Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0KHLY2)

DOT Name Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2)
Synonyms EC 6.2.1.4; GTP-specific succinyl-CoA synthetase subunit beta; G-SCS; GTPSCS; Succinyl-CoA synthetase beta-G chain; SCS-betaG
Gene Name SUCLG2
Related Disease
Alzheimer disease ( )
Endometriosis ( )
Lung adenocarcinoma ( )
Obesity ( )
Acute myelogenous leukaemia ( )
Methylmalonic acidemia ( )
Prostate carcinoma ( )
UniProt ID
SUCB2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6WCV; 7MSR; 7MSS; 7MST
EC Number
6.2.1.4
Pfam ID
PF08442 ; PF00549
Sequence
MASPVAAQAGKLLRALALRPRFLAAGSQAVQLTSRRWLNLQEYQSKKLMSDNGVRVQRFF
VADTANEALEAAKRLNAKEIVLKAQILAGGRGKGVFNSGLKGGVHLTKDPNVVGQLAKQM
IGYNLATKQTPKEGVKVNKVMVAEALDISRETYLAILMDRSCNGPVLVGSPQGGVDIEEV
AASNPELIFKEQIDIFEGIKDSQAQRMAENLGFVGPLKSQAADQITKLYNLFLKIDATQV
EVNPFGETPEGQVVCFDAKINFDDNAEFRQKDIFAMDDKSENEPIENEAAKYDLKYIGLD
GNIACFVNGAGLAMATCDIIFLNGGKPANFLDLGGGVKEAQVYQAFKLLTADPKVEAILV
NIFGGIVNCAIIANGITKACRELELKVPLVVRLEGTNVQEAQKILNNSGLPITSAIDLED
AAKKAVASVAKK
Function
GTP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit.
Tissue Specificity Mainly expressed in liver, kidney, heart, spleen and skeletal muscle. Also found in intestine and colon, and in low amounts in lung, brain, prostate, testis and ovary.
KEGG Pathway
Citrate cycle (TCA cycle) (hsa00020 )
Propanoate metabolism (hsa00640 )
Metabolic pathways (hsa01100 )
Carbon metabolism (hsa01200 )
Reactome Pathway
Citric acid cycle (TCA cycle) (R-HSA-71403 )
BioCyc Pathway
MetaCyc:HS10493-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Altered Expression [1]
Endometriosis DISX1AG8 Strong Biomarker [2]
Lung adenocarcinoma DISD51WR Strong Biomarker [3]
Obesity DIS47Y1K Strong Biomarker [4]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [5]
Methylmalonic acidemia DISHY8VB Limited Biomarker [6]
Prostate carcinoma DISMJPLE Limited Genetic Variation [7]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Methotrexate DM2TEOL Approved Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2) affects the response to substance of Methotrexate. [21]
PEITC DMOMN31 Phase 2 Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2) affects the binding of PEITC. [22]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [8]
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13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [9]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [10]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [12]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [13]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [14]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [15]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [16]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [17]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [18]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [19]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLG2). [20]
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⏷ Show the Full List of 13 Drug(s)

References

1 SUCLG2 identified as both a determinator of CSF A1-42 levels and an attenuator of cognitive decline in Alzheimer's disease.Hum Mol Genet. 2014 Dec 15;23(24):6644-58. doi: 10.1093/hmg/ddu372. Epub 2014 Jul 15.
2 Changes in eutopic endometrial gene expression during the progression of experimental endometriosis in the baboon, Papio anubis.Biol Reprod. 2013 Feb 21;88(2):44. doi: 10.1095/biolreprod.112.104497. Print 2013 Feb.
3 c-Myc targeted regulators of cell metabolism in a transgenic mouse model of papillary lung adenocarcinoma.Oncotarget. 2016 Oct 4;7(40):65514-65539. doi: 10.18632/oncotarget.11804.
4 Orchestrated downregulation of genes involved in oxidative metabolic pathways in obese vs. lean high-fat young male consumers.J Physiol Biochem. 2011 Mar;67(1):15-26. doi: 10.1007/s13105-010-0044-4. Epub 2010 Sep 30.
5 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
6 Quantitative analysis of mitochondrial protein expression in methylmalonic acidemia by two-dimensional difference gel electrophoresis.J Proteome Res. 2006 Jul;5(7):1602-10. doi: 10.1021/pr050481r.
7 Genome-wide association study of prostate cancer-specific survival.Cancer Epidemiol Biomarkers Prev. 2015 Nov;24(11):1796-800. doi: 10.1158/1055-9965.EPI-15-0543. Epub 2015 Aug 25.
8 Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
9 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
10 Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
11 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
12 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
13 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
14 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
15 A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and crosstalk pathways in the treatment of As2O3 in renal cancer. Ren Fail. 2018 Nov;40(1):331-339.
16 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
17 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
18 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
19 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
20 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
21 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
22 Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.