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Protein

E3 ubiquitin-protein ligase RFWD3

Gene

RFWD3

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

Functioni

E3 ubiquitin-protein ligase that mediates the ubiquitination of p53/TP53 in the late response to DNA damage, and acts as a positive regulator of p53/TP53 stability, thereby regulating the G1/S DNA damage checkpoint. May act by catalyzing the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome. In response to ionizing radiation, interacts with MDM2 and enhances p53/TP53 ubiquitination, possibly by restricting MDM2 from extending polyubiquitin chains on ubiquitinated p53/TP53. Plays a role in RPA-mediated DNA damage signaling and repair.3 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 fingeri287 – 331RING-type; degeneratePROSITE-ProRule annotationAdd BLAST45

GO - Molecular functioni

  • MDM2/MDM4 family protein binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • p53 binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • DNA repair Source: UniProtKB-KW
  • mitotic G1 DNA damage checkpoint Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • regulation of DNA damage checkpoint Source: UniProtKB
  • response to ionizing radiation Source: UniProtKB

Keywordsi

Molecular functionTransferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

SignaLinkiQ6PCD5.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RFWD3 (EC:2.3.2.27)
Alternative name(s):
RING finger and WD repeat domain-containing protein 3
RING finger protein 201
RING-type E3 ubiquitin transferase RFWD3Curated
Gene namesi
Name:RFWD3
Synonyms:RNF201
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:25539. RFWD3.

Subcellular locationi

  • Nucleus
  • NucleusPML body
  • Cytoplasm

  • Note: In undamaged cells, found both in the cytoplasm and in the nucleus, partially associated with PML nuclear bodies. In response to replication block, such as that caused by hydroxyurea treatment, or to DNA damage caused by ionizing radiations or doxorubicin, recruited to the nucleus, to stalled replication forks or to sites of DNA repair. This recruitment depends upon RPA2.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB-SubCell

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi46S → A: Markedly decreases phosphorylation following ionizing radiation and abolishes ability to stimulate p53/TP53 ubiquitination; when associated with A-63. 1 Publication1
Mutagenesisi63S → A: Markedly decreases phosphorylation following ionizing radiation and abolishes ability to stimulate p53/TP53 ubiquitination; when associated with A-46. 1 Publication1
Mutagenesisi315C → A: Abolishes ability to stimulate p53/TP53 ubiquitination. No effect on nuclear localization in response to DNA damage. 2 Publications1

Organism-specific databases

DisGeNETi55159.
OpenTargetsiENSG00000168411.
PharmGKBiPA134960063.

Polymorphism and mutation databases

BioMutaiRFWD3.
DMDMi126253679.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002782341 – 774E3 ubiquitin-protein ligase RFWD3Add BLAST774

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei46Phosphoserine; by ATM and ATR1 Publication1
Modified residuei63Phosphoserine; by ATM and ATR1 Publication1

Post-translational modificationi

Phosphorylated at Ser-46 and Ser-63 upon DNA damage by ATM or ATR. ATM phosphorylation occurs at early times upon DNA damage, while ATR is the major kinase at later times. Phosphorylation by ATM and ATR is required to stabilize p53/TP53. Part of the phosphorylation depends upon RPA2 presence.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6PCD5.
MaxQBiQ6PCD5.
PaxDbiQ6PCD5.
PeptideAtlasiQ6PCD5.
PRIDEiQ6PCD5.

PTM databases

iPTMnetiQ6PCD5.
PhosphoSitePlusiQ6PCD5.

Expressioni

Developmental stagei

Up-regulated in the S-G2 phase.1 Publication

Gene expression databases

BgeeiENSG00000168411.
CleanExiHS_RFWD3.
ExpressionAtlasiQ6PCD5. baseline and differential.
GenevisibleiQ6PCD5. HS.

Organism-specific databases

HPAiHPA048258.
HPA075649.

Interactioni

Subunit structurei

Interacts with MDM2 and p53/TP53. Binds to the RPA complex via direct interaction with RPA2.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
UBE2NP610882EBI-2129159,EBI-1052908

GO - Molecular functioni

  • MDM2/MDM4 family protein binding Source: UniProtKB
  • p53 binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120460. 51 interactors.
DIPiDIP-52688N.
IntActiQ6PCD5. 39 interactors.
STRINGi9606.ENSP00000354361.

Structurei

3D structure databases

ProteinModelPortaliQ6PCD5.
SMRiQ6PCD5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati495 – 537WD 1Add BLAST43
Repeati539 – 577WD 2Add BLAST39
Repeati583 – 628WD 3Add BLAST46

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili361 – 413Sequence analysisAdd BLAST53

Domaini

The coiled coil domain may be involved in RPA2-binding.

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri287 – 331RING-type; degeneratePROSITE-ProRule annotationAdd BLAST45

Keywords - Domaini

Coiled coil, Repeat, WD repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1645. Eukaryota.
ENOG410XPPE. LUCA.
GeneTreeiENSGT00390000008931.
HOVERGENiHBG093895.
InParanoidiQ6PCD5.
KOiK15691.
OMAiLEGACFW.
OrthoDBiEOG091G05D0.
PhylomeDBiQ6PCD5.
TreeFamiTF323359.

Family and domain databases

CDDicd00162. RING. 1 hit.
Gene3Di2.130.10.10. 1 hit.
3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR017986. WD40_repeat_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
PfamiView protein in Pfam
PF13639. zf-RING_2. 1 hit.
SMARTiView protein in SMART
SM00184. RING. 1 hit.
SM00320. WD40. 3 hits.
SUPFAMiSSF50978. SSF50978. 2 hits.
PROSITEiView protein in PROSITE
PS50089. ZF_RING_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Q6PCD5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAHEAMEYDV QVQLNHAEQQ PAPAGMASSQ GGPALLQPVP ADVVSSQGVP
60 70 80 90 100
SILQPAPAEV ISSQATPPLL QPAPQLSVDL TEVEVLGEDT VENINPRTSE
110 120 130 140 150
QHRQGSDGNH TIPASSLHSM TNFISGLQRL HGMLEFLRPS SSNHSVGPMR
160 170 180 190 200
TRRRVSASRR ARAGGSQRTD SARLRAPLDA YFQVSRTQPD LPATTYDSET
210 220 230 240 250
RNPVSEELQV SSSSDSDSDS SAEYGGVVDQ AEESGAVILE EQLAGVSAEQ
260 270 280 290 300
EVTCIDGGKT LPKQPSPQKS EPLLPSASMD EEEGDTCTIC LEQWTNAGDH
310 320 330 340 350
RLSALRCGHL FGYRCISTWL KGQVRKCPQC NKKARHSDIV VLYARTLRAL
360 370 380 390 400
DTSEQERMKS SLLKEQMLRK QAELESAQCR LQLQVLTDKC TRLQRRVQDL
410 420 430 440 450
QKLTSHQSQN LQQPRGSQAW VLSCSPSSQG QHKHKYHFQK TFTVSQAGNC
460 470 480 490 500
RIMAYCDALS CLVISQPSPQ ASFLPGFGVK MLSTANMKSS QYIPMHGKQI
510 520 530 540 550
RGLAFSSYLR GLLLSASLDN TIKLTSLETN TVVQTYNAGR PVWSCCWCLD
560 570 580 590 600
EANYIYAGLA NGSILVYDVR NTSSHVQELV AQKARCPLVS LSYMPRAASA
610 620 630 640 650
AFPYGGVLAG TLEDASFWEQ KMDFSHWPHV LPLEPGGCID FQTENSSRHC
660 670 680 690 700
LVTYRPDKNH TTIRSVLMEM SYRLDDTGNP ICSCQPVHTF FGGPTCKLLT
710 720 730 740 750
KNAIFQSPEN DGNILVCTGD EAANSALLWD AASGSLLQDL QTDQPVLDIC
760 770
PFEVNRNSYL ATLTEKMVHI YKWE
Length:774
Mass (Da):85,094
Last modified:February 20, 2007 - v3
Checksum:iEF6E0E186FD2E580
GO

Sequence cautioni

The sequence BAA91662 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAF83889 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG38132 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti221S → P in BAF83889 (PubMed:14702039).Curated1
Sequence conflicti552A → T in BAA91662 (PubMed:14702039).Curated1
Sequence conflicti597A → V in BAA91662 (PubMed:14702039).Curated1
Sequence conflicti741Q → R in BAB14169 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03070090T → N. Corresponds to variant dbSNP:rs8058922Ensembl.1
Natural variantiVAR_030701392R → K1 PublicationCorresponds to variant dbSNP:rs17854997Ensembl.1
Natural variantiVAR_030702564I → V1 PublicationCorresponds to variant dbSNP:rs7193541Ensembl.1
Natural variantiVAR_030703770I → T1 PublicationCorresponds to variant dbSNP:rs17854996Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK001382 mRNA. Translation: BAA91662.1. Different initiation.
AK022673 mRNA. Translation: BAB14169.1.
AK291200 mRNA. Translation: BAF83889.1. Different initiation.
AK315786 mRNA. Translation: BAG38132.1. Different initiation.
AC109599 Genomic DNA. No translation available.
CH471114 Genomic DNA. Translation: EAW95680.1.
CH471114 Genomic DNA. Translation: EAW95681.1.
BC002574 mRNA. Translation: AAH02574.2.
BC059371 mRNA. Translation: AAH59371.2.
CCDSiCCDS32486.1.
RefSeqiNP_060594.3. NM_018124.3.
XP_005256078.1. XM_005256021.4.
XP_005256079.1. XM_005256022.4.
XP_011521493.1. XM_011523191.2.
XP_016878880.1. XM_017023391.1.
UniGeneiHs.567525.

Genome annotation databases

EnsembliENST00000361070; ENSP00000354361; ENSG00000168411.
ENST00000571750; ENSP00000460049; ENSG00000168411.
GeneIDi55159.
KEGGihsa:55159.
UCSCiuc002fda.4. human.

Keywords - Coding sequence diversityi

Polymorphism

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.

Entry informationi

Entry nameiRFWD3_HUMAN
AccessioniPrimary (citable) accession number: Q6PCD5
Secondary accession number(s): A8K585
, B2RE35, D3DUJ8, Q5XKR3, Q9H9Q3, Q9NVT4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: July 5, 2017
This is version 130 of the entry and version 3 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways