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HAMAP rule MF_03066

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General rule information [?]

Accession MF_03066
Dates 5-MAR-2009 (Created)
1-MAR-2024 (Last updated, Version 6)
Name RNF168
Scope(s) Eukaryota
Vertebrata
Template(s) Q8IYW5 (RN168_HUMAN); [ Recover all ]
Triggered by HAMAP; MF_03066 (Get profile general information and statistics)

Propagated annotation [?]

Identifier, protein and gene names [?]

Identifier RN168
case <OC:Mammalia>
Protein name RecName: Full=E3 ubiquitin-protein ligase RNF168;
                 EC=2.3.2.27;
AltName: Full=RING finger protein 168;
AltName: Full=RING-type E3 ubiquitin transferase RNF168;
else
Protein name RecName: Full=E3 ubiquitin-protein ligase ;
                 EC=2.3.2.27;
AltName: Full=RING finger protein 168;
AltName: Full=RING-type E3 ubiquitin transferase ;
end case
Gene name Name=RNF168;

Comments [?]

case <OC:Mammalia>
FUNCTIONE3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with @gn(UBE2N)/@gn(UBC13) to amplify the @gn(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 @gn(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 @gn(TP53BP1) and @gn(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 @gn(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 @gn(JMJD2A)/@gn(KDM4A) in collaboration with @gn(RNF8), leading to unmask H4K20me2 mark and promote the recruitment of @gn(TP53BP1) at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the @gn(UBE2N)/@gn(UBC13)- binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).
SUBUNITMonomer. Interacts with UBE2N/UBC13.
else
FUNCTIONE3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with @gn(UBE2N)/@gn(UBC13) to amplify the @gn(RNF8)-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and ubiquitinates histone H2A and H2AX, leading to amplify the @gn(RNF8)-dependent H2A ubiquitination and 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 @gn(TP53BP1) and @gn(BRCA1). Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).
SUBUNITMonomer.
end case
CATALYTIC ACTIVITY Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;
PATHWAYProtein modification; protein ubiquitination.
SUBCELLULAR LOCATIONNucleus. Note=Localizes to double-strand breaks (DSBs) sites of DNA damage.
DOMAINThe 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).
case <OC:Mammalia>
PTMSumoylated with @gn(SUMO1) by @gn(PIAS4) in response to double- strand breaks (DSBs).
PTMUbiquitinated.
CAUTIONAccording to a well-established model, @gn(RNF168) cannot initiate H2A 'Lys-63'-linked ubiquitination and is recruited following @gn(RNF8)-dependent histone ubiquitination to amplify H2A 'Lys-63'- linked ubiquitination. However, other data suggest that @gn(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 @gn(RNF168) might be recruited to DSBs sites in a @gn(RNF8)-dependent manner by binding to non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is then amplified by @gn(RNF8). Additional evidences are however required to confirm these data.
end case
SIMILARITYBelongs to the RNF168 family.

Keywords [?]


Gene Ontology [?]

GO:0003682; Molecular function:chromatin binding
GO:0042393; Molecular function:histone binding
GO:0043130; Molecular function:ubiquitin binding
GO:0004842; Molecular function:ubiquitin-protein transferase activity
GO:0045739; Biological process:positive regulation of DNA repair
GO:0010212; Biological process:response to ionizing radiation
GO:0006302; Biological process:double-strand break repair
GO:0000151; Cellular component:ubiquitin ligase complex
GO:0005634; Cellular component:nucleus

Cross-references [?]

PROSITE PS00518; ZF_RING_1; 1;
PROSITE PS50089; ZF_RING_2; 1;
PROSITE PS50313; GLU_RICH; 0-unlimited;

Features [?]

From: RN168_HUMAN (Q8IYW5)
Key From To Description Tag Condition FTGroup
MOTIF 110 128 /note="LR motif 1" [ILV]-[SC]-[KQE]-P-G-E-[ILV]-R-[RQK]-E-Y-E-x-[EQ]-[ILV]-x-[RK]-x(2)
MOTIF 143 151 /note="UMI motif" E-[EDQ]-Y-I-[RQ]-[RK]-L-L-A
MOTIF 168 191 /note="MIU motif 1" x-E-[EKQR]-Q-[LM]-[KRLE]-x-D-E-x-L-A-[RW]-x-[LIV]-S-x-[DSNKEQ]-[LMI]-[DN]-x(1,4)
MOTIF 439 462 /note="MIU motif 2" R-[RHYWQ]-[RKQ]-Q-E-[EK]-[QHED]-D-[RH]-x-[LF]-A-L-[QER]-[LI]-Q-[RKE]-[EQ]-x-[DNEK]-[KQR]-[ER]-x(2)
MOTIF 466 477 /note="LR motif 2" R-x-[KN]-G-S-x(3)-Y-x-L-R

Additional information [?]

Size range 422-577 amino acids
Related rules None
Fusion Nter: None Cter: None



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