UniProtKB - Q8TBC4 (UBA3_HUMAN)
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Protein
NEDD8-activating enzyme E1 catalytic subunit
Gene
UBA3
Organism
Homo sapiens (Human)
Status
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.
Enzyme regulationi
Binding of TP53BP2 to the regulatory subunit NAE1 decreases activity.
: protein neddylation Pathwayi
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 211 | Determines specificity for NEDD8 | 1 | |
Active sitei | 237 | Glycyl thioester intermediate | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 100 – 124 | ATP1 PublicationAdd BLAST | 25 | |
Nucleotide bindingi | 148 – 171 | ATP1 PublicationAdd BLAST | 24 |
GO - Molecular functioni
- acid-amino acid ligase activity Source: InterPro
- ATP binding Source: UniProtKB-KW
- identical protein binding Source: IntAct
- ligand-dependent nuclear receptor binding Source: Ensembl
- NEDD8 activating enzyme activity Source: MGI
- NEDD8 transferase activity Source: Reactome
- protein heterodimerization activity Source: UniProtKB
GO - Biological processi
- cellular protein modification process Source: ProtInc
- endomitotic cell cycle Source: Ensembl
- negative regulation of transcription, DNA-templated Source: Ensembl
- NIK/NF-kappaB signaling Source: Reactome
- post-translational protein modification Source: Reactome
- protein neddylation Source: GO_Central
- proteolysis Source: ProtInc
- regulation of cell cycle Source: Ensembl
Keywordsi
Molecular function | Ligase |
Biological process | Cell cycle, Ubl conjugation pathway |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:HS07200-MONOMER |
BRENDAi | 2.3.2.B5 2681 6.2.1.B9 2681 |
Reactomei | R-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 |
SIGNORi | Q8TBC4 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000144744.16 |
HGNCi | HGNC:12470 UBA3 |
MIMi | 603172 gene |
neXtProti | NX_Q8TBC4 |
Subcellular locationi
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 65 | F → G: Reduces affinity for UBE2M. 1 Publication | 1 | |
Mutagenesisi | 148 | I → A: No effect on NEDD8 adenylation. 1 Publication | 1 | |
Mutagenesisi | 160 – 161 | HI → AA: Reduces affinity for UBE2M. 1 Publication | 2 | |
Mutagenesisi | 167 | D → A: Abolishes NEDD8 adenylation. 1 Publication | 1 | |
Mutagenesisi | 192 | P → A: Reduces affinity for UBE2M; when associated with A-195 and A-197. 1 Publication | 1 | |
Mutagenesisi | 195 | I → A: Reduces affinity for UBE2M; when associated with A-192 and A-197. 1 Publication | 1 | |
Mutagenesisi | 197 | P → A: Reduces affinity for UBE2M; when associated with A-192 and A-195. 1 Publication | 1 | |
Mutagenesisi | 211 | R → Q: Abolishes specificity for NEDD8. 1 Publication | 1 | |
Mutagenesisi | 214 | L → A: Reduces affinity for UBE2M; when associated with A-217. 1 Publication | 1 | |
Mutagenesisi | 217 | M → A: Reduces affinity for UBE2M; when associated with A-214. 1 Publication | 1 | |
Mutagenesisi | 227 – 228 | LY → DD: Strongly reduces NEDD8 adenylation. 1 Publication | 2 | |
Mutagenesisi | 237 | C → S: Abolishes thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 238 | T → A: No effect on NEDD8 adenylation; impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 310 | I → A: No effect on NEDD8 adenylation or thioester intermediate formation; impairs NEDD8 transfer to UBE2M. 1 Publication | 1 | |
Mutagenesisi | 331 | I → A: Reduces affinity for UBE2M. 1 Publication | 1 | |
Mutagenesisi | 352 – 357 | YTYTFE → ATATA: Abolishes NEDD8 adenylation. 1 Publication | 6 | |
Mutagenesisi | 368 | S → P: Impairs NEDD8 transfer to UBE2M. 1 Publication | 1 | |
Mutagenesisi | 369 | Q → P: No effect on NEDD8 transfer to UBE2M. 1 Publication | 1 | |
Mutagenesisi | 370 | L → P: Impairs NEDD8 transfer to UBE2M. 1 Publication | 1 | |
Mutagenesisi | 412 | T → A: Impairs NEDD8 transfer to UBE2M. 1 Publication | 1 | |
Mutagenesisi | 415 | L → A: Impairs NEDD8 transfer to UBE2M. 1 Publication | 1 | |
Mutagenesisi | 418 | V → A: Impairs NEDD8 transfer to UBE2M. 1 Publication | 1 | |
Mutagenesisi | 421 | I → A: Impairs NEDD8 transfer to UBE2M. 1 Publication | 1 | |
Mutagenesisi | 424 | R → A: No effect on NEDD8 transfer to UBE2M. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 9039 |
OpenTargetsi | ENSG00000144744 |
PharmGKBi | PA162407622 |
Chemistry databases
ChEMBLi | CHEMBL2016430 |
Polymorphism and mutation databases
BioMutai | UBA3 |
DMDMi | 83305811 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000194941 | 2 – 463 | NEDD8-activating enzyme E1 catalytic subunitAdd BLAST | 462 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 |
Keywords - PTMi
AcetylationProteomic databases
EPDi | Q8TBC4 |
MaxQBi | Q8TBC4 |
PaxDbi | Q8TBC4 |
PeptideAtlasi | Q8TBC4 |
PRIDEi | Q8TBC4 |
PTM databases
iPTMneti | Q8TBC4 |
PhosphoSitePlusi | Q8TBC4 |
Expressioni
Tissue specificityi
Ubiquitously expressed.1 Publication
Gene expression databases
Bgeei | ENSG00000144744 |
CleanExi | HS_UBA3 |
ExpressionAtlasi | Q8TBC4 baseline and differential |
Genevisiblei | Q8TBC4 HS |
Organism-specific databases
HPAi | HPA034873 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
- identical protein binding Source: IntAct
- ligand-dependent nuclear receptor binding Source: Ensembl
- protein heterodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGridi | 11450335 interactors. |
CORUMi | Q8TBC4 |
IntActi | Q8TBC4 16 interactors. |
MINTi | Q8TBC4 |
STRINGi | 9606.ENSP00000354340 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 31 – 33 | Combined sources | 3 | |
Turni | 35 – 38 | Combined sources | 4 | |
Helixi | 39 – 46 | Combined sources | 8 | |
Helixi | 63 – 67 | Combined sources | 5 | |
Beta strandi | 72 – 75 | Combined sources | 4 | |
Helixi | 80 – 90 | Combined sources | 11 | |
Beta strandi | 96 – 100 | Combined sources | 5 | |
Helixi | 106 – 108 | Combined sources | 3 | |
Turni | 109 – 111 | Combined sources | 3 | |
Helixi | 117 – 119 | Combined sources | 3 | |
Helixi | 124 – 135 | Combined sources | 12 | |
Beta strandi | 142 – 146 | Combined sources | 5 | |
Helixi | 148 – 150 | Combined sources | 3 | |
Helixi | 153 – 156 | Combined sources | 4 | |
Beta strandi | 160 – 164 | Combined sources | 5 | |
Helixi | 169 – 181 | Combined sources | 13 | |
Beta strandi | 185 – 188 | Combined sources | 4 | |
Beta strandi | 189 – 191 | Combined sources | 3 | |
Helixi | 192 – 194 | Combined sources | 3 | |
Beta strandi | 198 – 204 | Combined sources | 7 | |
Beta strandi | 207 – 213 | Combined sources | 7 | |
Turni | 215 – 217 | Combined sources | 3 | |
Helixi | 221 – 227 | Combined sources | 7 | |
Helixi | 236 – 241 | Combined sources | 6 | |
Helixi | 246 – 255 | Combined sources | 10 | |
Helixi | 257 – 260 | Combined sources | 4 | |
Helixi | 275 – 291 | Combined sources | 17 | |
Helixi | 299 – 306 | Combined sources | 8 | |
Helixi | 314 – 333 | Combined sources | 20 | |
Beta strandi | 341 – 346 | Combined sources | 6 | |
Beta strandi | 348 – 350 | Combined sources | 3 | |
Beta strandi | 352 – 356 | Combined sources | 5 | |
Turni | 365 – 367 | Combined sources | 3 | |
Beta strandi | 372 – 376 | Combined sources | 5 | |
Beta strandi | 377 – 379 | Combined sources | 3 | |
Helixi | 382 – 391 | Combined sources | 10 | |
Turni | 393 – 395 | Combined sources | 3 | |
Beta strandi | 401 – 406 | Combined sources | 6 | |
Beta strandi | 409 – 414 | Combined sources | 6 | |
Helixi | 419 – 430 | Combined sources | 12 | |
Beta strandi | 431 – 433 | Combined sources | 3 | |
Helixi | 434 – 436 | Combined sources | 3 | |
Helixi | 437 – 440 | Combined sources | 4 | |
Beta strandi | 443 – 447 | Combined sources | 5 | |
Beta strandi | 451 – 453 | Combined sources | 3 | |
Beta strandi | 455 – 460 | Combined sources | 6 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1R4M | X-ray | 3.00 | B/D/F/H | 33-463 | [»] | |
1R4N | X-ray | 3.60 | B/D/F/H | 33-463 | [»] | |
1TT5 | X-ray | 2.60 | B/D | 33-463 | [»] | |
1Y8X | X-ray | 2.40 | B | 368-463 | [»] | |
1YOV | X-ray | 2.60 | B/D | 22-463 | [»] | |
2LQ7 | NMR | - | A | 369-463 | [»] | |
2NVU | X-ray | 2.80 | B | 33-463 | [»] | |
3DBH | X-ray | 2.85 | B/D/F/H | 33-463 | [»] | |
3DBL | X-ray | 2.90 | B/D/F/H | 33-463 | [»] | |
3DBR | X-ray | 3.05 | B/D/F/H | 33-463 | [»] | |
3FN1 | X-ray | 2.50 | A | 368-463 | [»] | |
3GZN | X-ray | 3.00 | B/D | 1-463 | [»] | |
5JJM | X-ray | 2.15 | G/H/I/J | 62-69 | [»] | |
ProteinModelPortali | Q8TBC4 | |||||
SMRi | Q8TBC4 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q8TBC4 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 53 – 70 | Interaction with UBE2M N-terminusAdd BLAST | 18 | |
Regioni | 157 – 161 | Interaction with UBE2M N-terminus | 5 | |
Regioni | 192 – 217 | Interaction with UBE2M N-terminusAdd BLAST | 26 | |
Regioni | 227 – 229 | Interaction with NEDD8 | 3 | |
Regioni | 242 – 248 | Interaction with NAE11 Publication | 7 | |
Regioni | 292 – 295 | Interaction with NAE11 Publication | 4 | |
Regioni | 331 – 338 | Interaction with UBE2M N-terminus | 8 | |
Regioni | 352 – 357 | Interaction with NEDD8 | 6 | |
Regioni | 368 – 463 | Interaction with UBE2M core domainAdd BLAST | 96 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2015 Eukaryota COG0476 LUCA |
GeneTreei | ENSGT00550000074831 |
HOGENOMi | HOG000166793 |
HOVERGENi | HBG082736 |
InParanoidi | Q8TBC4 |
KOi | K10686 |
OMAi | IAASCCN |
OrthoDBi | EOG091G0B0K |
PhylomeDBi | Q8TBC4 |
TreeFami | TF300499 |
Family and domain databases
Gene3Di | 1.10.10.5201 hit |
InterProi | View 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 |
PANTHERi | PTHR10953:SF6 PTHR10953:SF6, 1 hit |
Pfami | View protein in Pfam PF08825 E2_bind, 1 hit PF00899 ThiF, 1 hit |
SMARTi | View protein in SMART SM01181 E2_bind, 1 hit |
SUPFAMi | SSF69572 SSF69572, 1 hit |
PROSITEi | View protein in PROSITE PS00865 UBIQUITIN_ACTIVAT_2, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basket
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.
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
Sequence cautioni
The sequence AAC27648 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 146 | N → Y in CAB55996 (PubMed:11230166).Curated | 1 | |
Sequence conflicti | 271 | D → G in CAB55996 (PubMed:11230166).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023945 | 9 | K → R2 PublicationsCorresponds to variant dbSNP:rs17852113Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_041127 | 8 – 21 | Missing in isoform 2. 1 PublicationAdd BLAST | 14 |
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 |
CCDSi | CCDS2909.1 [Q8TBC4-1] CCDS2910.1 [Q8TBC4-2] |
PIRi | T17306 |
RefSeqi | NP_003959.3, NM_003968.3 [Q8TBC4-1] NP_937838.1, NM_198195.1 [Q8TBC4-2] |
UniGenei | Hs.154320 |
Genome annotation databases
Ensembli | ENST00000349511; ENSP00000340041; ENSG00000144744 [Q8TBC4-2] ENST00000361055; ENSP00000354340; ENSG00000144744 [Q8TBC4-1] |
GeneIDi | 9039 |
KEGGi | hsa:9039 |
UCSCi | uc003dno.4 human [Q8TBC4-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | UBA3_HUMAN | |
Accessioni | Q8TBC4Primary (citable) accession number: Q8TBC4 Secondary accession number(s): A6NLB5 Q9NTU3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2004 |
Last sequence update: | December 6, 2005 | |
Last modified: | April 25, 2018 | |
This is version 167 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |