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Protein

E3 ubiquitin-protein ligase UBR2

Gene

Ubr2

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

Functioni

E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A. Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth (By similarity).By similarity2 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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri97 – 16872UBR-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri1108 – 1214107RING-type; atypicalAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • cellular response to leucine Source: UniProtKB
  • chromatin silencing Source: UniProtKB
  • histone H2A ubiquitination Source: UniProtKB
  • male meiosis I Source: MGI
  • negative regulation of TOR signaling Source: UniProtKB
  • spermatogenesis Source: MGI
  • ubiquitin-dependent protein catabolic process Source: MGI
  • ubiquitin-dependent protein catabolic process via the N-end rule pathway Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase UBR2 (EC:6.3.2.-)
Alternative name(s):
N-recognin-2
Ubiquitin-protein ligase E3-alpha-2
Ubiquitin-protein ligase E3-alpha-II
Gene namesi
Name:Ubr2
Synonyms:Kiaa0349
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1861099. Ubr2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • nucleoplasm Source: MGI
  • plasma membrane Source: MGI
  • ubiquitin ligase complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Male mice are viable but not fertile, due to massive apoptosis of spermatocytes. Female mice show severe prenatal lethality, but the rare surviving are fertile. Fibroblast cells display spontaneous chromosome instability and fragility. UBR1 and UBR2 double knockout embryos die at midgestation, with defects in neurogenesis and cardiovascular development. These defects included reduced proliferation as well as precocious migration and differentiation of neural progenitor cells.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 17551754E3 ubiquitin-protein ligase UBR2PRO_0000056141Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ6WKZ8.
PaxDbiQ6WKZ8.
PeptideAtlasiQ6WKZ8.
PRIDEiQ6WKZ8.

PTM databases

iPTMnetiQ6WKZ8.
PhosphoSiteiQ6WKZ8.

Expressioni

Tissue specificityi

Highly expressed in skeletal muscle. Also expressed in heart, kidney and testis. Expressed in acinar cells of the pancreas. In testes, expressed primarily in spermatocytes.3 Publications

Inductioni

In models of cancer cachexia, induced specifically at the onset and during the progression of muscle wasting.1 Publication

Gene expression databases

BgeeiENSMUSG00000023977.
ExpressionAtlasiQ6WKZ8. baseline and differential.
GenevisibleiQ6WKZ8. MM.

Interactioni

Subunit structurei

Interacts with UBE2B; promotes the UBE2B-H2A interaction and the ubiquitination of histone H2A by UBE2B and UBR2. Interacts with RECQL4 (By similarity). Interacts with Tex19.1 and Tex19.2.By similarity3 Publications

Protein-protein interaction databases

BioGridi230327. 2 interactions.
IntActiQ6WKZ8. 1 interaction.
MINTiMINT-4117378.
STRINGi10090.ENSMUSP00000108961.

Structurei

3D structure databases

ProteinModelPortaliQ6WKZ8.
SMRiQ6WKZ8. Positions 98-167.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili1019 – 105436Sequence analysisAdd
BLAST

Domaini

The RING-H2 zinc finger is an atypical RING finger with a His ligand in place of the fourth Cys of the classical motif.
The UBR-type zinc finger forms a pocket that mediates recognition of type 1 N-degrons. It exhibits preference for Arginine in first position, has poor affinity for histidine, and doesn't bind acetylated peptides (By similarity).By similarity

Sequence similaritiesi

Belongs to the UBR1 family.Curated
Contains 1 RING-type zinc finger.Curated
Contains 1 UBR-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri97 – 16872UBR-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri1108 – 1214107RING-type; atypicalAdd
BLAST

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG1140. Eukaryota.
ENOG410XPQU. LUCA.
GeneTreeiENSGT00530000063055.
HOVERGENiHBG080426.
InParanoidiQ6WKZ8.
KOiK10626.
OMAiDSERQHC.
PhylomeDBiQ6WKZ8.
TreeFamiTF323875.

Family and domain databases

Gene3Di3.30.1390.10. 1 hit.
InterProiIPR003769. ClpS_core.
IPR014719. Ribosomal_L7/12_C/ClpS-like.
IPR011991. WHTH_DNA-bd_dom.
IPR003126. Znf_UBR.
[Graphical view]
PfamiPF02617. ClpS. 1 hit.
PF02207. zf-UBR. 1 hit.
[Graphical view]
SMARTiSM00396. ZnF_UBR1. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF54736. SSF54736. 1 hit.
PROSITEiPS51157. ZF_UBR. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

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

Isoform 1 (identifier: Q6WKZ8-1) [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
MASEMEPEVQ AIDRSLLECS AEEIAGRWLQ ATDLNREVYQ HLAHCVPKIY
60 70 80 90 100
CRGPNPFPQK EDTLAQHILL GPMEWYICAE DPALGFPKLE QANKPSHLCG
110 120 130 140 150
RVFKVGEPTY SCRDCAVDPT CVLCMECFLG SIHRDHRYRM TTSGGGGFCD
160 170 180 190 200
CGDTEAWKEG PYCQKHKLSS SEVVEEEDPL VHLSEDVIAR TYNIFAIMFR
210 220 230 240 250
YAVDILTWEK ESELPEDLEV AEKSDTYYCM LFNDEVHTYE QVIYTLQKAV
260 270 280 290 300
NCTQKEAIGF ATTVDRDGRR SVRYGDFQYC DQAKTVIVRN TSRQTKPLKV
310 320 330 340 350
QVMHSSVAAH QNFGLKALSW LGSVIGYSDG LRRILCQVGL QEGPDGENSS
360 370 380 390 400
LVDRLMLNDS KLWKGARSVY HQLFMSSLLM DLKYKKLFAL RFAKNYRQLQ
410 420 430 440 450
RDFMEDDHER AVSVTALSVQ FFTAPTLARM LLTEENLMTV IIKAFMDHLK
460 470 480 490 500
HRDAQGRFQF ERYTALQAFK FRRVQSLILD LKYVLISKPT EWSDELRQKF
510 520 530 540 550
LQGFDAFLEL LKCMQGMDPI TRQVGQHIEM EPEWEAAFTL QMKLTHVISM
560 570 580 590 600
VQDWCALDEK VLIEAYKKCL AVLTQCHGGF TDGEQPITLS ICGHSVETIR
610 620 630 640 650
YCVSQEKVSI HLPISRLLAG LHVLLSKSEV AYKFPELLPL SELSPPMLIE
660 670 680 690 700
HPLRCLVLCA QVHAGMWRRN GFSLVNQIYY YHNVKCRREM FDKDIVMLQT
710 720 730 740 750
GVSMMDPNHF LMIMLSRFEL YQLFSTPDYG KRFSSEVTHK DVVQQNNTLI
760 770 780 790 800
EEMLYLIIML VGERFNPGVG QVAATDEIKR EIIHQLSIKP MAHSELVKSL
810 820 830 840 850
PEDENKETGM ESVIESVAHF KKPGLTGRGM YELKPECAKE FNLYFYHFSR
860 870 880 890 900
AEQSKAEEAQ RKLKRENKED TALPPPALPP FCPLFASLVN ILQCDVMLYI
910 920 930 940 950
MGTILQWAVE HHGSAWSESM LQRVLHLIGM ALQEEKHHLE NAVEGHVQTF
960 970 980 990 1000
TFTQKISKPG DAPHNSPSIL AMLETLQNAP SLEAHKDMIR WLLKMFNAIK
1010 1020 1030 1040 1050
KIRECSSSSP VAEAEGTIME ESSRDKDKAE RKRKAEIARL RREKIMAQMS
1060 1070 1080 1090 1100
EMQRHFIDEN KELFQQTLEL DTSASATLDS SPPVSDAALT ALGPAQTQVP
1110 1120 1130 1140 1150
EPRQFVTCIL CQEEQEVTVG SRAMVLAAFV QRSTVLSKDR TKTIADPEKY
1160 1170 1180 1190 1200
DPLFMHPDLS CGTHTGSCGH VMHAHCWQRY FDSVQAKEQR RQQRLRLHTS
1210 1220 1230 1240 1250
YDVENGEFLC PLCECLSNTV IPLLLPPRSI LSRRLNFSDQ PDLAQWTRAV
1260 1270 1280 1290 1300
TQQIKVVQML RRKHNAADTS SSEDTEAMNI IPIPEGFRPD FYPRNPYSDS
1310 1320 1330 1340 1350
IKEMLTTFGT AAYKVGLKVH PNEGDPRVPI LCWGTCAYTI QSIERILSDE
1360 1370 1380 1390 1400
EKPVFGPLPC RLDDCLRSLT RFAAAHWTVA LLPVVQGHFC KLFASLVPSD
1410 1420 1430 1440 1450
SYEDLPCILD IDMFHLLVGL VLAFPALQCQ DFSGSSLATG DLHIFHLVTM
1460 1470 1480 1490 1500
AHIVQILLTS CTEENGMDQE NPTGEEELAI LSLHKTLHQY TGSALKEAPS
1510 1520 1530 1540 1550
GWHLWRSVRA AIMPFLKCSA LFFHYLNGVP APPDLQVSGT SHFEHLCNYL
1560 1570 1580 1590 1600
SLPTNLIHLF QENSDIMNSL IESWCQNSEV KRYLNGERGA ISYPRGANKL
1610 1620 1630 1640 1650
IDLPEDYSSL INQASNFSCP KSGGDKSRAP TLCLVCGSLL CSQSYCCQAE
1660 1670 1680 1690 1700
LEGEDVGACT AHTYSCGSGA GIFLRVRECQ VLFLAGKTKG CFYSPPYLDD
1710 1720 1730 1740 1750
YGETDQGLRR GNPLHLCQER FRKIQKLWQQ HSITEEIGHA QEANQTLVGI

DWQHL
Length:1,755
Mass (Da):199,155
Last modified:August 16, 2005 - v2
Checksum:iE6D413D674FBBFDA
GO
Isoform 2 (identifier: Q6WKZ8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     397-426: RQLQRDFMEDDHERAVSVTALSVQFFTAPT → ERLQRDYVTDDHDREFSVADLSVQIFTVPS

Show »
Length:1,755
Mass (Da):199,198
Checksum:iF1B0354ED08414B9
GO
Isoform 3 (identifier: Q6WKZ8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-197: Missing.
     397-426: RQLQRDFMEDDHERAVSVTALSVQFFTAPT → ERLQRDYVTDDHDREFSVADLSVQIFTVPS

Note: No experimental confirmation available.
Show »
Length:1,558
Mass (Da):177,046
Checksum:i6A046013F707B3E0
GO

Sequence cautioni

The sequence AAH25617 differs from that shown. Reason: Erroneous initiation. Curated
The sequence AAH31403 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAC65536 differs from that shown.Intron retention.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti59 – 591Q → L in AAQ17202 (PubMed:14585983).Curated
Sequence conflicti137 – 1371R → Q in AAQ17202 (PubMed:14585983).Curated
Sequence conflicti137 – 1371R → Q in BAC65536 (PubMed:12693553).Curated
Sequence conflicti143 – 1431S → W in AAQ17202 (PubMed:14585983).Curated
Sequence conflicti271 – 2711S → P in AAL32102 (PubMed:15548684).Curated
Sequence conflicti429 – 4357RMLLTEE → PNAPHRKK in AAQ17202 (PubMed:14585983).Curated
Sequence conflicti656 – 6561L → P in AAQ17202 (PubMed:14585983).Curated
Sequence conflicti979 – 9791A → S in AAQ17202 (PubMed:14585983).Curated
Sequence conflicti1050 – 10501S → F in BAC38864 (PubMed:16141072).Curated
Sequence conflicti1332 – 13321C → W in AAQ17202 (PubMed:14585983).Curated
Sequence conflicti1619 – 16191C → S in AAH26391 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 197197Missing in isoform 3. 1 PublicationVSP_015172Add
BLAST
Alternative sequencei397 – 42630RQLQR…FTAPT → ERLQRDYVTDDHDREFSVAD LSVQIFTVPS in isoform 2 and isoform 3. 2 PublicationsVSP_015173Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY280958 mRNA. Translation: AAQ17202.1.
AY061885 mRNA. Translation: AAL32102.1.
AK122254 Unassigned DNA. Translation: BAC65536.3. Sequence problems.
BC025617 mRNA. Translation: AAH25617.1. Different initiation.
BC026391 mRNA. Translation: AAH26391.1.
BC031403 mRNA. Translation: AAH31403.1. Different initiation.
BC075642 mRNA. Translation: AAH75642.1.
AK083320 mRNA. Translation: BAC38864.1.
CCDSiCCDS28845.1. [Q6WKZ8-1]
CCDS50127.1. [Q6WKZ8-2]
RefSeqiNP_001170845.1. NM_001177374.1. [Q6WKZ8-2]
NP_666190.2. NM_146078.3. [Q6WKZ8-1]
UniGeneiMm.28234.

Genome annotation databases

EnsembliENSMUST00000113335; ENSMUSP00000108961; ENSMUSG00000023977. [Q6WKZ8-2]
ENSMUST00000113337; ENSMUSP00000108963; ENSMUSG00000023977. [Q6WKZ8-1]
GeneIDi224826.
KEGGimmu:224826.
UCSCiuc012aus.1. mouse. [Q6WKZ8-1]
uc012auu.1. mouse. [Q6WKZ8-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY280958 mRNA. Translation: AAQ17202.1.
AY061885 mRNA. Translation: AAL32102.1.
AK122254 Unassigned DNA. Translation: BAC65536.3. Sequence problems.
BC025617 mRNA. Translation: AAH25617.1. Different initiation.
BC026391 mRNA. Translation: AAH26391.1.
BC031403 mRNA. Translation: AAH31403.1. Different initiation.
BC075642 mRNA. Translation: AAH75642.1.
AK083320 mRNA. Translation: BAC38864.1.
CCDSiCCDS28845.1. [Q6WKZ8-1]
CCDS50127.1. [Q6WKZ8-2]
RefSeqiNP_001170845.1. NM_001177374.1. [Q6WKZ8-2]
NP_666190.2. NM_146078.3. [Q6WKZ8-1]
UniGeneiMm.28234.

3D structure databases

ProteinModelPortaliQ6WKZ8.
SMRiQ6WKZ8. Positions 98-167.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230327. 2 interactions.
IntActiQ6WKZ8. 1 interaction.
MINTiMINT-4117378.
STRINGi10090.ENSMUSP00000108961.

PTM databases

iPTMnetiQ6WKZ8.
PhosphoSiteiQ6WKZ8.

Proteomic databases

MaxQBiQ6WKZ8.
PaxDbiQ6WKZ8.
PeptideAtlasiQ6WKZ8.
PRIDEiQ6WKZ8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000113335; ENSMUSP00000108961; ENSMUSG00000023977. [Q6WKZ8-2]
ENSMUST00000113337; ENSMUSP00000108963; ENSMUSG00000023977. [Q6WKZ8-1]
GeneIDi224826.
KEGGimmu:224826.
UCSCiuc012aus.1. mouse. [Q6WKZ8-1]
uc012auu.1. mouse. [Q6WKZ8-3]

Organism-specific databases

CTDi23304.
MGIiMGI:1861099. Ubr2.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1140. Eukaryota.
ENOG410XPQU. LUCA.
GeneTreeiENSGT00530000063055.
HOVERGENiHBG080426.
InParanoidiQ6WKZ8.
KOiK10626.
OMAiDSERQHC.
PhylomeDBiQ6WKZ8.
TreeFamiTF323875.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

PROiQ6WKZ8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000023977.
ExpressionAtlasiQ6WKZ8. baseline and differential.
GenevisibleiQ6WKZ8. MM.

Family and domain databases

Gene3Di3.30.1390.10. 1 hit.
InterProiIPR003769. ClpS_core.
IPR014719. Ribosomal_L7/12_C/ClpS-like.
IPR011991. WHTH_DNA-bd_dom.
IPR003126. Znf_UBR.
[Graphical view]
PfamiPF02617. ClpS. 1 hit.
PF02207. zf-UBR. 1 hit.
[Graphical view]
SMARTiSM00396. ZnF_UBR1. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF54736. SSF54736. 1 hit.
PROSITEiPS51157. ZF_UBR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBR2_MOUSE
AccessioniPrimary (citable) accession number: Q6WKZ8
Secondary accession number(s): Q6DIB9
, Q80U31, Q8BUL9, Q8CGW0, Q8K2I6, Q8R0V7, Q8R130
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: August 16, 2005
Last modified: September 7, 2016
This is version 113 of the entry and version 2 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.