Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6X5RR1)

• DOT Name: Signal transducing adapter molecule 1 (STAM)
• Synonyms: STAM-1
• Gene Name: STAM
• Related Disease:
  Hepatocellular carcinoma
  Hyperglycemia
  Autism spectrum disorder
  Dengue
  Fatty liver disease
  Hepatitis B virus infection
  Non-alcoholic fatty liver disease
  Neoplasm
  Non-alcoholic steatohepatitis
  Type-1/2 diabetes
• UniProt ID: STAM1_HUMAN
• PDB ID: 2L0A; 3F1I; 3LDZ
• Pfam ID: PF00018 ; PF02809 ; PF00790
• Sequence:
  MPLFATNPFDQDVEKATSEMNTAEDWGLILDICDKVGQSRTGPKDCLRSIMRRVNHKDPH
  VAMQALTLLGACVSNCGKIFHLEVCSRDFASEVSNVLNKGHPKVCEKLKALMVEWTDEFK
  NDPQLSLISAMIKNLKEQGVTFPAIGSQAAEQAKASPALVAKDPGTVANKKEEEDLAKAI
  ELSLKEQRQQSTTLSTLYPSTSSLLTNHQHEGRKVRAIYDFEAAEDNELTFKAGEIITVL
  DDSDPNWWKGETHQGIGLFPSNFVTADLTAEPEMIKTEKKTVQFSDDVQVETIEPEPEPA
  FIDEDKMDQLLQMLQSTDPSDDQPDLPELLHLEAMCHQMGPLIDEKLEDIDRKHSELSEL
  NVKVMEALSLYTKLMNEDPMYSMYAKLQNQPYYMQSSGVSGSQVYAGPPPSGAYLVAGNA
  QMSHLQSYSLPPEQLSSLSQAVVPPSANPALPSQQTQAAYPNTMVSSVQGNTYPSQAPVY
  SPPPAATAAAATADVTLYQNAGPNMPQVPNYNLTSSTLPQPGGSQQPPQPQQPYSQKALL
• Function: Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as a sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes.; (Microbial infection) Plays an important role in Dengue virus entry.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway:
  Endocytosis (hsa04144)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway:
  Metalloprotease DUBs (R-HSA-5689901)
  Negative regulation of MET activity (R-HSA-6807004)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  InlB-mediated entry of Listeria monocytogenes into host cell (R-HSA-8875360)
  RHOU GTPase cycle (R-HSA-9013420)
  Endosomal Sorting Complex Required For Transport (ESCRT) (R-HSA-917729)
  EGFR downregulation (R-HSA-182971)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Hyperglycemia	DIS0BZB5	Definitive	Biomarker	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Dengue	DISKH221	Strong	Biomarker	[3]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[4]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[5]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[6]
Neoplasm	DISZKGEW	Limited	Altered Expression	[7]
Non-alcoholic steatohepatitis	DIST4788	Limited	Biomarker	[8]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Signal transducing adapter molecule 1 (STAM).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Signal transducing adapter molecule 1 (STAM).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Signal transducing adapter molecule 1 (STAM).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Signal transducing adapter molecule 1 (STAM).	[13]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Signal transducing adapter molecule 1 (STAM).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Signal transducing adapter molecule 1 (STAM).	[15]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Signal transducing adapter molecule 1 (STAM).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Signal transducing adapter molecule 1 (STAM).	[17]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Signal transducing adapter molecule 1 (STAM).	[18]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Signal transducing adapter molecule 1 (STAM).	[19]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Signal transducing adapter molecule 1 (STAM).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Signal transducing adapter molecule 1 (STAM).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Signal transducing adapter molecule 1 (STAM).	[24]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of Signal transducing adapter molecule 1 (STAM).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Signal transducing adapter molecule 1 (STAM).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Signal transducing adapter molecule 1 (STAM).	[22]

References

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• [2] Genome-wide copy number variation analysis in a Chinese autism spectrum disorder cohort.Sci Rep. 2017 Mar 10;7:44155. doi: 10.1038/srep44155.
• [3] TIM-1Ubiquitination Mediates Dengue Virus Entry.Cell Rep. 2018 May 8;23(6):1779-1793. doi: 10.1016/j.celrep.2018.04.013.
• [4] HIF-2 upregulation mediated by hypoxia promotes NAFLD-HCC progression by activating lipid synthesis via the PI3K-AKT-mTOR pathway.Aging (Albany NY). 2019 Dec 4;11(23):10839-10860. doi: 10.18632/aging.102488. Epub 2019 Dec 4.
• [5] The machinery for endocytosis of epidermal growth factor receptor coordinates the transport of incoming hepatitis B virus to the endosomal network.J Biol Chem. 2020 Jan 17;295(3):800-807. doi: 10.1074/jbc.AC119.010366. Epub 2019 Dec 12.
• [6] The A3 adenosine receptor agonist, namodenoson, ameliorates nonalcoholic steatohepatitis in mice.Int J Mol Med. 2019 Dec;44(6):2256-2264. doi: 10.3892/ijmm.2019.4364. Epub 2019 Oct 3.
• [7] Gene expression patterns in ependymomas correlate with tumor location, grade, and patient age.Am J Pathol. 2003 Nov;163(5):1721-7. doi: 10.1016/S0002-9440(10)63530-4.
• [8] Connectivity mapping of angiotensin-PPAR interactions involved in the amelioration of non-alcoholic steatohepatitis by Telmisartan.Sci Rep. 2019 Mar 8;9(1):4003. doi: 10.1038/s41598-019-40322-1.
• [9] Pathophysiological analysis of the progression of hepatic lesions in STAM mice.Physiol Res. 2017 Nov 24;66(5):791-799. doi: 10.33549/physiolres.933592. Epub 2017 Jul 18.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] 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.
• [15] 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.
• [16] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [17] 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.
• [18] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [19] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [20] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [21] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [22] 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.
• [23] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.