Ulk1 phospho S757

Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:10624947, PubMed:19258318, PubMed:21205641, PubMed:21258367, PubMed:21460634, PubMed:25040165, PubMed:25723488). 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). Also phosphorylates SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165, PubMed:25723488). 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).

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. Deubiquitinated by USP20; leading to ULK1 stability and autophagy initiation.

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.

• 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.

Serine/threonine-protein kinase ULK1, Serine/threonine-protein kinase Unc51.1, Unc-51-like kinase 1, Ulk1

• swissprot:O70405

Proteins

Oncology

• Neuroscience

112463Da