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ULK1 phospho S638

OverviewProducts

Function

Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:25040165). 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). May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165). Phosphorylates FLCN, promoting autophagy (PubMed:25126726).

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.

Acetylated by KAT5/TIP60 under autophagy induction, promoting protein kinase activity.

Sequence similarities

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

Tissue specificity

Ubiquitously expressed. Detected in the following adult tissues: skeletal muscle, heart, pancreas, brain, placenta, liver, kidney, and lung.

Cellular localization

  • 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.

Alternative names

  • Serine/threonine-protein kinase ULK1
  • Autophagy-related protein 1 homolog
  • Unc-51-like kinase 1
  • ATG1
  • hATG1
  • KIAA0722
  • ULK1

Database links

Target type

Proteins

Primary research area

Oncology

Other research areas

  • Neuroscience

Molecular weight

112631Da