:
  • mesoderm
Systems:
  • urinary
Regions:
Abdomen:
  • kidney
genes like me logo Genes that share expression patterns with RNF139: view

Primer products for research

No data available for mRNA differential expression in normal tissues for RNF139 Gene

Orthologs for RNF139 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for RNF139 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia RNF139 29 30
  • 99.55 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia RNF139 29 30
  • 94.78 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia RNF139 29 30
  • 93.47 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Rnf139 29 16 30
  • 91.57 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rnf139 29
  • 91.31 (n)
Oppossum
(Monodelphis domestica)
Mammalia RNF139 30
  • 89 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia RNF139 30
  • 83 (a)
OneToOne
Chicken
(Gallus gallus)
Aves RNF139 29 30
  • 74.95 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia RNF139 30
  • 76 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia rnf139 29
  • 68.52 (n)
Zebrafish
(Danio rerio)
Actinopterygii rnf139 29 30
  • 62.07 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Trc8 29 30
  • 50.23 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003666 29
  • 48.93 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HRD1 30
  • 13 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.9066 30
  • 47 (a)
OneToOne
Species where no ortholog for RNF139 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for RNF139 Gene

ENSEMBL:
Gene Tree for RNF139 (if available)
TreeFam:
Gene Tree for RNF139 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RNF139: view image
Alliance of Genome Resources:
Additional Orthologs for RNF139

Paralogs for RNF139 Gene

Paralogs for RNF139 Gene

genes like me logo Genes that share paralogs with RNF139: view

Variants for RNF139 Gene

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for RNF139 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for RNF139 Gene

Variant ID Type Subtype PubMed ID
dgv1307e199 CNV deletion 23128226
esv1584427 CNV insertion 17803354
esv2523354 CNV insertion 19546169
esv2660702 CNV deletion 23128226
esv3358926 CNV duplication 20981092
esv3618692 CNV loss 21293372
esv3618693 CNV loss 21293372
esv3618694 CNV loss 21293372
esv3618695 CNV loss 21293372
nsv1017848 CNV gain 25217958
nsv824727 CNV loss 20364138
nsv951466 CNV duplication 24416366

Variation tolerance for RNF139 Gene

Residual Variation Intolerance Score: 9.82% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.39; 27.38% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RNF139 Gene

Human Gene Mutation Database (HGMD)
RNF139
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RNF139
Leiden Open Variation Database (LOVD)
RNF139

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RNF139 Gene

Disorders for RNF139 Gene

MalaCards: The human disease database

(6) MalaCards diseases for RNF139 Gene - From: OMI, GTR, ORP, COP, and GCD

Disorder Aliases PubMed IDs
renal cell carcinoma, nonpapillary
  • rcc
hereditary renal cell carcinoma
dysgerminoma
clear cell renal cell carcinoma
  • clear cell carcinoma of kidney
dysgerminoma of ovary
  • ovarian dysgerminoma
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

RN139_HUMAN
  • Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype. Note=The disease may be caused by variants affecting the gene represented in this entry. A chromosomal aberration involving RNF139 has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation (3;8)(q14.2;q24.1) with FHIT. RNF139 is found to be fused to FHIT and disrupted within the sterol-sensing domain. In contrast, the FHIT coding region is maintained and expressed. Sporadic cases of renal carcinoma, where an acquired mutation in RNF139 results in the duplication of 12 nucleotides in the 5'-UTR, has also been identified.

Additional Disease Information for RNF139

genes like me logo Genes that share disorders with RNF139: view

No data available for Genatlas for RNF139 Gene

Publications for RNF139 Gene

  1. The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8. (PMID: 9689122) Gemmill RM … Drabkin HA (Proceedings of the National Academy of Sciences of the United States of America 1998) 2 3 4 22
  2. The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and protein biosynthetic pathways. (PMID: 20068067) Lee JP … Gemmill RM (Molecular cancer research : MCR 2010) 3 4 22
  3. The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER. (PMID: 19720873) Stagg HR … Lehner PJ (The Journal of cell biology 2009) 3 4 22
  4. RING-dependent tumor suppression and G2/M arrest induced by the TRC8 hereditary kidney cancer gene. (PMID: 17016439) Brauweiler A … Gemmill RM (Oncogene 2007) 3 4 22
  5. Signal peptide peptidase functions in ERAD to cleave the unfolded protein response regulator XBP1u. (PMID: 25239945) Chen CY … Lemberg MK (The EMBO journal 2014) 3 4

Products for RNF139 Gene

Sources for RNF139 Gene