Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTELM5C2)

• DOT Name: Secernin-1 (SCRN1)
• Gene Name: SCRN1
• Related Disease:
  ABeta amyloidosis, dutch type
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Corticobasal degeneration
  Lung neoplasm
  Oculocerebrorenal syndrome
  Pick disease
  Progressive supranuclear palsy
  Stomach cancer
  Tauopathy
  Alzheimer disease
  Colorectal carcinoma
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Keratoconjunctivitis sicca
  Neoplasm
  Osteoarthritis
  Psoriasis
• UniProt ID: SCRN1_HUMAN
• Pfam ID: PF03577
• Sequence:
  MAAAPPSYCFVAFPPRAKDGLVVFGKNSARPRDEVQEVVYFSAADHEPESKVECTYISID
  QVPRTYAIMISRPAWLWGAEMGANEHGVCIANEAINTREPAAEIEALLGMDLVRLGLERG
  ETAKEALDVIVSLLEEHGQGGNYFEDANSCHSFQSAYLIVDRDEAWVLETIGKYWAAEKV
  TEGVRCICSQLSLTTKMDAEHPELRSYAQSQGWWTGEGEFNFSEVFSPVEDHLDCGAGKD
  SLEKQEESITVQTMMNTLRDKASGVCIDSEFFLTTASGVSVLPQNRSSPCIHYFTGTPDP
  SRSIFKPFIFVDDVKLVPKTQSPCFGDDDPAKKEPRFQEKPDRRHELYKAHEWARAIIES
  DQEQGRKLRSTMLELEKQGLEAMEEILTSSEPLDPAEVGDLFYDCVDTEIKFFK
• Function: Regulates exocytosis in mast cells. Increases both the extent of secretion and the sensitivity of mast cells to stimulation with calcium.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
ABeta amyloidosis, dutch type	DIS6LNS5	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Corticobasal degeneration	DISSMOTT	Strong	Biomarker	[1]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[3]
Oculocerebrorenal syndrome	DIS8TEDY	Strong	Biomarker	[4]
Pick disease	DISP6X50	Strong	Biomarker	[1]
Progressive supranuclear palsy	DISO5KRQ	Strong	Biomarker	[1]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[5]
Tauopathy	DISY2IPA	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	moderate	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[6]
Gastric cancer	DISXGOUK	Limited	Genetic Variation	[5]
Gastric neoplasm	DISOKN4Y	Limited	Biomarker	[7]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[7]
Keratoconjunctivitis sicca	DISNOENH	Limited	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]
Osteoarthritis	DIS05URM	Limited	Biomarker	[9]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Secernin-1 (SCRN1) affects the response to substance of Topotecan.	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Secernin-1 (SCRN1).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Secernin-1 (SCRN1).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Secernin-1 (SCRN1).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Secernin-1 (SCRN1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Secernin-1 (SCRN1).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Secernin-1 (SCRN1).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Secernin-1 (SCRN1).	[17]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Secernin-1 (SCRN1).	[18]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Secernin-1 (SCRN1).	[19]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Secernin-1 (SCRN1).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Secernin-1 (SCRN1).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Secernin-1 (SCRN1).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Secernin-1 (SCRN1).	[24]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Secernin-1 (SCRN1).	[25]

1 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 decreases the methylation of Secernin-1 (SCRN1).	[23]

References

• [1] Secernin-1 is a novel phosphorylated tau binding protein that accumulates in Alzheimer's disease and not in other tauopathies.Acta Neuropathol Commun. 2019 Dec 3;7(1):195. doi: 10.1186/s40478-019-0848-6.
• [2] Secernin-1 contributes to colon cancer progression through enhancing matrix metalloproteinase-2/9 exocytosis.Dis Markers. 2015;2015:230703. doi: 10.1155/2015/230703. Epub 2015 Feb 26.
• [3] Integrated genomic approaches identify upregulation of SCRN1 as a novel mechanism associated with acquired resistance to erlotinib in PC9 cells harboring oncogenic EGFR mutation.Oncotarget. 2016 Mar 22;7(12):13797-809. doi: 10.18632/oncotarget.7318.
• [4] Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3511-6. doi: 10.1073/pnas.0914658107. Epub 2010 Feb 2.
• [5] A genetic variant of miR-148a binding site in the SCRN1 3'-UTR is associated with susceptibility and prognosis of gastric cancer.Sci Rep. 2014 Nov 17;4:7080. doi: 10.1038/srep07080.
• [6] SCRN1 is a novel marker for prognosis in colorectal cancer.J Surg Oncol. 2010 Feb 1;101(2):156-9. doi: 10.1002/jso.21459.
• [7] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [8] Incidence and Risk Factors of Dry Eye in a Spanish Adult Population: 11-Year Follow-Up From the Salns Eye Study.Cornea. 2018 Dec;37(12):1527-1534. doi: 10.1097/ICO.0000000000001713.
• [9] Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance.Mol Cell Proteomics. 2009 Jan;8(1):172-89. doi: 10.1074/mcp.M800292-MCP200. Epub 2008 Sep 9.
• [10] Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis.Nat Commun. 2015 Apr 9;6:6793. doi: 10.1038/ncomms7793.
• [11] 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.
• [12] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [13] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [14] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [17] 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.
• [18] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [19] Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy. 2010 Aug;6(6):711-24. doi: 10.4161/auto.6.6.12397. Epub 2010 Aug 17.
• [20] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [21] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [22] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [23] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [24] 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.
• [25] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [26] 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.