E3 ubiquitin-protein ligase RNF8 (IPR017335)

Short name: RNF8

Overlapping homologous superfamilies


Family relationships



This entry represents E3 ubiquitin-protein ligase RNF8, which may be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. This enzyme promotes the formation of 'Lys-63'-linked polyubiquitin chains and functions with the specific ubiquitin-conjugating UBC13-MMS2 (UBE2N-UBE2V2) heterodimer [PMID: 18793138, PMID: 18202552]. Substrates that are poly-ubiquitinated at 'Lys-63' are usually not targeted for degradation. RNF8 acts following DNA double-strand break (DSB) formation, and is recruited to the sites of damage by ATM-phosphorylated MDC1, where it promotes the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF) [PMID: 16488448, PMID: 14976165]. It may play a role in the regulation of RXRA-mediated transcriptional activity, but is not involved in RXRA ubiquitination by UBE2E2.

Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1, IPR000011), a ubiquitin-conjugating enzyme (E2, IPR000608), and a ubiquitin ligase (E3, IPR000569, IPR003613), which work sequentially in a cascade. There are many different E3 ligases, which are responsible for the type of ubiquitin chain formed, the specificity of the target protein, and the regulation of the ubiquitinylation process [PMID: 12646216]. Ubiquitinylation is an important regulatory tool that controls the concentration of key signalling proteins, such as those involved in cell cycle control, as well as removing misfolded, damaged or mutant proteins that could be harmful to the cell. Several ubiquitin-like molecules have been discovered, such as Ufm1 (IPR005375), SUMO1 (IPR003653), NEDD8, Rad23 (IPR004806), Elongin B and Parkin (IPR003977), the latter being involved in Parkinson's disease [PMID: 15564047].

GO terms

Biological Process

GO:0006974 cellular response to DNA damage stimulus
GO:0006302 double-strand break repair
GO:0016567 protein ubiquitination

Molecular Function

GO:0004842 ubiquitin-protein transferase activity

Cellular Component

GO:0005634 nucleus

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.