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Q9QZS2 (RNF4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase RNF4

EC=6.3.2.-
Alternative name(s):
RING finger protein 4
Gene names
Name:Rnf4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length194 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Homodimer (via RING-type zinc finger domain). Interacts with AR/the androgen receptor and TBP By similarity. Interacts with PATZ1 By similarity. Interacts with PML; SUMO1-dependent. Interacts with PML; SUMO2-dependent By similarity. Interacts with TRPS1; negatively regulates the TRPS1 transcriptional repressor activity. Interacts with GSC2. Interacts with TCF20. Interacts with PARP1. Interacts with PML By similarity. Ref.1 Ref.5 Ref.6 Ref.8 Ref.9

Subcellular location

Cytoplasm. Nucleus. NucleusPML body By similarity. Nucleusnucleoplasm By similarity.

Tissue specificity

In the embryo, expressed primarily in the developing nervous system with strong expression in the dorsal root ganglia and gonads. Ubiquitously expressed in the adult.

Developmental stage

Expression is detected from embryonic day 7 and continues throughout development and into adulthood.

Domain

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

Post-translational modification

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

Autoubiquitinated.

Sequence similarities

Contains 1 RING-type zinc finger.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Ligase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processpositive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein K11-linked ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein K48-linked ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein K6-linked ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein K63-linked ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein autoubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of kinetochore assembly

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of spindle assembly

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

microtubule cytoskeleton

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

SUMO polymer binding

Inferred from sequence or structural similarity. Source: UniProtKB

nucleosome binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.6. Source: UniProtKB

transcription factor binding

Inferred from physical interaction Ref.5. Source: MGI

ubiquitin-protein transferase activity

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 194194E3 ubiquitin-protein ligase RNF4
PRO_0000056044

Regions

Zinc finger136 – 18146RING-type
Region1 – 2020Required for ubiquitination activity
Region6 – 6560Mediates interaction with TRPS1
Motif40 – 434SUMO interaction motif 1; mediates the binding to polysumoylated substrates
Motif50 – 534SUMO interaction motif 2; mediates the binding to polysumoylated substrates
Motif61 – 633SUMO interaction motif 3; mediates the binding to polysumoylated substrates
Motif71 – 744SUMO interaction motif 4; mediates the binding to polysumoylated substrates

Amino acid modifications

Modified residue981Phosphoserine Ref.7
Modified residue991Phosphoserine By similarity

Experimental info

Mutagenesis1341V → E: Abolishes homodimerization. Strongly reduced E3 ubiquitin ligase activity. Ref.9
Mutagenesis1551S → A: No effect. Ref.9
Mutagenesis1551S → E: Abolishes homodimerization. Strongly reduced E3 ubiquitin ligase activity. Ref.9
Mutagenesis1611V → A: Abolishes homodimerization. Strongly reduced E3 ubiquitin ligase activity. Ref.9
Mutagenesis1931Y → A: Abolishes homodimerization. Loss of E3 ubiquitin ligase activity. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Q9QZS2 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 9A0A4277725C62E5

FASTA19421,911
        10         20         30         40         50         60 
MSTRNPQRKR RGGTVNSRQT QKRTRETTST PEVSLETEPI ELVETVGDEI VDLTCESLEP 

        70         80         90        100        110        120 
VVVDLTHNDS VVIVEERRRP RRNGRRLRQD HADSCVVSSD DEELSRDKDV YVTTHTPRST 

       130        140        150        160        170        180 
KDDGATGPRP SGTVSCPICM DGYSEIVQNG RLIVSTECGH VFCSQCLRDS LKNANTCPTC 

       190 
RKKINHKRYH PIYI 

« Hide

References

« Hide 'large scale' references
[1]"Rnf4, a RING protein expressed in the developing nervous and reproductive systems, interacts with Gscl, a gene within the DiGeorge critical region."
Galili N., Nayak S., Epstein J.A., Buck C.A.
Dev. Dyn. 218:102-111(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH GSC2.
Strain: CD-1.
Tissue: Embryo.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Bone marrow, Embryo, Kidney, Lymph node and Visual cortex.
[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].
[4]"Identification and characterization of a novel RING-finger gene (RNF4) mapping at 4p16.3."
Chiariotti L., Benvenuto G., Fedele M., Santoro M., Simeone A., Fusco A., Bruni C.B.
Genomics 47:258-265(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 16-178.
Tissue: Embryo.
[5]"Interaction between the transcription factor SPBP and the positive cofactor RNF4. An interplay between protein binding zinc fingers."
Lyngsoe C., Bouteiller G., Damgaard C.K., Ryom D., Sanchez-Munoz S., Noerby P.L., Bonven B.J., Joergensen P.
J. Biol. Chem. 275:26144-26149(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TCF20.
[6]"The RING finger protein RNF4, a co-regulator of transcription, interacts with the TRPS1 transcription factor."
Kaiser F.J., Moeroey T., Chang G.T., Horsthemke B., Luedecke H.J.
J. Biol. Chem. 278:38780-38785(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRPS1.
[7]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[8]"PARP-1 transcriptional activity is regulated by sumoylation upon heat shock."
Martin N., Schwamborn K., Schreiber V., Werner A., Guillier C., Zhang X.D., Bischof O., Seeler J.S., Dejean A.
EMBO J. 28:3534-3548(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARP1.
[9]"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: FUNCTION, AUTOUBIQUITINATION, MUTAGENESIS OF VAL-134; SER-155; VAL-161 AND TYR-193, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF169300 mRNA. Translation: AAF00620.1.
AK019171 mRNA. Translation: BAB31585.1.
AK090162 mRNA. Translation: BAC41119.1.
AK147057 mRNA. Translation: BAE27641.1.
AK151116 mRNA. Translation: BAE30125.1.
AK158987 mRNA. Translation: BAE34757.1.
AK159778 mRNA. Translation: BAE35362.1.
AK159949 mRNA. Translation: BAE35505.1.
BC003282 mRNA. Translation: AAH03282.1.
U95141 mRNA. Translation: AAC53539.1.
CCDSCCDS57336.1.
RefSeqNP_035408.1. NM_011278.4.
XP_006503866.1. XM_006503803.1.
XP_006503867.1. XM_006503804.1.
XP_006503868.1. XM_006503805.1.
UniGeneMm.21281.

3D structure databases

ProteinModelPortalQ9QZS2.
SMRQ9QZS2. Positions 129-194.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202920. 2 interactions.

PTM databases

PhosphoSiteQ9QZS2.

Proteomic databases

PRIDEQ9QZS2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000030992; ENSMUSP00000030992; ENSMUSG00000029110.
ENSMUST00000182047; ENSMUSP00000138411; ENSMUSG00000029110.
ENSMUST00000182709; ENSMUSP00000138555; ENSMUSG00000029110.
GeneID19822.
KEGGmmu:19822.
UCSCuc008xcc.1. mouse.

Organism-specific databases

CTD6047.
MGIMGI:1201691. Rnf4.

Phylogenomic databases

eggNOGNOG327779.
GeneTreeENSGT00390000010318.
HOVERGENHBG018577.
InParanoidQ9QZS2.
OMATHRQYHP.
OrthoDBEOG7SN8F1.
PhylomeDBQ9QZS2.
TreeFamTF328387.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9QZS2.
BgeeQ9QZS2.
CleanExMM_RNF4.
GenevestigatorQ9QZS2.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
[Graphical view]
PROSITEPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRNF4. mouse.
NextBio297289.
PMAP-CutDBQ9QZS2.
PROQ9QZS2.
SOURCESearch...

Entry information

Entry nameRNF4_MOUSE
AccessionPrimary (citable) accession number: Q9QZS2
Secondary accession number(s): O35941, Q541Z6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot