Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1J5IRN)

• DOT Name: SHC-transforming protein 1 (SHC1)
• Synonyms: SHC-transforming protein 3; SHC-transforming protein A; Src homology 2 domain-containing-transforming protein C1; SH2 domain protein C1
• Gene Name: SHC1
• Related Disease:
  Crohn disease
  Gastric cancer
  Non-insulin dependent diabetes
  Stomach cancer
  Adult glioblastoma
  Amyotrophic lateral sclerosis type 1
  Atrial fibrillation
  Breast neoplasm
  Carcinoma
  Cardiovascular disease
  Chronic renal failure
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Endometriosis
  Familial amyotrophic lateral sclerosis
  Fatty liver disease
  Glioblastoma multiforme
  High blood pressure
  Inflammatory bowel disease
  Liver cancer
  Lung cancer
  Lung carcinoma
  Melanoma
  Non-small-cell lung cancer
  Obesity
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Type-1/2 diabetes
  Advanced cancer
  Colorectal carcinoma
  Hepatocellular carcinoma
  Stroke
  Neoplasm
  Neuroblastoma
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Coronary heart disease
  Hyperlipidemia
  Hyperlipoproteinemia
  Pancreatic cancer
• UniProt ID: SHC1_HUMAN
• PDB ID: 1MIL; 1N3H; 1OY2; 1QG1; 1SHC; 1TCE; 2L1C; 4JMH; 4XWX; 5CZI; 6DM4
• Pfam ID: PF00640 ; PF00017
• Sequence:
  MDLLPPKPKYNPLRNESLSSLEEGASGSTPPEELPSPSASSLGPILPPLPGDDSPTTLCS
  FFPRMSNLRLANPAGGRPGSKGEPGRAADDGEGIVGAAMPDSGPLPLLQDMNKLSGGGGR
  RTRVEGGQLGGEEWTRHGSFVNKPTRGWLHPNDKVMGPGVSYLVRYMGCVEVLQSMRALD
  FNTRTQVTREAISLVCEAVPGAKGATRRRKPCSRPLSSILGRSNLKFAGMPITLTVSTSS
  LNLMAADCKQIIANHHMQSISFASGGDPDTAEYVAYVAKDPVNQRACHILECPEGLAQDV
  ISTIGQAFELRFKQYLRNPPKLVTPHDRMAGFDGSAWDEEEEEPPDHQYYNDFPGKEPPL
  GGVVDMRLREGAAPGAARPTAPNAQTPSHLGATLPVGQPVGGDPEVRKQMPPPPPCPGRE
  LFDDPSYVNVQNLDKARQAVGGAGPPNPAINGSAPRDLFDMKPFEDALRVPPPPQSVSMA
  EQLRGEPWFHGKLSRREAEALLQLNGDFLVRESTTTPGQYVLTGLQSGQPKHLLLVDPEG
  VVRTKDHRFESVSHLISYHMDNHLPIISAGSELCLQQPVERKL
• Function: Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span. Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis.
• Tissue Specificity: Widely expressed. Expressed in neural stem cells but absent in mature neurons.
• 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)
  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)
  MicroR.s in cancer (hsa05206)
  Glioma (hsa05214)
  Chronic myeloid leukemia (hsa05220)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  SHC1 events in ERBB2 signaling (R-HSA-1250196)
  SHC1 events in ERBB4 signaling (R-HSA-1250347)
  Signalling to RAS (R-HSA-167044)
  SHC1 events in EGFR signaling (R-HSA-180336)
  Signaling by ALK (R-HSA-201556)
  Tie2 Signaling (R-HSA-210993)
  SHC-related events triggered by IGF1R (R-HSA-2428933)
  Integrin signaling (R-HSA-354192)
  XBP1(S) activates chaperone genes (R-HSA-381038)
  Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988)
  Constitutive Signaling by EGFRvIII (R-HSA-5637810)
  SHC-mediated cascade (R-HSA-5654688)
  SHC-mediated cascade (R-HSA-5654699)
  SHC-mediated cascade (R-HSA-5654704)
  SHC-mediated cascade (R-HSA-5654719)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Signal attenuation (R-HSA-74749)
  Insulin receptor signalling cascade (R-HSA-74751)
  RET signaling (R-HSA-8853659)
  Interleukin-15 signaling (R-HSA-8983432)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  Interleukin-2 signaling (R-HSA-9020558)
  Activated NTRK2 signals through RAS (R-HSA-9026519)
  Erythropoietin activates RAS (R-HSA-9027284)
  Activated NTRK3 signals through RAS (R-HSA-9034864)
  Interleukin receptor SHC signaling (R-HSA-912526)
  Constitutive Signaling by Overexpressed ERBB2 (R-HSA-9634285)
  GPER1 signaling (R-HSA-9634597)
  Signaling by ERBB2 KD Mutants (R-HSA-9664565)
  Signaling by ERBB2 ECD mutants (R-HSA-9665348)
  Signaling by ERBB2 TMD/JMD mutants (R-HSA-9665686)
  Signaling by CSF3 (G-CSF) (R-HSA-9674555)
  Signaling by CSF1 (M-CSF) in myeloid cells (R-HSA-9680350)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants (R-HSA-1236382)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Crohn disease	DIS2C5Q8	Definitive	Biomarker	[1]
Gastric cancer	DISXGOUK	Definitive	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Altered Expression	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Strong	Biomarker	[4]
Atrial fibrillation	DIS15W6U	Strong	Altered Expression	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Carcinoma	DISH9F1N	Strong	Altered Expression	[7]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[8]
Chronic renal failure	DISGG7K6	Strong	Altered Expression	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[11]
Endometriosis	DISX1AG8	Strong	Altered Expression	[12]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Biomarker	[4]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[13]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[14]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[15]
Liver cancer	DISDE4BI	Strong	Biomarker	[16]
Lung cancer	DISCM4YA	Strong	Altered Expression	[17]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[17]
Melanoma	DIS1RRCY	Strong	Altered Expression	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[19]
Obesity	DIS47Y1K	Strong	Biomarker	[20]
Prostate cancer	DISF190Y	Strong	Altered Expression	[21]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[21]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[22]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[23]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[24]
Colorectal carcinoma	DIS5PYL0	moderate	Genetic Variation	[25]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[26]
Stroke	DISX6UHX	moderate	Altered Expression	[27]
Neoplasm	DISZKGEW	Disputed	Genetic Variation	[28]
Neuroblastoma	DISVZBI4	Disputed	Biomarker	[29]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[30]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[30]
Breast cancer	DIS7DPX1	Limited	Biomarker	[31]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[31]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[32]
Coronary heart disease	DIS5OIP1	Limited	Altered Expression	[30]
Hyperlipidemia	DIS61J3S	Limited	Biomarker	[33]
Hyperlipoproteinemia	DISVBLBO	Limited	Biomarker	[33]
Pancreatic cancer	DISJC981	Limited	Biomarker	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	SHC-transforming protein 1 (SHC1) increases the response to substance of Cisplatin.	[61]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of SHC-transforming protein 1 (SHC1).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SHC-transforming protein 1 (SHC1).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SHC-transforming protein 1 (SHC1).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SHC-transforming protein 1 (SHC1).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SHC-transforming protein 1 (SHC1).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SHC-transforming protein 1 (SHC1).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SHC-transforming protein 1 (SHC1).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of SHC-transforming protein 1 (SHC1).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of SHC-transforming protein 1 (SHC1).	[44]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of SHC-transforming protein 1 (SHC1).	[45]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SHC-transforming protein 1 (SHC1).	[46]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of SHC-transforming protein 1 (SHC1).	[47]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of SHC-transforming protein 1 (SHC1).	[48]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of SHC-transforming protein 1 (SHC1).	[49]
Malathion	DMXZ84M	Approved	Malathion increases the expression of SHC-transforming protein 1 (SHC1).	[50]
Nicotinamide	DMUPE07	Approved	Nicotinamide increases the expression of SHC-transforming protein 1 (SHC1).	[51]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of SHC-transforming protein 1 (SHC1).	[52]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of SHC-transforming protein 1 (SHC1).	[53]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of SHC-transforming protein 1 (SHC1).	[54]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of SHC-transforming protein 1 (SHC1).	[55]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of SHC-transforming protein 1 (SHC1).	[57]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of SHC-transforming protein 1 (SHC1).	[45]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of SHC-transforming protein 1 (SHC1).	[58]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of SHC-transforming protein 1 (SHC1).	[59]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of SHC-transforming protein 1 (SHC1).	[51]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the expression of SHC-transforming protein 1 (SHC1).	[60]
Suramin	DMTOUY9	Investigative	Suramin increases the expression of SHC-transforming protein 1 (SHC1).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the phosphorylation of SHC-transforming protein 1 (SHC1).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of SHC-transforming protein 1 (SHC1).	[56]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of SHC-transforming protein 1 (SHC1).	[56]

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