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Protein

NEDD8-activating enzyme E1 catalytic subunit

Gene

UBA3

Organism
Homo sapiens (Human)
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.3 Publications

Miscellaneous

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

Activity regulationi

Binding of TP53BP2 to the regulatory subunit NAE1 decreases activity.

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 NEDD81
Active sitei237Glycyl thioester intermediate1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi100 – 124ATP1 PublicationAdd BLAST25
Nucleotide bindingi148 – 171ATP1 PublicationAdd BLAST24

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionLigase
Biological processCell cycle, Ubl conjugation pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS07200-MONOMER
BRENDAi2.3.2.B5 2681
6.2.1.B9 2681
ReactomeiR-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5676590 NIK-->noncanonical NF-kB signaling
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SIGNORiQ8TBC4
UniPathwayi
UPA00885

Protein family/group databases

MoonDBiQ8TBC4 Predicted

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000144744.16
HGNCiHGNC:12470 UBA3
MIMi603172 gene
neXtProtiNX_Q8TBC4

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi65F → G: Reduces affinity for UBE2M. 1 Publication1
Mutagenesisi148I → A: No effect on NEDD8 adenylation. 1 Publication1
Mutagenesisi160 – 161HI → AA: Reduces affinity for UBE2M. 1 Publication2
Mutagenesisi167D → A: Abolishes NEDD8 adenylation. 1 Publication1
Mutagenesisi192P → A: Reduces affinity for UBE2M; when associated with A-195 and A-197. 1 Publication1
Mutagenesisi195I → A: Reduces affinity for UBE2M; when associated with A-192 and A-197. 1 Publication1
Mutagenesisi197P → A: Reduces affinity for UBE2M; when associated with A-192 and A-195. 1 Publication1
Mutagenesisi211R → Q: Abolishes specificity for NEDD8. 1 Publication1
Mutagenesisi214L → A: Reduces affinity for UBE2M; when associated with A-217. 1 Publication1
Mutagenesisi217M → A: Reduces affinity for UBE2M; when associated with A-214. 1 Publication1
Mutagenesisi227 – 228LY → DD: Strongly reduces NEDD8 adenylation. 1 Publication2
Mutagenesisi237C → S: Abolishes thioester intermediate formation. 1 Publication1
Mutagenesisi238T → A: No effect on NEDD8 adenylation; impairs thioester intermediate formation. 1 Publication1
Mutagenesisi310I → A: No effect on NEDD8 adenylation or thioester intermediate formation; impairs NEDD8 transfer to UBE2M. 1 Publication1
Mutagenesisi331I → A: Reduces affinity for UBE2M. 1 Publication1
Mutagenesisi352 – 357YTYTFE → ATATA: Abolishes NEDD8 adenylation. 1 Publication6
Mutagenesisi368S → P: Impairs NEDD8 transfer to UBE2M. 1 Publication1
Mutagenesisi369Q → P: No effect on NEDD8 transfer to UBE2M. 1 Publication1
Mutagenesisi370L → P: Impairs NEDD8 transfer to UBE2M. 1 Publication1
Mutagenesisi412T → A: Impairs NEDD8 transfer to UBE2M. 1 Publication1
Mutagenesisi415L → A: Impairs NEDD8 transfer to UBE2M. 1 Publication1
Mutagenesisi418V → A: Impairs NEDD8 transfer to UBE2M. 1 Publication1
Mutagenesisi421I → A: Impairs NEDD8 transfer to UBE2M. 1 Publication1
Mutagenesisi424R → A: No effect on NEDD8 transfer to UBE2M. 1 Publication1

Organism-specific databases

DisGeNETi9039
OpenTargetsiENSG00000144744
PharmGKBiPA162407622

Chemistry databases

ChEMBLiCHEMBL2016430

Polymorphism and mutation databases

BioMutaiUBA3
DMDMi83305811

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001949412 – 463NEDD8-activating enzyme E1 catalytic subunitAdd BLAST462

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ8TBC4
MaxQBiQ8TBC4
PaxDbiQ8TBC4
PeptideAtlasiQ8TBC4
PRIDEiQ8TBC4
ProteomicsDBi73991
73992 [Q8TBC4-2]

PTM databases

iPTMnetiQ8TBC4
PhosphoSitePlusiQ8TBC4

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000144744 Expressed in 235 organ(s), highest expression level in substantia nigra
CleanExiHS_UBA3
ExpressionAtlasiQ8TBC4 baseline and differential
GenevisibleiQ8TBC4 HS

Organism-specific databases

HPAiHPA034873
HPA034874
HPA065335

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 similarity).By similarity

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114503, 46 interactors
CORUMiQ8TBC4
IntActiQ8TBC4, 16 interactors
MINTiQ8TBC4
STRINGi9606.ENSP00000354340

Structurei

Secondary structure

1463
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8TBC4
SMRiQ8TBC4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8TBC4

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni53 – 70Interaction with UBE2M N-terminusAdd BLAST18
Regioni157 – 161Interaction with UBE2M N-terminus5
Regioni192 – 217Interaction with UBE2M N-terminusAdd BLAST26
Regioni227 – 229Interaction with NEDD83
Regioni242 – 248Interaction with NAE11 Publication7
Regioni292 – 295Interaction with NAE11 Publication4
Regioni331 – 338Interaction with UBE2M N-terminus8
Regioni352 – 357Interaction with NEDD86
Regioni368 – 463Interaction with UBE2M core domainAdd BLAST96

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2015 Eukaryota
COG0476 LUCA
GeneTreeiENSGT00550000074831
HOGENOMiHOG000166793
HOVERGENiHBG082736
InParanoidiQ8TBC4
KOiK10686
OMAiTAFPICT
OrthoDBiEOG091G0B0K
PhylomeDBiQ8TBC4
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 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8TBC4-1) [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 RQFLFRPKDI 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 EQPFGEGVPL DGDDPEHIQW IFQKSLERAS 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 FTS
Length:463
Mass (Da):51,852
Last modified:December 6, 2005 - v2
Checksum:i4C16DC0EEDE31A76
GO
Isoform 2 (identifier: Q8TBC4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     8-21: Missing.

Show »
Length:449
Mass (Da):50,072
Checksum:iC624B0B917B2482B
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8W8D4F8W8D4_HUMAN
NEDD8-activating enzyme E1 catalyti...
UBA3
422Annotation score:
F8WF86F8WF86_HUMAN
NEDD8-activating enzyme E1 catalyti...
UBA3
129Annotation score:
F8WAT6F8WAT6_HUMAN
NEDD8-activating enzyme E1 catalyti...
UBA3
64Annotation score:
A0A0D9SF81A0A0D9SF81_HUMAN
NEDD8-activating enzyme E1 catalyti...
UBA3
41Annotation score:

Sequence cautioni

The sequence AAC27648 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti146N → Y in CAB55996 (PubMed:11230166).Curated1
Sequence conflicti271D → G in CAB55996 (PubMed:11230166).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0239459K → R2 PublicationsCorresponds to variant dbSNP:rs17852113Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0411278 – 21Missing in isoform 2. 1 PublicationAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL117566 mRNA Translation: CAB55996.2
AK002159 mRNA Translation: BAG51021.1
AK289392 mRNA Translation: BAF82081.1
AC092060 Genomic DNA No translation available.
AC109587 Genomic DNA No translation available.
CH471055 Genomic DNA Translation: EAW65470.1
BC022853 mRNA Translation: AAH22853.1
AF046024 mRNA Translation: AAC27648.1 Different initiation.
AB012190 mRNA Translation: BAA33144.1
CCDSiCCDS2909.1 [Q8TBC4-1]
CCDS2910.1 [Q8TBC4-2]
PIRiT17306
RefSeqiNP_003959.3, NM_003968.3 [Q8TBC4-1]
NP_937838.1, NM_198195.1 [Q8TBC4-2]
UniGeneiHs.154320

Genome annotation databases

EnsembliENST00000349511; ENSP00000340041; ENSG00000144744 [Q8TBC4-2]
ENST00000361055; ENSP00000354340; ENSG00000144744 [Q8TBC4-1]
GeneIDi9039
KEGGihsa:9039
UCSCiuc003dno.4 human [Q8TBC4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL117566 mRNA Translation: CAB55996.2
AK002159 mRNA Translation: BAG51021.1
AK289392 mRNA Translation: BAF82081.1
AC092060 Genomic DNA No translation available.
AC109587 Genomic DNA No translation available.
CH471055 Genomic DNA Translation: EAW65470.1
BC022853 mRNA Translation: AAH22853.1
AF046024 mRNA Translation: AAC27648.1 Different initiation.
AB012190 mRNA Translation: BAA33144.1
CCDSiCCDS2909.1 [Q8TBC4-1]
CCDS2910.1 [Q8TBC4-2]
PIRiT17306
RefSeqiNP_003959.3, NM_003968.3 [Q8TBC4-1]
NP_937838.1, NM_198195.1 [Q8TBC4-2]
UniGeneiHs.154320

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1R4MX-ray3.00B/D/F/H33-463[»]
1R4NX-ray3.60B/D/F/H33-463[»]
1TT5X-ray2.60B/D33-463[»]
1Y8XX-ray2.40B368-463[»]
1YOVX-ray2.60B/D22-463[»]
2LQ7NMR-A369-463[»]
2NVUX-ray2.80B33-463[»]
3DBHX-ray2.85B/D/F/H33-463[»]
3DBLX-ray2.90B/D/F/H33-463[»]
3DBRX-ray3.05B/D/F/H33-463[»]
3FN1X-ray2.50A368-463[»]
3GZNX-ray3.00B/D1-463[»]
5JJMX-ray2.15G/H/I/J62-69[»]
ProteinModelPortaliQ8TBC4
SMRiQ8TBC4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114503, 46 interactors
CORUMiQ8TBC4
IntActiQ8TBC4, 16 interactors
MINTiQ8TBC4
STRINGi9606.ENSP00000354340

Chemistry databases

ChEMBLiCHEMBL2016430

Protein family/group databases

MoonDBiQ8TBC4 Predicted

PTM databases

iPTMnetiQ8TBC4
PhosphoSitePlusiQ8TBC4

Polymorphism and mutation databases

BioMutaiUBA3
DMDMi83305811

Proteomic databases

EPDiQ8TBC4
MaxQBiQ8TBC4
PaxDbiQ8TBC4
PeptideAtlasiQ8TBC4
PRIDEiQ8TBC4
ProteomicsDBi73991
73992 [Q8TBC4-2]

Protocols and materials databases

DNASUi9039
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000349511; ENSP00000340041; ENSG00000144744 [Q8TBC4-2]
ENST00000361055; ENSP00000354340; ENSG00000144744 [Q8TBC4-1]
GeneIDi9039
KEGGihsa:9039
UCSCiuc003dno.4 human [Q8TBC4-1]

Organism-specific databases

CTDi9039
DisGeNETi9039
EuPathDBiHostDB:ENSG00000144744.16
GeneCardsiUBA3
HGNCiHGNC:12470 UBA3
HPAiHPA034873
HPA034874
HPA065335
MIMi603172 gene
neXtProtiNX_Q8TBC4
OpenTargetsiENSG00000144744
PharmGKBiPA162407622
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2015 Eukaryota
COG0476 LUCA
GeneTreeiENSGT00550000074831
HOGENOMiHOG000166793
HOVERGENiHBG082736
InParanoidiQ8TBC4
KOiK10686
OMAiTAFPICT
OrthoDBiEOG091G0B0K
PhylomeDBiQ8TBC4
TreeFamiTF300499

Enzyme and pathway databases

UniPathwayi
UPA00885

BioCyciMetaCyc:HS07200-MONOMER
BRENDAi2.3.2.B5 2681
6.2.1.B9 2681
ReactomeiR-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5676590 NIK-->noncanonical NF-kB signaling
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SIGNORiQ8TBC4

Miscellaneous databases

ChiTaRSiUBA3 human
EvolutionaryTraceiQ8TBC4
GeneWikiiUBE1C
GenomeRNAii9039
PROiPR:Q8TBC4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144744 Expressed in 235 organ(s), highest expression level in substantia nigra
CleanExiHS_UBA3
ExpressionAtlasiQ8TBC4 baseline and differential
GenevisibleiQ8TBC4 HS

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_HUMAN
AccessioniPrimary (citable) accession number: Q8TBC4
Secondary accession number(s): A6NLB5
, A8K027, O76088, Q9NTU3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: December 6, 2005
Last modified: November 7, 2018
This is version 172 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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