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NEDD8-activating enzyme E1 catalytic subunit; NEDD8-activating enzyme E1C; ubiquitin-activating enzyme E1C; ubiquitin-like modifier-activating enzyme 3; ubiquitin-activating enzyme 3 (UBA3, UBE1C)
Function:
- NEDD8-specific E1 complex
- catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme
- E1 activates NEDD8 by first adenylating its C-terminal Gly with ATP, thus linking NEDD8-Gly to UBA3's catalytic Cys, yielding a NEDD8-UBA3 thioester & AMP
- E1 finally transfers NEDD8 to the catalytic Cys of UBE2M
- down-regulates steroid receptor activity
- necessary for cell cycle progression
- binding of TP53BP2 to the regulatory subunit
- NAE1 decreases activity
- protein modification; protein neddylation
- heterodimer of UBA3 & NAE1
- interacts with NEDD8, UBE2F & UBE2M.
- binds ESR1 & ESR2 with bound steroid ligand
Structure:
- belongs to the ubiquitin-activating E1 family, UBA3 subfamily
Alternative splicing: named isoforms=2
Expression:
- ubiquitously expressed
Notes:
- Arg-211 acts as a selectivity gate, preventing misactivation of ubiquitin
Related
NEDD8; ubiquitin-like protein Nedd8; neddylin; neural cell expressed developmentally down-regulated protein 8; NEDD-8 (NEDD8)
ubiquitin (UBCEP2, UBB, UBC)
General
ligase or synthetase
oligomerizing protein
Properties
SIZE: entity length = 463 aa
MW = 52 kD
MOTIF: UBE2M interaction {53-70}
ATP-binding site
NAME: ATP-binding site
SITE: 100-124
ATP-binding site
NAME: ATP-binding site
SITE: 148-171
MOTIF: UBE2M interaction {157-161}
UBE2M interaction {192-217}
MOTIF: arginine residue {211}
NEDD8 interaction {227-229}
active site
cysteine residue {C237}
NAE1 interaction {242-248}
NAE1 interaction {292-295}
UBE2M interaction {331-338}
NEDD8 interaction {352-357}
UBE2M core interaction {368-463}
Database Correlations
OMIM 603172
UniProt Q8TBC4
PFAM correlations
Entrez Gene 9039
Kegg hsa:9039
References
- OMIM :accession 603172
- UniProt :accession Q8TBB1