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Protein / target

NEDD8-activating enzyme E1 catalytic subunit

Encoded byUBA3Q8TBC4Homo sapiensSwiss-Prot
Clinical-stage
Therapeutic maturity
1
Clinical candidates
30
Clinical trials
Small-molecule tractable
Druggability
Advanced Clinical

Protein at a glance

Biological role

Protein heterodimerization

Strongest disease association

Alcohol drinking

Via encoding gene UBA3 · Genetic evidence · score 0.10

Therapeutic position

Clinically advancing target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme.

View complete UniProt function annotation

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

Domains and Gene Ontology detail (13)

Gene Ontology

  • Ccytoplasm
  • Ccytosol
  • Cnucleus
  • Cprotein-containing complex
  • FATP binding
  • Fidentical protein binding
  • FNEDD8 activating enzyme activity
  • FNEDD8 transferase activity
  • Fprotein heterodimerization activity
  • Ppost-translational protein modification
  • Pprotein modification process
  • Pprotein neddylation

463 aa · 52 kDa · 2 isoforms

Drugs targeting this protein

1

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.

Pevonedistat
Phase 3Inhibitor

NEDD8 activating enzyme inhibitor

Acts on a complex — shared with NAE1 · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

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 UBA3

Gene-level evidence surfaced through the gene UBA3 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.

Leukemia, Myeloid, Acute
0.46Limited support

Clinical evidence dominant · Open Targets 0.36

Dengue
0.24Preliminary

Pathway evidence dominant · Open Targets 0.37 · no direct causal or clinical evidence

Cholangiocarcinoma
0.18Preliminary

Literature evidence dominant · Open Targets 0.10

Neurodegenerative Diseases
0.14Preliminary

Pathway evidence dominant · Open Targets 0.21 · no direct causal or clinical evidence

Carcinoma, Non-Small-Cell Lung
0.12Preliminary

Clinical evidence dominant · Open Targets 0.09

View evidence synthesis (5)
Leukemia, Myeloid, AcuteLimited support
0.46
agreement 0.300.61
Clinical90%Literature10%

Open Targets aggregate 0.36 · 2 independent evidence families

DenguePreliminary
0.24
agreement 0.010.47
Pathway100%

Open Targets aggregate 0.37 · 1 independent evidence family · no direct causal or clinical evidence

CholangiocarcinomaPreliminary
0.18
agreement 0.030.34
Literature52%Clinical48%

Open Targets aggregate 0.10 · 2 independent evidence families

Neurodegenerative DiseasesPreliminary
0.14
agreement 0.000.36
Pathway100%

Open Targets aggregate 0.21 · 1 independent evidence family · no direct causal or clinical evidence

Carcinoma, Non-Small-Cell LungPreliminary
0.12
agreement 0.000.27
Clinical95%Literature5%

Open Targets aggregate 0.09 · 2 independent evidence families

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.

Show all associations
Dengue0.37
Leukemia, Myeloid, Acute0.36
Neurodegenerative Diseases0.21
Cholangiocarcinoma0.10
Carcinoma, Non-Small-Cell Lung0.09
Alcohol drinking0.06
Celiac Disease0.06

Drug development

1 compounds recorded · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph: these count different sets and are not a subset relation.

View all recorded compounds (1)
PEVONEDISTATPhase 3

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 moleculesStrong

Advanced Clinical and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (human protein atlas loc) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketAB · Human Protein Atlas locPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

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.

View all trials (26)

RECRUITING · via Pevonedistat · NCT03013998

ClinicalTrials.gov via the drug-target graph.