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Protein

E3 ubiquitin-protein ligase RNF139

Gene

RNF139

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

E3-ubiquitin ligase; acts as a negative regulator of the cell proliferation through mechanisms involving G2/M arrest and cell death. Required for MHC class I ubiquitination in cells expressing the cytomegalovirus protein US2 before dislocation from the endoplasmic reticulum (ER). Affects SREBP processing by hindering the SREBP/SCAP complex translocation from the ER to the Golgi, thereby reducing SREBF2 target gene expression. Required for INSIG1 ubiquitination. May be required for EIF3 complex ubiquitination. May function as a signaling receptor.6 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri547 – 586RING-type; atypicalPROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

  • ligase activity Source: UniProtKB
  • protease binding Source: UniProtKB
  • signaling receptor activity Source: UniProtKB
  • ubiquitin-like protein transferase activity Source: UniProtKB
  • ubiquitin protein ligase activity Source: Reactome
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionReceptor, Transferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-901032 ER Quality Control Compartment (ERQC)
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF139 (EC:2.3.2.27)
Alternative name(s):
RING finger protein 139
RING-type E3 ubiquitin transferase RNF139Curated
Translocation in renal carcinoma on chromosome 8 protein
Gene namesi
Name:RNF139Imported
Synonyms:TRC8Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000170881.4
HGNCiHGNC:17023 RNF139
MIMi603046 gene
neXtProtiNX_Q8WU17

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei51 – 71HelicalSequence analysisAdd BLAST21
Transmembranei85 – 105HelicalSequence analysisAdd BLAST21
Transmembranei125 – 145HelicalSequence analysisAdd BLAST21
Transmembranei154 – 174HelicalSequence analysisAdd BLAST21
Transmembranei178 – 198HelicalSequence analysisAdd BLAST21
Transmembranei293 – 313HelicalSequence analysisAdd BLAST21
Transmembranei323 – 343HelicalSequence analysisAdd BLAST21
Transmembranei356 – 376HelicalSequence analysisAdd BLAST21
Transmembranei390 – 410HelicalSequence analysisAdd BLAST21
Transmembranei420 – 440HelicalSequence analysisAdd BLAST21
Transmembranei469 – 489HelicalSequence analysisAdd BLAST21
Transmembranei495 – 512HelicalSequence analysisAdd BLAST18

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Renal cell carcinoma (RCC)
The disease may be caused by mutations 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.
Disease descriptionRenal 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.
See also OMIM:144700

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi547 – 586Missing : Increases proliferation. Rescues MHC class I to the cell surface. Fails to down-regulate SREBF1 and SREBF2. 4 PublicationsAdd BLAST40
Mutagenesisi547 – 550CAIC → SAIS: Abolishes ubiquitination activity. Increases proliferation. Does not phosphorylates CHEK2 on T-68. Does not phosphorylates ATM on S-1981. Rescues MHC class I to the cell surface. Suppresses SREBF2 processing in the presence or absence of sterols. Fails to down-regulate SREBF1 and SREBF2. Decreases INSIG1 ubiquitination. 4 Publications4
Mutagenesisi557 – 559SAR → AAA: Retaines about 30% of ubiquitination activity. 1 Publication3
Mutagenesisi572 – 574LRK → AAA: Abolishes ubiquitination activity. Increases proliferation. 1 Publication3
Mutagenesisi582 – 585CPMC → APMA: Abolishes ubiquitination activity. Increases proliferation. 1 Publication4

Organism-specific databases

DisGeNETi11236
MalaCardsiRNF139
MIMi144700 phenotype
OpenTargetsiENSG00000170881
Orphaneti422526 Hereditary clear cell renal cell carcinoma
PharmGKBiPA134945850

Polymorphism and mutation databases

BioMutaiRNF139
DMDMi74760542

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000560982 – 664E3 ubiquitin-protein ligase RNF139Add BLAST663

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei634PhosphoserineCombined sources1
Modified residuei635PhosphothreonineCombined sources1
Modified residuei663PhosphothreonineCombined sources1

Post-translational modificationi

Autoubiquitinated. Ubiquitination is induced by sterol and leads to ist degradation via the ubiquitin-proteasome pathway.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8WU17
MaxQBiQ8WU17
PaxDbiQ8WU17
PeptideAtlasiQ8WU17
PRIDEiQ8WU17
ProteomicsDBi74623

PTM databases

iPTMnetiQ8WU17
PhosphoSitePlusiQ8WU17

Expressioni

Tissue specificityi

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.1 Publication

Inductioni

Down-regulated by sterols (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000170881 Expressed in 231 organ(s), highest expression level in sperm
CleanExiHS_RNF139
ExpressionAtlasiQ8WU17 baseline and differential
GenevisibleiQ8WU17 HS

Organism-specific databases

HPAiHPA001202

Interactioni

Subunit structurei

Interacts with MHC class I and HM13 (PubMed:19720873, PubMed:25239945). Interacts with VHL. 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. Interacts with SREBF2 (via C-terminal domain). Interacts with SCAP; the interaction inhibits the interaction of SCAP with SEC24B and hampering the ER to Golgi transport of the SCAP/SREBP complex. Interacts with SEC24B. Interacts with INSIG1 and INSIG2. Interacts with EIF3F and EIF3H; the interaction leads to protein translation inhibitions in a ubiquitination-dependent manner (PubMed:12032852, PubMed:19706601, PubMed:20068067). Interacts with XBP1 isoform 1; the interaction induces ubiquitination and degradation of XBP1 isoform 1 (PubMed:25239945).5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116401, 18 interactors
IntActiQ8WU17, 8 interactors
MINTiQ8WU17
STRINGi9606.ENSP00000304051

Structurei

3D structure databases

ProteinModelPortaliQ8WU17
SMRiQ8WU17
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The RING-type zinc finger domain mediates ubiquitin ligase activity.

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri547 – 586RING-type; atypicalPROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG0802 Eukaryota
COG5243 LUCA
GeneTreeiENSGT00530000062938
HOGENOMiHOG000267029
HOVERGENiHBG053146
InParanoidiQ8WU17
KOiK15703
OMAiNNNGFIA
OrthoDBiEOG091G020N
PhylomeDBiQ8WU17
TreeFamiTF318635

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR025754 TRC8_N_dom
IPR001841 Znf_RING
IPR011016 Znf_RING-CH
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF13705 TRC8_N, 1 hit
PF13639 zf-RING_2, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00744 RINGv, 1 hit
PROSITEiView protein in PROSITE
PS50089 ZF_RING_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q8WU17-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAAVGPPQQQ VRMAHQQVWA ALEVALRVPC LYIIDAIFNS YPDSSQSRFC
60 70 80 90 100
IVLQIFLRLF GVFASSIVLI LSQRSLFKFY TYSSAFLLAA TSVLVNYYAS
110 120 130 140 150
LHIDFYGAYN TSAFGIELLP RKGPSLWMAL IVLQLTFGIG YVTLLQIHSI
160 170 180 190 200
YSQLIILDLL VPVIGLITEL PLHIRETLLF TSSLILTLNT VFVLAVKLKW
210 220 230 240 250
FYYSTRYVYL LVRHMYRIYG LQLLMEDTWK RIRFPDILRV FWLTRVTAQA
260 270 280 290 300
TVLMYILRMA NETDSFFISW DDFWDLICNL IISGCDSTLT VLGMSAVISS
310 320 330 340 350
VAHYLGLGIL AFIGSTEEDD RRLGFVAPVL FFILALQTGL SGLRPEERLI
360 370 380 390 400
RLSRNMCLLL TAVLHFIHGM TDPVLMSLSA SHVSSFRRHF PVLFVSACLF
410 420 430 440 450
ILPVLLSYVL WHHYALNTWL FAVTAFCVEL CLKVIVSLTV YTLFMIDGYY
460 470 480 490 500
NVLWEKLDDY VYYVRSTGSI IEFIFGVVMF GNGAYTMMFE SGSKIRAFMM
510 520 530 540 550
CLHAYFNIYL QAKNGWKTFM NRRTAVKKIN SLPEIKGSRL QEINDVCAIC
560 570 580 590 600
YHEFTTSARI TPCNHYFHAL CLRKWLYIQD TCPMCHQKVY IEDDIKDNSN
610 620 630 640 650
VSNNNGFIPP NETPEEAVRE AAAESDRELN EDDSTDCDDD VQRERNGVIQ
660
HTGAAAEEFN DDTD
Length:664
Mass (Da):75,994
Last modified:March 1, 2002 - v1
Checksum:i9885F5915F019EF5
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RH85E5RH85_HUMAN
E3 ubiquitin-protein ligase RNF139
RNF139
68Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18V → I in AAC39930 (PubMed:9689122).Curated1
Sequence conflicti18V → I in AAC39931 (PubMed:9689122).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF064800 Genomic DNA Translation: AAC39931.1
AF064801 mRNA Translation: AAC39930.1
AK001602 mRNA Translation: BAG50947.1
CH471060 Genomic DNA Translation: EAW92064.1
BC021571 mRNA Translation: AAH21571.1
BC064636 mRNA Translation: AAH64636.1
CCDSiCCDS6350.1
RefSeqiNP_009149.2, NM_007218.3
UniGeneiHs.744151

Genome annotation databases

EnsembliENST00000303545; ENSP00000304051; ENSG00000170881
GeneIDi11236
KEGGihsa:11236
UCSCiuc003yrc.4 human

Keywords - Coding sequence diversityi

Chromosomal rearrangement

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF064800 Genomic DNA Translation: AAC39931.1
AF064801 mRNA Translation: AAC39930.1
AK001602 mRNA Translation: BAG50947.1
CH471060 Genomic DNA Translation: EAW92064.1
BC021571 mRNA Translation: AAH21571.1
BC064636 mRNA Translation: AAH64636.1
CCDSiCCDS6350.1
RefSeqiNP_009149.2, NM_007218.3
UniGeneiHs.744151

3D structure databases

ProteinModelPortaliQ8WU17
SMRiQ8WU17
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116401, 18 interactors
IntActiQ8WU17, 8 interactors
MINTiQ8WU17
STRINGi9606.ENSP00000304051

PTM databases

iPTMnetiQ8WU17
PhosphoSitePlusiQ8WU17

Polymorphism and mutation databases

BioMutaiRNF139
DMDMi74760542

Proteomic databases

EPDiQ8WU17
MaxQBiQ8WU17
PaxDbiQ8WU17
PeptideAtlasiQ8WU17
PRIDEiQ8WU17
ProteomicsDBi74623

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000303545; ENSP00000304051; ENSG00000170881
GeneIDi11236
KEGGihsa:11236
UCSCiuc003yrc.4 human

Organism-specific databases

CTDi11236
DisGeNETi11236
EuPathDBiHostDB:ENSG00000170881.4
GeneCardsiRNF139
HGNCiHGNC:17023 RNF139
HPAiHPA001202
MalaCardsiRNF139
MIMi144700 phenotype
603046 gene
neXtProtiNX_Q8WU17
OpenTargetsiENSG00000170881
Orphaneti422526 Hereditary clear cell renal cell carcinoma
PharmGKBiPA134945850
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0802 Eukaryota
COG5243 LUCA
GeneTreeiENSGT00530000062938
HOGENOMiHOG000267029
HOVERGENiHBG053146
InParanoidiQ8WU17
KOiK15703
OMAiNNNGFIA
OrthoDBiEOG091G020N
PhylomeDBiQ8WU17
TreeFamiTF318635

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-901032 ER Quality Control Compartment (ERQC)

Miscellaneous databases

GeneWikiiRNF139
GenomeRNAii11236
PROiPR:Q8WU17
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170881 Expressed in 231 organ(s), highest expression level in sperm
CleanExiHS_RNF139
ExpressionAtlasiQ8WU17 baseline and differential
GenevisibleiQ8WU17 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR025754 TRC8_N_dom
IPR001841 Znf_RING
IPR011016 Znf_RING-CH
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF13705 TRC8_N, 1 hit
PF13639 zf-RING_2, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00744 RINGv, 1 hit
PROSITEiView protein in PROSITE
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRN139_HUMAN
AccessioniPrimary (citable) accession number: Q8WU17
Secondary accession number(s): B3KMD5, O75485, Q7LDL3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: March 1, 2002
Last modified: November 7, 2018
This is version 154 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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