Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJDS1NN)

• DOT Name: SH2 domain-containing protein 5 (SH2D5)
• Gene Name: SH2D5
• Related Disease:
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Neuroblastoma
• UniProt ID: SH2D5_HUMAN
• Sequence:
  MQKAGAGGRRASDCGLAPHRPRCITKFAQYVGSFPVDDLDTQESVWLVQQQLWALKDCPR
  RRAVILKFSLQGLKIYSGEGEVLLMAHALRRILYSTWCPADCQFAFMARNPRSPASKLFC
  HLFVGSQPGEVQILHLLLCRSFQLAYLLQHPEERAQPEPCPGPTGEVPLKPLSSSGGLVR
  EPFGRDQLSQNVHALVSFRRLPAEGLVGSGKELPESEGRARHARLGNPYCSPTLVRKKAI
  RSKVIRSGAYRGCTYETQLQLSAREAFPAAWEAWPRGPGGHSCLVESEGSLTENIWAFAG
  ISRPCALALLRRDVLGAFLLWPELGASGQWCLSVRTQCGVVPHQVFRNHLGRYCLEHLPA
  EFPSLEALVENHAVTERSLFCPLDMGRLNPTYEEQDCGPPGRPPRTLRPLSHAKSEAELQ
  GLG
• Function: May be involved in synaptic plasticity regulation through the control of Rac-GTP levels.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[2]

16 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 SH2 domain-containing protein 5 (SH2D5).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SH2 domain-containing protein 5 (SH2D5).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SH2 domain-containing protein 5 (SH2D5).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of SH2 domain-containing protein 5 (SH2D5).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of SH2 domain-containing protein 5 (SH2D5).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of SH2 domain-containing protein 5 (SH2D5).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of SH2 domain-containing protein 5 (SH2D5).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of SH2 domain-containing protein 5 (SH2D5).	[8]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of SH2 domain-containing protein 5 (SH2D5).	[9]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of SH2 domain-containing protein 5 (SH2D5).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of SH2 domain-containing protein 5 (SH2D5).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SH2 domain-containing protein 5 (SH2D5).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of SH2 domain-containing protein 5 (SH2D5).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of SH2 domain-containing protein 5 (SH2D5).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of SH2 domain-containing protein 5 (SH2D5).	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of SH2 domain-containing protein 5 (SH2D5).	[18]

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 increases the methylation of SH2 domain-containing protein 5 (SH2D5).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of SH2 domain-containing protein 5 (SH2D5).	[15]

References

• [1] Hepatitis B virus X protein-induced SH2 domain-containing 5 (SH2D5) expression promotes hepatoma cell growth via an SH2D5-transketolase interaction.J Biol Chem. 2019 Mar 29;294(13):4815-4827. doi: 10.1074/jbc.RA118.005739. Epub 2019 Jan 18.
• [2] Src homology 2 domain containing protein 5 (SH2D5) binds the breakpoint cluster region protein, BCR, and regulates levels of Rac1-GTP.J Biol Chem. 2014 Dec 19;289(51):35397-408. doi: 10.1074/jbc.M114.615112. Epub 2014 Oct 20.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [9] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] 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.
• [13] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [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] 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.