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Protein

E3 ubiquitin-protein ligase RNF125

Gene

RNF125

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins, such as DDX58/RIG-I, MAVS/IPS1, IFIH1/MDA5, JAK1 and p53/TP53 (PubMed:15843525, PubMed:17460044, PubMed:17643463, PubMed:26027934, PubMed:26471729, PubMed:25591766, PubMed:27411375). Acts as a negative regulator of type I interferon production by mediating ubiquitination of DDX58/RIG-I at 'Lys-181', leading to DDX58/RIG-I degradation (PubMed:17460044, PubMed:26471729). Mediates ubiquitination and subsequent degradation of p53/TP53 (PubMed:25591766). Mediates ubiquitination and subsequent degradation of JAK1 (PubMed:26027934). Acts as a positive regulator of T-cell activation (PubMed:15843525).7 Publications

Catalytic activityi

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.7 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.7 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi37Zinc 1Combined sources1 Publication1
Metal bindingi40Zinc 1Combined sources1 Publication1
Metal bindingi52Zinc 2Combined sources1 Publication1
Metal bindingi54Zinc 2Combined sources1 Publication1
Metal bindingi57Zinc 1Combined sources1 Publication1
Metal bindingi60Zinc 1Combined sources1 Publication1
Metal bindingi72Zinc 2Combined sources1 Publication1
Metal bindingi75Zinc 2Combined sources1 Publication1
Metal bindingi100Zinc 3Combined sources1 Publication1
Metal bindingi103Zinc 3Combined sources1 Publication1
Metal bindingi115Zinc 3Combined sources1 Publication1
Metal bindingi119Zinc 3Combined sources1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri37 – 76RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri100 – 119C2HC RNF-type1 PublicationPROSITE-ProRule annotationAdd BLAST20

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processAdaptive immunity, Immunity, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF125Curated (EC:2.3.2.277 Publications)
Alternative name(s):
RING finger protein 125Imported
T-cell RING activation protein 11 Publication
Short name:
TRAC-11 Publication
Gene namesi
Name:RNF125Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:21150. RNF125.

Subcellular locationi

  • Golgi apparatus membrane 1 Publication; Lipid-anchor 1 Publication

  • Note: Shows a reticular staining pattern within the cell and is probably expressed at other intracellular membranes in addition to the Golgi membrane. Not detected at the plasma membrane.1 Publication

GO - Cellular componenti

  • Golgi membrane Source: UniProtKB
  • intracellular Source: GO_Central
  • intracellular membrane-bounded organelle Source: UniProtKB

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Tenorio syndrome (TNORS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by overgrowth, macrocephaly, and intellectual disability. Some patients may have mild hydrocephaly, hypoglycemia, and inflammatory diseases resembling Sjogren syndrome.
See also OMIM:616260
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073353112M → I in TNORS. 1 PublicationCorresponds to variant dbSNP:rs786201014Ensembl.1
Natural variantiVAR_073354163S → L in TNORS. 1 PublicationCorresponds to variant dbSNP:rs373764886Ensembl.1
Natural variantiVAR_073355174R → C in TNORS. 1 PublicationCorresponds to variant dbSNP:rs370242930Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2G → A: Abolishes ability to regulate T-cell activation but not E3 ligase activity in vitro. Also abolishes myristoylation and membrane localization. 3 Publications1
Mutagenesisi37C → A: Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-40. 3 Publications1
Mutagenesisi40C → A: Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-37. 2 Publications1
Mutagenesisi54H → A: Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-57. 1 Publication1
Mutagenesisi57C → A: Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-54. 1 Publication1
Mutagenesisi72C → A: Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-75. 3 Publications1
Mutagenesisi75C → A: Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-72. 3 Publications1
Mutagenesisi100 – 103CAEC → AAEA: Abolished E3 ubiquitin-protein ligase activity in vitro. 1 Publication4
Mutagenesisi109 – 113LSEMR → ASEAA: Abolished E3 ubiquitin-protein ligase activity in vitro. 1 Publication5
Mutagenesisi217V → P: Reduced ubiquitination and reduced binding to ubiquitinated proteins; when associated with Q-221. 1 Publication1
Mutagenesisi221S → Q: Reduced ubiquitination and reduced binding to ubiquitinated proteins; when associated with P-217. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi54941.
MalaCardsiRNF125.
MIMi616260. phenotype.
OpenTargetsiENSG00000101695.
PharmGKBiPA134950383.

Polymorphism and mutation databases

BioMutaiRNF125.
DMDMi143811449.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000560902 – 232E3 ubiquitin-protein ligase RNF125Add BLAST231

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1

Post-translational modificationi

Autoubiquitinated, leading to its subsequent proteasomal degradation.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Ubl conjugation

Proteomic databases

PaxDbiQ96EQ8.
PeptideAtlasiQ96EQ8.
PRIDEiQ96EQ8.

PTM databases

iPTMnetiQ96EQ8.
PhosphoSitePlusiQ96EQ8.

Expressioni

Tissue specificityi

Predominantly expressed in lymphoid tissues, including bone marrow, spleen and thymus. Also weakly expressed in other tissues. Predominant in the CD4+ and CD8+ T-cells, suggesting that it is preferentially confined to T-cells.2 Publications

Inductioni

Down-regulated by miR-15b (PubMed:26202983). Down-regulated in BRAFi resistant melanomas, leading to increased levels of JAK1 and possibly promoting BRAFi resistance.2 Publications

Gene expression databases

BgeeiENSG00000101695.
CleanExiHS_RNF125.
ExpressionAtlasiQ96EQ8. baseline and differential.
GenevisibleiQ96EQ8. HS.

Organism-specific databases

HPAiHPA041514.

Interactioni

Subunit structurei

Interacts with UBE2D1 (PubMed:27411375). Interacts with VCP/p97; leading to recruit RNF125 to DDX58/RIG-I and promote ubiquitination of DDX58/RIG-I (PubMed:26471729).2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120281. 20 interactors.
DIPiDIP-52778N.
IntActiQ96EQ8. 19 interactors.
STRINGi9606.ENSP00000217740.

Structurei

Secondary structure

1232
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni38 – 40Combined sources3
Beta strandi45 – 49Combined sources5
Beta strandi55 – 57Combined sources3
Helixi58 – 67Combined sources10
Turni73 – 75Combined sources3
Beta strandi80 – 82Combined sources3
Helixi87 – 93Combined sources7
Beta strandi97 – 99Combined sources3
Turni101 – 103Combined sources3
Beta strandi106 – 108Combined sources3
Helixi109 – 111Combined sources3
Helixi112 – 118Combined sources7
Helixi120 – 126Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DKAX-ray1.55A/B1-232[»]
ProteinModelPortaliQ96EQ8.
SMRiQ96EQ8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni43 – 45Interaction with the C2HC RNF-type zinc finger1 Publication3
Regioni109 – 113Interaction with the RING-type zinc finger1 Publication5
Regioni120 – 128Linker region1 Publication9
Regioni210 – 224Required for interaction with ubiquitin and for autoubiquitination1 PublicationAdd BLAST15

Domaini

The C2HC RNF-type zinc finger and the linker region stabilize the RING-type zinc finger, leading to promote binding of the RING-type zinc finger to the ubiquitin-conjugating enzyme E2 (donor ubiquitin) (PubMed:27411375).1 Publication

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri37 – 76RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri100 – 119C2HC RNF-type1 PublicationPROSITE-ProRule annotationAdd BLAST20

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IJHI. Eukaryota.
ENOG410YBNH. LUCA.
GeneTreeiENSGT00530000063064.
HOGENOMiHOG000230946.
HOVERGENiHBG098958.
InParanoidiQ96EQ8.
KOiK12170.
OMAiVTSFDCS.
OrthoDBiEOG090A0BFR.
PhylomeDBiQ96EQ8.
TreeFamiTF331012.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR008598. Di19_Zn_binding_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
PfamiView protein in Pfam
PF05605. zf-Di19. 1 hit.
SMARTiView protein in SMART
SM00184. RING. 1 hit.
PROSITEiView protein in PROSITE
PS51803. ZF_C2HC_RNF. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q96EQ8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSVLSTDSG KSAPASATAR ALERRRDPEL PVTSFDCAVC LEVLHQPVRT
60 70 80 90 100
RCGHVFCRSC IATSLKNNKW TCPYCRAYLP SEGVPATDVA KRMKSEYKNC
110 120 130 140 150
AECDTLVCLS EMRAHIRTCQ KYIDKYGPLQ ELEETAARCV CPFCQRELYE
160 170 180 190 200
DSLLDHCITH HRSERRPVFC PLCRLIPDEN PSSFSGSLIR HLQVSHTLFY
210 220 230
DDFIDFNIIE EALIRRVLDR SLLEYVNHSN TT
Length:232
Mass (Da):26,454
Last modified:April 3, 2007 - v4
Checksum:iE3D93D546AD99D81
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti105 – 108TLVC → IVLY in AAH12021 (PubMed:15489334).Curated4
Sequence conflicti187S → N in BAA91182 (PubMed:14702039).Curated1
Sequence conflicti232T → A in AAH12021 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073353112M → I in TNORS. 1 PublicationCorresponds to variant dbSNP:rs786201014Ensembl.1
Natural variantiVAR_073354163S → L in TNORS. 1 PublicationCorresponds to variant dbSNP:rs373764886Ensembl.1
Natural variantiVAR_073355174R → C in TNORS. 1 PublicationCorresponds to variant dbSNP:rs370242930Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK000463 mRNA. Translation: BAA91182.1.
BC012021 mRNA. Translation: AAH12021.1.
CCDSiCCDS11902.1.
RefSeqiNP_060301.2. NM_017831.3.
UniGeneiHs.633703.

Genome annotation databases

EnsembliENST00000217740; ENSP00000217740; ENSG00000101695.
GeneIDi54941.
KEGGihsa:54941.
UCSCiuc002kxf.2. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK000463 mRNA. Translation: BAA91182.1.
BC012021 mRNA. Translation: AAH12021.1.
CCDSiCCDS11902.1.
RefSeqiNP_060301.2. NM_017831.3.
UniGeneiHs.633703.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DKAX-ray1.55A/B1-232[»]
ProteinModelPortaliQ96EQ8.
SMRiQ96EQ8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120281. 20 interactors.
DIPiDIP-52778N.
IntActiQ96EQ8. 19 interactors.
STRINGi9606.ENSP00000217740.

PTM databases

iPTMnetiQ96EQ8.
PhosphoSitePlusiQ96EQ8.

Polymorphism and mutation databases

BioMutaiRNF125.
DMDMi143811449.

Proteomic databases

PaxDbiQ96EQ8.
PeptideAtlasiQ96EQ8.
PRIDEiQ96EQ8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000217740; ENSP00000217740; ENSG00000101695.
GeneIDi54941.
KEGGihsa:54941.
UCSCiuc002kxf.2. human.

Organism-specific databases

CTDi54941.
DisGeNETi54941.
GeneCardsiRNF125.
H-InvDBHIX0014384.
HGNCiHGNC:21150. RNF125.
HPAiHPA041514.
MalaCardsiRNF125.
MIMi610432. gene.
616260. phenotype.
neXtProtiNX_Q96EQ8.
OpenTargetsiENSG00000101695.
PharmGKBiPA134950383.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJHI. Eukaryota.
ENOG410YBNH. LUCA.
GeneTreeiENSGT00530000063064.
HOGENOMiHOG000230946.
HOVERGENiHBG098958.
InParanoidiQ96EQ8.
KOiK12170.
OMAiVTSFDCS.
OrthoDBiEOG090A0BFR.
PhylomeDBiQ96EQ8.
TreeFamiTF331012.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.

Miscellaneous databases

GeneWikiiRNF125.
GenomeRNAii54941.
PROiQ96EQ8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101695.
CleanExiHS_RNF125.
ExpressionAtlasiQ96EQ8. baseline and differential.
GenevisibleiQ96EQ8. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR008598. Di19_Zn_binding_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
PfamiView protein in Pfam
PF05605. zf-Di19. 1 hit.
SMARTiView protein in SMART
SM00184. RING. 1 hit.
PROSITEiView protein in PROSITE
PS51803. ZF_C2HC_RNF. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiRN125_HUMAN
AccessioniPrimary (citable) accession number: Q96EQ8
Secondary accession number(s): Q9NX39
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: April 3, 2007
Last modified: February 15, 2017
This is version 135 of the entry and version 4 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.