Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

ULK1 (O75385) - Overview - Molecular Target Synopsis

Protein


ULK1, Serine/threonine-protein kinase ULK1
Enzyme Classification 2.7.11.1
UniProt O75385

Also Known as ULK1_HUMAN, ULK1, KIAA0722

Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. 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. 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. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165). Interacts with GABARAP and GABARAPL2 (PubMed:11146101). Interacts (via C-terminus) with ATG13 (PubMed:18936157). Part of a complex consisting of ATG13, ATG101, ULK1 and RB1CC1 (PubMed:19287211). Associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR; the association depends on nutrient conditions and is reduced during starvation (PubMed:19211835, PubMed:21795849). Interacts with FEZ1; SCOC interferes with FEZ1-binding (PubMed:22354037). Interacts with TBC1D14 (PubMed:22613832). Interacts (phosphorylated form) with TRIM5 (PubMed:25127057). When phosphorylated at Ser-317, interacts with MEFV and BECN1 simultaneously (PubMed:26347139). Interacts with TRIM21 and IRF3, in the presence of TRIM21 (PubMed:26347139). Interacts with SESN2 (PubMed:25040165). Interacts with SQSTM1 (PubMed:25040165). Interacts with C9orf72 (PubMed:27334615). Interacts with WDR45 (PubMed:28561066).

6HYO
STRUCTURE OF ULK1 LIR MOTIF BOUND TO GABARAP
RCSB/PDB
Inspect Structure
See all 3D Structures for ULK1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


Gene Copy Number Variation


In COSMIC - Cell Lines Project ULK1 has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MOLT_4, T47D, NCI_H460

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H2795, MDA-MB-361, NCI-H187

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, A549, K562

(see details)

RNA Interference


ULK1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: KPD, MCF12A. (see details)

3D Structures


For ULK1 there are:
6 structures (10 chains) solved
5 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


ULK1 has been screened with 296 compounds (353 bioactivities), 19 compounds have bioactivities that show binding affinity of <= 500nM (20 bioactivities). (see details)