RNF8 Recombinant Rabbit Monoclonal Antibody [JE56-43]

Function

E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes '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. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases.

Background References

1. Ito K., Adachi S., Iwakami R., Yasuda H., Muto Y., Seki N., Okano Y. N-terminally extended human ubiquitin-conjugating enzymes (E2s) mediate the ubiquitination of RING-finger proteins, ARA54 and RNF8. Eur. J. Biochem. 268:2725-2732 (2001).

2. Takano Y., Adachi S., Okuno M., Muto Y., Yoshioka T., Matsushima-Nishiwaki R., Tsurumi H., Ito K., Friedman S.L., Moriwaki H., Kojima S., Okano Y. The RING finger protein, RNF8, interacts with retinoid X receptor alpha and enhances its transcription-stimulating activity. J. Biol. Chem. 279:18926-18934 (2004)

Subcellular Location

Chromosome, Cytoplasm, Nucleus, Telomere.

UNIPROT

SwissProt: O76064 Human

Synonyms