Summary

Name RNF168
Full Name E3 ubiquitin-protein ligase RNF168
Synonyms hRNF168, RING finger protein 168
Primary ID Q8IYW5
Links - -
Type protein
Relations 11
Function 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/C1orf86 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).

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Modifications Tables

Relations

Regulator Mechanism target score
+ img/unknown.png ubiquitination H2AX 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png binding RNF168 0.249
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png ubiquitination RNF168 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png polyubiquitination H1-2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding RNF168 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding RNF168 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity img/direct-activation.png ubiquitination Histone H2A 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png ubiquitination RNF168 0.457
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png DNA_repair 0.7
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png ubiquitination RNF168 0.482
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png ubiquitination BLM 0.266
Publications: 1 Organism: Homo Sapiens