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

More general terms

• serine/threonine kinase

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8408
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8408
• OMIM: https://mirror.omim.org/entry/603168
• UniProt: http://www.uniprot.org/uniprot/O75385.html