Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM0KLPH)

• DOT Name: SH2 domain-containing protein 4B (SH2D4B)
• Gene Name: SH2D4B
• Related Disease:
  Alzheimer disease
  Cholelithiasis
  Ewing sarcoma
  Ovarian neoplasm
• UniProt ID: SH24B_HUMAN
• Pfam ID: PF00017
• Sequence:
  MLQQILHDMYIDPELLAELSDVQKHILFYKMREEQLRRWKERETWEALAQDEGLRPPKTK
  RASDKHIQWLLGADGEVWVWIMGEGPGDKPYEEISEELIAERARLQAQREAEELWRQKEA
  EITKKFRDALANEKARILAEKWKVEMEDRKAAKVLEERIHEEFKRKEEEERKRGEEQIRL
  QEEQRAKELYWTLKQAQLHCQASEKEEREWEEQLRRSKAADEERSRRAQRARDEYRHHSL
  RAIQKGTVAGLSSMFRELGQSHEQEARLYHHLPDPGLPQPLALPVRTWERPLRPVSRDVI
  VRWFKEEQLPRRAGFERNTKFIAPWFHGIISREDAEALLENMTEGAFLVRVSEKIWGYTL
  SYRLQKGFKHFLVDASGDFYSFLGVDPNRHATLTDLVDFHKEEIITVSGGELLQEPCGQR
  DSPPDYHLLFE

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Cholelithiasis	DISERLZB	Strong	Genetic Variation	[2]
Ewing sarcoma	DISQYLV3	Strong	Altered Expression	[3]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of SH2 domain-containing protein 4B (SH2D4B).	[5]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of SH2 domain-containing protein 4B (SH2D4B).	[7]

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 SH2 domain-containing protein 4B (SH2D4B).	[6]

References

• [1] A novel Alzheimer disease locus located near the gene encoding tau protein.Mol Psychiatry. 2016 Jan;21(1):108-17. doi: 10.1038/mp.2015.23. Epub 2015 Mar 17.
• [2] A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.Nat Genet. 2007 Aug;39(8):995-9. doi: 10.1038/ng2101. Epub 2007 Jul 15.
• [3] EAT-2 is a novel SH2 domain containing protein that is up regulated by Ewing's sarcoma EWS/FLI1 fusion gene.Oncogene. 1996 Dec 19;13(12):2649-58.
• [4] Genome-wide association study evaluating single-nucleotide polymorphisms and outcomes in patients with advanced stage serous ovarian or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study.Gynecol Oncol. 2017 Nov;147(2):396-401. doi: 10.1016/j.ygyno.2017.08.024. Epub 2017 Sep 19.
• [5] 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.
• [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 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.