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Protein

E3 ubiquitin-protein ligase RFWD2

Gene

Rfwd2

Organism
Mus musculus (Mouse)
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. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in JUN ubiquitination and degradation. Directly involved in p53 (TP53) ubiquitination and degradation, thereby abolishing p53-dependent transcription and apoptosis. Ubiquitinates p53 independently of MDM2 or RCHY1. Probably mediates E3 ubiquitin ligase activity by functioning as the essential RING domain subunit of larger E3 complexes. In contrast, it does not constitute the catalytic RING subunit in the DCX DET1-COP1 complex that negatively regulates JUN, the ubiquitin ligase activity being mediated by RBX1 (By similarity). Involved in 14-3-3 protein sigma/SFN ubiquitination and proteasomal degradation, leading to AKT activation and promotion of cell survival. Ubiquitinates MTA1 leading to its proteasomal degradation (By similarity).By similarity

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 fingeri138 – 17639RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-349425. Autodegradation of the E3 ubiquitin ligase COP1.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RFWD2 (EC:6.3.2.-)
Alternative name(s):
Constitutive photomorphogenesis protein 1 homolog
Short name:
mCOP1
RING finger and WD repeat domain protein 2
Gene namesi
Name:Rfwd2
Synonyms:Cop1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1347046. Rfwd2.

Subcellular locationi

  • Nucleus speckle 1 Publication
  • Cytoplasm 1 Publication

  • Note: In the nucleus, it forms nuclear speckles.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi113 – 1142RK → SN: Abolishes nuclear localization. 1 Publication
Mutagenesisi197 – 2015KQKQR → NQNQS: Does not affect the subcellular localization. 1 Publication
Mutagenesisi205 – 2084KRFK → TSFT: Abolishes nuclear localization. 1 Publication
Mutagenesisi244 – 2463LEL → AEA: Abolishes nuclear export. 1 Publication
Mutagenesisi358 – 3603RRK → SRT: Abolishes the nuclear speckle localization but not the nuclear localization. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 733733E3 ubiquitin-protein ligase RFWD2PRO_0000055880Add
BLAST

Proteomic databases

EPDiQ9R1A8.
MaxQBiQ9R1A8.
PaxDbiQ9R1A8.
PRIDEiQ9R1A8.

PTM databases

iPTMnetiQ9R1A8.
PhosphoSiteiQ9R1A8.

Expressioni

Gene expression databases

BgeeiQ9R1A8.
CleanExiMM_RFWD2.
ExpressionAtlasiQ9R1A8. baseline and differential.
GenevisibleiQ9R1A8. MM.

Interactioni

Subunit structurei

Homodimer. Homodimerization is mediated by the coiled coil domain. Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1. Isoform 2 does not interact with CUL4A but still binds to RBX1, suggesting that the interaction may be mediated by another cullin protein. Isoform 1 and isoform 2 interact with CUL5 but not with CUL1, CUL2 not CUL3. Interacts with bZIP transcription factors JUN, JUNB and JUND but not with FOS, ATF2 nor XBP1. Interacts with p53 (TP53) (By similarity). Interacts with COPS6; this interaction stabilizes RFWD2 through reducing its auto-ubiquitination and decelerating its turnover rate (By similarity). Interacts with SFN; this interaction leads to SFN degradation. Interacts with p53/TP53 and MTA1 (By similarity).By similarity

Protein-protein interaction databases

BioGridi204934. 8 interactions.
DIPiDIP-60522N.
STRINGi10090.ENSMUSP00000076160.

Structurei

3D structure databases

ProteinModelPortaliQ9R1A8.
SMRiQ9R1A8. Positions 136-195, 423-714.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati421 – 46040WD 1Add
BLAST
Repeati470 – 51041WD 2Add
BLAST
Repeati513 – 55341WD 3Add
BLAST
Repeati555 – 59541WD 4Add
BLAST
Repeati599 – 63739WD 5Add
BLAST
Repeati640 – 67940WD 6Add
BLAST
Repeati695 – 73137WD 7Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili231 – 30676Sequence analysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi111 – 1155Nuclear localization signal 1
Motifi197 – 20812Nuclear localization signal 2Add
BLAST
Motifi237 – 24711Nuclear export signalAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi2 – 112111Ser-richAdd
BLAST

Domaini

The RING finger domain, in addition to its role in ubiquitination, functions as a structural scaffold to bring two clusters of positive-charged residues within spatial proximity to mimic a bipartite nuclear localization signal (NLS).1 Publication

Sequence similaritiesi

Belongs to the COP1 family.Curated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 7 WD repeats.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri138 – 17639RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Coiled coil, Repeat, WD repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IE71. Eukaryota.
ENOG410XNTU. LUCA.
GeneTreeiENSGT00570000079069.
HOGENOMiHOG000006123.
HOVERGENiHBG054995.
InParanoidiQ9R1A8.
KOiK10143.
OMAiFSTRMTR.
OrthoDBiEOG75TMB6.
PhylomeDBiQ9R1A8.
TreeFamiTF328912.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR033313. RFWD2/COP1.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR22847:SF451. PTHR22847:SF451. 2 hits.
PfamiPF00400. WD40. 5 hits.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 2 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9R1A8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGSRQAGSG SAGTSPGSSA ASSVTSASSS LSSSPSPPSV AASAATLVSG
60 70 80 90 100
GVAPAAGSGG LGGPGRPVLV AAAVSGSASA GGAVSAGQSR LSCAARPSAG
110 120 130 140 150
VGGSSSSLGS SSRKRPLLVP LCNGLLNSYE DKSNDFVCPI CFDMIEEAYM
160 170 180 190 200
TKCGHSFCYK CIHQSLEDNN RCPKCNYVVD NIDHLYPNFL VNELILKQKQ
210 220 230 240 250
RFEEKRFKLD HSVSSTNGHR WQIFQDLLGT DQDNLDLANV NLMLELLVQK
260 270 280 290 300
KKQLEAESHA AQLQILMEFL KVARRNKREQ LEQIQKELSV LEEDIKRVEE
310 320 330 340 350
MSGLYSPVSE DSTVPQFEAP SPSHSSIIDS TEYSQPPGFS GTSQTKKQPW
360 370 380 390 400
YNSTLASRRK RLTAHFEDLE QCYFSTRMSR ISDDSRTASQ LDEFQECLSK
410 420 430 440 450
FTRYNSVRPL ATLSYASDLY NGSSIVSSIE FDRDCDYFAI AGVTKKIKVY
460 470 480 490 500
EYGTVIQDAV DIHYPENEMT CNSKISCISW SSYHKNLLAS SDYEGTVILW
510 520 530 540 550
DGFTGQRSKV YQEHEKRCWS VDFNLMDPKL LASGSDDAKV KLWSTNLDNS
560 570 580 590 600
VASIEAKANV CCVKFSPSSR YHLAFGCADH CVHYYDLRNT KQPIMVFKGH
610 620 630 640 650
RKAVSYAKFV SGEEIVSAST DSQLKLWNVG KPYCLRSFKG HINEKNFVGL
660 670 680 690 700
ASNGDYIACG SENNSLYLYY KGLSKTLLTF KFDTVKSVLD KDRKEDDTNE
710 720 730
FVSAVCWRAL SDGESNVLIA ANSQGTIKVL ELV
Length:733
Mass (Da):80,441
Last modified:October 1, 2002 - v2
Checksum:i894AEA412BACC737
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF151110 mRNA. Translation: AAD51094.2.
BC082804 mRNA. Translation: AAH82804.1.
CCDSiCCDS35745.1.
RefSeqiNP_036061.1. NM_011931.3.
UniGeneiMm.328135.

Genome annotation databases

EnsembliENSMUST00000076894; ENSMUSP00000076160; ENSMUSG00000040782.
GeneIDi26374.
KEGGimmu:26374.
UCSCiuc007ddz.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF151110 mRNA. Translation: AAD51094.2.
BC082804 mRNA. Translation: AAH82804.1.
CCDSiCCDS35745.1.
RefSeqiNP_036061.1. NM_011931.3.
UniGeneiMm.328135.

3D structure databases

ProteinModelPortaliQ9R1A8.
SMRiQ9R1A8. Positions 136-195, 423-714.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204934. 8 interactions.
DIPiDIP-60522N.
STRINGi10090.ENSMUSP00000076160.

PTM databases

iPTMnetiQ9R1A8.
PhosphoSiteiQ9R1A8.

Proteomic databases

EPDiQ9R1A8.
MaxQBiQ9R1A8.
PaxDbiQ9R1A8.
PRIDEiQ9R1A8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000076894; ENSMUSP00000076160; ENSMUSG00000040782.
GeneIDi26374.
KEGGimmu:26374.
UCSCiuc007ddz.1. mouse.

Organism-specific databases

CTDi64326.
MGIiMGI:1347046. Rfwd2.

Phylogenomic databases

eggNOGiENOG410IE71. Eukaryota.
ENOG410XNTU. LUCA.
GeneTreeiENSGT00570000079069.
HOGENOMiHOG000006123.
HOVERGENiHBG054995.
InParanoidiQ9R1A8.
KOiK10143.
OMAiFSTRMTR.
OrthoDBiEOG75TMB6.
PhylomeDBiQ9R1A8.
TreeFamiTF328912.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-349425. Autodegradation of the E3 ubiquitin ligase COP1.

Miscellaneous databases

ChiTaRSiRfwd2. mouse.
PROiQ9R1A8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9R1A8.
CleanExiMM_RFWD2.
ExpressionAtlasiQ9R1A8. baseline and differential.
GenevisibleiQ9R1A8. MM.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR033313. RFWD2/COP1.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR22847:SF451. PTHR22847:SF451. 2 hits.
PfamiPF00400. WD40. 5 hits.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 2 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Evidence for functional conservation of a mammalian homologue of the light-responsive plant protein COP1."
    Wang H., Kang D., Deng X.-W., Wei N.
    Curr. Biol. 9:711-714(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, MUTAGENESIS OF 113-ARG-LYS-114; 197-LYS--ARG-201; 205-LYS--LYS-208; 244-LEU--LEU-246 AND 358-ARG--LYS-360.
    Strain: C57BL/6J.
  2. "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].
    Strain: C57BL/6J.
    Tissue: Brain.

Entry informationi

Entry nameiRFWD2_MOUSE
AccessioniPrimary (citable) accession number: Q9R1A8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: October 1, 2002
Last modified: June 8, 2016
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  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.