Rnf2 phospho S168
Function
E3 ubiquitin-protein ligase that mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub), thereby playing a central role in histone code and gene regulation (PubMed:15525528, PubMed:22325148, PubMed:28596365). H2AK119Ub gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals (PubMed:15525528, PubMed:28596365). May be involved in the initiation of both imprinted and random X inactivation (PubMed:15525528). Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:16710298, PubMed:22325148). PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility (PubMed:15525528, PubMed:16710298, PubMed:22325148). E3 ubiquitin-protein ligase activity is enhanced by BMI1/PCGF4 (PubMed:16710298). Acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity (PubMed:15525528, PubMed:16710298). Plays a role in the transcriptional repression of genes that are required for pluripotency in embryonic stem cells, thereby contributing to differentiation of the ectodermal and endodermal germ layers (PubMed:22226355). Association with the chromosomal DNA is cell-cycle dependent. In resting B- and T-lymphocytes, interaction with AURKB leads to block its activity, thereby maintaining transcription in resting lymphocytes (PubMed:24034696). Also acts as a negative regulator of autophagy by mediating ubiquitination of AMBRA1, leading to its subsequent degradation (PubMed:24980959).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Monoubiquitinated, by auto-ubiquitination (PubMed:16710298). Polyubiquitinated in the presence of UBE2D3 (in vitro) (By similarity).
Tissue Specificity
Expressed in embryonic stem cells.
Cellular localization
- Nucleus
- Cytoplasm
- Chromosome
- Enriched on inactive X chromosome (Xi) in female trophoblast stem (TS) cells as well as differentiating embryonic stem (ES) cells (PubMed:12183370). The enrichment on Xi is transient during TS and ES cell differentiation. The association with Xi is mitotically stable in non-differentiated TS cells (PubMed:12183370). Co-localizes with SAMD7 in nuclear polycomb bodies (PubMed:28900001).
Alternative names
DinG, Ring1b, Rnf2, E3 ubiquitin-protein ligase RING2, RING finger protein 1B, RING finger protein 2, RING-type E3 ubiquitin transferase RING2, RING1b