UniProtKB - O08759 (UBE3A_MOUSE)
Protein
Ubiquitin-protein ligase E3A
Gene
Ube3a
Organism
Mus musculus (Mouse)
Status
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 + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication EC:2.3.2.26
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.1 PublicationView all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 838 | Glycyl thioester intermediatePROSITE-ProRule annotation1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 42 – 81 | C4-type; atypicalBy similarityAdd BLAST | 40 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
- transcription coactivator activity Source: MGI
- ubiquitin protein ligase activity Source: MGI
- ubiquitin-protein transferase activity Source: UniProtKB
GO - Biological processi
- androgen receptor signaling pathway Source: MGI
- cellular response to brain-derived neurotrophic factor stimulus Source: Ensembl
- negative regulation of dendritic spine morphogenesis Source: MGI
- ovarian follicle development Source: MGI
- positive regulation of phosphatidylinositol 3-kinase signaling Source: MGI
- positive regulation of protein ubiquitination Source: MGI
- positive regulation of transcription by RNA polymerase II Source: MGI
- progesterone receptor signaling pathway Source: UniProtKB
- prostate gland growth Source: MGI
- proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
- protein autoubiquitination Source: MGI
- protein K48-linked ubiquitination Source: UniProtKB
- protein polyubiquitination Source: GO_Central
- protein ubiquitination Source: MGI
- regulation of circadian rhythm Source: UniProtKB
- regulation of ubiquitin-dependent protein catabolic process Source: UniProtKB
- response to cocaine Source: Ensembl
- response to hydrogen peroxide Source: Ensembl
- response to progesterone Source: UniProtKB
- rhythmic process Source: UniProtKB-KW
- sperm entry Source: MGI
- ubiquitin-dependent protein catabolic process Source: MGI
Keywordsi
Molecular function | Transferase |
Biological process | Biological rhythms, Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 6.3.2.19 3474 |
Reactomei | R-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 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:105098 Ube3a |
Subcellular locationi
Cytosol
- cytosol Source: MGI
Nucleus
- nucleus Source: MGI
Other locations
- proteasome complex Source: UniProtKB-KW
Keywords - Cellular componenti
Cytoplasm, Nucleus, ProteasomePathology & 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 838 | C → A: Abolishes catalytic activity. Abolishes ability to ubiquitinate ARC. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000194981 | 1 – 870 | Ubiquitin-protein ligase E3AAdd BLAST | 870 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 8 | PhosphoserineCombined sources | 1 | |
Modified residuei | 213 | PhosphoserineCombined sources | 1 | |
Modified residuei | 654 | Phosphotyrosine; by ABL1By similarity | 1 |
Post-translational modificationi
Phosphorylation at Tyr-654 by ABL1 impairs E3 ligase activity.By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | O08759 |
MaxQBi | O08759 |
PaxDbi | O08759 |
PeptideAtlasi | O08759 |
PRIDEi | O08759 |
PTM databases
iPTMneti | O08759 |
PhosphoSitePlusi | O08759 |
SwissPalmi | O08759 |
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
Bgeei | ENSMUSG00000025326 Expressed in 291 organ(s), highest expression level in vas deferens |
ExpressionAtlasi | O08759 baseline and differential |
Genevisiblei | O08759 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
IntActi | O08759, 3 interactors |
MINTi | O08759 |
STRINGi | 10090.ENSMUSP00000103161 |
Structurei
3D structure databases
ProteinModelPortali | O08759 |
SMRi | O08759 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 542 – 870 | HECTPROSITE-ProRule annotationAdd BLAST | 329 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 389 – 394 | Asp/Glu-rich (acidic) | 6 |
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 42 – 81 | C4-type; atypicalBy similarityAdd BLAST | 40 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG0941 Eukaryota COG5021 LUCA |
GeneTreei | ENSGT00940000155050 |
HOGENOMi | HOG000261634 |
HOVERGENi | HBG059326 |
InParanoidi | O08759 |
KOi | K10587 |
OMAi | KIVYYAN |
OrthoDBi | 339404at2759 |
TreeFami | TF315189 |
Family and domain databases
CDDi | cd00078 HECTc, 1 hit |
InterProi | View protein in InterPro IPR032353 AZUL IPR000569 HECT_dom IPR035983 Hect_E3_ubiquitin_ligase IPR017134 UBE3A |
Pfami | View protein in Pfam PF16558 AZUL, 1 hit PF00632 HECT, 1 hit |
PIRSFi | PIRSF037201 Ubiquitin-protein_ligase_E6-AP, 1 hit |
SMARTi | View protein in SMART SM00119 HECTc, 1 hit |
SUPFAMi | SSF56204 SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50237 HECT, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis 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.
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
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0J9YVG1 | A0A0J9YVG1_MOUSE | Ubiquitin-protein ligase E3A | Ube3a | 143 | Annotation score: | ||
A0A0J9YUY4 | A0A0J9YUY4_MOUSE | Ubiquitin-protein ligase E3A | Ube3a | 192 | Annotation score: | ||
A0A0J9YUK0 | A0A0J9YUK0_MOUSE | Ubiquitin-protein ligase E3A | Ube3a | 313 | Annotation score: | ||
A0A0J9YTX6 | A0A0J9YTX6_MOUSE | Ubiquitin-protein ligase E3A | Ube3a | 49 | Annotation score: | ||
A0A140LI50 | A0A140LI50_MOUSE | Ubiquitin-protein ligase E3A | Ube3a | 78 | Annotation score: | ||
A0A140LHS2 | A0A140LHS2_MOUSE | Ubiquitin-protein ligase E3A | Ube3a | 126 | Annotation score: | ||
A0A0J9YV26 | A0A0J9YV26_MOUSE | Ubiquitin-protein ligase E3A | Ube3a | 15 | Annotation score: | ||
A0A0J9YUF2 | A0A0J9YUF2_MOUSE | Ubiquitin-protein ligase E3A | Ube3a | 40 | Annotation score: |
Sequence cautioni
The sequence AAB47756 differs from that shown. Reason: Frameshift at positions 561, 567, 607 and 612.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 7 | R → S in AAB63361 (PubMed:9182527).Curated | 1 | |
Sequence conflicti | 171 | E → D in AAB63361 (PubMed:9182527).Curated | 1 | |
Sequence conflicti | 285 | V → L in AAB63361 (PubMed:9182527).Curated | 1 | |
Sequence conflicti | 327 | S → T in AAB63361 (PubMed:9182527).Curated | 1 | |
Sequence conflicti | 368 | K → N in AAB63361 (PubMed:9182527).Curated | 1 | |
Sequence conflicti | 444 | F → S in AAB63361 (PubMed:9182527).Curated | 1 | |
Sequence conflicti | 470 | F → G in AAB63361 (PubMed:9182527).Curated | 1 | |
Sequence conflicti | 519 | R → T in AAB63361 (PubMed:9182527).Curated | 1 | |
Sequence conflicti | 581 | D → N in AAB47756 (PubMed:9110176).Curated | 1 | |
Sequence conflicti | 613 | Missing in AAB63361 (PubMed:9182527).Curated | 1 | |
Sequence conflicti | 710 – 711 | NL → IS in AAB63361 (PubMed:9182527).Curated | 2 | |
Sequence conflicti | 802 | Q → L in AAB63361 (PubMed:9182527).Curated | 1 | |
Sequence conflicti | 854 – 855 | KE → NV in AAB63361 (PubMed:9182527).Curated | 2 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_057563 | 1 – 21 | Missing in isoform 2 and isoform 3. Add BLAST | 21 | |
Alternative sequenceiVSP_057564 | 784 – 870 | Missing in isoform 3. Add BLAST | 87 |
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 |
CCDSi | CCDS39973.1 [O08759-1] CCDS80733.1 [O08759-2] |
RefSeqi | NP_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] |
UniGenei | Mm.9002 |
Genome annotation databases
Ensembli | ENSMUST00000107537; ENSMUSP00000103161; ENSMUSG00000025326 [O08759-2] ENSMUST00000200758; ENSMUSP00000143859; ENSMUSG00000025326 [O08759-1] ENSMUST00000202945; ENSMUSP00000143962; ENSMUSG00000025326 [O08759-3] |
GeneIDi | 22215 |
KEGGi | mmu:22215 |
UCSCi | uc009heg.1 mouse uc009hei.1 mouse |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS39973.1 [O08759-1] CCDS80733.1 [O08759-2] |
RefSeqi | NP_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] |
UniGenei | Mm.9002 |
3D structure databases
ProteinModelPortali | O08759 |
SMRi | O08759 |
ModBasei | Search... |
MobiDBi | Search... |
Protein-protein interaction databases
IntActi | O08759, 3 interactors |
MINTi | O08759 |
STRINGi | 10090.ENSMUSP00000103161 |
PTM databases
iPTMneti | O08759 |
PhosphoSitePlusi | O08759 |
SwissPalmi | O08759 |
Proteomic databases
EPDi | O08759 |
MaxQBi | O08759 |
PaxDbi | O08759 |
PeptideAtlasi | O08759 |
PRIDEi | O08759 |
Protocols and materials databases
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENSMUST00000107537; ENSMUSP00000103161; ENSMUSG00000025326 [O08759-2] ENSMUST00000200758; ENSMUSP00000143859; ENSMUSG00000025326 [O08759-1] ENSMUST00000202945; ENSMUSP00000143962; ENSMUSG00000025326 [O08759-3] |
GeneIDi | 22215 |
KEGGi | mmu:22215 |
UCSCi | uc009heg.1 mouse uc009hei.1 mouse |
Organism-specific databases
CTDi | 7337 |
MGIi | MGI:105098 Ube3a |
Phylogenomic databases
eggNOGi | KOG0941 Eukaryota COG5021 LUCA |
GeneTreei | ENSGT00940000155050 |
HOGENOMi | HOG000261634 |
HOVERGENi | HBG059326 |
InParanoidi | O08759 |
KOi | K10587 |
OMAi | KIVYYAN |
OrthoDBi | 339404at2759 |
TreeFami | TF315189 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
BRENDAi | 6.3.2.19 3474 |
Reactomei | R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation |
Miscellaneous databases
ChiTaRSi | Ube3a mouse |
PROi | PR:O08759 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000025326 Expressed in 291 organ(s), highest expression level in vas deferens |
ExpressionAtlasi | O08759 baseline and differential |
Genevisiblei | O08759 MM |
Family and domain databases
CDDi | cd00078 HECTc, 1 hit |
InterProi | View protein in InterPro IPR032353 AZUL IPR000569 HECT_dom IPR035983 Hect_E3_ubiquitin_ligase IPR017134 UBE3A |
Pfami | View protein in Pfam PF16558 AZUL, 1 hit PF00632 HECT, 1 hit |
PIRSFi | PIRSF037201 Ubiquitin-protein_ligase_E6-AP, 1 hit |
SMARTi | View protein in SMART SM00119 HECTc, 1 hit |
SUPFAMi | SSF56204 SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50237 HECT, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | UBE3A_MOUSE | |
Accessioni | O08759Primary (citable) accession number: O08759 Secondary accession number(s): E9QKT1, P97482, Q8CE29 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | April 1, 2015 | |
Last modified: | February 13, 2019 | |
This is version 150 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways