Details of Drug Off-Target (DOT)

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

• DOT Name: SH3 and cysteine-rich domain-containing protein (STAC)
• Synonyms: Src homology 3 and cysteine-rich domain-containing protein
• Gene Name: STAC
• Related Disease:
  Allergic contact dermatitis
  Insomnia
  Sleep disorder
• UniProt ID: STAC_HUMAN
• PDB ID: 2DL4; 6B25
• Pfam ID: PF00130 ; PF00018 ; PF07653 ; PF16664
• Sequence:
  MIPPSSPREDGVDGLPKEAVGAEQPPSPASTSSQESKLQKLKRSLSFKTKSLRSKSADNF
  FQRTNSEDMKLQAHMVAEISPSSSPLPAPGSLTSTPARAGLHPGGKAHAFQEYIFKKPTF
  CDVCNHMIVGTNAKHGLRCKACKMSIHHKCTDGLAPQRCMGKLPKGFRRYYSSPLLIHEQ
  FGCIKEVMPIACGNKVDPVYETLRFGTSLAQRTKKGSSGSGSDSPHRTSTSDLVEVPEEA
  NGPGGGYDLRKRSNSVFTYPENGTDDFRDPAKNINHQGSLSKDPLQMNTYVALYKFVPQE
  NEDLEMRPGDIITLLEDSNEDWWKGKIQDRIGFFPANFVQRLQQNEKIFRCVRTFIGCKE
  QGQITLKENQICVSSEEEQDGFIRVLSGKKKGLIPLDVLENI
• Function: Promotes expression of the ion channel CACNA1H at the cell membrane, and thereby contributes to the regulation of channel activity. Plays a minor and redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. Slows down the inactivation rate of the calcium channel CACNA1C.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic contact dermatitis	DISFFVF9	Strong	Biomarker	[1]
Insomnia	DIS0AFR7	Strong	Biomarker	[2]
Sleep disorder	DIS3JP1U	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of SH3 and cysteine-rich domain-containing protein (STAC).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SH3 and cysteine-rich domain-containing protein (STAC).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SH3 and cysteine-rich domain-containing protein (STAC).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SH3 and cysteine-rich domain-containing protein (STAC).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SH3 and cysteine-rich domain-containing protein (STAC).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SH3 and cysteine-rich domain-containing protein (STAC).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of SH3 and cysteine-rich domain-containing protein (STAC).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of SH3 and cysteine-rich domain-containing protein (STAC).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of SH3 and cysteine-rich domain-containing protein (STAC).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SH3 and cysteine-rich domain-containing protein (STAC).	[10]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of SH3 and cysteine-rich domain-containing protein (STAC).	[11]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of SH3 and cysteine-rich domain-containing protein (STAC).	[12]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of SH3 and cysteine-rich domain-containing protein (STAC).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of SH3 and cysteine-rich domain-containing protein (STAC).	[9]

References

• [1] Gene transcripts as potential diagnostic markers for allergic contact dermatitis.Contact Dermatitis. 2005 Aug;53(2):100-6. doi: 10.1111/j.0105-1873.2005.00658.x.
• [2] Stabilising sleep for patients admitted at acute crisis to a psychiatric hospital (OWLS): an assessor-blind pilot randomised controlled trial.Psychol Med. 2018 Jul;48(10):1694-1704. doi: 10.1017/S0033291717003191. Epub 2017 Nov 7.
• [3] 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.
• [4] 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.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] 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.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [12] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [13] 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.
• [14] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
• [15] 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.