Q9CQJ4 · RING2_MOUSE
- ProteinE3 ubiquitin-protein ligase RING2
- GeneRnf2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids336 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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).
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).
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | euchromatin | |
Cellular Component | heterochromatin | |
Cellular Component | MLL1 complex | |
Cellular Component | nuclear body | |
Cellular Component | nucleus | |
Cellular Component | PcG protein complex | |
Cellular Component | PRC1 complex | |
Cellular Component | sex chromatin | |
Cellular Component | ubiquitin ligase complex | |
Molecular Function | chromatin binding | |
Molecular Function | histone H2AK119 ubiquitin ligase activity | |
Molecular Function | RING-like zinc finger domain binding | |
Molecular Function | ubiquitin protein ligase activity | |
Molecular Function | zinc ion binding | |
Biological Process | anterior/posterior axis specification | |
Biological Process | chromatin organization | |
Biological Process | epigenetic regulation of gene expression | |
Biological Process | gastrulation with mouth forming second | |
Biological Process | gene expression | |
Biological Process | germ cell development | |
Biological Process | mitotic cell cycle | |
Biological Process | negative regulation of transcription by RNA polymerase II | |
Biological Process | protein ubiquitination |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase RING2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9CQJ4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: 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).
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).
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 69 | Loss of ubiquitin ligase activity. | ||||
Sequence: H → Y |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 23 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylserine | ||||
Sequence: S | ||||||
Chain | PRO_0000056039 | 2-336 | E3 ubiquitin-protein ligase RING2 | |||
Sequence: SQAVQTNGTQPLSKTWELSLYELQRTPQEAITDGLEIVVSPRSLHSELMCPICLDMLKNTMTTKECLHRFCADCIITALRSGNKECPTCRKKLVSKRSLRPDPNFDALISKIYPSRDEYEAHQERVLARINKHNNQQALSHSIEEGLKIQAMNRLQRGKKQQIENGSGAEDNGDSSHCSNASTHSNQEAGPSNKRTKTSDDSGLELDNNNAAVAIDPVMDGASEIELVFRPHPTLMEKDDSAQTRYIKTSGNATVDHLSKYLAVRLALEELRSKGESNQMNLDTASEKQYTIYIATASGQFTVLNGSFSLELVSEKYWKVNKPMELYYAPTKEHK | ||||||
Modified residue | 41 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 112 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 143 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 168 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 249 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 323 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K |
Post-translational modification
Monoubiquitinated, by auto-ubiquitination (PubMed:16710298).
Polyubiquitinated in the presence of UBE2D3 (in vitro) (By similarity).
Polyubiquitinated in the presence of UBE2D3 (in vitro) (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Component of chromatin-associated Polycomb (PcG) complexes (PubMed:22325148).
Component of a number of PRC1-like complexes; these complexes contain either the polycomb group ring finger protein PCGF1, or PCGF2, or PCGF3, or BMI1, or PCGF5, or PCGF6 (PubMed:16710298, PubMed:28596365).
Distinct PRC1-like complexes are composed of a RING1 subunit (RING1B or RING1A), one of the six PCGF proteins (PCGF1, PCGF2, PCGF3, BMI1, PCGF5 or PCGF6), one PHC protein (PHC1, PHC2 or PHC3) and one of the CBX proteins (CBX2, CBX4, CBX6, CBX7 or CBX8) (Probable). Part of a complex that contains RNF2, UB2D3 and BMI1; within that complex RNF2 and BMI1 form a tight heterodimer, where UB2D3 interacts only with RNF2. The complex composed of RNF2, UB2D3 and BMI1 binds nucleosomes, and has activity only with nucleosomal histone H2A (By similarity).
Part of a complex that contains PCGF5, RNF2 and UBE2D3. Part of a complex that contains AUTS2, PCGF5, RNF2, CSNK2B and RYBP (By similarity).
Interacts with CBX6 and CBX8 (By similarity).
Interacts with PHC1, PCGF2, RYBP, CBX7, CBX4, CBX2, RNF1/RING1, BMI1 and PHC2 (PubMed:10369680, PubMed:12183370, PubMed:16024804, PubMed:16710298, PubMed:19170609, PubMed:22226355, PubMed:22325148, PubMed:9312051).
Interaction with RYBP and CBX7 is mutually exclusive; both compete for the same binding site on RNF2 (PubMed:22325148).
Component of repressive BCOR complex containing a Polycomb group subcomplex at least composed of RYBP, PCGF1, BCOR and RING1 (By similarity).
Interacts with CBX2 and PHC1 (PubMed:22226355).
Interacts with CHTOP (PubMed:22872859).
Interacts with AURKB (PubMed:24034696).
Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RNF1/RING1, RNF2/RING2, MBLR, L3MBTL2 and YAF2 (By similarity).
Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with RYBP, HIP2 and TFCP2 (By similarity).
Interacts with NUPR1 (By similarity).
Interacts with SAMD7 in a PHC2-dependent manner (PubMed:28900001).
Component of a number of PRC1-like complexes; these complexes contain either the polycomb group ring finger protein PCGF1, or PCGF2, or PCGF3, or BMI1, or PCGF5, or PCGF6 (PubMed:16710298, PubMed:28596365).
Distinct PRC1-like complexes are composed of a RING1 subunit (RING1B or RING1A), one of the six PCGF proteins (PCGF1, PCGF2, PCGF3, BMI1, PCGF5 or PCGF6), one PHC protein (PHC1, PHC2 or PHC3) and one of the CBX proteins (CBX2, CBX4, CBX6, CBX7 or CBX8) (Probable). Part of a complex that contains RNF2, UB2D3 and BMI1; within that complex RNF2 and BMI1 form a tight heterodimer, where UB2D3 interacts only with RNF2. The complex composed of RNF2, UB2D3 and BMI1 binds nucleosomes, and has activity only with nucleosomal histone H2A (By similarity).
Part of a complex that contains PCGF5, RNF2 and UBE2D3. Part of a complex that contains AUTS2, PCGF5, RNF2, CSNK2B and RYBP (By similarity).
Interacts with CBX6 and CBX8 (By similarity).
Interacts with PHC1, PCGF2, RYBP, CBX7, CBX4, CBX2, RNF1/RING1, BMI1 and PHC2 (PubMed:10369680, PubMed:12183370, PubMed:16024804, PubMed:16710298, PubMed:19170609, PubMed:22226355, PubMed:22325148, PubMed:9312051).
Interaction with RYBP and CBX7 is mutually exclusive; both compete for the same binding site on RNF2 (PubMed:22325148).
Component of repressive BCOR complex containing a Polycomb group subcomplex at least composed of RYBP, PCGF1, BCOR and RING1 (By similarity).
Interacts with CBX2 and PHC1 (PubMed:22226355).
Interacts with CHTOP (PubMed:22872859).
Interacts with AURKB (PubMed:24034696).
Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RNF1/RING1, RNF2/RING2, MBLR, L3MBTL2 and YAF2 (By similarity).
Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with RYBP, HIP2 and TFCP2 (By similarity).
Interacts with NUPR1 (By similarity).
Interacts with SAMD7 in a PHC2-dependent manner (PubMed:28900001).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9CQJ4 | Auts2 A0A087WPF7 | 2 | EBI-927321, EBI-27122375 | |
BINARY | Q9CQJ4 | Bmi1 P25916 | 17 | EBI-927321, EBI-927401 | |
BINARY | Q9CQJ4 | Cbx8 Q9QXV1 | 5 | EBI-927321, EBI-1216641 | |
BINARY | Q9CQJ4 | Csnk2a1 Q61177 | 4 | EBI-927321, EBI-1216438 | |
BINARY | Q9CQJ4 | Kdm1a Q6ZQ88 | 3 | EBI-927321, EBI-1216284 | |
BINARY | Q9CQJ4 | Kdm2b Q6P1G2 | 4 | EBI-927321, EBI-1216214 | |
BINARY | Q9CQJ4 | Pcgf2 P23798 | 15 | EBI-927321, EBI-926857 | |
BINARY | Q9CQJ4 | Phc1 Q64028 | 7 | EBI-927321, EBI-927346 | |
BINARY | Q9CQJ4 | Phc2 Q9QWH1 | 7 | EBI-927321, EBI-642357 | |
BINARY | Q9CQJ4 | Ring1 O35730 | 3 | EBI-927321, EBI-929310 | |
BINARY | Q9CQJ4 | Rybp Q8CCI5 | 8 | EBI-927321, EBI-929290 | |
BINARY | Q9CQJ4 | Skp1 Q9WTX5 | 4 | EBI-927321, EBI-1202363 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, zinc finger, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-179 | Interaction with HIP2 | ||||
Sequence: SQAVQTNGTQPLSKTWELSLYELQRTPQEAITDGLEIVVSPRSLHSELMCPICLDMLKNTMTTKECLHRFCADCIITALRSGNKECPTCRKKLVSKRSLRPDPNFDALISKIYPSRDEYEAHQERVLARINKHNNQQALSHSIEEGLKIQAMNRLQRGKKQQIENGSGAEDNGDSSHC | ||||||
Zinc finger | 51-91 | RING-type | ||||
Sequence: CPICLDMLKNTMTTKECLHRFCADCIITALRSGNKECPTCR | ||||||
Region | 93-98 | Interaction with nucleosomes via an acidic patch on histone H2A and histone H2B | ||||
Sequence: KLVSKR | ||||||
Compositional bias | 157-194 | Polar residues | ||||
Sequence: QRGKKQQIENGSGAEDNGDSSHCSNASTHSNQEAGPSN | ||||||
Region | 157-206 | Disordered | ||||
Sequence: QRGKKQQIENGSGAEDNGDSSHCSNASTHSNQEAGPSNKRTKTSDDSGLE |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length336
- Mass (Da)37,623
- Last updated2001-06-01 v1
- Checksum84BA5B3E044DB7EC
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A087WP87 | A0A087WP87_MOUSE | Rnf2 | 211 | ||
A0A087WQQ3 | A0A087WQQ3_MOUSE | Rnf2 | 73 | ||
A0A087WRE9 | A0A087WRE9_MOUSE | Rnf2 | 264 |
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 157-194 | Polar residues | ||||
Sequence: QRGKKQQIENGSGAEDNGDSSHCSNASTHSNQEAGPSN | ||||||
Sequence conflict | 253 | in Ref. 2; BAC41075 | ||||
Sequence: N → H | ||||||
Sequence conflict | 299 | in Ref. 2; BAC41075 | ||||
Sequence: S → T | ||||||
Sequence conflict | 304 | in Ref. 2; BAC41075 | ||||
Sequence: V → L | ||||||
Sequence conflict | 332-336 | in Ref. 1; CAA73380 | ||||
Sequence: TKEHK → FTASGNVR |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Y12880 EMBL· GenBank· DDBJ | CAA73380.1 EMBL· GenBank· DDBJ | mRNA | ||
Y12783 EMBL· GenBank· DDBJ | CAA73321.1 EMBL· GenBank· DDBJ | mRNA | ||
AK145767 EMBL· GenBank· DDBJ | BAE26638.1 EMBL· GenBank· DDBJ | mRNA | ||
AK012358 EMBL· GenBank· DDBJ | BAB28186.1 EMBL· GenBank· DDBJ | mRNA | ||
AK013124 EMBL· GenBank· DDBJ | BAB28663.1 EMBL· GenBank· DDBJ | mRNA | ||
AK030319 EMBL· GenBank· DDBJ | BAC26898.1 EMBL· GenBank· DDBJ | mRNA | ||
AK090066 EMBL· GenBank· DDBJ | BAC41075.1 EMBL· GenBank· DDBJ | mRNA | ||
CT010297 EMBL· GenBank· DDBJ | CAJ18505.1 EMBL· GenBank· DDBJ | mRNA | ||
BC020122 EMBL· GenBank· DDBJ | AAH20122.1 EMBL· GenBank· DDBJ | mRNA |