ULK1

Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. 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. 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. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165).

Full Name

Unc-51 Like Autophagy Activating Kinase 1

Function

Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:23524951, PubMed:25040165, 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).
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).
May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165).
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).

Biological Process

Autophagosome assemblyManual Assertion Based On ExperimentIDA:UniProtKB
AutophagyManual Assertion Based On ExperimentIDA:UniProtKB
Autophagy of mitochondrionManual Assertion Based On ExperimentIBA:GO_Central
Axon extensionManual Assertion Based On ExperimentIBA:GO_Central
Cellular response to nutrient levelsISS:UniProtKB
Late nucleophagyManual Assertion Based On ExperimentIBA:GO_Central
MacroautophagyManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of cell population proliferationManual Assertion Based On ExperimentIDA:ComplexPortal
Negative regulation of collateral sproutingManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of protein-containing complex assemblyManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Neuron projection developmentManual Assertion Based On ExperimentIMP:UniProtKB
Neuron projection regenerationIEA:Ensembl
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Peptidyl-threonine phosphorylationManual Assertion Based On ExperimentIDA:HGNC
Piecemeal microautophagy of the nucleusManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of autophagosome assemblyIEA:Ensembl
Positive regulation of autophagyManual Assertion Based On ExperimentIDA:UniProtKB
Protein autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein localizationManual Assertion Based On ExperimentIMP:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:ComplexPortal
Regulation of macroautophagyManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of protein lipidationManual Assertion Based On ExperimentIDA:ComplexPortal
Response to starvationISS:UniProtKB
ReticulophagyManual Assertion Based On ExperimentIBA:GO_Central
Signal transductionIEA:InterPro

Cellular Location

Cytoplasm, cytosol
Preautophagosomal structure
Under starvation conditions, is localized to puncate structures primarily representing the isolation membrane that sequesters a portion of the cytoplasm resulting in the formation of an autophagosome.

PTM

Autophosphorylated. Phosphorylated under nutrient-rich conditions; dephosphorylated during starvation or following treatment with rapamycin. Under nutrient sufficiency, phosphorylated by MTOR/mTOR, disrupting the interaction with AMPK and preventing activation of ULK1 (By similarity).
In response to nutrient limitation, phosphorylated and activated by AMPK, leading to activate autophagy.
Ubiquitinated via 'Lys-63'-linkage by a complex composed of AMBRA1 and TRAF6 following autophagy induction, promoting ULK1 stability and kinase activity.
Acetylated by KAT5/TIP60 under autophagy induction, promoting protein kinase activity.