Protein / target
NEDD8-activating enzyme E1 regulatory subunit
Protein at a glance
Biological role
Protein heterodimerization
Strongest disease association
Neurodegenerative Diseases
Therapeutic position
Clinically advancing target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme.
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Regulatory 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. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation. The covalent attachment of NEDD8 to target proteins is known as 'neddylation' and the process is involved in the regulation of cell growth, viability and development
Subcellular location
Domains and Gene Ontology detail (15)Hide
Gene Ontology
- Ccytoplasm
- Ccytosol
- Cglutamatergic synapse
- Cplasma membrane
- Cprotein-containing complex
- FNEDD8 activating enzyme activity
- Fprotein heterodimerization activity
- Fubiquitin protein ligase binding
- Pmitotic DNA replication checkpoint signaling
- Pneuron apoptotic process
- Pprotein neddylation
- Pregulation of apoptotic process
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Synaptic signalling
- ·glutamatergic synapse
- ·regulation of postsynapse assembly
Apoptosis & cell death
- ·neuron apoptotic process
- ·regulation of apoptotic process
- ·regulation of neuron apoptotic process
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
NEDD8 activating enzyme inhibitor
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene NAE1
Gene-level evidence surfaced through the gene NAE1 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
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This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.
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Drug development
1 compounds recorded · 1 in clinical development
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Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (11)Hide
Raw Open Targets tractability assessment buckets, by modality.
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
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ClinicalTrials.gov via the drug-target graph.