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Protein

E3 ubiquitin-protein ligase RNF168

Gene

Rnf168

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).UniRule annotation1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.UniRule annotation
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 fingeri16 – 55RING-typeUniRule annotationAdd BLAST40

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Ligase

Keywords - Biological processi

DNA damage, DNA repair, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-3108214. SUMOylation of DNA damage response and repair proteins.
R-MMU-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-MMU-5693571. Nonhomologous End-Joining (NHEJ).
R-MMU-5693607. Processing of DNA double-strand break ends.
R-MMU-69473. G2/M DNA damage checkpoint.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF168UniRule annotation (EC:6.3.2.-UniRule annotation)
Alternative name(s):
RING finger protein 168UniRule annotation
Gene namesi
Name:Rnf168UniRule annotation
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1917488. Rnf168.

Subcellular locationi

  • Nucleus UniRule annotation

  • Note: Localizes to double-strand breaks (DSBs) sites of DNA damage.UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002455971 – 565E3 ubiquitin-protein ligase RNF168Add BLAST565

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei70PhosphoserineCombined sources1
Modified residuei134PhosphoserineBy similarity1
Modified residuei197PhosphoserineBy similarity1
Modified residuei413PhosphoserineBy similarity1
Modified residuei414PhosphoserineBy similarity1
Modified residuei469PhosphoserineBy similarity1

Post-translational modificationi

Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks (DSBs).UniRule annotation
Ubiquitinated.UniRule annotation

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ80XJ2.
MaxQBiQ80XJ2.
PaxDbiQ80XJ2.
PRIDEiQ80XJ2.

PTM databases

iPTMnetiQ80XJ2.
PhosphoSitePlusiQ80XJ2.

Expressioni

Gene expression databases

BgeeiENSMUSG00000014074.
CleanExiMM_RNF168.
ExpressionAtlasiQ80XJ2. baseline and differential.
GenevisibleiQ80XJ2. MM.

Interactioni

Subunit structurei

Monomer. Interacts with UBE2N/UBC13.UniRule annotation

GO - Molecular functioni

Protein-protein interaction databases

BioGridi213933. 2 interactors.
STRINGi10090.ENSMUSP00000126484.

Structurei

3D structure databases

ProteinModelPortaliQ80XJ2.
SMRiQ80XJ2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi110 – 128LR motif 1UniRule annotationAdd BLAST19
Motifi143 – 151UMI motifUniRule annotation9
Motifi168 – 191MIU motif 1UniRule annotationAdd BLAST24
Motifi438 – 461MIU motif 2UniRule annotationAdd BLAST24
Motifi465 – 476LR motif 2UniRule annotationAdd BLAST12

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi96 – 177Glu-richUniRule annotationAdd BLAST82
Compositional biasi115 – 177Glu-richAdd BLAST63

Domaini

The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains. The UMI motif mediates interaction with ubiquitin with a preference for 'Lys-63'-linked ubiquitin. The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs).UniRule annotation

Sequence similaritiesi

Belongs to the RNF168 family.UniRule annotation
Contains 1 RING-type zinc finger.UniRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri16 – 55RING-typeUniRule annotationAdd BLAST40

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4159. Eukaryota.
COG2802. LUCA.
GeneTreeiENSGT00730000111120.
HOGENOMiHOG000154156.
HOVERGENiHBG067220.
InParanoidiQ80XJ2.
KOiK20779.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
HAMAPiMF_03066. RNF168. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q80XJ2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAPKTSIPS LAECQCGICM EILLEPVTLP CNHTLCNPCF QSTVEKANLC
60 70 80 90 100
CPFCRRRVSS WTRYHTRRNS LVNTDLWEII QKHYAKECKL RISGQESKEI
110 120 130 140 150
IDECQPVRRL SEPGELRREY EEEISRVEAE RQASKEEENK ASEEYIQRLL
160 170 180 190 200
AEEEEEEKRQ REKRRSEMEE QLRGDEELAR SLSTSINSNY ERNTLASPLS
210 220 230 240 250
SRKSDPVTNK SQKKNTSKQK TFGDIQKYLS PKLKPGTALA CKAELEEDIC
260 270 280 290 300
KSKETDRSDT KSPVLQDTEI EKNIPTLSPQ TCLETQEQGS ESSAGIPGPQ
310 320 330 340 350
LCVGDTKESL EGKVETVSTS PDDLCIVNDD GPRATVFYSN EAAVNSSSKI
360 370 380 390 400
ENEEYSVTGV PQLTGGNRVP TESRVYHLLV EEEISDRENQ ESVFEEVMDP
410 420 430 440 450
CFSAKRRKIF IESSSDQEET EVNFTQKLID LEHMLFERHK QEEQDRLLAL
460 470 480 490 500
QLQKEVDKEQ MVPNRQKGSP DQYQLRTPSP PDRLLNRQRK NSKDRNSLQQ
510 520 530 540 550
TNADHSKSPR NTKGDYWEPF KNTWKDSVNG TKMPTSTQDN CNVSKSAYTV
560
QHRKSQRSIV QMFQR
Length:565
Mass (Da):64,779
Last modified:March 24, 2009 - v3
Checksum:iF862617604CB1229
GO

Sequence cautioni

The sequence AAH46815 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH46815 differs from that shown. Reason: Erroneous termination at position 551. Translated as Gln.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC126265 Genomic DNA. No translation available.
BC046815 mRNA. Translation: AAH46815.1. Sequence problems.
RefSeqiNP_081631.2. NM_027355.2.
UniGeneiMm.228263.

Genome annotation databases

EnsembliENSMUST00000014218; ENSMUSP00000014218; ENSMUSG00000014074.
GeneIDi70238.
KEGGimmu:70238.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC126265 Genomic DNA. No translation available.
BC046815 mRNA. Translation: AAH46815.1. Sequence problems.
RefSeqiNP_081631.2. NM_027355.2.
UniGeneiMm.228263.

3D structure databases

ProteinModelPortaliQ80XJ2.
SMRiQ80XJ2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi213933. 2 interactors.
STRINGi10090.ENSMUSP00000126484.

PTM databases

iPTMnetiQ80XJ2.
PhosphoSitePlusiQ80XJ2.

Proteomic databases

EPDiQ80XJ2.
MaxQBiQ80XJ2.
PaxDbiQ80XJ2.
PRIDEiQ80XJ2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000014218; ENSMUSP00000014218; ENSMUSG00000014074.
GeneIDi70238.
KEGGimmu:70238.

Organism-specific databases

CTDi165918.
MGIiMGI:1917488. Rnf168.

Phylogenomic databases

eggNOGiKOG4159. Eukaryota.
COG2802. LUCA.
GeneTreeiENSGT00730000111120.
HOGENOMiHOG000154156.
HOVERGENiHBG067220.
InParanoidiQ80XJ2.
KOiK20779.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-3108214. SUMOylation of DNA damage response and repair proteins.
R-MMU-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-MMU-5693571. Nonhomologous End-Joining (NHEJ).
R-MMU-5693607. Processing of DNA double-strand break ends.
R-MMU-69473. G2/M DNA damage checkpoint.

Miscellaneous databases

PROiQ80XJ2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000014074.
CleanExiMM_RNF168.
ExpressionAtlasiQ80XJ2. baseline and differential.
GenevisibleiQ80XJ2. MM.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
HAMAPiMF_03066. RNF168. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRN168_MOUSE
AccessioniPrimary (citable) accession number: Q80XJ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: March 24, 2009
Last modified: November 30, 2016
This is version 122 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

According to a well-established model, RNF168 cannot initiate H2A 'Lys-63'-linked ubiquitination and is recruited following RNF8-dependent histone ubiquitination to amplify H2A 'Lys-63'-linked ubiquitination. However, other data suggest that RNF168 is the priming ubiquitin ligase by mediating monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub respectively). These data suggest that RNF168 might be recruited to DSBs sites in a RNF8-dependent manner by binding to non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is then amplified by RNF8. Additional evidences are however required to confirm these data.UniRule annotation

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.