Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKWG3PS)

• DOT Name: SNW domain-containing protein 1 (SNW1)
• Synonyms: Nuclear protein SkiP; Nuclear receptor coactivator NCoA-62; Ski-interacting protein
• Gene Name: SNW1
• Related Disease:
  Rheumatoid arthritis
  Adult glioblastoma
  Advanced cancer
  Aicardi-Goutieres syndrome
  Alzheimer disease
  Bladder cancer
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Sciatic neuropathy
  Skin cancer
  Skin carcinoma
  Tauopathy
  Urinary bladder cancer
  Urinary bladder neoplasm
  Breast cancer
  Breast carcinoma
  Cutaneous melanoma
  Melanoma
  Neuroblastoma
• UniProt ID: SNW1_HUMAN
• PDB ID: 5MQF; 5XJC; 5YZG; 5Z58; 6FF4; 6FF7; 6ICZ; 6ID0; 6ID1; 6QDV; 6ZYM; 7A5P; 7AAV; 7ABF; 7ABG; 7ABI; 7DVQ; 7QTT; 7W59; 7W5A; 7W5B; 8C6J; 8CH6
• Pfam ID: PF02731
• Sequence:
  MALTSFLPAPTQLSQDQLEAEEKARSQRSRQTSLVSSRREPPPYGYRKGWIPRLLEDFGD
  GGAFPEIHVAQYPLDMGRKKKMSNALAIQVDSEGKIKYDAIARQGQSKDKVIYSKYTDLV
  PKEVMNADDPDLQRPDEEAIKEITEKTRVALEKSVSQKVAAAMPVRAADKLAPAQYIRYT
  PSQQGVAFNSGAKQRVIRMVEMQKDPMEPPRFKINKKIPRGPPSPPAPVMHSPSRKMTVK
  EQQEWKIPPCISNWKNAKGYTIPLDKRLAADGRGLQTVHINENFAKLAEALYIADRKARE
  AVEMRAQVERKMAQKEKEKHEEKLREMAQKARERRAGIKTHVEKEDGEARERDEIRHDRR
  KERQHDRNLSRAAPDKRSKLQRNENRDISEVIALGVPNPRTSNEVQYDQRLFNQSKGMDS
  GFAGGEDEIYNVYDQAWRGGKDMAQSIYRPSKNLDKDMYGDDLEARIKTNRFVPDKEFSG
  SDRRQRGREGPVQFEEDPFGLDKFLEEAKQHGGSKRPSDSSRPKEHEHEGKKRRKE
• Function: Involved in pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Required for the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. May recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD; (Microbial infection) Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter; (Microbial infection) Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters.
• KEGG Pathway:
  Spliceosome (hsa03040)
  Notch sig.ling pathway (hsa04330)
  Epstein-Barr virus infection (hsa05169)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells (R-HSA-210744)
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)
  Downregulation of SMAD2/3 (R-HSA-2173795)
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  Notch-HLH transcription pathway (R-HSA-350054)
  mRNA Splicing - Major Pathway (R-HSA-72163)
  RUNX3 regulates NOTCH signaling (R-HSA-8941856)
  NOTCH3 Intracellular Domain Regulates Transcription (R-HSA-9013508)
  NOTCH4 Intracellular Domain Regulates Transcription (R-HSA-9013695)
  Formation of paraxial mesoderm (R-HSA-9793380)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Aicardi-Goutieres syndrome	DIS1NH4X	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[5]
Bladder cancer	DISUHNM0	Strong	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Prostate cancer	DISF190Y	Strong	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[3]
Sciatic neuropathy	DISMGDKX	Strong	Biomarker	[9]
Skin cancer	DISTM18U	Strong	Biomarker	[10]
Skin carcinoma	DISUZREN	Strong	Genetic Variation	[11]
Tauopathy	DISY2IPA	Strong	Altered Expression	[5]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[6]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	moderate	Biomarker	[12]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[12]
Cutaneous melanoma	DIS3MMH9	moderate	Biomarker	[13]
Melanoma	DIS1RRCY	moderate	Biomarker	[13]
Neuroblastoma	DISVZBI4	Disputed	Biomarker	[14]

8 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 SNW domain-containing protein 1 (SNW1).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SNW domain-containing protein 1 (SNW1).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SNW domain-containing protein 1 (SNW1).	[18]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of SNW domain-containing protein 1 (SNW1).	[19]
Enzalutamide	DMGL19D	Approved	Enzalutamide affects the expression of SNW domain-containing protein 1 (SNW1).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of SNW domain-containing protein 1 (SNW1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of SNW domain-containing protein 1 (SNW1).	[23]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of SNW domain-containing protein 1 (SNW1).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the phosphorylation of SNW domain-containing protein 1 (SNW1).	[17]
G1	DMTV42K	Phase 1/2	G1 decreases the phosphorylation of SNW domain-containing protein 1 (SNW1).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of SNW domain-containing protein 1 (SNW1).	[22]

References

• [1] Dissecting the Role of NF-b Protein Family and Its Regulators in Rheumatoid Arthritis Using Weighted Gene Co-Expression Network.Front Genet. 2019 Nov 20;10:1163. doi: 10.3389/fgene.2019.01163. eCollection 2019.
• [2] Lipid phosphatases SKIP and SHIP2 regulate fibronectin-dependent cell migration in glioblastoma.FEBS J. 2019 Mar;286(6):1120-1135. doi: 10.1111/febs.14769. Epub 2019 Feb 16.
• [3] SNW1 is a prognostic biomarker in prostate cancer.Diagn Pathol. 2019 May 1;14(1):33. doi: 10.1186/s13000-019-0810-8.
• [4] A precisely regulated gene expression cassette potently modulates metastasis and survival in multiple solid cancers.PLoS Genet. 2008 Jul 18;4(7):e1000129. doi: 10.1371/journal.pgen.1000129.
• [5] A Novel Microtubule-Tau Association Enhancer and Neuroprotective Drug Candidate: Ac-SKIP.Front Cell Neurosci. 2019 Oct 1;13:435. doi: 10.3389/fncel.2019.00435. eCollection 2019.
• [6] SKIP expression is correlated with clinical prognosis in patients with bladder cancer.Int J Clin Exp Pathol. 2014 Mar 15;7(4):1695-701. eCollection 2014.
• [7] High SKIP expression is correlated with poor prognosis and cell proliferation of hepatocellular carcinoma.Med Oncol. 2013;30(3):537. doi: 10.1007/s12032-013-0537-4. Epub 2013 May 22.
• [8] Differential SKIP expression in PTEN-deficient glioblastoma regulates cellular proliferation and migration.Oncogene. 2015 Jul;34(28):3711-27. doi: 10.1038/onc.2014.303. Epub 2014 Sep 22.
• [9] Spatiotemporal expression of SKIP after rat sciatic nerve crush.Neurochem Res. 2013 Apr;38(4):857-65. doi: 10.1007/s11064-013-0990-7. Epub 2013 Feb 7.
• [10] Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project: study design and methods for pooling results of genetic epidemiological studies.BMC Med Res Methodol. 2012 Aug 3;12:116. doi: 10.1186/1471-2288-12-116.
• [11] MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project.Br J Cancer. 2015 Jul 14;113(2):354-63. doi: 10.1038/bjc.2015.231. Epub 2015 Jun 23.
• [12] Inhibition of SNW1 association with spliceosomal proteins promotes apoptosis in breast cancer cells.Cancer Med. 2015 Feb;4(2):268-77. doi: 10.1002/cam4.366. Epub 2014 Dec 1.
• [13] MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project.Int J Cancer. 2015 Feb 1;136(3):618-31. doi: 10.1002/ijc.29018. Epub 2014 Jun 18.
• [14] SNW1 regulates Notch signaling in neuroblastoma through interacting with RBPJ.Biochem Biophys Res Commun. 2019 Feb 19;509(4):869-876. doi: 10.1016/j.bbrc.2019.01.036. Epub 2019 Jan 12.
• [15] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [16] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [17] The G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Nuclear Estrogen Receptor Activity and Stimulates Novel Phosphoproteomic Signatures. Toxicol Sci. 2016 Jun;151(2):434-46. doi: 10.1093/toxsci/kfw057. Epub 2016 Mar 29.
• [18] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [19] 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.
• [20] NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.
• [21] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [22] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [23] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [24] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.