Protein / target
Serine/threonine-protein kinase ULK1
Protein at a glance
Biological role
Protein serine/threonine kinase
Strongest disease association
Ovarian dysfunction
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Serine/threonine-protein kinase involved in autophagy in response to starvation.
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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
Domains and Gene Ontology detail (46)Hide
Domains & features
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
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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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
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.
View evidence synthesis (5)Hide
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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Tractability
Small molecules — Emerging
Protein degraders — Emerging
View underlying tractability evidence (8)Hide
Raw Open Targets tractability assessment buckets, by modality.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.