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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).UniRule annotation

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.UniRule annotation

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

Keywordsi

Molecular functionChromatin regulator, Transferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF168UniRule annotation (EC:2.3.2.27UniRule annotation)
Alternative name(s):
RING finger protein 168UniRule annotation
RING-type E3 ubiquitin transferase RNF168
Gene namesi
Name:Rnf168UniRule annotation
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1585168. Rnf168.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003672821 – 564E3 ubiquitin-protein ligase RNF168Add BLAST564

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei70PhosphoserineBy similarity1
Modified residuei134PhosphoserineBy similarity1
Modified residuei197PhosphoserineCombined sources1
Cross-linki210Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei348PhosphothreonineCombined sources1
Modified residuei361PhosphothreonineCombined sources1
Modified residuei413PhosphoserineBy similarity1
Modified residuei414PhosphoserineBy similarity1
Modified residuei469PhosphoserineBy similarity1
Cross-linki524Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Post-translational modificationi

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

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiB2RYR0.
PRIDEiB2RYR0.

PTM databases

iPTMnetiB2RYR0.

Expressioni

Gene expression databases

GenevisibleiB2RYR0. RN.

Interactioni

Subunit structurei

Monomer. Interacts with UBE2N/UBC13.UniRule annotation

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000002395.

Structurei

3D structure databases

ProteinModelPortaliB2RYR0.
SMRiB2RYR0.
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 biasi115 – 177Glu-richUniRule annotationAdd 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

Zinc finger

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

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4159. Eukaryota.
COG2802. LUCA.
HOGENOMiHOG000154156.
HOVERGENiHBG067220.
InParanoidiB2RYR0.
KOiK20779.
OrthoDBiEOG091G0FWX.
PhylomeDBiB2RYR0.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
HAMAPiMF_03066. RNF168. 1 hit.
InterProiView protein in InterPro
IPR034725. RNF168.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
SMARTiView protein in SMART
SM00184. RING. 1 hit.
PROSITEiView protein in PROSITE
PS50089. ZF_RING_2. 1 hit.

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.

Similar proteinsi

Entry informationi

Entry nameiRN168_RAT
AccessioniPrimary (citable) accession number: B2RYR0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 24, 2009
Last sequence update: July 1, 2008
Last modified: September 27, 2017
This is version 78 of the entry and version 1 of the sequence. See 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families