Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXNP0N5)

• DOT Name: Serine/threonine-protein kinase ULK1
• Synonyms: EC 2.7.11.1; Autophagy-related protein 1 homolog; ATG1; hATG1; Unc-51-like kinase 1
• Gene Name: ULK1
• UniProt ID: ULK1_HUMAN
• PDB ID: 4WNO; 4WNP; 5CI7; 6HYO; 6MNH; 6QAS; 8SOI; 8SQZ; 8SRM; 8SRQ
• EC Number: 2.7.11.1
• Pfam ID: PF12063 ; PF21127 ; PF00069
• Sequence:
  MEPGRGGTETVGKFEFSRKDLIGHGAFAVVFKGRHREKHDLEVAVKCINKKNLAKSQTLL
  GKEIKILKELKHENIVALYDFQEMANSVYLVMEYCNGGDLADYLHAMRTLSEDTIRLFLQ
  QIAGAMRLLHSKGIIHRDLKPQNILLSNPAGRRANPNSIRVKIADFGFARYLQSNMMAAT
  LCGSPMYMAPEVIMSQHYDGKADLWSIGTIVYQCLTGKAPFQASSPQDLRLFYEKNKTLV
  PTIPRETSAPLRQLLLALLQRNHKDRMDFDEFFHHPFLDASPSVRKSPPVPVPSYPSSGS
  GSSSSSSSTSHLASPPSLGEMQQLQKTLASPADTAGFLHSSRDSGGSKDSSCDTDDFVMV
  PAQFPGDLVAEAPSAKPPPDSLMCSGSSLVASAGLESHGRTPSPSPPCSSSPSPSGRAGP
  FSSSRCGASVPIPVPTQVQNYQRIERNLQSPTQFQTPRSSAIRRSGSTSPLGFARASPSP
  PAHAEHGGVLARKMSLGGGRPYTPSPQVGTIPERPGWSGTPSPQGAEMRGGRSPRPGSSA
  PEHSPRTSGLGCRLHSAPNLSDLHVVRPKLPKPPTDPLGAVFSPPQASPPQPSHGLQSCR
  NLRGSPKLPDFLQRNPLPPILGSPTKAVPSFDFPKTPSSQNLLALLARQGVVMTPPRNRT
  LPDLSEVGPFHGQPLGPGLRPGEDPKGPFGRSFSTSRLTDLLLKAAFGTQAPDPGSTESL
  QEKPMEIAPSAGFGGSLHPGARAGGTSSPSPVVFTVGSPPSGSTPPQGPRTRMFSAGPTG
  SASSSARHLVPGPCSEAPAPELPAPGHGCSFADPITANLEGAVTFEAPDLPEETLMEQEH
  TEILRGLRFTLLFVQHVLEIAALKGSASEAAGGPEYQLQESVVADQISLLSREWGFAEQL
  VLYLKVAELLSSGLQSAIDQIRAGKLCLSSTVKQVVRRLNELYKASVVSCQGLSLRLQRF
  FLDKQRLLDRIHSITAERLIFSHAVQMVQSAALDEMFQHREGCVPRYHKALLLLEGLQHM
  LSDQADIENVTKCKLCIERRLSALLTGICA
• Function: 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. Also phosphorylates SESN2 and SQSTM1 to regulate autophagy. Phosphorylates FLCN, promoting autophagy. Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation. Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B.
• Tissue Specificity: Ubiquitously expressed. Detected in the following adult tissues: skeletal muscle, heart, pancreas, brain, placenta, liver, kidney, and lung.
• KEGG Pathway:
  Mitophagy - animal (hsa04137)
  Autophagy - animal (hsa04140)
  mTOR sig.ling pathway (hsa04150)
  AMPK sig.ling pathway (hsa04152)
  Longevity regulating pathway (hsa04211)
  Alzheimer disease (hsa05010)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Spinocerebellar ataxia (hsa05017)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  Regulation of TNFR1 signaling (R-HSA-5357905)
  TBC/RABGAPs (R-HSA-8854214)
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  Receptor Mediated Mitophagy (R-HSA-8934903)
  Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

8 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Serine/threonine-protein kinase ULK1.	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Serine/threonine-protein kinase ULK1.	[7]
Imatinib	DM7RJXL	Approved	Imatinib decreases the phosphorylation of Serine/threonine-protein kinase ULK1.	[13]
Artesunate	DMR27C8	Approved	Artesunate increases the phosphorylation of Serine/threonine-protein kinase ULK1.	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Serine/threonine-protein kinase ULK1.	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Serine/threonine-protein kinase ULK1.	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Serine/threonine-protein kinase ULK1.	[21]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Serine/threonine-protein kinase ULK1.	[20]

19 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine/threonine-protein kinase ULK1.	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Serine/threonine-protein kinase ULK1.	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serine/threonine-protein kinase ULK1.	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Serine/threonine-protein kinase ULK1.	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Serine/threonine-protein kinase ULK1.	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Serine/threonine-protein kinase ULK1.	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Serine/threonine-protein kinase ULK1.	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Serine/threonine-protein kinase ULK1.	[10]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Serine/threonine-protein kinase ULK1.	[11]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Serine/threonine-protein kinase ULK1.	[12]
Promethazine	DM6I5GR	Approved	Promethazine increases the expression of Serine/threonine-protein kinase ULK1.	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Serine/threonine-protein kinase ULK1.	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Serine/threonine-protein kinase ULK1.	[18]
Tetrandrine	DMAOJBX	Phase 1	Tetrandrine decreases the expression of Serine/threonine-protein kinase ULK1.	[19]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of Serine/threonine-protein kinase ULK1.	[22]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Serine/threonine-protein kinase ULK1.	[23]
Dorsomorphin	DMKYXJW	Investigative	Dorsomorphin decreases the expression of Serine/threonine-protein kinase ULK1.	[23]
torin 1	DMZD0NA	Investigative	torin 1 decreases the expression of Serine/threonine-protein kinase ULK1.	[23]
Thenoyltrifluoroacetone	DM54OKX	Investigative	Thenoyltrifluoroacetone increases the expression of Serine/threonine-protein kinase ULK1.	[23]

References

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