Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUYSV2S)

• DOT Name: Secretogranin-3 (SCG3)
• Synonyms: Secretogranin III; SgIII
• Gene Name: SCG3
• UniProt ID: SCG3_HUMAN
• Pfam ID: PF15467
• Sequence:
  MGFLGTGTWILVLVLPIQAFPKPGGSQDKSLHNRELSAERPLNEQIAEAEEDKIKKTYPP
  ENKPGQSNYSFVDNLNLLKAITEKEKIEKERQSIRSSPLDNKLNVEDVDSTKNRKLIDDY
  DSTKSGLDHKFQDDPDGLHQLDGTPLTAEDIVHKIAARIYEENDRAVFDKIVSKLLNLGL
  ITESQAHTLEDEVAEVLQKLISKEANNYEEDPNKPTSWTENQAGKIPEKVTPMAAIQDGL
  AKGENDETVSNTLTLTNGLERRTKTYSEDNFEELQYFPNFYALLKSIDSEKEAKEKETLI
  TIMKTLIDFVKMMVKYGTISPEEGVSYLENLDEMIALQTKNKLEKNATDNISKLFPAPSE
  KSHEETDSTKEEAAKMEKEYGSLKDSTKDDNSNPGGKTDEPKGKTEAYLEAIRKNIEWLK
  KHDKKGNKEDYDLSKMRDFINKQADAYVEKGILDKEEAEAIKRIYSSL
• Function: Member of the granin protein family that regulates the biogenesis of secretory granules. Acts as a sorting receptor for intragranular proteins including chromogranin A/CHGA. May also play a role in angiogenesis. Promotes endothelial proliferation, migration and tube formation through MEK/ERK signaling pathway.
• Tissue Specificity: Detected in urine (at protein level) . Expressed in brain, heart, kidney, liver and skeletal muscle.
• Reactome Pathway:
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

10 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-3 (SCG3).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Secretogranin-3 (SCG3).	[2]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Secretogranin-3 (SCG3).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Secretogranin-3 (SCG3).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Secretogranin-3 (SCG3).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Secretogranin-3 (SCG3).	[3]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Secretogranin-3 (SCG3).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Secretogranin-3 (SCG3).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Secretogranin-3 (SCG3).	[7]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Secretogranin-3 (SCG3).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] 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.
• [6] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [7] 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.
• [8] Dysregulated expression of secretogranin III is involved in neurotoxin-induced dopaminergic neuron apoptosis. J Neurosci Res. 2012 Dec;90(12):2237-46. doi: 10.1002/jnr.23121. Epub 2012 Sep 18.