Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRJ9PG0)

• DOT Name: SH3 and cysteine-rich domain-containing protein 2 (STAC2)
• Synonyms: 24b2/STAC2; Src homology 3 and cysteine-rich domain-containing protein 2
• Gene Name: STAC2
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: STAC2_HUMAN
• PDB ID: 6B26; 6B27; 6B28
• Pfam ID: PF00130 ; PF07653 ; PF14604 ; PF16664
• Sequence:
  MTEMSEKENEPDDAATHSPPGTVSALQETKLQRFKRSLSLKTILRSKSLENFFLRSGSEL
  KCPTEVLLTPPTPLPPPSPPPTASDRGLATPSPSPCPVPRPLAALKPVRLHSFQEHVFKR
  ASPCELCHQLIVGNSKQGLRCKMCKVSVHLWCSEEISHQQCPGKTSTSFRRNFSSPLLVH
  EPPPVCATSKESPPTGDSGKVDPVYETLRYGTSLALMNRSSFSSTSESPTRSLSERDELT
  EDGEGSIRSSEEGPGDSASPVFTAPAESEGPGPEEKSPGQQLPKATLRKDVGPMYSYVAL
  YKFLPQENNDLALQPGDRIMLVDDSNEDWWKGKIGDRVGFFPANFVQRVRPGENVWRCCQ
  PFSGNKEQGYMSLKENQICVGVGRSKDADGFIRVSSGKKRGLVPVDALTEI
• Function: Plays a 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SH3 and cysteine-rich domain-containing protein 2 (STAC2).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SH3 and cysteine-rich domain-containing protein 2 (STAC2).	[3]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of SH3 and cysteine-rich domain-containing protein 2 (STAC2).	[4]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of SH3 and cysteine-rich domain-containing protein 2 (STAC2).	[5]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of SH3 and cysteine-rich domain-containing protein 2 (STAC2).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of SH3 and cysteine-rich domain-containing protein 2 (STAC2).	[8]

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 affects the methylation of SH3 and cysteine-rich domain-containing protein 2 (STAC2).	[6]

References

• [1] RWCFusion: identifying phenotype-specific cancer driver gene fusions based on fusion pair random walk scoring method.Oncotarget. 2016 Sep 20;7(38):61054-61068. doi: 10.18632/oncotarget.11064.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [6] 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.
• [7] 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.
• [8] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.