Recombinant human ULK1 protein

Specifications

Form

Liquid

Additional notes

Purity was determined to be >70% by densitometry. Affinity purified.

General info

Function

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). 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).

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.

Post-translational modifications

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 (PubMed:21205641, PubMed:25891078).. 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 (PubMed:29487085).. Acetylated by KAT5/TIP60 under autophagy induction, promoting protein kinase activity.