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Protein

Ubiquitin-protein ligase E3A

Gene

Ube3a

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

Functioni

E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates. Several substrates have been identified including the ARNTL/BMAL1, ARC, RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B (PubMed:20211139, PubMed:24728990). Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins. Finally, UBE3A also promotes its own degradation in vivo (By similarity). Plays an important role in the regulation of the circadian clock: involved in the ubiquitination of the core clock component ARNTL/BMAL1, leading to its proteasomal degradation (PubMed:24728990). Acts as a regulator of synaptic development by mediating ubiquitination and degradation of ARC (PubMed:20211139). Synergizes with WBP2 in enhancing PGR activity (By similarity).By similarity2 Publications

Miscellaneous

The Ube3a locus is imprinted with silencing of the paternal allele in hippocampus and cerebellum in mice.1 Publication
A cysteine residue is required for ubiquitin-thioester formation.

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.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.1 Publication
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei838Glycyl thioester intermediatePROSITE-ProRule annotation1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri42 – 81C4-type; atypicalBy similarityAdd BLAST40

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processBiological rhythms, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi6.3.2.19 3474
ReactomeiR-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-protein ligase E3A (EC:2.3.2.261 Publication)
Alternative name(s):
HECT-type ubiquitin transferase E3A
Oncogenic protein-associated protein E6-AP
Gene namesi
Name:Ube3a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:105098 Ube3a

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

Cytoplasm, Nucleus, Proteasome

Pathology & Biotechi

Disruption phenotypei

Mice with maternal deficiency display autism spectrum disorders, characterized by motor dysfunction, inducible seizures and a context-dependent learning deficit (PubMed:9808466, PubMed:11895368). Long-term potentiation (LTP) is severely impaired despite normal baseline synaptic transmission and neuroanatomy (PubMed:9808466). The cytoplasmic abundance of p53/TP53 is increased in postmitotic neurons (PubMed:9808466). Accumulation of ARC protein in neurons, resulting in the excessive internalization of AMPA receptors (AMPARs) at synapses and impaired synaptic function (PubMed:20211139).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi838C → A: Abolishes catalytic activity. Abolishes ability to ubiquitinate ARC. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001949811 – 870Ubiquitin-protein ligase E3AAdd BLAST870

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei8PhosphoserineCombined sources1
Modified residuei213PhosphoserineCombined sources1
Modified residuei654Phosphotyrosine; by ABL1By similarity1

Post-translational modificationi

Phosphorylation at Tyr-654 by ABL1 impairs E3 ligase activity.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO08759
MaxQBiO08759
PaxDbiO08759
PeptideAtlasiO08759
PRIDEiO08759

PTM databases

iPTMnetiO08759
PhosphoSitePlusiO08759
SwissPalmiO08759

Expressioni

Tissue specificityi

Widely expressed. Most abundant in brain, heart and thymus.2 Publications

Inductioni

Up-regulated in response to neuronal activity.1 Publication

Gene expression databases

BgeeiENSMUSG00000025326 Expressed in 291 organ(s), highest expression level in vas deferens
CleanExiMM_UBE3A
ExpressionAtlasiO08759 baseline and differential
GenevisibleiO08759 MM

Interactioni

Subunit structurei

The active form is probably a homotrimer. Binds UBQLN1 and UBQLN2. Interacts with the 26S proteasome. Interacts with BPY2. Interacts with HIF1AN, MAPK6 AND NEURL4; interaction with MAPK6 may be mediated by NEURL4. Interacts with the proteasomal subunit PSMD4. Interacts with ARNTL/BMAL1 (PubMed:24728990). Interacts with ARC (PubMed:20211139). Interacts with ESR1 and WBP2 (By similarity).By similarity2 Publications

Protein-protein interaction databases

IntActiO08759, 3 interactors
MINTiO08759
STRINGi10090.ENSMUSP00000103161

Structurei

3D structure databases

ProteinModelPortaliO08759
SMRiO08759
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini542 – 870HECTPROSITE-ProRule annotationAdd BLAST329

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi389 – 394Asp/Glu-rich (acidic)6

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri42 – 81C4-type; atypicalBy similarityAdd BLAST40

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0941 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00910000144004
HOGENOMiHOG000261634
HOVERGENiHBG059326
InParanoidiO08759
KOiK10587
OMAiKIVYYAN
OrthoDBiEOG091G01LV
TreeFamiTF315189

Family and domain databases

CDDicd00078 HECTc, 1 hit
InterProiView protein in InterPro
IPR032353 AZUL
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR017134 UBE3A
PfamiView protein in Pfam
PF16558 AZUL, 1 hit
PF00632 HECT, 1 hit
PIRSFiPIRSF037201 Ubiquitin-protein_ligase_E6-AP, 1 hit
SMARTiView protein in SMART
SM00119 HECTc, 1 hit
SUPFAMiSSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50237 HECT, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O08759-1) [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
MATACKRSPG ESQSEDIEAS RMKRAAAKHL IERYYHQLTE GCGNEACTNE
60 70 80 90 100
FCASCPTFLR MDNNAAAIKA LELYKINAKL CDPHPSKKGA SSAYLENSKG
110 120 130 140 150
ASNNSEIKMN KKEGKDFKDV IYLTEEKVYE IYEFCRESED YSPLIRVIGR
160 170 180 190 200
IFSSAEALVL SFRKVKQHTK EELKSLQEKD EDKDEDEKEK AACSAAAMEE
210 220 230 240 250
DSEASSSRMG DSSQGDNNVQ KLGPDDVTVD IDAIRRVYSS LLANEKLETA
260 270 280 290 300
FLNALVYLSP NVECDLTYHN VYTRDPNYLN LFIIVMENSN LHSPEYLEMA
310 320 330 340 350
LPLFCKAMCK LPLEAQGKLI RLWSKYSADQ IRRMMETFQQ LITYKVISNE
360 370 380 390 400
FNSRNLVNDD DAIVAASKCL KMVYYANVVG GDVDTNHNEE DDEEPIPESS
410 420 430 440 450
ELTLQELLGD ERRNKKGPRV DPLETELGVK TLDCRKPLIS FEEFINEPLN
460 470 480 490 500
DVLEMDKDYT FFKVETENKF SFMTCPFILN AVTKNLGLYY DNRIRMYSER
510 520 530 540 550
RITVLYSLVQ GQQLNPYLRL KVRRDHIIDD ALVRLEMIAM ENPADLKKQL
560 570 580 590 600
YVEFEGEQGV DEGGVSKEFF QLVVEEIFNP DIGMFTYDEA TKLFWFNPSS
610 620 630 640 650
FETEGQFTLI GIVLGLAIYN NCILDVHFPM VVYRKLMGKK GTFRDLGDSH
660 670 680 690 700
PVLYQSLKDL LEYEGSVEDD MMITFQISQT DLFGNPMMYD LKENGDKIPI
710 720 730 740 750
TNENRKEFVN LYSDYILNKS VEKQFKAFRR GFHMVTNESP LKYLFRPEEI
760 770 780 790 800
ELLICGSRNL DFQALEETTE YDGGYTRESV VIREFWEIVH SFTDEQKRLF
810 820 830 840 850
LQFTTGTDRA PVGGLGKLKM IIAKNGPDTE RLPTSHTCFN VLLLPEYSSK
860 870
EKLKERLLKA ITYAKGFGML
Length:870
Mass (Da):99,819
Last modified:April 1, 2015 - v2
Checksum:iCC6BBDDD5AE9C164
GO
Isoform 2 (identifier: O08759-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.

Show »
Length:849
Mass (Da):97,584
Checksum:i840AD5E681DBB45E
GO
Isoform 3 (identifier: O08759-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.
     784-870: Missing.

Show »
Length:762
Mass (Da):87,700
Checksum:iBB189D5380C3F25B
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0J9YUY4A0A0J9YUY4_MOUSE
Ubiquitin-protein ligase E3A
Ube3a
192Annotation score:
A0A0J9YVG1A0A0J9YVG1_MOUSE
Ubiquitin-protein ligase E3A
Ube3a
143Annotation score:
A0A0J9YUK0A0A0J9YUK0_MOUSE
Ubiquitin-protein ligase E3A
Ube3a
313Annotation score:
A0A0J9YTX6A0A0J9YTX6_MOUSE
Ubiquitin-protein ligase E3A
Ube3a
49Annotation score:
A0A140LHS2A0A140LHS2_MOUSE
Ubiquitin-protein ligase E3A
Ube3a
126Annotation score:
A0A140LI50A0A140LI50_MOUSE
Ubiquitin-protein ligase E3A
Ube3a
78Annotation score:
A0A0J9YUF2A0A0J9YUF2_MOUSE
Ubiquitin-protein ligase E3A
Ube3a
40Annotation score:
A0A0J9YV26A0A0J9YV26_MOUSE
Ubiquitin-protein ligase E3A
Ube3a
15Annotation score:

Sequence cautioni

The sequence AAB47756 differs from that shown. Reason: Frameshift at positions 561, 567, 607 and 612.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7R → S in AAB63361 (PubMed:9182527).Curated1
Sequence conflicti171E → D in AAB63361 (PubMed:9182527).Curated1
Sequence conflicti285V → L in AAB63361 (PubMed:9182527).Curated1
Sequence conflicti327S → T in AAB63361 (PubMed:9182527).Curated1
Sequence conflicti368K → N in AAB63361 (PubMed:9182527).Curated1
Sequence conflicti444F → S in AAB63361 (PubMed:9182527).Curated1
Sequence conflicti470F → G in AAB63361 (PubMed:9182527).Curated1
Sequence conflicti519R → T in AAB63361 (PubMed:9182527).Curated1
Sequence conflicti581D → N in AAB47756 (PubMed:9110176).Curated1
Sequence conflicti613Missing in AAB63361 (PubMed:9182527).Curated1
Sequence conflicti710 – 711NL → IS in AAB63361 (PubMed:9182527).Curated2
Sequence conflicti802Q → L in AAB63361 (PubMed:9182527).Curated1
Sequence conflicti854 – 855KE → NV in AAB63361 (PubMed:9182527).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0575631 – 21Missing in isoform 2 and isoform 3. Add BLAST21
Alternative sequenceiVSP_057564784 – 870Missing in isoform 3. Add BLAST87

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U96636 mRNA Translation: AAB63361.1
U82122 mRNA Translation: AAB47756.1 Frameshift.
AK029133 mRNA Translation: BAC26314.1
AC167971 Genomic DNA No translation available.
BC131658 mRNA Translation: AAI31659.1
BC131659 mRNA Translation: AAI31660.1
CCDSiCCDS39973.1 [O08759-1]
CCDS80733.1 [O08759-2]
RefSeqiNP_035798.2, NM_011668.2 [O08759-1]
NP_766598.1, NM_173010.3
XP_006540862.1, XM_006540799.3 [O08759-1]
XP_011249149.1, XM_011250847.2 [O08759-2]
XP_017177614.1, XM_017322125.1 [O08759-1]
UniGeneiMm.9002

Genome annotation databases

EnsembliENSMUST00000107537; ENSMUSP00000103161; ENSMUSG00000025326 [O08759-2]
ENSMUST00000200758; ENSMUSP00000143859; ENSMUSG00000025326 [O08759-1]
ENSMUST00000202945; ENSMUSP00000143962; ENSMUSG00000025326 [O08759-3]
GeneIDi22215
KEGGimmu:22215
UCSCiuc009heg.1 mouse
uc009hei.1 mouse

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U96636 mRNA Translation: AAB63361.1
U82122 mRNA Translation: AAB47756.1 Frameshift.
AK029133 mRNA Translation: BAC26314.1
AC167971 Genomic DNA No translation available.
BC131658 mRNA Translation: AAI31659.1
BC131659 mRNA Translation: AAI31660.1
CCDSiCCDS39973.1 [O08759-1]
CCDS80733.1 [O08759-2]
RefSeqiNP_035798.2, NM_011668.2 [O08759-1]
NP_766598.1, NM_173010.3
XP_006540862.1, XM_006540799.3 [O08759-1]
XP_011249149.1, XM_011250847.2 [O08759-2]
XP_017177614.1, XM_017322125.1 [O08759-1]
UniGeneiMm.9002

3D structure databases

ProteinModelPortaliO08759
SMRiO08759
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO08759, 3 interactors
MINTiO08759
STRINGi10090.ENSMUSP00000103161

PTM databases

iPTMnetiO08759
PhosphoSitePlusiO08759
SwissPalmiO08759

Proteomic databases

EPDiO08759
MaxQBiO08759
PaxDbiO08759
PeptideAtlasiO08759
PRIDEiO08759

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000107537; ENSMUSP00000103161; ENSMUSG00000025326 [O08759-2]
ENSMUST00000200758; ENSMUSP00000143859; ENSMUSG00000025326 [O08759-1]
ENSMUST00000202945; ENSMUSP00000143962; ENSMUSG00000025326 [O08759-3]
GeneIDi22215
KEGGimmu:22215
UCSCiuc009heg.1 mouse
uc009hei.1 mouse

Organism-specific databases

CTDi7337
MGIiMGI:105098 Ube3a

Phylogenomic databases

eggNOGiKOG0941 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00910000144004
HOGENOMiHOG000261634
HOVERGENiHBG059326
InParanoidiO08759
KOiK10587
OMAiKIVYYAN
OrthoDBiEOG091G01LV
TreeFamiTF315189

Enzyme and pathway databases

UniPathwayi
UPA00143

BRENDAi6.3.2.19 3474
ReactomeiR-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

ChiTaRSiUbe3a mouse
PROiPR:O08759
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025326 Expressed in 291 organ(s), highest expression level in vas deferens
CleanExiMM_UBE3A
ExpressionAtlasiO08759 baseline and differential
GenevisibleiO08759 MM

Family and domain databases

CDDicd00078 HECTc, 1 hit
InterProiView protein in InterPro
IPR032353 AZUL
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR017134 UBE3A
PfamiView protein in Pfam
PF16558 AZUL, 1 hit
PF00632 HECT, 1 hit
PIRSFiPIRSF037201 Ubiquitin-protein_ligase_E6-AP, 1 hit
SMARTiView protein in SMART
SM00119 HECTc, 1 hit
SUPFAMiSSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50237 HECT, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUBE3A_MOUSE
AccessioniPrimary (citable) accession number: O08759
Secondary accession number(s): E9QKT1, P97482, Q8CE29
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: April 1, 2015
Last modified: November 7, 2018
This is version 147 of the entry and version 2 of the sequence. See 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
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Main funding by: National Institutes of Health

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