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Protein

E3 ubiquitin-protein ligase RING2

Gene

RNF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. 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. 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. PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. E3 ubiquitin-protein ligase activity is enhanced by BMI1/PCGF4. 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. In resting B- and T-lymphocytes, interaction with AURKB leads to block its activity, thereby maintaining transcription in resting lymphocytes.5 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
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
  • ligase activity Source: UniProtKB-KW
  • RING-like zinc finger domain binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: Ensembl
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000121481-MONOMER.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
R-HSA-4570464. SUMOylation of RNA binding proteins.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RING2 (EC:6.3.2.-)
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
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

HGNCiHGNC:10061. RNF2.

Subcellular locationi

  • Nucleus 1 Publication
  • Chromosome By similarity

  • Note: Enriched on inactive X chromosome (Xi) in female trophoblast stem (TS) cells as well as differentiating embryonic stem (ES) cells. The enrichment on Xi is transient during TS and ES cell differentiation. The association with Xi is mitotically stable in non-differentiated TS cells (By similarity).By similarity

GO - Cellular componenti

  • euchromatin Source: Ensembl
  • MLL1 complex Source: UniProtKB
  • nuclear body Source: Ensembl
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • PcG protein complex Source: UniProtKB
  • PRC1 complex Source: UniProtKB
  • sex chromatin Source: Ensembl
  • ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
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
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
Cross-linki112Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei143PhosphoserineCombined sources1
Modified residuei168PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99496.
MaxQBiQ99496.
PaxDbiQ99496.
PeptideAtlasiQ99496.
PRIDEiQ99496.

PTM databases

iPTMnetiQ99496.
PhosphoSitePlusiQ99496.

Expressioni

Gene expression databases

BgeeiENSG00000121481.
CleanExiHS_BAP1.
HS_RNF2.
ExpressionAtlasiQ99496. baseline and differential.
GenevisibleiQ99496. HS.

Organism-specific databases

HPAiHPA026803.

Interactioni

Subunit structurei

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. Component of a PRC1-like complex. 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. Association to the chromosomal DNA is cell-cycle dependent. Component of repressive BCOR complex containing Polycomb group subcomplex at least composed of RYBP, PCGF1, BCOR and RING1. Component of chromatin-associated Polycomb (PcG) complexes. Interacts with RYBP, PCGF2, CBX4, CBX6, CBX7 and CBX8. Interacts with RNF1/RING1, BMI1 and PHC2. Interacts with PCGF1 (PubMed:26687479).By similarity12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ABCB1P081832EBI-722416,EBI-1057359
BMI1P3522612EBI-722416,EBI-2341576
CBX4O002575EBI-722416,EBI-722425
CBX4O00257-32EBI-722416,EBI-4392727
CBX6O955035EBI-722416,EBI-3951758
CBX7O959315EBI-722416,EBI-3923843
CBX8Q9HC529EBI-722416,EBI-712912
CSNK2A1P684003EBI-722416,EBI-347804
CSNK2BP678702EBI-722416,EBI-348169
KAT8Q9H7Z62EBI-722416,EBI-896414
PCGF1Q9BSM17EBI-722416,EBI-749901
PCGF2P352279EBI-722416,EBI-2129767
PCGF3Q3KNV84EBI-722416,EBI-2339807
PCGF5Q86SE94EBI-722416,EBI-2827999
PCGF6Q9BYE74EBI-722416,EBI-1048026
RING1Q065875EBI-722416,EBI-752313
RYBPQ8N4884EBI-722416,EBI-752324
USP11P517844EBI-722416,EBI-306876
USP7Q930095EBI-722416,EBI-302474

GO - Molecular functioni

  • RING-like zinc finger domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111972. 720 interactors.
DIPiDIP-40034N.
IntActiQ99496. 85 interactors.
MINTiMINT-1420125.
STRINGi9606.ENSP00000356480.

Structurei

Secondary structure

1336
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi13 – 16Combined sources4
Helixi21 – 24Combined sources4
Beta strandi37 – 39Combined sources3
Helixi42 – 45Combined sources4
Helixi46 – 49Combined sources4
Turni52 – 54Combined sources3
Beta strandi55 – 57Combined sources3
Beta strandi59 – 64Combined sources6
Turni65 – 67Combined sources3
Beta strandi70 – 72Combined sources3
Helixi73 – 80Combined sources8
Turni88 – 90Combined sources3
Helixi97 – 99Combined sources3
Beta strandi100 – 102Combined sources3
Helixi104 – 113Combined sources10
Beta strandi225 – 232Combined sources8
Turni234 – 236Combined sources3
Beta strandi246 – 251Combined sources6
Helixi256 – 277Combined sources22
Helixi283 – 285Combined sources3
Helixi288 – 290Combined sources3
Beta strandi291 – 296Combined sources6
Beta strandi302 – 304Combined sources3
Helixi311 – 318Combined sources8
Beta strandi321 – 323Combined sources3
Beta strandi325 – 331Combined sources7

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...

Miscellaneous databases

EvolutionaryTraceiQ99496.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 179Interaction with HIP21 PublicationAdd BLAST178

Sequence similaritiesi

Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

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.
OMAiPTLMEND.
OrthoDBiEOG091G06VO.
PhylomeDBiQ99496.
TreeFamiTF105501.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR032443. RAWUL.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF16207. RAWUL. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

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

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

Sequence cautioni

The sequence CAI17849 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI17850 differs from that shown. Reason: Erroneous gene model prediction.Curated

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. Translation: CAC00611.1.
AL109865 Genomic DNA. Translation: CAI17849.1. Sequence problems.
AL109865 Genomic DNA. Translation: CAI17850.1. Sequence problems.
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

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. Translation: CAC00611.1.
AL109865 Genomic DNA. Translation: CAI17849.1. Sequence problems.
AL109865 Genomic DNA. Translation: CAI17850.1. Sequence problems.
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. 720 interactors.
DIPiDIP-40034N.
IntActiQ99496. 85 interactors.
MINTiMINT-1420125.
STRINGi9606.ENSP00000356480.

PTM databases

iPTMnetiQ99496.
PhosphoSitePlusiQ99496.

Polymorphism and mutation databases

BioMutaiRNF2.
DMDMi62901044.

Proteomic databases

EPDiQ99496.
MaxQBiQ99496.
PaxDbiQ99496.
PeptideAtlasiQ99496.
PRIDEiQ99496.

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.
GeneCardsiRNF2.
HGNCiHGNC:10061. RNF2.
HPAiHPA026803.
MIMi608985. gene.
neXtProtiNX_Q99496.
OpenTargetsiENSG00000121481.
PharmGKBiPA34426.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000121481-MONOMER.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
R-HSA-4570464. SUMOylation of RNA binding proteins.

Miscellaneous databases

EvolutionaryTraceiQ99496.
GeneWikiiRNF2.
GenomeRNAii6045.
PROiQ99496.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121481.
CleanExiHS_BAP1.
HS_RNF2.
ExpressionAtlasiQ99496. baseline and differential.
GenevisibleiQ99496. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR032443. RAWUL.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF16207. RAWUL. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRING2_HUMAN
AccessioniPrimary (citable) accession number: Q99496
Secondary accession number(s): B2RBS7
, B3KRH1, Q5TEN1, Q5TEN2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: May 1, 1997
Last modified: November 30, 2016
This is version 164 of the entry and version 1 of the sequence. [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

Miscellaneous

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

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
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.