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Protein / target

Serine/threonine-protein kinase ULK1

Encoded byULK1O75385Homo sapiensSwiss-Prot
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Protein serine/threonine kinase

Strongest disease association

Ovarian dysfunction

Via encoding gene ULK1 · Genetic evidence · score 0.44

Research activity

Emerging research

1 papers · latest 2023

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

Serine/threonine-protein kinase involved in autophagy in response to starvation.

View complete UniProt function annotation

Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:23524951, PubMed:25040165, PubMed:29487085, PubMed:31123703). Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:25040165, PubMed:39384743). Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR (PubMed:21795849). Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity (PubMed:21460634). May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences (PubMed:18936157). Plays a role early in neuronal differentiation and is required for granule cell axon formation (PubMed:11146101). Also phosphorylates SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165, PubMed:37306101). Phosphorylates FLCN, promoting autophagy (PubMed:25126726). Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (PubMed:20921139). Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (PubMed:28821708)

Subcellular location

Cytoplasm, cytosolPreautophagosomal structure
Domains and Gene Ontology detail (46)

Domains & features

Protein kinase

Gene Ontology

  • CAtg1/ULK1 kinase complex
  • Cautophagosome
  • Cautophagosome membrane
  • Caxon
  • Ccytoplasm
  • Ccytosol
  • Cendoplasmic reticulum membrane
  • Cmitochondrial outer membrane
  • Comegasome membrane
  • Cphagophore assembly site
  • Cphagophore assembly site membrane
  • Crecycling endosome

1050 aa · 113 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell proliferation & survivalGOKinase signallingUniProt · GO
View supporting evidence

Cell proliferation & survival

  • ·negative regulation of cell population proliferation

Kinase signalling

  • ·Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:…
  • ·protein serine kinase activity
  • ·protein serine/threonine kinase activity

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

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 ULK1

Gene-level evidence surfaced through the gene ULK1that 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.

Ovarian dysfunction
0.44Limited support

Genetic evidence dominant · Open Targets 0.27

Parasitic Diseases
0.39Limited support

Genetic evidence dominant · Open Targets 0.23

Stroke
0.37Limited support

Genetic evidence dominant · Open Targets 0.22

Neurodegenerative Diseases
0.36Preliminary

Pathway evidence dominant · Open Targets 0.54 · no direct causal or clinical evidence

Alcohol drinking
0.35Limited support

Genetic evidence dominant · Open Targets 0.22

View evidence synthesis (5)
Ovarian dysfunctionLimited support
0.44
agreement 0.320.56
Genetic100%

Open Targets aggregate 0.27 · 1 independent evidence family

Parasitic DiseasesLimited support
0.39
agreement 0.270.51
Genetic100%

Open Targets aggregate 0.23 · 1 independent evidence family

StrokeLimited support
0.37
agreement 0.230.51
Genetic93%Literature7%

Open Targets aggregate 0.22 · 2 independent evidence families

Neurodegenerative DiseasesPreliminary
0.36
agreement 0.180.54
Pathway97%Literature3%

Open Targets aggregate 0.54 · 2 independent evidence families · no direct causal or clinical evidence

Alcohol drinkingLimited support
0.35
agreement 0.230.47
Genetic100%

Open Targets aggregate 0.22 · 1 independent evidence family

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
Neurodegenerative Diseases0.54
Lysosomal Storage Diseases0.46
Alzheimer's Disease0.39
Parkinson's Disease0.39
Multiple Sclerosis0.37
Ovarian dysfunction0.27
Parasitic Diseases0.23
Stroke0.22
Alcohol drinking0.22
Carcinoma, Hepatocellular0.10

Tractability

Small moleculesEmerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2023

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Xue Q · Autophagy · 2023

Recent

Europe PMC papers linked directly to this protein.