Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUHXX8U)

• DOT Name: Secretogranin-2 (SCG2)
• Synonyms: Chromogranin-C; Secretogranin II; SgII
• Gene Name: SCG2
• UniProt ID: SCG2_HUMAN
• Pfam ID: PF01271
• Sequence:
  MAEAKTHWLGAALSLIPLIFLISGAEAASFQRNQLLQKEPDLRLENVQKFPSPEMIRALE
  YIENLRQQAHKEESSPDYNPYQGVSVPLQQKENGDESHLPERDSLSEEDWMRIILEALRQ
  AENEPQSAPKENKPYALNSEKNFPMDMSDDYETQQWPERKLKHMQFPPMYEENSRDNPFK
  RTNEIVEEQYTPQSLATLESVFQELGKLTGPNNQKRERMDEEQKLYTDDEDDIYKANNIA
  YEDVVGGEDWNPVEEKIESQTQEEVRDSKENIEKNEQINDEMKRSGQLGIQEEDLRKESK
  DQLSDDVSKVIAYLKRLVNAAGSGRLQNGQNGERATRLFEKPLDSQSIYQLIEISRNLQI
  PPEDLIEMLKTGEKPNGSVEPERELDLPVDLDDISEADLDHPDLFQNRMLSKSGYPKTPG
  RAGTEALPDGLSVEDILNLLGMESAANQKTSYFPNPYNQEKVLPRLPYGAGRSRSNQLPK
  AAWIPHVENRQMAYENLNDKDQELGEYLARMLVKYPEIINSNQVKRVPGQGSSEDDLQEE
  EQIEQAIKEHLNQGSSQETDKLAPVSKRFPVGPPKNDDTPNRQYWDEDLLMKVLEYLNQE
  KAEKGREHIAKRAMENM
• Function: Neuroendocrine protein of the granin family that regulates the biogenesis of secretory granules.
• Reactome Pathway:
  Post-translational protein phosphorylation (R-HSA-8957275)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

15 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 Secretogranin-2 (SCG2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Secretogranin-2 (SCG2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Secretogranin-2 (SCG2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Secretogranin-2 (SCG2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Secretogranin-2 (SCG2).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Secretogranin-2 (SCG2).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Secretogranin-2 (SCG2).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Secretogranin-2 (SCG2).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Secretogranin-2 (SCG2).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Secretogranin-2 (SCG2).	[11]
Wortmannin	DM8EVK5	Terminated	Wortmannin decreases the activity of Secretogranin-2 (SCG2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Secretogranin-2 (SCG2).	[14]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Secretogranin-2 (SCG2).	[15]
Paraquat	DMR8O3X	Investigative	Paraquat affects the expression of Secretogranin-2 (SCG2).	[16]
isobutylmethylxanthine	DM46F5X	Investigative	isobutylmethylxanthine decreases the activity of Secretogranin-2 (SCG2).	[12]

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 decreases the methylation of Secretogranin-2 (SCG2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Secretogranin-2 (SCG2).	[13]

References

• [1] 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.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [7] 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.
• [8] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [9] 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.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [12] Secretoneurin, a novel neuropeptide, is a potent chemoattractant for human eosinophils. Blood. 1998 Mar 1;91(5):1527-32.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [16] Effects of PQ's cytotoxicity on secretory vesicles in astroglia: Expression alternation of secretogranin II and its potential interaction with intracellular factors. Biochem Biophys Res Commun. 2018 Mar 4;497(2):675-682. doi: 10.1016/j.bbrc.2018.02.130. Epub 2018 Feb 16.