Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKPS9AM)

• DOT Name: Starch-binding domain-containing protein 1 (STBD1)
• Synonyms: Genethonin-1; Glycophagy cargo receptor STBD1
• Gene Name: STBD1
• UniProt ID: STBD1_HUMAN
• Pfam ID: PF00686
• Sequence:
  MGAVWSALLVGGGLAGALFVWLLRGGPGDTGKDGDAEQEKDAPLGGAAIPGGHQSGSSGL
  SPGPSGQELVTKPEHLQESNGHLISKTKDLGKLQAASWRLQNPSREVCDNSREHVPSGQF
  PDTEAPATSETSNSRSYSEVSRNESLESPMGEWGFQKGQEISAKAATCFAEKLPSSNLLK
  NRAKEEMSLSDLNSQDRVDHEEWEMVPRHSSWGDVGVGGSLKAPVLNLNQGMDNGRSTLV
  EARGQQVHGKMERVAVMPAGSQQVSVRFQVHYVTSTDVQFIAVTGDHECLGRWNTYIPLH
  YNKDGFWSHSIFLPADTVVEWKFVLVENGGVTRWEECSNRFLETGHEDKVVHAWWGIH
• Function: Acts as a cargo receptor for glycogen. Delivers its cargo to an autophagic pathway called glycophagy, resulting in the transport of glycogen to lysosomes.
• Tissue Specificity: Expressed at high level in skeletal and cardiac muscles. Moderately expressed in liver and placenta. No expression is found in pancreas, kidney or lung. Present in skeletal muscle, heart and placenta (at protein level).
• Reactome Pathway:
  RHOA GTPase cycle (R-HSA-8980692)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOD GTPase cycle (R-HSA-9013405)
  RHOG GTPase cycle (R-HSA-9013408)
  RAC3 GTPase cycle (R-HSA-9013423)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Starch-binding domain-containing protein 1 (STBD1) affects the response to substance of Fluorouracil.	[18]

15 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 Starch-binding domain-containing protein 1 (STBD1).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Starch-binding domain-containing protein 1 (STBD1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Starch-binding domain-containing protein 1 (STBD1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Starch-binding domain-containing protein 1 (STBD1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Starch-binding domain-containing protein 1 (STBD1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Starch-binding domain-containing protein 1 (STBD1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Starch-binding domain-containing protein 1 (STBD1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Starch-binding domain-containing protein 1 (STBD1).	[9]
Selenium	DM25CGV	Approved	Selenium increases the expression of Starch-binding domain-containing protein 1 (STBD1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Starch-binding domain-containing protein 1 (STBD1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Starch-binding domain-containing protein 1 (STBD1).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Starch-binding domain-containing protein 1 (STBD1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Starch-binding domain-containing protein 1 (STBD1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Starch-binding domain-containing protein 1 (STBD1).	[16]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Starch-binding domain-containing protein 1 (STBD1).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Starch-binding domain-containing protein 1 (STBD1).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Starch-binding domain-containing protein 1 (STBD1).	[15]

References

• [1] 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.
• [2] 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.
• [3] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [4] 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.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] 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.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] 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.
• [16] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [17] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [18] 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.