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Protein

E3 ubiquitin-protein ligase RNF4

Gene

RNF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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 fingeri132 – 177RING-typePROSITE-ProRule annotationAdd BLAST46

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Transferase
Biological processTranscription, Transcription regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SIGNORiP78317
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF4 (EC:2.3.2.27)
Alternative name(s):
RING finger protein 4
RING-type E3 ubiquitin transferase RNF4Curated
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

EuPathDBiHostDB:ENSG00000063978.15
HGNCiHGNC:10067 RNF4
MIMi602850 gene
neXtProtiNX_P78317

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

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
ProteomicsDBi57562

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 Expressed in 227 organ(s), highest expression level in thymus
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111974, 61 interactors
IntActiP78317, 116 interactors
MINTiP78317
STRINGi9606.ENSP00000315212

Structurei

Secondary structure

1190
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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 11 Publication4
Motifi46 – 49SUMO interaction motif 21 Publication4
Motifi57 – 59SUMO interaction motif 31 Publication3
Motifi67 – 70SUMO interaction motif 41 Publication4

Domaini

The SUMO interaction motifs (SIMs) mediates the binding to polysumoylated substrate.1 Publication
The RING-type zinc finger domain is required for the ubiquitination of polysumoylated substrates.By similarity

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
KOiK22651
OMAiTHRQYHP
OrthoDBiEOG091G0AKN
PhylomeDBiP78317
TreeFamiTF328387

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PfamiView protein in Pfam
PF13639 zf-RING_2, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RA71D6RA71_HUMAN
E3 ubiquitin-protein ligase RNF4
RNF4
188Annotation score:
H0YAI5H0YAI5_HUMAN
E3 ubiquitin-protein ligase RNF4
RNF4
106Annotation score:
D6R9E0D6R9E0_HUMAN
E3 ubiquitin-protein ligase RNF4
RNF4
47Annotation score:
D6RJ08D6RJ08_HUMAN
E3 ubiquitin-protein ligase RNF4
RNF4
43Annotation score:
D6RBZ1D6RBZ1_HUMAN
E3 ubiquitin-protein ligase RNF4
RNF4
89Annotation score:
D6RJF5D6RJF5_HUMAN
E3 ubiquitin-protein ligase RNF4
RNF4
68Annotation score:
D6RAD8D6RAD8_HUMAN
E3 ubiquitin-protein ligase RNF4
RNF4
101Annotation score:
D6RBQ7D6RBQ7_HUMAN
E3 ubiquitin-protein ligase RNF4
RNF4
54Annotation score:

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

Similar proteinsi

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, 61 interactors
IntActiP78317, 116 interactors
MINTiP78317
STRINGi9606.ENSP00000315212

PTM databases

iPTMnetiP78317
PhosphoSitePlusiP78317

Polymorphism and mutation databases

BioMutaiRNF4
DMDMi18202358

Proteomic databases

EPDiP78317
MaxQBiP78317
PaxDbiP78317
PeptideAtlasiP78317
PRIDEiP78317
ProteomicsDBi57562

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
EuPathDBiHostDB:ENSG00000063978.15
GeneCardsiRNF4
HGNCiHGNC:10067 RNF4
HPAiHPA049356
MIMi602850 gene
neXtProtiNX_P78317
OpenTargetsiENSG00000063978
PharmGKBiPA34439
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0320 Eukaryota
ENOG410XV78 LUCA
GeneTreeiENSGT00390000010318
HOGENOMiHOG000059548
HOVERGENiHBG018577
InParanoidiP78317
KOiK22651
OMAiTHRQYHP
OrthoDBiEOG091G0AKN
PhylomeDBiP78317
TreeFamiTF328387

Enzyme and pathway databases

UniPathwayi
UPA00143

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
PROiPR:P78317
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000063978 Expressed in 227 organ(s), highest expression level in thymus
CleanExiHS_RNF4
ExpressionAtlasiP78317 baseline and differential
GenevisibleiP78317 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PfamiView protein in Pfam
PF13639 zf-RING_2, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRNF4_HUMAN
AccessioniPrimary (citable) accession number: P78317
Secondary accession number(s): B2R6D6, D6RF58, Q49AR8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: May 1, 1997
Last modified: September 12, 2018
This is version 167 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

3D-structure, Complete proteome, Reference proteome

Documents

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