Details of Drug Off-Target (DOT)

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

• DOT Name: SHC-transforming protein 2 (SHC2)
• Synonyms: Protein Sck; SHC-transforming protein B; Src homology 2 domain-containing-transforming protein C2; SH2 domain protein C2
• Gene Name: SHC2
• Related Disease:
  Neoplasm
  Autism
  Breast cancer
  Breast carcinoma
  Cholangiocarcinoma
  Epilepsy
  Fragile X syndrome
  Hepatitis C virus infection
  Language disorder
  Specific language impairment
• UniProt ID: SHC2_HUMAN
• Pfam ID: PF00640 ; PF00017
• Sequence:
  MTQGPGGRAPPAPPAPPEPEAPTTFCALLPRMPQWKFAAPGGFLGRGPAAARAAGASGGA
  DPQPEPAGPGGVPALAAAVLGACEPRCAAPCPLPALSRCRGAGSRGSRGGRGAAGSGDAA
  AAAEWIRKGSFIHKPAHGWLHPDARVLGPGVSYVVRYMGCIEVLRSMRSLDFNTRTQVTR
  EAINRLHEAVPGVRGSWKKKAPNKALASVLGKSNLRFAGMSISIHISTDGLSLSVPATRQ
  VIANHHMPSISFASGGDTDMTDYVAYVAKDPINQRACHILECCEGLAQSIISTVGQAFEL
  RFKQYLHSPPKVALPPERLAGPEESAWGDEEDSLEHNYYNSIPGKEPPLGGLVDSRLALT
  QPCALTALDQGPSPSLRDACSLPWDVGSTGTAPPGDGYVQADARGPPDHEEHLYVNTQGL
  DAPEPEDSPKKDLFDMRPFEDALKLHECSVAAGVTAAPLPLEDQWPSPPTRRAPVAPTEE
  QLRQEPWYHGRMSRRAAERMLRADGDFLVRDSVTNPGQYVLTGMHAGQPKHLLLVDPEGV
  VRTKDVLFESISHLIDHHLQNGQPIVAAESELHLRGVVSREP
• Function: Signaling adapter that couples activated growth factor receptors to signaling pathway in neurons. Involved in the signal transduction pathways of neurotrophin-activated Trk receptors in cortical neurons.
• Tissue Specificity: Expressed in brain. Expressed at high level in the hypothalamus and at low level in the caudate nucleus.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  Endocrine resistance (hsa01522)
  ErbB sig.ling pathway (hsa04012)
  Ras sig.ling pathway (hsa04014)
  Chemokine sig.ling pathway (hsa04062)
  Phospholipase D sig.ling pathway (hsa04072)
  VEGF sig.ling pathway (hsa04370)
  Focal adhesion (hsa04510)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Neurotrophin sig.ling pathway (hsa04722)
  Insulin sig.ling pathway (hsa04910)
  Estrogen sig.ling pathway (hsa04915)
  Prolactin sig.ling pathway (hsa04917)
  Relaxin sig.ling pathway (hsa04926)
  Growth hormone synthesis, secretion and action (hsa04935)
  Alcoholism (hsa05034)
  Bacterial invasion of epithelial cells (hsa05100)
  Glioma (hsa05214)
  Chronic myeloid leukemia (hsa05220)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Signalling to RAS (R-HSA-167044)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Autism	DISV4V1Z	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[4]
Epilepsy	DISBB28L	Strong	Biomarker	[5]
Fragile X syndrome	DISE8W3A	Strong	Genetic Variation	[6]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[7]
Language disorder	DISTLKP7	Strong	Genetic Variation	[8]
Specific language impairment	DISEKRML	Strong	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of SHC-transforming protein 2 (SHC2).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of SHC-transforming protein 2 (SHC2).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SHC-transforming protein 2 (SHC2).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SHC-transforming protein 2 (SHC2).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SHC-transforming protein 2 (SHC2).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SHC-transforming protein 2 (SHC2).	[13]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of SHC-transforming protein 2 (SHC2).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of SHC-transforming protein 2 (SHC2).	[16]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of SHC-transforming protein 2 (SHC2).	[16]

References

• [1] Association of ki67 and tumor marker p53 in locally advanced breast cancer patients and evaluation of response to neoadjuvant chemotherapy: a survey in South Iran.Cancer Manag Res. 2019 Jul 11;11:6489-6497. doi: 10.2147/CMAR.S203831. eCollection 2019.
• [2] ASD Is Not DLI: Individuals With Autism and Individuals With Syntactic DLI Show Similar Performance Level in Syntactic Tasks, but Different Error Patterns.Front Psychol. 2018 Apr 4;9:279. doi: 10.3389/fpsyg.2018.00279. eCollection 2018.
• [3] NRF1 motif sequence-enriched genes involved in ER/PR -ve HER2 +ve breast cancer signaling pathways.Breast Cancer Res Treat. 2018 Nov;172(2):469-485. doi: 10.1007/s10549-018-4905-9. Epub 2018 Aug 20.
• [4] Genetic and expression alterations in association with the sarcomatous change of cholangiocarcinoma cells.Exp Mol Med. 2009 Feb 28;41(2):102-15. doi: 10.3858/emm.2009.41.2.013.
• [5] Congenital bilateral perisylvian syndrome: familial occurrence, clinical and psycholinguistic aspects correlated with MRI.Neuropediatrics. 2008 Jun;39(3):139-45. doi: 10.1055/s-0028-1085462. Epub 2008 Nov 7.
• [6] Finiteness marking in boys with fragile X syndrome.J Speech Lang Hear Res. 2012 Dec;55(6):1704-15. doi: 10.1044/1092-4388(2012/10-0106). Epub 2012 May 4.
• [7] Structure-function analysis of the equine hepacivirus 5' untranslated region highlights the conservation of translational mechanisms across the hepaciviruses.J Gen Virol. 2019 Nov;100(11):1501-1514. doi: 10.1099/jgv.0.001316.
• [8] Putative miRNAs for the diagnosis of dyslexia, dyspraxia, and specific language impairment.Epigenetics. 2013 Oct;8(10):1023-9. doi: 10.4161/epi.26026. Epub 2013 Aug 15.
• [9] A morpho-phonological Past Tense processing as a clinical marker in SLI EFL learners.Clin Linguist Phon. 2017;31(7-9):542-556. doi: 10.1080/02699206.2017.1283710. Epub 2017 Feb 15.
• [10] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [11] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [12] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] 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.
• [15] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [16] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [17] 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.