Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFAVSX0)

• DOT Name: Serglycin (SRGN)
• Synonyms: Hematopoietic proteoglycan core protein; Platelet proteoglycan core protein; P.PG; Secretory granule proteoglycan core protein
• Gene Name: SRGN
• UniProt ID: SRGN_HUMAN
• Pfam ID: PF04360
• Sequence:
  MMQKLLKCSRLVLALALILVLESSVQGYPTRRARYQWVRCNPDSNSANCLEEKGPMFELL
  PGESNKIPRLRTDLFPKTRIQDLNRIFPLSEDYSGSGFGSGSGSGSGSGSGFLTEMEQDY
  QLVDESDAFHDNLRSLDRNLPSDSQDLGQHGLEEDFML
• Function: Plays a role in formation of mast cell secretory granules and mediates storage of various compounds in secretory vesicles. Required for storage of some proteases in both connective tissue and mucosal mast cells and for storage of granzyme B in T-lymphocytes. Plays a role in localizing neutrophil elastase in azurophil granules of neutrophils. Mediates processing of MMP2. Plays a role in cytotoxic cell granule-mediated apoptosis by forming a complex with granzyme B which is delivered to cells by perforin to induce apoptosis. Regulates the secretion of TNF-alpha and may also regulate protease secretion. Inhibits bone mineralization.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Serglycin (SRGN) affects the response to substance of Doxorubicin.	[21]
Paclitaxel	DMLB81S	Approved	Serglycin (SRGN) affects the response to substance of Paclitaxel.	[21]
Mitomycin	DMH0ZJE	Approved	Serglycin (SRGN) affects the response to substance of Mitomycin.	[21]
Topotecan	DMP6G8T	Approved	Serglycin (SRGN) affects the response to substance of Topotecan.	[21]
Vinblastine	DM5TVS3	Approved	Serglycin (SRGN) affects the response to substance of Vinblastine.	[21]

21 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 Serglycin (SRGN).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serglycin (SRGN).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Serglycin (SRGN).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Serglycin (SRGN).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Serglycin (SRGN).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Serglycin (SRGN).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Serglycin (SRGN).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Serglycin (SRGN).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Serglycin (SRGN).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Serglycin (SRGN).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Serglycin (SRGN).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Serglycin (SRGN).	[7]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Serglycin (SRGN).	[12]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Serglycin (SRGN).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serglycin (SRGN).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Serglycin (SRGN).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Serglycin (SRGN).	[6]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Serglycin (SRGN).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Serglycin (SRGN).	[18]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Serglycin (SRGN).	[19]
Pyrrolidine dithiocarbamate	DM5ZAS6	Investigative	Pyrrolidine dithiocarbamate increases the expression of Serglycin (SRGN).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Serglycin (SRGN).	[16]

References

• [1] 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.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [8] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [9] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [12] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [13] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [14] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [15] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [16] 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.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [18] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
• [19] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.
• [20] Effects of a redox-active agent on lymphocyte activation and early gene expression patterns. Free Radic Biol Med. 2004 Nov 15;37(10):1550-63.
• [21] 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.