Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:10624947, PubMed:19258318, PubMed:21205641, PubMed:21258367, PubMed:21460634, PubMed:25040165). Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:10624947, PubMed:19258318, PubMed:21205641, PubMed:21258367, PubMed:21460634, 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:21205641, PubMed:21258367). 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:19258318). Plays a role early in neuronal differentiation and is required for granule cell axon formation (By similarity). May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165). Phosphorylates FLCN, promoting autophagy (By similarity). Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (By similarity). Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (By similarity). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Acetylation by KAT5/TIP60 stimulates the protein kinase activity (PubMed:22539723). The protein kinase activity is activated by unanchored 'Lys-63'-linked polyubiquitin chains: unanchored 'Lys-63'-linked polyubiquitin chains are catalyzed by TRIM32 in an AMBRA1-dependent manner (By similarity). Interacts with GABARAP and GABARAPL2 (By similarity). Interacts (via C-terminus) with ATG13 (PubMed:19258318). Part of a complex consisting of ATG13, ATG101, ULK1 and RB1CC1 (PubMed:19258318). Associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR; the association depends on nutrient conditions and is reduced during starvation (By similarity). Interacts with FEZ1; SCOC interferes with FEZ1-binding (By similarity). Interacts with TBC1D14 (By similarity). Interacts (phosphorylated form) with TRIM5 (By similarity). When phosphorylated at Ser-317, interacts with MEFV and BECN1 simultaneously. Interacts with TRIM21 and IRF3, in the presence of TRIM21 (By similarity). Interacts with SESN2 (PubMed:25040165). Interacts with SQSTM1 (PubMed:25040165). Interacts with C9orf72 (By similarity). Interacts with WDR45 (By similarity). Interacts with ATG13; this interaction is increased in the absence of TMEM39A (By similarity). Interacts with WIPI2 (By similarity). Interacts with ATP2A2 (By similarity). Interacts with AMBRA1 (By similarity). 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. Autophosphorylated. Phosphorylated under nutrient-rich conditions; dephosphorylated during starvation or following treatment with rapamycin. In response to nutrient limitation, phosphorylated and activated by AMPK, leading to activate autophagy. Under nutrient sufficiency, phosphorylated by MTOR/mTOR, disrupting the interaction with AMPK and preventing activation of ULK1. 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. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.