Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIUA60B)

• DOT Name: SH3 domain-containing kinase-binding protein 1 (SH3KBP1)
• Synonyms: CD2-binding protein 3; CD2BP3; Cbl-interacting protein of 85 kDa; Human Src family kinase-binding protein 1; HSB-1
• Gene Name: SH3KBP1
• Related Disease:
  Breast carcinoma
  Neoplasm
  Adrenocortical carcinoma
  Advanced cancer
  Breast cancer
  Breast neoplasm
  Colon cancer
  Colonic neoplasm
  Head-neck squamous cell carcinoma
  Herpes simplex infection
  Squamous cell carcinoma
  Immunodeficiency 61
  Prostate cancer
  Type-1/2 diabetes
• UniProt ID: SH3K1_HUMAN
• PDB ID: 2BZ8; 2K6D; 2K9G; 2N64; 2O2O; 2YDL; 5ABS
• Pfam ID: PF14604
• Sequence:
  MVEAIVEFDYQAQHDDELTISVGEIITNIRKEDGGWWEGQINGRRGLFPDNFVREIKKEM
  KKDPLTNKAPEKPLHEVPSGNSLLSSETILRTNKRGERRRRRCQVAFSYLPQNDDELELK
  VGDIIEVVGEVEEGWWEGVLNGKTGMFPSNFIKELSGESDELGISQDEQLSKSSLRETTG
  SESDGGDSSSTKSEGANGTVATAAIQPKKVKGVGFGDIFKDKPIKLRPRSIEVENDFLPV
  EKTIGKKLPATTATPDSSKTEMDSRTKSKDYCKVIFPYEAQNDDELTIKEGDIVTLINKD
  CIDVGWWEGELNGRRGVFPDNFVKLLPPDFEKEGNRPKKPPPPSAPVIKQGAGTTERKHE
  IKKIPPERPEMLPNRTEEKERPEREPKLDLQKPSVPAIPPKKPRPPKTNSLSRPGALPPR
  RPERPVGPLTHTRGDSPKIDLAGSSLSGILDKDLSDRSNDIDLEGFDSVVSSTEKLSHPT
  TSRPKATGRRPPSQSLTSSSLSSPDIFDSPSPEEDKEEHISLAHRGVDASKKTSKTVTIS
  QVSDNKASLPPKPGTMAAGGGGPAPLSSAAPSPLSSSLGTAGHRANSPSLFGTEGKPKME
  PAASSQAAVEELRTQVRELRSIIETMKDQQKREIKQLLSELDEEKKIRLRLQMEVNDIKK
  ALQSK
• Function: Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit. May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Has an essential role in the stimulation of B cell activation.
• Tissue Specificity: Ubiquitously expressed. Also expressed in some cancer cell lines.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway:
  Negative regulation of MET activity (R-HSA-6807004)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Reelin signalling pathway (R-HSA-8866376)
  InlB-mediated entry of Listeria monocytogenes into host cell (R-HSA-8875360)
  Potential therapeutics for SARS (R-HSA-9679191)
  Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)
  EGFR downregulation (R-HSA-182971)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Adrenocortical carcinoma	DISZF4HX	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[5]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[5]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[6]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[7]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[6]
Immunodeficiency 61	DISBJ7JK	Limited	X-linked	[8]
Prostate cancer	DISF190Y	Limited	Altered Expression	[9]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[10]

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 SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[17]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[18]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[19]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[20]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[21]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[22]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[15]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[24]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[27]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of SH3 domain-containing kinase-binding protein 1 (SH3KBP1).	[16]

References

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• [17] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [18] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
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• [21] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
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• [23] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
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