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Protein

NEDD8-activating enzyme E1 catalytic subunit

Gene

Uba3

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

Functioni

Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression.1 Publication

Enzyme regulationi

Binding of TP53BP2 to the regulatory subunit NAE1 decreases activity.By similarity

Pathwayi: protein neddylation

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei211Determines specificity for NEDD8By similarity1
Active sitei237Glycyl thioester intermediatePROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi100 – 124ATPBy similarityAdd BLAST25
Nucleotide bindingi148 – 171ATPBy similarityAdd BLAST24

GO - Molecular functioni

GO - Biological processi

  • endomitotic cell cycle Source: MGI
  • mitotic cell cycle Source: MGI
  • negative regulation of transcription, DNA-templated Source: Ensembl
  • protein neddylation Source: GO_Central
  • regulation of cell cycle Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Cell cycle, Ubl conjugation pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-MMU-5676590. NIK-->noncanonical NF-kB signaling.
R-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00885.

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD8-activating enzyme E1 catalytic subunit (EC:6.3.2.-)
Alternative name(s):
NEDD8-activating enzyme E1C
Ubiquitin-activating enzyme E1C
Ubiquitin-like modifier-activating enzyme 3
Short name:
Ubiquitin-activating enzyme 3
Gene namesi
Name:Uba3
Synonyms:Ube1c
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1341217. Uba3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Defects in Uba3 are a cause of embryonic lethality. Mouse embryos deficient in Uba3 die at the preimplantation stage (PubMed:11696557).

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001949422 – 462NEDD8-activating enzyme E1 catalytic subunitAdd BLAST461

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ8C878.
PaxDbiQ8C878.
PeptideAtlasiQ8C878.
PRIDEiQ8C878.

PTM databases

iPTMnetiQ8C878.
PhosphoSitePlusiQ8C878.
SwissPalmiQ8C878.

Expressioni

Gene expression databases

BgeeiENSMUSG00000030061.
CleanExiMM_UBA3.
ExpressionAtlasiQ8C878. baseline and differential.
GenevisibleiQ8C878. MM.

Interactioni

Subunit structurei

Heterodimer of UBA3 and NAE1. Interacts with NEDD8, UBE2F and UBE2M. Binds ESR1 and ESR2 with bound steroid ligand (By similarity). Interacts with TBATA.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204409. 1 interactor.
STRINGi10090.ENSMUSP00000086701.

Structurei

3D structure databases

ProteinModelPortaliQ8C878.
SMRiQ8C878.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni53 – 70Interaction with UBE2M N-terminusBy similarityAdd BLAST18
Regioni157 – 161Interaction with UBE2M N-terminusBy similarity5
Regioni192 – 217Interaction with UBE2M N-terminusBy similarityAdd BLAST26
Regioni227 – 229Interaction with NEDD8By similarity3
Regioni242 – 248Interaction with NAE1By similarity7
Regioni292 – 295Interaction with NAE1By similarity4
Regioni331 – 338Interaction with UBE2M N-terminusBy similarity8
Regioni352 – 357Interaction with NEDD8By similarity6
Regioni368 – 462Interaction with UBE2M core domainBy similarityAdd BLAST95

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2015. Eukaryota.
COG0476. LUCA.
GeneTreeiENSGT00550000074831.
HOGENOMiHOG000166793.
HOVERGENiHBG082736.
InParanoidiQ8C878.
KOiK10686.
OMAiNNASLQM.
OrthoDBiEOG091G0B0K.
TreeFamiTF300499.

Family and domain databases

Gene3Di1.10.10.520. 1 hit.
3.10.20.260. 1 hit.
3.40.50.720. 2 hits.
InterProiIPR014929. E2_binding.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
IPR023318. Ub_act_enz_dom_a.
IPR030468. Uba3.
IPR033127. UBQ-activ_enz_E1_Cys_AS.
[Graphical view]
PANTHERiPTHR10953:SF6. PTHR10953:SF6. 1 hit.
PfamiPF08825. E2_bind. 1 hit.
PF00899. ThiF. 1 hit.
[Graphical view]
SMARTiSM01181. E2_bind. 1 hit.
[Graphical view]
SUPFAMiSSF69572. SSF69572. 1 hit.
PROSITEiPS00865. UBIQUITIN_ACTIVAT_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: Q8C878-1) [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
MADGEEPEKK RRRIEELLAE KMAVDGGCGD TGDWEGRWNH VKKFLERSGP
60 70 80 90 100
FTHPDFEPST ESLQFLLDTC KVLVIGAGGL GCELLKNLAL SGFRQIHVID
110 120 130 140 150
MDTIDVSNLN RQFLFRPKDV GRPKAEVAAE FLNDRVPNCN VVPHFNKIQD
160 170 180 190 200
FNDTFYRQFH IIVCGLDSII ARRWINGMLI SLLNYEDGVL DPSSIVPLID
210 220 230 240 250
GGTEGFKGNA RVILPGMTAC IECTLELYPP QVNFPMCTIA SMPRLPEHCI
260 270 280 290 300
EYVRMLQWPK EQPFGDGVPL DGDDPEHIQW IFQKSIERAS QYNIRGVTYR
310 320 330 340 350
LTQGVVKRII PAVASTNAVI AAVCATEVFK IATSAYIPLN NYLVFNDVDG
360 370 380 390 400
LYTYTFEAER KENCPACSQL PQNIQFSPSA KLQEVLDYLT NSASLQMKSP
410 420 430 440 450
AITATLEGKN RTLYLQSVTS IEERTRPNLS KTLKELGLVD GQELAVADVT
460
TPQTVLFKLH FT
Length:462
Mass (Da):51,737
Last modified:July 27, 2011 - v2
Checksum:i4034CE39E6E9A14E
GO
Isoform 2 (identifier: Q8C878-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     396-462: Missing.

Show »
Length:395
Mass (Da):44,326
Checksum:i01E494E63C4166CB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti147K → E in BAB29346 (PubMed:16141072).Curated1
Sequence conflicti334S → G in BAB29346 (PubMed:16141072).Curated1
Sequence conflicti397M → I in BAC33258 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010787396 – 462Missing in isoform 2. 1 PublicationAdd BLAST67

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK014433 mRNA. Translation: BAB29346.1.
AK032514 mRNA. Translation: BAC27905.1.
AK048148 mRNA. Translation: BAC33258.1.
AK159381 mRNA. Translation: BAE35036.1.
AK168859 mRNA. Translation: BAE40680.1.
CH466523 Genomic DNA. Translation: EDK99352.1.
BC002002 mRNA. Translation: AAH02002.1.
AF077330 mRNA. Translation: AAC27323.1.
AY029181 mRNA. Translation: AAK33015.1.
CCDSiCCDS51860.1. [Q8C878-1]
RefSeqiNP_001104576.1. NM_001111106.2.
NP_001288786.1. NM_001301857.1.
NP_001288787.1. NM_001301858.1.
NP_001288788.1. NM_001301859.1. [Q8C878-2]
NP_035796.2. NM_011666.3. [Q8C878-1]
XP_006505976.1. XM_006505913.3.
XP_011239592.1. XM_011241290.2.
UniGeneiMm.277626.
Mm.431883.

Genome annotation databases

EnsembliENSMUST00000089287; ENSMUSP00000086701; ENSMUSG00000030061. [Q8C878-1]
GeneIDi22200.
KEGGimmu:22200.
UCSCiuc009dam.3. mouse. [Q8C878-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK014433 mRNA. Translation: BAB29346.1.
AK032514 mRNA. Translation: BAC27905.1.
AK048148 mRNA. Translation: BAC33258.1.
AK159381 mRNA. Translation: BAE35036.1.
AK168859 mRNA. Translation: BAE40680.1.
CH466523 Genomic DNA. Translation: EDK99352.1.
BC002002 mRNA. Translation: AAH02002.1.
AF077330 mRNA. Translation: AAC27323.1.
AY029181 mRNA. Translation: AAK33015.1.
CCDSiCCDS51860.1. [Q8C878-1]
RefSeqiNP_001104576.1. NM_001111106.2.
NP_001288786.1. NM_001301857.1.
NP_001288787.1. NM_001301858.1.
NP_001288788.1. NM_001301859.1. [Q8C878-2]
NP_035796.2. NM_011666.3. [Q8C878-1]
XP_006505976.1. XM_006505913.3.
XP_011239592.1. XM_011241290.2.
UniGeneiMm.277626.
Mm.431883.

3D structure databases

ProteinModelPortaliQ8C878.
SMRiQ8C878.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204409. 1 interactor.
STRINGi10090.ENSMUSP00000086701.

PTM databases

iPTMnetiQ8C878.
PhosphoSitePlusiQ8C878.
SwissPalmiQ8C878.

Proteomic databases

EPDiQ8C878.
PaxDbiQ8C878.
PeptideAtlasiQ8C878.
PRIDEiQ8C878.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000089287; ENSMUSP00000086701; ENSMUSG00000030061. [Q8C878-1]
GeneIDi22200.
KEGGimmu:22200.
UCSCiuc009dam.3. mouse. [Q8C878-1]

Organism-specific databases

CTDi9039.
MGIiMGI:1341217. Uba3.

Phylogenomic databases

eggNOGiKOG2015. Eukaryota.
COG0476. LUCA.
GeneTreeiENSGT00550000074831.
HOGENOMiHOG000166793.
HOVERGENiHBG082736.
InParanoidiQ8C878.
KOiK10686.
OMAiNNASLQM.
OrthoDBiEOG091G0B0K.
TreeFamiTF300499.

Enzyme and pathway databases

UniPathwayiUPA00885.
ReactomeiR-MMU-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-MMU-5676590. NIK-->noncanonical NF-kB signaling.
R-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

PROiQ8C878.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030061.
CleanExiMM_UBA3.
ExpressionAtlasiQ8C878. baseline and differential.
GenevisibleiQ8C878. MM.

Family and domain databases

Gene3Di1.10.10.520. 1 hit.
3.10.20.260. 1 hit.
3.40.50.720. 2 hits.
InterProiIPR014929. E2_binding.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
IPR023318. Ub_act_enz_dom_a.
IPR030468. Uba3.
IPR033127. UBQ-activ_enz_E1_Cys_AS.
[Graphical view]
PANTHERiPTHR10953:SF6. PTHR10953:SF6. 1 hit.
PfamiPF08825. E2_bind. 1 hit.
PF00899. ThiF. 1 hit.
[Graphical view]
SMARTiSM01181. E2_bind. 1 hit.
[Graphical view]
SUPFAMiSSF69572. SSF69572. 1 hit.
PROSITEiPS00865. UBIQUITIN_ACTIVAT_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBA3_MOUSE
AccessioniPrimary (citable) accession number: Q8C878
Secondary accession number(s): O88598, Q3TG68, Q9D6B7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Arg-211 acts as a selectivity gate, preventing misactivation of ubiquitin by this NEDD8-specific E1 complex.By similarity

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.