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Protein

E3 ubiquitin-protein ligase RING2

Gene

RNF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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:15386022, PubMed:16359901, PubMed:25519132, PubMed:21772249, PubMed:25355358, PubMed:26151332). H2AK119Ub gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. May be involved in the initiation of both imprinted and random X inactivation (By similarity). 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:16359901, PubMed:26151332). PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility (PubMed:26151332). E3 ubiquitin-protein ligase activity is enhanced by BMI1/PCGF4 (PubMed:21772249). 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 (Probable). 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 (By similarity).By similarityCurated9 Publications

Miscellaneous

The hPRC-H complex purification reported by PubMed:12167701 probably presents a mixture of different PRC1-like complexes.

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.3 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.3 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri51 – 91RING-typePROSITE-ProRule annotationAdd BLAST41

GO - Molecular functioni

  • chromatin binding Source: MGI
  • RING-like zinc finger domain binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: Ensembl
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionRepressor, Transferase
Biological processTranscription, Transcription regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-3108214 SUMOylation of DNA damage response and repair proteins
R-HSA-3899300 SUMOylation of transcription cofactors
R-HSA-4551638 SUMOylation of chromatin organization proteins
R-HSA-4570464 SUMOylation of RNA binding proteins
R-HSA-4655427 SUMOylation of DNA methylation proteins
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-8943724 Regulation of PTEN gene transcription
R-HSA-8953750 Transcriptional Regulation by E2F6
SIGNORiQ99496
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RING2 (EC:2.3.2.273 Publications)
Alternative name(s):
Huntingtin-interacting protein 2-interacting protein 3
Short name:
HIP2-interacting protein 3
Protein DinG
RING finger protein 1B
Short name:
RING1b
RING finger protein 2
RING finger protein BAP-1
RING-type E3 ubiquitin transferase RING2Curated
Gene namesi
Name:RNF2
Synonyms:BAP1, DING, HIPI3, RING1B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000121481.10
HGNCiHGNC:10061 RNF2
MIMi608985 gene
neXtProtiNX_Q99496

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi41S → A or D: No effect on ubiquitin ligase activity on histone H2A. 1 Publication1
Mutagenesisi51C → W: Strong decrease in HIP2-binding; when associated with S-54. 1 Publication1
Mutagenesisi54C → S: Strong decrease in HIP2-binding; when associated with W-51. 1 Publication1
Mutagenesisi56D → K: Loss of ubiquitin ligase activity on histone H2A. 1 Publication1
Mutagenesisi69H → Y: Loss of HIP2-binding and loss of ubiquitin ligase activity on histone H2A. 2 Publications1
Mutagenesisi70R → C: Loss of ubiquitin ligase activity on histone H2A. 1 Publication1
Mutagenesisi81R → A: Decreases ubiquitin ligase activity on histone H2A. 1 Publication1
Mutagenesisi93K → A: Mildly decreases ubiquitin ligase activity on histone H2A. 1 Publication1
Mutagenesisi97 – 98KR → AA: Loss of ubiquitin ligase activity on histone H2A. 1 Publication2
Mutagenesisi97K → A: Strongly decreases ubiquitin ligase activity on histone H2A. 1 Publication1
Mutagenesisi98R → A: Nearly abolishes ubiquitin ligase activity on histone H2A. 1 Publication1
Mutagenesisi168S → E: Decreases ubiquitin ligase activity on histone H2A. 1 Publication1
Mutagenesisi247Y → A: Reduced interaction with CBX7. 1 Publication1
Mutagenesisi258H → A: Reduced interaction with CBX7. 1 Publication1
Mutagenesisi262Y → A: Reduced interaction with CBX7. 2 Publications1

Organism-specific databases

DisGeNETi6045
OpenTargetsiENSG00000121481
PharmGKBiPA34426

Polymorphism and mutation databases

BioMutaiRNF2
DMDMi62901044

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000560382 – 336E3 ubiquitin-protein ligase RING2Add BLAST335

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei41Phosphoserine1 Publication1
Cross-linki112Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei143PhosphoserineCombined sources1
Modified residuei168PhosphoserineCombined sources1 Publication1
Cross-linki249Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki323Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Polyubiquitinated in the presence of UBE2D3 (in vitro).1 Publication
Monoubiquitinated, by auto-ubiquitination.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99496
MaxQBiQ99496
PaxDbiQ99496
PeptideAtlasiQ99496
PRIDEiQ99496
ProteomicsDBi78297

PTM databases

iPTMnetiQ99496
PhosphoSitePlusiQ99496

Expressioni

Gene expression databases

BgeeiENSG00000121481 Expressed in 146 organ(s), highest expression level in kidney
CleanExiHS_BAP1
HS_RNF2
ExpressionAtlasiQ99496 baseline and differential
GenevisibleiQ99496 HS

Organism-specific databases

HPAiHPA026803

Interactioni

Subunit structurei

Component of chromatin-associated Polycomb (PcG) complexes. Component of a number of PRC1-like complexes; these complexes contain either the polycomb group ring finger protein PCGF1, or PCGF2, or PCGF3, or PCGF4, or PCGF5, or PCGF6 (PubMed:12167701, PubMed:15386022, PubMed:19636380, PubMed:21282530, PubMed:26687479, PubMed:26151332). 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 (PubMed:21772249, PubMed:25355358). The complex composed of RNF2, UB2D3 and BMI1 binds nucleosomes, and has activity only with nucleosomal histone H2A (PubMed:21772249). Part of a complex that contains PCGF5, RNF2 and UBE2D3 (PubMed:26151332). Part of a complex that contains AUTS2, PCGF5, RNF2, CSNK2B AND RYBP (PubMed:25519132). Interacts with RYBP, PCGF2, CBX4, CBX6, CBX7 and CBX8 (PubMed:19636380, PubMed:21282530, PubMed:19791798, PubMed:20696397). Interacts with RNF1/RING1, BMI1 and PHC2 (PubMed:15386022, PubMed:16714294). Interaction with RYBP and CBX7 is mutually exclusive; both compete for the same binding site on RNF2 (By similarity). Component of repressive BCOR complex containing a Polycomb group subcomplex at least composed of RYBP, PCGF1, BCOR and RING1 (PubMed:16943429). Interacts with CBX2 and PHC1. Interacts with CHTOP. Interacts with AURKB (By similarity). 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 (PubMed:12004135). 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 (PubMed:15960975). Interacts with RYBP, HIP2 and TFCP2 (PubMed:11513855, PubMed:11865070, PubMed:20696397).By similarity16 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111972, 736 interactors
CORUMiQ99496
DIPiDIP-40034N
IntActiQ99496, 96 interactors
MINTiQ99496
STRINGi9606.ENSP00000356480

Structurei

Secondary structure

1336
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ99496
SMRiQ99496
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99496

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 179Interaction with HIP21 PublicationAdd BLAST178
Regioni93 – 98Interaction with nucleosomes via an acidic patch on histone H2A and histone H2B1 Publication6

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri51 – 91RING-typePROSITE-ProRule annotationAdd BLAST41

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0311 Eukaryota
ENOG410XQ5G LUCA
GeneTreeiENSGT00390000016977
HOGENOMiHOG000273917
HOVERGENiHBG079942
InParanoidiQ99496
KOiK10695
OMAiFNQTQSQ
OrthoDBiEOG091G06VO
PhylomeDBiQ99496
TreeFamiTF105501

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR039642 E3_Ub_ligase/polycomb_RING
IPR032443 RAWUL
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR10825 PTHR10825, 1 hit
PfamiView protein in Pfam
PF16207 RAWUL, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q99496-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSQAVQTNGT QPLSKTWELS LYELQRTPQE AITDGLEIVV SPRSLHSELM
60 70 80 90 100
CPICLDMLKN TMTTKECLHR FCADCIITAL RSGNKECPTC RKKLVSKRSL
110 120 130 140 150
RPDPNFDALI SKIYPSRDEY EAHQERVLAR INKHNNQQAL SHSIEEGLKI
160 170 180 190 200
QAMNRLQRGK KQQIENGSGA EDNGDSSHCS NASTHSNQEA GPSNKRTKTS
210 220 230 240 250
DDSGLELDNN NAAMAIDPVM DGASEIELVF RPHPTLMEKD DSAQTRYIKT
260 270 280 290 300
SGNATVDHLS KYLAVRLALE ELRSKGESNQ MNLDTASEKQ YTIYIATASG
310 320 330
QFTVLNGSFS LELVSEKYWK VNKPMELYYA PTKEHK
Length:336
Mass (Da):37,655
Last modified:May 1, 1997 - v1
Checksum:i90EA546E1F4DB7EC
GO
Isoform 2 (identifier: Q99496-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     84-155: Missing.

Note: No experimental confirmation available.
Show »
Length:264
Mass (Da):29,258
Checksum:i332219DF283B16C8
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
X6RFN3X6RFN3_HUMAN
E3 ubiquitin-protein ligase RING2
RNF2
245Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05543984 – 155Missing in isoform 2. 1 PublicationAdd BLAST72

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10571 mRNA Translation: CAA71596.1
AF141327 mRNA Translation: AAD29717.1
AK091574 mRNA Translation: BAG52383.1
AK314793 mRNA Translation: BAG37324.1
AL109865 Genomic DNA No translation available.
CH471067 Genomic DNA Translation: EAW91187.1
CH471067 Genomic DNA Translation: EAW91188.1
BC012583 mRNA Translation: AAH12583.1
CCDSiCCDS1365.1 [Q99496-1]
RefSeqiNP_009143.1, NM_007212.3 [Q99496-1]
XP_011508153.1, XM_011509851.2 [Q99496-1]
XP_011508154.1, XM_011509852.2 [Q99496-1]
UniGeneiHs.591490

Genome annotation databases

EnsembliENST00000367509; ENSP00000356479; ENSG00000121481 [Q99496-2]
ENST00000367510; ENSP00000356480; ENSG00000121481 [Q99496-1]
GeneIDi6045
KEGGihsa:6045
UCSCiuc001grc.2 human [Q99496-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10571 mRNA Translation: CAA71596.1
AF141327 mRNA Translation: AAD29717.1
AK091574 mRNA Translation: BAG52383.1
AK314793 mRNA Translation: BAG37324.1
AL109865 Genomic DNA No translation available.
CH471067 Genomic DNA Translation: EAW91187.1
CH471067 Genomic DNA Translation: EAW91188.1
BC012583 mRNA Translation: AAH12583.1
CCDSiCCDS1365.1 [Q99496-1]
RefSeqiNP_009143.1, NM_007212.3 [Q99496-1]
XP_011508153.1, XM_011509851.2 [Q99496-1]
XP_011508154.1, XM_011509852.2 [Q99496-1]
UniGeneiHs.591490

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H0DX-ray2.50B15-114[»]
3GS2X-ray1.70A/C223-333[»]
3H8HX-ray2.00A220-330[»]
3IXSX-ray1.70A/C/E/G/I/K223-333[»]
3RPGX-ray2.65C1-116[»]
4R8PX-ray3.28L/N2-116[»]
4S3OX-ray2.00B/E1-116[»]
ProteinModelPortaliQ99496
SMRiQ99496
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111972, 736 interactors
CORUMiQ99496
DIPiDIP-40034N
IntActiQ99496, 96 interactors
MINTiQ99496
STRINGi9606.ENSP00000356480

PTM databases

iPTMnetiQ99496
PhosphoSitePlusiQ99496

Polymorphism and mutation databases

BioMutaiRNF2
DMDMi62901044

Proteomic databases

EPDiQ99496
MaxQBiQ99496
PaxDbiQ99496
PeptideAtlasiQ99496
PRIDEiQ99496
ProteomicsDBi78297

Protocols and materials databases

DNASUi6045
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000367509; ENSP00000356479; ENSG00000121481 [Q99496-2]
ENST00000367510; ENSP00000356480; ENSG00000121481 [Q99496-1]
GeneIDi6045
KEGGihsa:6045
UCSCiuc001grc.2 human [Q99496-1]

Organism-specific databases

CTDi6045
DisGeNETi6045
EuPathDBiHostDB:ENSG00000121481.10
GeneCardsiRNF2
HGNCiHGNC:10061 RNF2
HPAiHPA026803
MIMi608985 gene
neXtProtiNX_Q99496
OpenTargetsiENSG00000121481
PharmGKBiPA34426
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0311 Eukaryota
ENOG410XQ5G LUCA
GeneTreeiENSGT00390000016977
HOGENOMiHOG000273917
HOVERGENiHBG079942
InParanoidiQ99496
KOiK10695
OMAiFNQTQSQ
OrthoDBiEOG091G06VO
PhylomeDBiQ99496
TreeFamiTF105501

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-3108214 SUMOylation of DNA damage response and repair proteins
R-HSA-3899300 SUMOylation of transcription cofactors
R-HSA-4551638 SUMOylation of chromatin organization proteins
R-HSA-4570464 SUMOylation of RNA binding proteins
R-HSA-4655427 SUMOylation of DNA methylation proteins
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-8943724 Regulation of PTEN gene transcription
R-HSA-8953750 Transcriptional Regulation by E2F6
SIGNORiQ99496

Miscellaneous databases

EvolutionaryTraceiQ99496
GeneWikiiRNF2
GenomeRNAii6045
PROiPR:Q99496
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121481 Expressed in 146 organ(s), highest expression level in kidney
CleanExiHS_BAP1
HS_RNF2
ExpressionAtlasiQ99496 baseline and differential
GenevisibleiQ99496 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR039642 E3_Ub_ligase/polycomb_RING
IPR032443 RAWUL
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR10825 PTHR10825, 1 hit
PfamiView protein in Pfam
PF16207 RAWUL, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRING2_HUMAN
AccessioniPrimary (citable) accession number: Q99496
Secondary accession number(s): B2RBS7
, B3KRH1, Q5TEN1, Q5TEN2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: May 1, 1997
Last modified: November 7, 2018
This is version 183 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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