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Protein

E3 ubiquitin-protein ligase RNF4

Gene

RNF4

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

Functioni

E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation.6 Publications

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 fingeri132 – 177RING-typePROSITE-ProRule annotationAdd BLAST46

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • ligase activity Source: UniProtKB-KW
  • nucleosome binding Source: UniProtKB
  • SUMO polymer binding Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc
  • transcription factor binding Source: GO_Central
  • ubiquitin protein ligase activity Source: GO_Central
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: ProtInc

GO - Biological processi

  • androgen receptor signaling pathway Source: UniProtKB
  • negative regulation of protein sumoylation Source: GO_Central
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein autoubiquitination Source: UniProtKB
  • protein K11-linked ubiquitination Source: UniProtKB
  • protein K48-linked ubiquitination Source: UniProtKB
  • protein K63-linked ubiquitination Source: UniProtKB
  • protein K6-linked ubiquitination Source: UniProtKB
  • protein ubiquitination Source: GO_Central
  • regulation of kinetochore assembly Source: UniProtKB
  • regulation of spindle assembly Source: UniProtKB
  • response to arsenic-containing substance Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Ligase

Keywords - Biological processi

Transcription, Transcription regulation, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000063978-MONOMER.
ReactomeiR-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiP78317.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF4 (EC:6.3.2.-)
Alternative name(s):
RING finger protein 4
Small nuclear ring finger protein
Short name:
Protein SNURF
Gene namesi
Name:RNF4
Synonyms:SNURF
ORF Names:RES4-26
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:10067. RNF4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB-SubCell
  • SUMO-targeted ubiquitin ligase complex Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi6047.
OpenTargetsiENSG00000063978.
PharmGKBiPA34439.

Polymorphism and mutation databases

BioMutaiRNF4.
DMDMi18202358.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000560431 – 190E3 ubiquitin-protein ligase RNF4Add BLAST190

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei94PhosphoserineCombined sources1
Modified residuei95PhosphoserineCombined sources1

Post-translational modificationi

Sumoylated; conjugated by one or two SUMO1 moieties.By similarity
Autoubiquitinated.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP78317.
MaxQBiP78317.
PaxDbiP78317.
PeptideAtlasiP78317.
PRIDEiP78317.

PTM databases

iPTMnetiP78317.
PhosphoSitePlusiP78317.

Expressioni

Tissue specificityi

Widely expressed at low levels in many tissues; highly expressed in testis.1 Publication

Gene expression databases

BgeeiENSG00000063978.
CleanExiHS_RNF4.
ExpressionAtlasiP78317. baseline and differential.
GenevisibleiP78317. HS.

Organism-specific databases

HPAiHPA049356.

Interactioni

Subunit structurei

Homodimer (via RING-type zinc finger domain). Interacts with GSC2 (By similarity). Interacts with AR/the androgen receptor and TBP (By similarity). Interacts with TCF20 (By similarity). Interacts with PATZ1. Interacts with TRPS1; negatively regulates TRPS1 transcriptional repressor activity. Interacts with PML; SUMO1-dependent. Interacts with PML; SUMO2-dependent. Interacts with PARP1. Interacts with PML (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4, isoform PML-5 and isoform PML-6).By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-2340927,EBI-2340927
TRPS1Q9UHF72EBI-2340927,EBI-2556151

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • SUMO polymer binding Source: UniProtKB
  • transcription factor binding Source: GO_Central

Protein-protein interaction databases

BioGridi111974. 54 interactors.
IntActiP78317. 23 interactors.
MINTiMINT-271054.
STRINGi9606.ENSP00000315212.

Structurei

Secondary structure

1190
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni133 – 135Combined sources3
Helixi139 – 144Combined sources6
Beta strandi149 – 152Combined sources4
Beta strandi153 – 155Combined sources3
Beta strandi157 – 159Combined sources3
Helixi160 – 169Combined sources10
Turni174 – 176Combined sources3
Turni181 – 183Combined sources3
Beta strandi185 – 187Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EA6NMR-A122-183[»]
2XEUX-ray1.50A130-190[»]
4PPEX-ray2.00A/B120-190[»]
ProteinModelPortaliP78317.
SMRiP78317.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP78317.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 16Required for ubiquitination activityBy similarityAdd BLAST16
Regioni4 – 61Mediates interaction with TRPS1By similarityAdd BLAST58

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi36 – 39SUMO interaction motif 1; mediates the binding to polysumoylated substrates4
Motifi46 – 49SUMO interaction motif 2; mediates the binding to polysumoylated substrates4
Motifi57 – 59SUMO interaction motif 3; mediates the binding to polysumoylated substrates3
Motifi67 – 70SUMO interaction motif 4; mediates the binding to polysumoylated substrates4

Domaini

The RING-type zinc finger domain is required for the ubiquitination of polysumoylated substrates.By similarity

Sequence similaritiesi

Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri132 – 177RING-typePROSITE-ProRule annotationAdd BLAST46

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0320. Eukaryota.
ENOG410XV78. LUCA.
GeneTreeiENSGT00390000010318.
HOGENOMiHOG000059548.
HOVERGENiHBG018577.
InParanoidiP78317.
OMAiTHRQYHP.
OrthoDBiEOG091G0AKN.
PhylomeDBiP78317.
TreeFamiTF328387.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P78317-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSTRKRRGGA INSRQAQKRT REATSTPEIS LEAEPIELVE TAGDEIVDLT
60 70 80 90 100
CESLEPVVVD LTHNDSVVIV DERRRPRRNA RRLPQDHADS CVVSSDDEEL
110 120 130 140 150
SRDRDVYVTT HTPRNARDEG ATGLRPSGTV SCPICMDGYS EIVQNGRLIV
160 170 180 190
STECGHVFCS QCLRDSLKNA NTCPTCRKKI NHKRYHPIYI
Length:190
Mass (Da):21,319
Last modified:May 1, 1997 - v1
Checksum:iE5E3AE4A9B28CF9D
GO
Isoform 2 (identifier: P78317-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     72-113: ERRRPRRNAR...RDVYVTTHTP → GPQVLSVVPS...SSVASASVIP
     114-190: Missing.

Note: No experimental confirmation available.
Show »
Length:113
Mass (Da):12,126
Checksum:iC65BF8B284670597
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04578972 – 113ERRRP…TTHTP → GPQVLSVVPSAWTDTQRSCR MDVSSFPQNAAMSSVASASV IP in isoform 2. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_045790114 – 190Missing in isoform 2. 1 PublicationAdd BLAST77

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000468 mRNA. Translation: BAA19122.1.
U95140 mRNA. Translation: AAC52022.1.
AK128038 mRNA. Translation: BAG54620.1.
AK309509 mRNA. No translation available.
AK312534 mRNA. Translation: BAG35433.1.
AL110117 Genomic DNA. No translation available.
AL645924 Genomic DNA. No translation available.
BX322586 Genomic DNA. No translation available.
CR450722 Genomic DNA. No translation available.
CR545473 Genomic DNA. No translation available.
BC031935 mRNA. Translation: AAH31935.1.
CCDSiCCDS47001.1. [P78317-1]
CCDS54713.1. [P78317-2]
RefSeqiNP_001171938.1. NM_001185009.2. [P78317-1]
NP_001171939.1. NM_001185010.2. [P78317-2]
NP_002929.1. NM_002938.4. [P78317-1]
UniGeneiHs.66394.

Genome annotation databases

EnsembliENST00000314289; ENSP00000315212; ENSG00000063978. [P78317-1]
ENST00000506706; ENSP00000424076; ENSG00000063978. [P78317-1]
ENST00000511600; ENSP00000426503; ENSG00000063978. [P78317-1]
ENST00000511859; ENSP00000426615; ENSG00000063978. [P78317-2]
ENST00000541204; ENSP00000446369; ENSG00000063978. [P78317-2]
GeneIDi6047.
KEGGihsa:6047.
UCSCiuc003gfb.4. human. [P78317-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000468 mRNA. Translation: BAA19122.1.
U95140 mRNA. Translation: AAC52022.1.
AK128038 mRNA. Translation: BAG54620.1.
AK309509 mRNA. No translation available.
AK312534 mRNA. Translation: BAG35433.1.
AL110117 Genomic DNA. No translation available.
AL645924 Genomic DNA. No translation available.
BX322586 Genomic DNA. No translation available.
CR450722 Genomic DNA. No translation available.
CR545473 Genomic DNA. No translation available.
BC031935 mRNA. Translation: AAH31935.1.
CCDSiCCDS47001.1. [P78317-1]
CCDS54713.1. [P78317-2]
RefSeqiNP_001171938.1. NM_001185009.2. [P78317-1]
NP_001171939.1. NM_001185010.2. [P78317-2]
NP_002929.1. NM_002938.4. [P78317-1]
UniGeneiHs.66394.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EA6NMR-A122-183[»]
2XEUX-ray1.50A130-190[»]
4PPEX-ray2.00A/B120-190[»]
ProteinModelPortaliP78317.
SMRiP78317.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111974. 54 interactors.
IntActiP78317. 23 interactors.
MINTiMINT-271054.
STRINGi9606.ENSP00000315212.

PTM databases

iPTMnetiP78317.
PhosphoSitePlusiP78317.

Polymorphism and mutation databases

BioMutaiRNF4.
DMDMi18202358.

Proteomic databases

EPDiP78317.
MaxQBiP78317.
PaxDbiP78317.
PeptideAtlasiP78317.
PRIDEiP78317.

Protocols and materials databases

DNASUi6047.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000314289; ENSP00000315212; ENSG00000063978. [P78317-1]
ENST00000506706; ENSP00000424076; ENSG00000063978. [P78317-1]
ENST00000511600; ENSP00000426503; ENSG00000063978. [P78317-1]
ENST00000511859; ENSP00000426615; ENSG00000063978. [P78317-2]
ENST00000541204; ENSP00000446369; ENSG00000063978. [P78317-2]
GeneIDi6047.
KEGGihsa:6047.
UCSCiuc003gfb.4. human. [P78317-1]

Organism-specific databases

CTDi6047.
DisGeNETi6047.
GeneCardsiRNF4.
HGNCiHGNC:10067. RNF4.
HPAiHPA049356.
MIMi602850. gene.
neXtProtiNX_P78317.
OpenTargetsiENSG00000063978.
PharmGKBiPA34439.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0320. Eukaryota.
ENOG410XV78. LUCA.
GeneTreeiENSGT00390000010318.
HOGENOMiHOG000059548.
HOVERGENiHBG018577.
InParanoidiP78317.
OMAiTHRQYHP.
OrthoDBiEOG091G0AKN.
PhylomeDBiP78317.
TreeFamiTF328387.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000063978-MONOMER.
ReactomeiR-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiP78317.

Miscellaneous databases

ChiTaRSiRNF4. human.
EvolutionaryTraceiP78317.
GeneWikiiRNF4.
GenomeRNAii6047.
PROiP78317.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000063978.
CleanExiHS_RNF4.
ExpressionAtlasiP78317. baseline and differential.
GenevisibleiP78317. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRNF4_HUMAN
AccessioniPrimary (citable) accession number: P78317
Secondary accession number(s): B2R6D6, D6RF58, Q49AR8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: May 1, 1997
Last modified: November 2, 2016
This is version 153 of the entry and version 1 of the sequence. [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 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

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.