Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNBXH32)

• DOT Name: Ski-like protein (SKIL)
• Synonyms: Ski-related oncogene; Ski-related protein
• Gene Name: SKIL
• Related Disease:
  Squamous cell carcinoma
  Adenoma
  Alzheimer disease
  Autism spectrum disorder
  Autosomal recessive early-onset Parkinson disease 6
  Autosomal recessive juvenile Parkinson disease 2
  Barrett esophagus
  Brain neoplasm
  Carcinoma
  Carcinoma of esophagus
  Chagas disease
  Colorectal neoplasm
  Diabetic kidney disease
  Esophageal cancer
  Familial hyperinsulinism
  Huntington disease
  Neoplasm of esophagus
  Pancreatic cancer
  Pancreatic tumour
  Parkinson disease
  Pulmonary arterial hypertension
  Pulmonary fibrosis
  Renal fibrosis
  Schizophrenia
  Skin disease
  Advanced cancer
  Coronary heart disease
  Melanoma
  Neuroblastoma
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
• UniProt ID: SKIL_HUMAN
• PDB ID: 3EQ5; 5C4V
• Pfam ID: PF08782 ; PF02437
• Sequence:
  MENLQTNFSLVQGSTKKLNGMGDDGSPPAKKMITDIHANGKTINKVPTVKKEHLDDYGEA
  PVETDGEHVKRTCTSVPETLHLNPSLKHTLAQFHLSSQSSLGGPAAFSARHSQESMSPTV
  FLPLPSPQVLPGPLLIPSDSSTELTQTVLEGESISCFQVGGEKRLCLPQVLNSVLREFTL
  QQINTVCDELYIYCSRCTSDQLHILKVLGILPFNAPSCGLITLTDAQRLCNALLRPRTFP
  QNGSVLPAKSSLAQLKETGSAFEVEHECLGKCQGLFAPQFYVQPDAPCIQCLECCGMFAP
  QTFVMHSHRSPDKRTCHWGFESAKWHCYLHVNQKYLGTPEEKKLKIILEEMKEKFSMRSG
  KRNQSKTDAPSGMELQSWYPVIKQEGDHVSQTHSFLHPSYYLYMCDKVVAPNVSLTSAVS
  QSKELTKTEASKSISRQSEKAHSSGKLQKTVSYPDVSLEEQEKMDLKTSRELCSRLDASI
  SNNSTSKRKSESATCNLVRDINKVGIGLVAAASSPLLVKDVICEDDKGKIMEEVMRTYLK
  QQEKLNLILQKKQQLQMEVKMLSSSKSMKELTEEQQNLQKELESLQNEHAQRMEEFYVEQ
  KDLEKKLEQIMKQKCTCDSNLEKDKEAEYAGQLAELRQRLDHAEADRQELQDELRQEREA
  RQKLEMMIKELKLQILKSSKTAKE
• Function: May have regulatory role in cell division or differentiation in response to extracellular signals.
• Tissue Specificity: Isoform SNON and isoform SNOA are widely expressed. Highest expression is found in skeletal muscle, followed by placenta and lung. Lowest expression in heart, brain and pancreas. Isoform SNOI expression is restricted to skeletal muscle.
• KEGG Pathway:
  TGF-beta sig.ling pathway (hsa04350)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
• Reactome Pathway: Downregulation of SMAD2/3 (R-HSA-2173795)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Squamous cell carcinoma	DISQVIFL	Definitive	Altered Expression	[1]
Adenoma	DIS78ZEV	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[4]
Autosomal recessive early-onset Parkinson disease 6	DISHVLD5	Strong	Biomarker	[5]
Autosomal recessive juvenile Parkinson disease 2	DISNSTD1	Strong	Biomarker	[5]
Barrett esophagus	DIS416Y7	Strong	Altered Expression	[6]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[9]
Chagas disease	DIS8KNVF	Strong	Biomarker	[10]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[11]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[12]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[9]
Familial hyperinsulinism	DISHQKQE	Strong	Genetic Variation	[13]
Huntington disease	DISQPLA4	Strong	Biomarker	[14]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[9]
Pancreatic cancer	DISJC981	Strong	Biomarker	[15]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[13]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[16]
Pulmonary arterial hypertension	DISP8ZX5	Strong	Biomarker	[17]
Pulmonary fibrosis	DISQKVLA	Strong	Therapeutic	[18]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[19]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[20]
Skin disease	DISDW8R6	Strong	Biomarker	[21]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[22]
Coronary heart disease	DIS5OIP1	Limited	Altered Expression	[23]
Melanoma	DIS1RRCY	Limited	Altered Expression	[24]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[25]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[23]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[26]
Prostate cancer	DISF190Y	Limited	Biomarker	[27]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[27]

19 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 Ski-like protein (SKIL).	[28]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ski-like protein (SKIL).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ski-like protein (SKIL).	[30]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ski-like protein (SKIL).	[31]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ski-like protein (SKIL).	[32]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ski-like protein (SKIL).	[33]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ski-like protein (SKIL).	[34]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Ski-like protein (SKIL).	[21]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Ski-like protein (SKIL).	[36]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Ski-like protein (SKIL).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ski-like protein (SKIL).	[39]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Ski-like protein (SKIL).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ski-like protein (SKIL).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ski-like protein (SKIL).	[44]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Ski-like protein (SKIL).	[45]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Ski-like protein (SKIL).	[46]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Ski-like protein (SKIL).	[47]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Ski-like protein (SKIL).	[48]
N-nonylphenol	DMH3OUX	Investigative	N-nonylphenol increases the expression of Ski-like protein (SKIL).	[43]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Ski-like protein (SKIL).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Ski-like protein (SKIL).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Ski-like protein (SKIL).	[42]

References

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