serine/threonine protein kinase ULK1; autophagy-related protein 1 homolog; ATG1; hATG1; Unc-51-like kinase 1 (ULK1, KIAA0722)

Function: - serine/threonine protein kinase - involved 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 mediates phosphorylation of AMPK subunits PRKAA1, PRKAB2 & PRKAG1, down-regulating AMPK activity - may phosphorylate ATG13/KIAA0652 & RPTOR - role in early in neuronal differentiation - required for granule cell axon formation - 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 & preventing activation of ULK1 (putative) - in response to nutrient limitation, phosphorylated & activated by AMPK, leading to autophagy activation - interacts with GABARAP & GABARAPL2 - interacts (via C- terminus) with ATG13/KIAA0652 - part of a complex consisting of ATG13/KIAA0652, ULK1 & RB1CC1 - associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR - the association depends on nutrient conditions & is reduced during starvation - may play a role in calorie restriction Structure: - belongs to the protein kinase superfamily, Ser/Thr protein kinase family, APG1/unc-51/ULK1 subfamily - contains 1 protein kinase domain Compartment: - cytoplasm, cytosol (putative) - preautophagosomal structure (putative) - 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 Expression: - ubiquitously expressed - detected in adult skeletal muscle, heart, pancreas, brain, placenta, liver, kidney, & lung

Properties

SIZE: entity length = 1050 aa MW = 113 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: kinase domain SITE: 16-278 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 22-30 ATP-binding site NAME: ATP-binding site SITE: 46-46 aspartate residue {D138} GABARAP/GABARAPL2 {287-416} MOTIF: serine-rich region {297-310} MOTIF: serine residue (SEVERAL) Ser phosphorylation site {S317} Ser phosphorylation site {S450} Thr phosphorylation site {T456} Ser phosphorylation site {S467} Ser phosphorylation site {S469} Ser phosphorylation site {S477} Ser phosphorylation site {S479} Ser phosphorylation site {S556} Thr phosphorylation site {T575} Ser phosphorylation site {S623} Thr phosphorylation site {T625} Ser phosphorylation site {S638} Thr phosphorylation site {T717} Ser phosphorylation site {S758}

Database Correlations

OMIM 603168 UniProt O75385 PFAM correlations Entrez Gene 8408 Kegg hsa:8408 ENZYME 2.7.11.1

References

UniProt :accession O75385