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Protein

E3 ubiquitin-protein ligase RNF4

Gene

Rnf4

Organism
Rattus norvegicus (Rat)
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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri136 – 18146RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • androgen receptor binding Source: RGD
  • DNA binding Source: UniProtKB
  • estrogen receptor binding Source: RGD
  • ligase activity Source: UniProtKB-KW
  • nucleosome binding Source: UniProtKB
  • progesterone receptor binding Source: RGD
  • protein homodimerization activity Source: RGD
  • SUMO polymer binding Source: UniProtKB
  • TBP-class protein binding Source: RGD
  • ubiquitin conjugating enzyme binding Source: RGD
  • ubiquitin protein ligase activity Source: RGD
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: RGD

GO - Biological processi

  • cellular response to arsenic-containing substance Source: RGD
  • cellular response to cytokine stimulus Source: RGD
  • cellular response to gamma radiation Source: RGD
  • cellular response to hydroxyurea Source: RGD
  • cellular response to testosterone stimulus Source: RGD
  • male gonad development Source: RGD
  • negative regulation of cell death Source: RGD
  • 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: UniProtKB
  • regulation of kinetochore assembly Source: UniProtKB
  • regulation of spindle assembly Source: UniProtKB
  • response to arsenic-containing substance Source: UniProtKB
  • response to estradiol Source: RGD
  • response to human chorionic gonadotropin Source: RGD
  • spermatogenesis Source: RGD
  • 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

BRENDAi6.3.2.19. 5301.
ReactomeiR-RNO-5693607. Processing of DNA double-strand break ends.
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 14

Organism-specific databases

RGDi3583. Rnf4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: RGD
  • nucleoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi8 – 114RKRR → AAAA: Altered DNA-binding activity. 1 Publication
Mutagenesisi40 – 434IELV → AEAA: No effect. Loss of binding and ubiquitination of poly-SUMO chains; when associated with 50-A--A-53; 61-A--A-63 and 71-A--A-74. 1 Publication
Mutagenesisi50 – 534IVDL → AADA: Alters binding to poly-SUMO chains. Loss of binding and ubiquitination of poly-SUMO chains; when associated with 40-A--A-43; 61-A--A-63 and 71-A--A-74. 1 Publication
Mutagenesisi61 – 633VVV → AAA: No effect. Loss of binding and ubiquitination of poly-SUMO chains; when associated with 40-A--A-43; 50-A--A-53 and 71-A--A-74. 1 Publication
Mutagenesisi71 – 744VVIV → AAAA: No effect. Loss of binding and ubiquitination of poly-SUMO chains; when associated with 40-A--A-43; 50-A--A-53 and 61-A--A-63. 1 Publication
Mutagenesisi136 – 1361C → S: Loss of ubiquitination activity; when associated with S-139. 1 Publication
Mutagenesisi139 – 1391C → S: Loss of ubiquitination activity; when associated with S-136. 1 Publication
Mutagenesisi177 – 1771C → S: Loss of ubiquitination activity; when associated with S-180. 1 Publication
Mutagenesisi180 – 1801C → S: Loss of ubiquitination activity; when associated with S-177. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 194194E3 ubiquitin-protein ligase RNF4PRO_0000056045Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei98 – 981PhosphoserineCombined sources
Modified residuei99 – 991PhosphoserineCombined sources

Post-translational modificationi

Sumoylated; conjugated by one or two SUMO1 moieties.1 Publication
Autoubiquitinated.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO88846.
PRIDEiO88846.

PTM databases

iPTMnetiO88846.
PhosphoSiteiO88846.

Expressioni

Tissue specificityi

Widely expressed with highest levels in testis.

Gene expression databases

ExpressionAtlasiO88846. baseline and differential.
GenevisibleiO88846. RN.

Interactioni

Subunit structurei

Homodimer (via RING-type zinc finger domain). Interacts with PATZ1 (By similarity). Interacts with TRPS1; negatively regulates the TRPS1 transcriptional repressor activity (By similarity). Interacts with GSC2 (By similarity). Interacts with TCF20 (By similarity). Interacts with PARP1 (By similarity). Interacts with AR/the androgen receptor and TBP. Interacts with PML; SUMO1-dependent. Interacts with PML; SUMO2-dependent. Interacts with PML (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
SUMO2P619562EBI-7258907,EBI-473220From a different organism.

GO - Molecular functioni

  • androgen receptor binding Source: RGD
  • estrogen receptor binding Source: RGD
  • nucleosome binding Source: UniProtKB
  • progesterone receptor binding Source: RGD
  • protein homodimerization activity Source: RGD
  • SUMO polymer binding Source: UniProtKB
  • TBP-class protein binding Source: RGD
  • ubiquitin conjugating enzyme binding Source: RGD

Protein-protein interaction databases

BioGridi247945. 10 interactions.
IntActiO88846. 7 interactions.
STRINGi10116.ENSRNOP00000019555.

Structurei

Secondary structure

1
194
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi131 – 1333Combined sources
Turni137 – 1393Combined sources
Helixi143 – 1475Combined sources
Turni148 – 1503Combined sources
Beta strandi153 – 1553Combined sources
Beta strandi161 – 1633Combined sources
Helixi164 – 17310Combined sources
Turni178 – 1803Combined sources
Helixi186 – 1883Combined sources
Beta strandi189 – 1924Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3NG2X-ray1.80A/B124-194[»]
4AP4X-ray2.21A131-194[»]
5AITX-ray3.40A131-194[»]
5AIUX-ray2.21A131-194[»]
ProteinModelPortaliO88846.
SMRiO88846. Positions 128-187.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO88846.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2020Required for ubiquitination activityBy similarityAdd
BLAST
Regioni6 – 6560Mediates interaction with TRPS1By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi40 – 434SUMO interaction motif 1; mediates the binding to polysumoylated substrates
Motifi50 – 534SUMO interaction motif 2; mediates the binding to polysumoylated substrates
Motifi61 – 633SUMO interaction motif 3; mediates the binding to polysumoylated substrates
Motifi71 – 744SUMO interaction motif 4; mediates the binding to polysumoylated substrates

Domaini

The RING-type zinc finger domain is required for the ubiquitination of polysumoylated substrates.1 Publication

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri136 – 18146RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0320. Eukaryota.
ENOG410XV78. LUCA.
GeneTreeiENSGT00390000010318.
HOGENOMiHOG000059548.
HOVERGENiHBG018577.
InParanoidiO88846.
OrthoDBiEOG7SN8F1.
PhylomeDBiO88846.
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]

Sequencei

Sequence statusi: Complete.

O88846-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTRNPQRKR RGGAVNSRQT QKRTRETTST PEISLEAEPI ELVETVGDEI
60 70 80 90 100
VDLTCESLEP VVVDLTHNDS VVIVEERRRP RRNGRRLRQD HADSCVVSSD
110 120 130 140 150
DEELSKDKDV YVTTHTPRST KDEGTTGLRP SGTVSCPICM DGYSEIVQNG
160 170 180 190
RLIVSTECGH VFCSQCLRDS LKNANTCPTC RKKINHKRYH PIYI
Length:194
Mass (Da):21,897
Last modified:November 1, 1998 - v1
Checksum:i40C13970FC11DFF2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF022081 mRNA. Translation: AAC35248.1.
AY050655 mRNA. Translation: AAL06715.1.
BC062024 mRNA. Translation: AAH62024.1.
RefSeqiNP_062055.1. NM_019182.2.
XP_008768493.1. XM_008770271.1.
XP_008768494.1. XM_008770272.1.
XP_008768495.1. XM_008770273.1.
UniGeneiRn.30015.

Genome annotation databases

EnsembliENSRNOT00000019555; ENSRNOP00000019555; ENSRNOG00000013930.
GeneIDi29274.
KEGGirno:29274.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF022081 mRNA. Translation: AAC35248.1.
AY050655 mRNA. Translation: AAL06715.1.
BC062024 mRNA. Translation: AAH62024.1.
RefSeqiNP_062055.1. NM_019182.2.
XP_008768493.1. XM_008770271.1.
XP_008768494.1. XM_008770272.1.
XP_008768495.1. XM_008770273.1.
UniGeneiRn.30015.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3NG2X-ray1.80A/B124-194[»]
4AP4X-ray2.21A131-194[»]
5AITX-ray3.40A131-194[»]
5AIUX-ray2.21A131-194[»]
ProteinModelPortaliO88846.
SMRiO88846. Positions 128-187.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247945. 10 interactions.
IntActiO88846. 7 interactions.
STRINGi10116.ENSRNOP00000019555.

PTM databases

iPTMnetiO88846.
PhosphoSiteiO88846.

Proteomic databases

PaxDbiO88846.
PRIDEiO88846.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000019555; ENSRNOP00000019555; ENSRNOG00000013930.
GeneIDi29274.
KEGGirno:29274.

Organism-specific databases

CTDi6047.
RGDi3583. Rnf4.

Phylogenomic databases

eggNOGiKOG0320. Eukaryota.
ENOG410XV78. LUCA.
GeneTreeiENSGT00390000010318.
HOGENOMiHOG000059548.
HOVERGENiHBG018577.
InParanoidiO88846.
OrthoDBiEOG7SN8F1.
PhylomeDBiO88846.
TreeFamiTF328387.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi6.3.2.19. 5301.
ReactomeiR-RNO-5693607. Processing of DNA double-strand break ends.

Miscellaneous databases

EvolutionaryTraceiO88846.
PROiO88846.

Gene expression databases

ExpressionAtlasiO88846. baseline and differential.
GenevisibleiO88846. RN.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of a novel RING finger protein as a coregulator in steroid receptor-mediated gene transcription."
    Moilanen A.-M., Poukka H., Karvonen U., Hakli M., Janne O.A., Palvimo J.J.
    Mol. Cell. Biol. 18:5128-5139(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH AR AND TBP, SUBCELLULAR LOCATION.
    Tissue: Testis.
  2. "Analysis of androgen receptor coregulator SNURF/RNF4 expression in rat testis."
    Yan W., Hirvonen S.J., Moilanen A.-M., Janne O.A., Palvimo J.J., Toppari J.
    Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.
  4. "The RING finger protein SNURF is a bifunctional protein possessing DNA binding activity."
    Haekli M., Karvonen U., Jaenne O.A., Palvimo J.J.
    J. Biol. Chem. 276:23653-23660(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF 8-ARG--ARG-11, SUBCELLULAR LOCATION.
  5. "Transcriptional coregulator SNURF (RNF4) possesses ubiquitin E3 ligase activity."
    Haekli M., Lorick K.L., Weissman A.M., Jaenne O.A., Palvimo J.J.
    FEBS Lett. 560:56-62(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, AUTOUBIQUITINATION, MUTAGENESIS OF CYS-136; CYS-139; CYS-177 AND CYS-180.
  6. "SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies."
    Haekli M., Karvonen U., Jaenne O.A., Palvimo J.J.
    Exp. Cell Res. 304:224-233(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUMOYLATION, INTERACTION WITH PML.
  7. "RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation."
    Tatham M.H., Geoffroy M.C., Shen L., Plechanovova A., Hattersley N., Jaffray E.G., Palvimo J.J., Hay R.T.
    Nat. Cell Biol. 10:538-546(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF 40-ILE--VAL-43; 50-ILE--ASP-53; 61-VAL--VAL-63 AND 71-VAL--VAL-74.
  8. "Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear bodies."
    Geoffroy M.C., Jaffray E.G., Walker K.J., Hay R.T.
    Mol. Biol. Cell 21:4227-4239(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SUMOYLATED PML, SUBCELLULAR LOCATION.
  9. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98 AND SER-99, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. "RING domain dimerization is essential for RNF4 function."
    Liew C.W., Sun H., Hunter T., Day C.L.
    Biochem. J. 431:23-29(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 124-194 IN COMPLEX WITH ZINC IONS, DOMAIN, SUBUNIT.

Entry informationi

Entry nameiRNF4_RAT
AccessioniPrimary (citable) accession number: O88846
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: November 1, 1998
Last modified: June 8, 2016
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.