RNF168 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). Belongs to the RNF168 family. Note: This description may include information from UniProtKB.
Protein type: EC 6.3.2.-; Ubiquitin conjugating system; Ubiquitin ligase
Chromosomal Location of human Ortholog: 3q29
Cellular Component:  cytosol; nucleoplasm; nucleus; protein-containing complex; site of double-strand break; ubiquitin ligase complex
Molecular Function:  chromatin binding; histone binding; histone H2AK15 ubiquitin ligase activity; histone ubiquitin ligase activity; K63-linked polyubiquitin modification-dependent protein binding; metal ion binding; nucleosome binding; protein binding; ubiquitin binding; ubiquitin-protein transferase activity
Biological Process:  DNA damage response; DNA repair-dependent chromatin remodeling; double-strand break repair; double-strand break repair via nonhomologous end joining; epigenetic regulation of gene expression; histone H2A-K15 ubiquitination; interstrand cross-link repair; isotype switching; negative regulation of transcription elongation by RNA polymerase II; positive regulation of DNA repair; protein K63-linked ubiquitination; protein ubiquitination; response to ionizing radiation; ubiquitin-dependent protein catabolic process
Disease: Riddle Syndrome
Reference #:  Q8IYW5 (UniProtKB)
Alt. Names/Synonyms: E3 ubiquitin-protein ligase RNF168; FLJ35794; hRNF168; RIDL; RING finger protein 168; ring finger protein 168, E3 ubiquitin protein ligase; RING-type E3 ubiquitin transferase RNF168; RN168; RNF168
Gene Symbols: RNF168
Molecular weight: 65,020 Da
Basal Isoelectric point: 8.26  Predict pI for various phosphorylation states
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Protein Structure Not Found.

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