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Protein

E3 ubiquitin-protein ligase RNF168

Gene

Rnf168

Organism
Rattus norvegicus (Rat)
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) (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 fingeri16 – 5540RING-typePROSITE-ProRule annotationAdd
BLAST

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

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF168 (EC:6.3.2.-)
Alternative name(s):
RING finger protein 168
Gene namesi
Name:Rnf168
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1585168. Rnf168.

Subcellular locationi

  • Nucleus By similarity

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 564564E3 ubiquitin-protein ligase RNF168PRO_0000367282Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei70 – 701PhosphoserineBy similarity
Modified residuei134 – 1341PhosphoserineBy similarity
Modified residuei197 – 1971PhosphoserineCombined sources
Modified residuei348 – 3481PhosphothreonineCombined sources
Modified residuei361 – 3611PhosphothreonineCombined sources
Modified residuei413 – 4131PhosphoserineBy similarity
Modified residuei414 – 4141PhosphoserineBy similarity
Modified residuei469 – 4691PhosphoserineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiB2RYR0.
PRIDEiB2RYR0.

PTM databases

iPTMnetiB2RYR0.

Expressioni

Gene expression databases

BgeeiENSRNOG00000043345.
GenevisibleiB2RYR0. RN.

Interactioni

Subunit structurei

Monomer. Interacts with UBE2N/UBC13 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000002395.

Structurei

3D structure databases

ProteinModelPortaliB2RYR0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi110 – 12819LR motif 1Add
BLAST
Motifi143 – 1519UMI motif
Motifi168 – 19124MIU motif 1Add
BLAST
Motifi438 – 46124MIU motif 2Add
BLAST
Motifi465 – 47612LR motif 2Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi115 – 17763Glu-richAdd
BLAST

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) (By similarity).By similarity

Sequence similaritiesi

Belongs to the RNF168 family.Curated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri16 – 5540RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4159. Eukaryota.
COG2802. LUCA.
HOGENOMiHOG000154156.
HOVERGENiHBG067220.
InParanoidiB2RYR0.
OrthoDBiEOG091G0FWX.
PhylomeDBiB2RYR0.

Family and domain databases

Gene3Di3.30.40.10. 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.

B2RYR0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAPKNSIPS LAECQCGICM EILVEPVTLP CNHTLCNPCF QSTVEKANLC
60 70 80 90 100
CPFCRRRVSS WTRYHTRRNS LVNTDLWEII QKHYAKECKL RISGQESKEI
110 120 130 140 150
VDEYQPVRLL SKPGELRREY EEEISKVEAE RQASKEEENK ASEEYIQRLL
160 170 180 190 200
AEEEEEEKRR TERRRSEMEE QLRGDEELAR RLSTSINSNY ERNILASPLS
210 220 230 240 250
SRKSDPVTNK SQKKNTNKQK NFGDIQRYLS PKSKPGTAWA CKTEHGEDMC
260 270 280 290 300
KSKETDSSDT KSPVLQDTDV EESMPTHSPQ TCPETQGQGP EPLTEMPVPW
310 320 330 340 350
LCARNAEQCL EGKAEAVSTN PDDSCIVNDG GPRAIVSNSK EAAVKPPTKI
360 370 380 390 400
ENEEYSVSGV TQLTGGNGVP TESRVYDLLV GKEISERENQ ESVFEEVMDP
410 420 430 440 450
CFSAKRRKIF ITSSLDQEET EVNFTQKLID LEHMLFERHK QEEQDRLLAL
460 470 480 490 500
QLQKEADKEK MVPNRQKGSP DQYQLRTSSP PDGLLNGQRK NVKDRNSPKQ
510 520 530 540 550
TADRSKSQRS RKGEYWETFE STWKGSVNGT KMPTPRKDSC NVSKRACPLQ
560
HRSAQKSILQ MFQR
Length:564
Mass (Da):64,404
Last modified:July 1, 2008 - v1
Checksum:i4975BF9E08445E71
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC166869 mRNA. Translation: AAI66869.1.
RefSeqiNP_001121069.2. NM_001127597.2.
UniGeneiRn.101441.

Genome annotation databases

GeneIDi690043.
KEGGirno:690043.
UCSCiRGD:1585168. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC166869 mRNA. Translation: AAI66869.1.
RefSeqiNP_001121069.2. NM_001127597.2.
UniGeneiRn.101441.

3D structure databases

ProteinModelPortaliB2RYR0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000002395.

PTM databases

iPTMnetiB2RYR0.

Proteomic databases

PaxDbiB2RYR0.
PRIDEiB2RYR0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi690043.
KEGGirno:690043.
UCSCiRGD:1585168. rat.

Organism-specific databases

CTDi165918.
RGDi1585168. Rnf168.

Phylogenomic databases

eggNOGiKOG4159. Eukaryota.
COG2802. LUCA.
HOGENOMiHOG000154156.
HOVERGENiHBG067220.
InParanoidiB2RYR0.
OrthoDBiEOG091G0FWX.
PhylomeDBiB2RYR0.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

PROiB2RYR0.

Gene expression databases

BgeeiENSRNOG00000043345.
GenevisibleiB2RYR0. RN.

Family and domain databases

Gene3Di3.30.40.10. 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_RAT
AccessioniPrimary (citable) accession number: B2RYR0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 24, 2009
Last sequence update: July 1, 2008
Last modified: September 7, 2016
This is version 69 of the entry and version 1 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.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. 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.