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Ubiquitin-like modifier activating enzyme 3
Protein UBE1C PDB 1r4m.png
PDB rendering based on 1r4m.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols UBA3 ; NAE2; UBE1C; hUBA3
External IDs OMIM603172 MGI1341217 HomoloGene2951 GeneCards: UBA3 Gene
RNA expression pattern
PBB GE UBE1C 209115 at tn.png
More reference expression data
Species Human Mouse
Entrez 9039 22200
Ensembl ENSG00000144744 ENSMUSG00000030061
UniProt Q8TBC4 Q8C878
RefSeq (mRNA) NM_003968 NM_001111106
RefSeq (protein) NP_003959 NP_001104576
Location (UCSC) Chr 3:
69.05 – 69.08 Mb
Chr 6:
97.18 – 97.21 Mb
PubMed search [1] [2]
E2 binding domain
PDB 1r4n EBI.jpg
appbp1-uba3-nedd8, an e1-ubiquitin-like protein complex with atp
Symbol E2_bind
Pfam PF08825
InterPro IPR014929

NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3 gene.[1][2]

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin-activating enzyme family. The encoded enzyme associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then the enzyme complex activates NEDD8, a ubiquitin-like protein, which regulates cell division, signaling and embryogenesis. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[2]

This enzyme contains an E2 binding domain, which resembles ubiquitin, and recruits the catalytic core of the E2 enzyme UBE2M (Ubc12) in a similar manner to that in which ubiquitin interacts with ubiquitin binding domains.[3]


UBE1C has been shown to interact with NEDD8,[4] APPBP1[5] and UBE2M.[3]


  1. ^ Osaka F, Kawasaki H, Aida N, Saeki M, Chiba T, Kawashima S, Tanaka K, Kato S (August 1998). "A new NEDD8-ligating system for cullin-4A". Genes Dev 12 (15): 2263–8. doi:10.1101/gad.12.15.2263. PMC 317039. PMID 9694792. 
  2. ^ a b "Entrez Gene: UBE1C ubiquitin-activating enzyme E1C (UBA3 homolog, yeast)". 
  3. ^ a b Huang DT, Paydar A, Zhuang M, Waddell MB, Holton JM, Schulman BA (February 2005). "Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1". Mol. Cell 17 (3): 341–50. doi:10.1016/j.molcel.2004.12.020. PMID 15694336. 
  4. ^ Gong, L; Yeh E T (April 1999). "Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway". J. Biol. Chem. (UNITED STATES) 274 (17): 12036–42. doi:10.1074/jbc.274.17.12036. ISSN 0021-9258. PMID 10207026. 
  5. ^ Chen, Y; McPhie D L; Hirschberg J; Neve R L (March 2000). "The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons". J. Biol. Chem. (UNITED STATES) 275 (12): 8929–35. doi:10.1074/jbc.275.12.8929. ISSN 0021-9258. PMID 10722740. 

Further reading[edit]

This article incorporates text from the public domain Pfam and InterPro IPR014929