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Protein

E3 ubiquitin-protein ligase UHRF2

Gene

Uhrf2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 SUMO-, but not ubiquitin-, protein ligase for ZNF131 (By similarity). E3 ubiquitin-protein ligase that is an intermolecular hub protein in the cell cycle network. Ubiquitinates cyclins, CCND1 and CCNE1, in an apparently phosphorylation-independent manner and induces G1 arrest. Also ubiquitinates PCNP leading to its degradation by the proteasome. Through cooperative DNA and histone binding, may contribute to a tighter epigenetic control of gene expression in differentiated cells.By similarity1 Publication

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 fingeri340 – 396PHD-typePROSITE-ProRule annotationAdd BLAST57
Zinc fingeri734 – 773RING-typePROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • histone binding Source: UniProtKB
  • ligase activity Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: MGI
  • ubiquitin-protein transferase activity Source: HGNC
  • zinc ion binding Source: InterPro

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cell differentiation Source: HGNC
  • cell proliferation Source: HGNC
  • maintenance of DNA methylation Source: GO_Central
  • positive regulation of cell cycle arrest Source: UniProtKB
  • protein autoubiquitination Source: HGNC
  • protein ubiquitination Source: HGNC
  • regulation of methylation-dependent chromatin silencing Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Cell cycle, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase UHRF2 (EC:6.3.2.-)
Alternative name(s):
NIRF
Np95-like ring finger protein
Nuclear protein 97
Nuclear zinc finger protein Np97
Ubiquitin-like PHD and RING finger domain-containing protein 2
Ubiquitin-like-containing PHD and RING finger domains protein 2
Gene namesi
Name:Uhrf2
Synonyms:Nirf
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1923718. Uhrf2.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation1 Publication

  • Note: Enriched at pericentric heterochromatin (PH). This localization is dependent on the interaction with H3K9me3.

GO - Cellular componenti

  • nuclear heterochromatin Source: UniProtKB
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi214Y → A: Abolishes in vitro binding to H3K9me3. Prevents enrichment at pericentric heterochromatin. 1 Publication1
Mutagenesisi217Y → A: Abolishes in vitro binding to 'Lys-10' methylated H3, H3K9me3. Prevents enrichment at pericentric heterochromatin. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000561481 – 803E3 ubiquitin-protein ligase UHRF2Add BLAST803

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei668PhosphoserineCombined sources1
Disulfide bondi705InterchainBy similarity

Post-translational modificationi

May be autoubiquitinated; which may lead to proteasomal degradation.By similarity
Phosphorylated. Phosphorylation may be mediated by CDK2 (By similarity).By similarity
Autosumoylated.By similarity

Keywords - PTMi

Disulfide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ7TMI3.
PaxDbiQ7TMI3.
PeptideAtlasiQ7TMI3.
PRIDEiQ7TMI3.

PTM databases

iPTMnetiQ7TMI3.
PhosphoSitePlusiQ7TMI3.

Expressioni

Inductioni

Up-regulated during cell differentiation.1 Publication

Gene expression databases

BgeeiENSMUSG00000024817.
ExpressionAtlasiQ7TMI3. baseline and differential.
GenevisibleiQ7TMI3. MM.

Interactioni

Subunit structurei

Homodimer; disulfide-linked (By similarity). Binds methylated CpG containing oligonucleotides. Interacts with PCNP, HDAC1 and CDK2 (inactive form). Component of a complex at least composed of UHRF2, CDK2 and CCNE1. Interacts directly with CCNE1; the interaction ubiquitinates CCNE1 and appears independent of CCNE1 phosphorylation. Interacts with CCND1; the interaction ubiquitinates CCND1 and appears independent of CCND1 phosphorylation. Interacts with p53/TP53 and RB1 (By similarity). Interacts with H3; the interaction has a preference for the 'Lys-9' trimethylated form of H3 (H3K9me3). Interacts with UBE2I (By similarity).By similarity

GO - Molecular functioni

  • histone binding Source: UniProtKB

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000025739.

Structurei

3D structure databases

ProteinModelPortaliQ7TMI3.
SMRiQ7TMI3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 78Ubiquitin-likePROSITE-ProRule annotationAdd BLAST78
Domaini449 – 613YDGPROSITE-ProRule annotationAdd BLAST165

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni118 – 312Required for interaction with histone H3Add BLAST195
Regioni195 – 289Interaction with PCNPBy similarityAdd BLAST95
Regioni415 – 645Methyl-CpG binding and interaction with HDAC1By similarityAdd BLAST231

Sequence similaritiesi

Contains 1 PHD-type zinc finger.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 1 ubiquitin-like domain.PROSITE-ProRule annotation
Contains 1 YDG domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri340 – 396PHD-typePROSITE-ProRule annotationAdd BLAST57
Zinc fingeri734 – 773RING-typePROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IFAP. Eukaryota.
COG3440. LUCA.
GeneTreeiENSGT00390000008296.
HOGENOMiHOG000124662.
HOVERGENiHBG059298.
InParanoidiQ7TMI3.
KOiK15713.
OMAiCRFCSCC.
OrthoDBiEOG091G06BT.
PhylomeDBiQ7TMI3.
TreeFamiTF106434.

Family and domain databases

Gene3Di2.30.280.10. 1 hit.
2.30.30.30. 1 hit.
3.30.40.10. 2 hits.
InterProiIPR015947. PUA-like_domain.
IPR014722. Rib_L2_dom2.
IPR003105. SRA_YDG.
IPR021991. TTD_dom.
IPR029071. Ubiquitin-rel_dom.
IPR000626. Ubiquitin_dom.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00628. PHD. 1 hit.
PF02182. SAD_SRA. 1 hit.
PF12148. TTD. 1 hit.
PF00240. ubiquitin. 1 hit.
[Graphical view]
SMARTiSM00249. PHD. 1 hit.
SM00184. RING. 2 hits.
SM00466. SRA. 1 hit.
SM00213. UBQ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF57903. SSF57903. 1 hit.
SSF88697. SSF88697. 1 hit.
PROSITEiPS50053. UBIQUITIN_2. 1 hit.
PS51015. YDG. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7TMI3-1) [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
MWIQVRTIDG SQTRTIEDVS RKATIEELRE RVWALFDVRP ECQRLFYRGK
60 70 80 90 100
QLENGYTLFD YDVGLNDIIQ LLVRPDSSLP STSKQNDAQV KPSSHNPPKV
110 120 130 140 150
KKTARGGSSS QPSTSARTCL IDPGFGLYKV NELVDARDVG LGAWFEAHIH
160 170 180 190 200
SVTRASDGHS RGKTPLKNGS SYKRTNGNVN HNSKENTNKL DNVPSTSNSD
210 220 230 240 250
SVAADEDVIY HIEYDEYPES GILEMNVKDL RPRARTILKW NELNVGDVVM
260 270 280 290 300
VNYNVENPGK RGFWYDAEIT TLKTISRTKK EVRVKVFLGG SEGTLNDCRV
310 320 330 340 350
MSVDEIFKIE KPGAHPISFA DGKFLRKNDP ECDLCGGDPD KTCHMCSCHK
360 370 380 390 400
CGEKRDPNMQ LLCDECNMAY HIYCLSPPLD KVPEEEYWYC PSCKTDSSEV
410 420 430 440 450
VKAGERLKLS KKKAKMPSAS TESRRDWGRG MACVGRTKEC TIVPSNHYGP
460 470 480 490 500
IPGIPVGSTW RFRVQVSEAG VHRPHVGGIH GRSNDGAYSL VLAGGFEDEV
510 520 530 540 550
DRGDEFTYTG SGGKNLAGNK RIGAPSADQT LTNMNRALAL NCDAPLDDKI
560 570 580 590 600
GAESRNWRAG KPVRVIRSFK GRKISKYAPE EGNRYDGIYK VVKYWPEISS
610 620 630 640 650
SHGFLVWRYL LRRDDVEPAP WTSEGIERSR RLCLRLQYPA GYPSEKEGKK
660 670 680 690 700
TKGQSKKQGS EATKRPASDD ECPGDSKVLK ASDSTDAVEA FQLTPQQQRL
710 720 730 740 750
IREDCQNQKL WDEVLASLVE GPNFLKKLEQ SFMCVCCQEL VYQPVTTECF
760 770 780 790 800
HNVCKDCLQR SFKAQVFSCP ACRHDLGQNY VMVLNETLQT LLDLFFPGYS

KGR
Length:803
Mass (Da):90,106
Last modified:October 1, 2003 - v1
Checksum:iD799B0205E0E036E
GO
Isoform 2 (identifier: Q7TMI3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     501-516: DRGDEFTYTGSGGKNL → VSNDVTLFFRTNLDHF
     517-803: Missing.

Show »
Length:516
Mass (Da):57,761
Checksum:i3D6862E9D1E1DEDD
GO
Isoform 3 (identifier: Q7TMI3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     217-803: Missing.

Note: No experimental confirmation available.
Show »
Length:216
Mass (Da):24,138
Checksum:iC2C868076470EBCC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti274T → S in AAM33798 (Ref. 1) Curated1
Sequence conflicti278T → S in AAM33798 (Ref. 1) Curated1
Sequence conflicti793D → E in AAM33798 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013876217 – 803Missing in isoform 3. 1 PublicationAdd BLAST587
Alternative sequenceiVSP_013877501 – 516DRGDE…GGKNL → VSNDVTLFFRTNLDHF in isoform 2. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_013878517 – 803Missing in isoform 2. 1 PublicationAdd BLAST287

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB116653 mRNA. Translation: BAC81739.1.
AF274047 mRNA. Translation: AAM33798.1.
AK031036 mRNA. Translation: BAC27224.1.
AK041564 mRNA. Translation: BAC30987.1.
AK042321 mRNA. Translation: BAC31223.1.
AK051743 mRNA. Translation: BAC34750.1.
AK080925 mRNA. Translation: BAC38081.1.
BC060241 mRNA. Translation: AAH60241.1.
CCDSiCCDS37955.1. [Q7TMI3-1]
RefSeqiNP_659122.2. NM_144873.2. [Q7TMI3-1]
UniGeneiMm.313364.

Genome annotation databases

EnsembliENSMUST00000025739; ENSMUSP00000025739; ENSMUSG00000024817. [Q7TMI3-1]
GeneIDi109113.
KEGGimmu:109113.
UCSCiuc008hef.1. mouse. [Q7TMI3-3]
uc008heh.1. mouse. [Q7TMI3-2]
uc008hei.1. mouse. [Q7TMI3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB116653 mRNA. Translation: BAC81739.1.
AF274047 mRNA. Translation: AAM33798.1.
AK031036 mRNA. Translation: BAC27224.1.
AK041564 mRNA. Translation: BAC30987.1.
AK042321 mRNA. Translation: BAC31223.1.
AK051743 mRNA. Translation: BAC34750.1.
AK080925 mRNA. Translation: BAC38081.1.
BC060241 mRNA. Translation: AAH60241.1.
CCDSiCCDS37955.1. [Q7TMI3-1]
RefSeqiNP_659122.2. NM_144873.2. [Q7TMI3-1]
UniGeneiMm.313364.

3D structure databases

ProteinModelPortaliQ7TMI3.
SMRiQ7TMI3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000025739.

PTM databases

iPTMnetiQ7TMI3.
PhosphoSitePlusiQ7TMI3.

Proteomic databases

EPDiQ7TMI3.
PaxDbiQ7TMI3.
PeptideAtlasiQ7TMI3.
PRIDEiQ7TMI3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025739; ENSMUSP00000025739; ENSMUSG00000024817. [Q7TMI3-1]
GeneIDi109113.
KEGGimmu:109113.
UCSCiuc008hef.1. mouse. [Q7TMI3-3]
uc008heh.1. mouse. [Q7TMI3-2]
uc008hei.1. mouse. [Q7TMI3-1]

Organism-specific databases

CTDi115426.
MGIiMGI:1923718. Uhrf2.

Phylogenomic databases

eggNOGiENOG410IFAP. Eukaryota.
COG3440. LUCA.
GeneTreeiENSGT00390000008296.
HOGENOMiHOG000124662.
HOVERGENiHBG059298.
InParanoidiQ7TMI3.
KOiK15713.
OMAiCRFCSCC.
OrthoDBiEOG091G06BT.
PhylomeDBiQ7TMI3.
TreeFamiTF106434.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

PROiQ7TMI3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024817.
ExpressionAtlasiQ7TMI3. baseline and differential.
GenevisibleiQ7TMI3. MM.

Family and domain databases

Gene3Di2.30.280.10. 1 hit.
2.30.30.30. 1 hit.
3.30.40.10. 2 hits.
InterProiIPR015947. PUA-like_domain.
IPR014722. Rib_L2_dom2.
IPR003105. SRA_YDG.
IPR021991. TTD_dom.
IPR029071. Ubiquitin-rel_dom.
IPR000626. Ubiquitin_dom.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00628. PHD. 1 hit.
PF02182. SAD_SRA. 1 hit.
PF12148. TTD. 1 hit.
PF00240. ubiquitin. 1 hit.
[Graphical view]
SMARTiSM00249. PHD. 1 hit.
SM00184. RING. 2 hits.
SM00466. SRA. 1 hit.
SM00213. UBQ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF57903. SSF57903. 1 hit.
SSF88697. SSF88697. 1 hit.
PROSITEiPS50053. UBIQUITIN_2. 1 hit.
PS51015. YDG. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUHRF2_MOUSE
AccessioniPrimary (citable) accession number: Q7TMI3
Secondary accession number(s): Q8BG56
, Q8BJP6, Q8BY30, Q8K1I5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: October 1, 2003
Last modified: November 30, 2016
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.