General Information of Drug Off-Target (DOT) (ID: OT8OEPYT)

DOT Name Diacylglycerol kinase theta (DGKQ)
Synonyms DAG kinase theta; DGKtheta; EC 2.7.1.107; EC 2.7.1.93; Diglyceride kinase theta; DGK-theta
Gene Name DGKQ
Related Disease
Type-1/2 diabetes ( )
Alzheimer disease ( )
Myositis disease ( )
Primary biliary cholangitis ( )
Rheumatoid arthritis ( )
Sjogren syndrome ( )
Systemic lupus erythematosus ( )
Systemic sclerosis ( )
Parkinson disease ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Liver cancer ( )
UniProt ID
DGKQ_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
2.7.1.107; 2.7.1.93
Pfam ID
PF00130 ; PF00609 ; PF00781 ; PF00788
Sequence
MAAAAEPGARAWLGGGSPRPGSPACSPVLGSGGRARPGPGPGPGPERAGVRAPGPAAAPG
HSFRKVTLTKPTFCHLCSDFIWGLAGFLCDVCNFMSHEKCLKHVRIPCTSVAPSLVRVPV
AHCFGPRGLHKRKFCAVCRKVLEAPALHCEVCELHLHPDCVPFACSDCRQCHQDGHQDHD
THHHHWREGNLPSGARCEVCRKTCGSSDVLAGVRCEWCGVQAHSLCSAALAPECGFGRLR
SLVLPPACVRLLPGGFSKTQSFRIVEAAEPGEGGDGADGSAAVGPGRETQATPESGKQTL
KIFDGDDAVRRSQFRLVTVSRLAGAEEVLEAALRAHHIPEDPGHLELCRLPPSSQACDAW
AGGKAGSAVISEEGRSPGSGEATPEAWVIRALPRAQEVLKIYPGWLKVGVAYVSVRVTPK
STARSVVLEVLPLLGRQAESPESFQLVEVAMGCRHVQRTMLMDEQPLLDRLQDIRQMSVR
QVSQTRFYVAESRDVAPHVSLFVGGLPPGLSPEEYSSLLHEAGATKATVVSVSHIYSSQG
AVVLDVACFAEAERLYMLLKDMAVRGRLLTALVLPDLLHAKLPPDSCPLLVFVNPKSGGL
KGRDLLCSFRKLLNPHQVFDLTNGGPLPGLHLFSQVPCFRVLVCGGDGTVGWVLGALEET
RYRLACPEPSVAILPLGTGNDLGRVLRWGAGYSGEDPFSVLLSVDEADAVLMDRWTILLD
AHEAGSAENDTADAEPPKIVQMSNYCGIGIDAELSLDFHQAREEEPGKFTSRLHNKGVYV
RVGLQKISHSRSLHKQIRLQVERQEVELPSIEGLIFINIPSWGSGADLWGSDSDTRFEKP
RMDDGLLEVVGVTGVVHMGQVQGGLRSGIRIAQGSYFRVTLLKATPVQVDGEPWVQAPGH
MIISAAGPKVHMLRKAKQKPRRAGTTRDARADAAPAPESDPR
Function
Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids. Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes. Within the adrenocorticotropic hormone signaling pathway, produces phosphatidic acid which in turn activates NR5A1 and subsequent steroidogenic gene transcription. Also functions downstream of the nerve growth factor signaling pathway being specifically activated in the nucleus by the growth factor. Through its diacylglycerol activity also regulates synaptic vesicle endocytosis.
KEGG Pathway
Glycerolipid metabolism (hsa00561 )
Glycerophospholipid metabolism (hsa00564 )
Metabolic pathways (hsa01100 )
Phosphatidylinositol sig.ling system (hsa04070 )
Phospholipase D sig.ling pathway (hsa04072 )
Choline metabolism in cancer (hsa05231 )
Reactome Pathway
Effects of PIP2 hydrolysis (R-HSA-114508 )

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Type-1/2 diabetes DISIUHAP Definitive Altered Expression [1]
Alzheimer disease DISF8S70 Strong Genetic Variation [2]
Myositis disease DISCIXF0 Strong Genetic Variation [3]
Primary biliary cholangitis DIS43E0O Strong Genetic Variation [4]
Rheumatoid arthritis DISTSB4J Strong Genetic Variation [3]
Sjogren syndrome DISUBX7H Strong Biomarker [5]
Systemic lupus erythematosus DISI1SZ7 Strong Genetic Variation [3]
Systemic sclerosis DISF44L6 Strong Genetic Variation [3]
Parkinson disease DISQVHKL moderate Biomarker [6]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Limited Biomarker [7]
Liver cancer DISDE4BI Limited Biomarker [7]
------------------------------------------------------------------------------------
⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Diacylglycerol kinase theta (DGKQ). [8]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Diacylglycerol kinase theta (DGKQ). [10]
------------------------------------------------------------------------------------
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Diacylglycerol kinase theta (DGKQ). [9]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Diacylglycerol kinase theta (DGKQ). [11]
QUERCITRIN DM1DH96 Investigative QUERCITRIN affects the expression of Diacylglycerol kinase theta (DGKQ). [12]
------------------------------------------------------------------------------------

References

1 Establishment of a DGK Endogenous Promoter Luciferase Reporter HepG2 Cell Line for Studying the Transcriptional Regulation of DGK Gene.Appl Biochem Biotechnol. 2019 Apr;187(4):1344-1355. doi: 10.1007/s12010-018-2890-4. Epub 2018 Sep 19.
2 Association of Parkinson's Disease GWAS-Linked Loci with Alzheimer's Disease in Han Chinese.Mol Neurobiol. 2017 Jan;54(1):308-318. doi: 10.1007/s12035-015-9649-5. Epub 2016 Jan 6.
3 Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.Ann Rheum Dis. 2019 Mar;78(3):311-319. doi: 10.1136/annrheumdis-2018-214127. Epub 2018 Dec 20.
4 International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.Nat Commun. 2015 Sep 22;6:8019. doi: 10.1038/ncomms9019.
5 Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjgren's syndrome.Nat Genet. 2013 Nov;45(11):1284-92. doi: 10.1038/ng.2792. Epub 2013 Oct 6.
6 Genetic, Structural, and Functional Evidence Link TMEM175 to Synucleinopathies.Ann Neurol. 2020 Jan;87(1):139-153. doi: 10.1002/ana.25629. Epub 2019 Nov 18.
7 Establishment of a novel hepatic steatosis cell model by Cas9/sgRNA-mediated DGK gene knockout.Mol Med Rep. 2018 Feb;17(2):2169-2176. doi: 10.3892/mmr.2017.8140. Epub 2017 Nov 22.
8 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
9 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
11 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
12 Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.