Details of Drug Off-Target (DOT)

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

• DOT Name: SH3 domain-binding protein 5 (SH3BP5)
• Synonyms: SH3BP-5; SH3 domain-binding protein that preferentially associates with BTK
• Gene Name: SH3BP5
• Related Disease:
  Acute myelogenous leukaemia
  B-cell lymphoma
  Neoplasm
  Parkinson disease
  Cherubism
  Ebola virus infection
  Middle East Respiratory Syndrome (MERS)
• UniProt ID: 3BP5_HUMAN
• PDB ID: 4H3B; 6DJL; 6IXE; 6IXF; 6IXG; 6IXV
• Pfam ID: PF05276
• Sequence:
  MDAALKRSRSEEPAEILPPARDEEEEEEEGMEQGLEEEEEVDPRIQGELEKLNQSTDDIN
  RRETELEDARQKFRSVLVEATVKLDELVKKIGKAVEDSKPYWEARRVARQAQLEAQKATQ
  DFQRATEVLRAAKETISLAEQRLLEDDKRQFDSAWQEMLNHATQRVMEAEQTKTRSELVH
  KETAARYNAAMGRMRQLEKKLKRAINKSKPYFELKAKYYVQLEQLKKTVDDLQAKLTLAK
  GEYKMALKNLEMISDEIHERRRSSAMGPRGCGVGAEGSSTSVEDLPGSKPEPDAISVASE
  AFEDDSCSNFVSEDDSETQSVSSFSSGPTSPSEMPDQFPAVVRPGSLDLPSPVSLSEFGM
  MFPVLGPRSECSGASSPECEVERGDRAEGAENKTSDKANNNRGLSSSSGSGGSSKSQSST
  SPEGQALENRMKQLSLQCSKGRDGIIADIKMVQIG
• Function: Functions as a guanine nucleotide exchange factor (GEF) with specificity for RAB11A and RAB25. Inhibits the auto- and transphosphorylation activity of BTK. Plays a negative regulatory role in BTK-related cytoplasmic signaling in B-cells. May be involved in BCR-induced apoptotic cell death.
• Tissue Specificity: Highly expressed in testis and ovaries. It is also expressed in a variety of tissues including spleen, lymph node, thymus, bone marrow, fetal liver, colon, small intestine and prostate.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Parkinson disease	DISQVHKL	Strong	Biomarker	[4]
Cherubism	DISHLJI0	Disputed	Genetic Variation	[5]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[6]
Middle East Respiratory Syndrome (MERS)	DIS5VPYU	Limited	Biomarker	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	SH3 domain-binding protein 5 (SH3BP5) affects the response to substance of Mitomycin.	[19]

11 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 SH3 domain-binding protein 5 (SH3BP5).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SH3 domain-binding protein 5 (SH3BP5).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SH3 domain-binding protein 5 (SH3BP5).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SH3 domain-binding protein 5 (SH3BP5).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of SH3 domain-binding protein 5 (SH3BP5).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SH3 domain-binding protein 5 (SH3BP5).	[13]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of SH3 domain-binding protein 5 (SH3BP5).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of SH3 domain-binding protein 5 (SH3BP5).	[15]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl affects the expression of SH3 domain-binding protein 5 (SH3BP5).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of SH3 domain-binding protein 5 (SH3BP5).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SH3 domain-binding protein 5 (SH3BP5).	[18]

References

• [1] Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells.Biomolecules. 2019 Sep 19;9(9):505. doi: 10.3390/biom9090505.
• [2] Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B-cell lymphoma cells and their association with clinical features.Cancer Med. 2016 Aug;5(8):1802-9. doi: 10.1002/cam4.753. Epub 2016 May 17.
• [3] Co-delivery of Bee Venom Melittin and a Photosensitizer with an Organic-Inorganic Hybrid Nanocarrier for Photodynamic Therapy and Immunotherapy.ACS Nano. 2019 Nov 26;13(11):12638-12652. doi: 10.1021/acsnano.9b04181. Epub 2019 Oct 22.
• [4] Phosphoregulation on mitochondria: Integration of cell and organelle responses.CNS Neurosci Ther. 2019 Jul;25(7):837-858. doi: 10.1111/cns.13141. Epub 2019 Apr 25.
• [5] Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism. Nat Genet. 2001 Jun;28(2):125-6. doi: 10.1038/88832.
• [6] Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate.J Infect Dis. 2018 Nov 22;218(suppl_5):S636-S648. doi: 10.1093/infdis/jiy377.
• [7] Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, single-dose-escalation study.Lancet Infect Dis. 2018 Apr;18(4):410-418. doi: 10.1016/S1473-3099(18)30002-1. Epub 2018 Jan 9.
• [8] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [9] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [10] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [11] Gene expression data from acetaminophen-induced toxicity in human hepatic in vitro systems and clinical liver samples. Data Brief. 2016 Mar 26;7:1052-1057. doi: 10.1016/j.dib.2016.03.069. eCollection 2016 Jun.
• [12] 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.
• [13] 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.
• [14] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Fluorescent tagging of endogenous Heme oxygenase-1 in human induced pluripotent stem cells for high content imaging of oxidative stress in various differentiated lineages. Arch Toxicol. 2021 Oct;95(10):3285-3302. doi: 10.1007/s00204-021-03127-8. Epub 2021 Sep 4.
• [17] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [18] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [19] 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.