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Protein

NEDD8-activating enzyme E1 catalytic subunit

Gene

Uba3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

Activity 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: MGI
  • protein neddylation Source: GO_Central
  • regulation of cell cycle Source: MGI

Keywordsi

Molecular functionLigase
Biological processCell cycle, Ubl conjugation pathway
LigandATP-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-8951664 Neddylation
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayi
UPA00885

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD8-activating enzyme E1 catalytic subunit (EC:6.2.1.-)
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1341217 Uba3

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

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).1 Publication

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 Expressed in 286 organ(s), highest expression level in cochlea
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
OrthoDBiEOG091G0B0K
TreeFamiTF300499

Family and domain databases

Gene3Di1.10.10.520, 1 hit
InterProiView protein in InterPro
IPR014929 E2_binding
IPR000594 ThiF_NAD_FAD-bd
IPR023318 Ub_act_enz_dom_a_sf
IPR030468 Uba3
IPR035985 Ubiquitin-activating_enz
IPR033127 UBQ-activ_enz_E1_Cys_AS
PANTHERiPTHR10953:SF6 PTHR10953:SF6, 1 hit
PfamiView protein in Pfam
PF08825 E2_bind, 1 hit
PF00899 ThiF, 1 hit
SMARTiView protein in SMART
SM01181 E2_bind, 1 hit
SUPFAMiSSF69572 SSF69572, 1 hit
PROSITEiView protein in PROSITE
PS00865 UBIQUITIN_ACTIVAT_2, 1 hit

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q3TL72Q3TL72_MOUSE
NEDD8-activating enzyme E1 catalyti...
Uba3 Ube1c
448Annotation score:
A0A0N4SVZ2A0A0N4SVZ2_MOUSE
NEDD8-activating enzyme E1 catalyti...
Uba3
66Annotation score:

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

Similar proteinsi

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
OrthoDBiEOG091G0B0K
TreeFamiTF300499

Enzyme and pathway databases

UniPathwayi
UPA00885

ReactomeiR-MMU-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-MMU-5676590 NIK-->noncanonical NF-kB signaling
R-MMU-8951664 Neddylation
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

PROiPR:Q8C878
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030061 Expressed in 286 organ(s), highest expression level in cochlea
CleanExiMM_UBA3
ExpressionAtlasiQ8C878 baseline and differential
GenevisibleiQ8C878 MM

Family and domain databases

Gene3Di1.10.10.520, 1 hit
InterProiView protein in InterPro
IPR014929 E2_binding
IPR000594 ThiF_NAD_FAD-bd
IPR023318 Ub_act_enz_dom_a_sf
IPR030468 Uba3
IPR035985 Ubiquitin-activating_enz
IPR033127 UBQ-activ_enz_E1_Cys_AS
PANTHERiPTHR10953:SF6 PTHR10953:SF6, 1 hit
PfamiView protein in Pfam
PF08825 E2_bind, 1 hit
PF00899 ThiF, 1 hit
SMARTiView protein in SMART
SM01181 E2_bind, 1 hit
SUPFAMiSSF69572 SSF69572, 1 hit
PROSITEiView protein in PROSITE
PS00865 UBIQUITIN_ACTIVAT_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUBA3_MOUSE
AccessioniPrimary (citable) accession number: Q8C878
Secondary accession number(s): O88598, Q3TG68, Q9D6B7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 138 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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Main funding by: National Institutes of Health

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