serine/threonine protein kinase ULK2; Unc-51-like kinase 2 (ULK2, KIAA0623)

Function: - serine/threonine protein kinase - role in autophagy in response to starvation - acts upstream of phosphatidylinositol-3-kinase PIK3C3 to regulate formation of autophagophores, precursors of autophagosomes - part of regulatory feedback loops in autophagy - acts both as a downstream effector & negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR - activated via phosphorylation by AMPK - also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 & PRKAG1, leading to negatively regulate AMPK activity - may phosphorylate ATG13/KIAA0652, FRS2, FRS3 & RPTOR - not involved in ammonia-induced autophagy or in autophagic response of cerebellar granule neurons (CGN) to low K⁺ - role early in neuronal differentiation - required for granule cell axon formation - may govern axon formation via Ras-like GTPase signaling & through regulation of the Rab5-mediated endocytic pathways within developing axons - autophosphorylated - in response to nutrient limitation, probably phosphorylated & activated by AMPK, leading to activate autophagy - interacts with SYNGAP1 (putative) - component of a complex consisting of ATG13/KIAA0652, ULK1 & RB1CC1/FIP200 - interacts (via C-terminus) with ATG13/KIAA0652 - associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR Structure: - the CTD-like region mediates membrane-binding & incorporation into large protein complexes - belongs to the protein kinase superfamily, Ser/Thr protein kinase family, APG1/unc-51/ULK1 subfamily - contains 1 protein kinase domain Compartment: - cytoplasmic vesicle membrane - peripheral membrane - localizes to pre-autophagosomal membrane

Properties

SIZE: entity length = 1036 aa MW = 113 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: kinase domain SITE: 9-271 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 15-23 ATP-binding site NAME: ATP-binding site SITE: 39-39 aspartate residue {D131} Tyr phosphorylation site CTD-like region {812-1036}

Database Correlations

OMIM 608650 UniProt Q8IYT8 PFAM correlations Entrez Gene 9706 Kegg hsa:9706 ENZYME 2.7.11.1

References

UniProt :accession Q8IYT8