Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT503VJG)

• DOT Name: Suppressor of cytokine signaling 7 (SOCS7)
• Synonyms: SOCS-7; Nck, Ash and phospholipase C gamma-binding protein; Nck-associated protein 4; NAP-4
• Gene Name: SOCS7
• Related Disease:
  Alzheimer disease
  Colorectal carcinoma
  Epithelial ovarian cancer
  Lipid metabolism disorder
  Neoplasm
  Obesity
  Renal fibrosis
  Hypoglycemia
  Breast cancer
  Breast carcinoma
• UniProt ID: SOCS7_HUMAN
• Pfam ID: PF00017 ; PF07525
• Sequence:
  MVFRNVGRPPEEEDVEAAPEPGPSELLCPRHRCALDPKALPPGLALERTWGPAAGLEAQL
  AALGLGQPAGPGVKTVGGGCCPCPCPPQPPPPQPQPPAAAPQAGEDPTETSDALLVLEGL
  ESEAESLETNSCSEEELSSPGRGGGGGGRLLLQPPGPELPPVPFPLQDLVPLGRLSRGEQ
  QQQQQQQPPPPPPPPGPLRPLAGPSRKGSFKIRLSRLFRTKSCNGGSGGGDGTGKRPSGE
  LAASAASLTDMGGSAGRELDAGRKPKLTRTQSAFSPVSFSPLFTGETVSLVDVDISQRGL
  TSPHPPTPPPPPRRSLSLLDDISGTLPTSVLVAPMGSSLQSFPLPPPPPPHAPDAFPRIA
  PIRAAESLHSQPPQHLQCPLYRPDSSSFAASLRELEKCGWYWGPMNWEDAEMKLKGKPDG
  SFLVRDSSDPRYILSLSFRSQGITHHTRMEHYRGTFSLWCHPKFEDRCQSVVEFIKRAIM
  HSKNGKFLYFLRSRVPGLPPTPVQLLYPVSRFSNVKSLQHLCRFRIRQLVRIDHIPDLPL
  PKPLISYIRKFYYYDPQEEVYLSLKEAQLISKQKQEVEPST
• Function: Regulates signaling cascades probably through protein ubiquitination and/or sequestration. Functions in insulin signaling and glucose homeostasis through IRS1 ubiquitination and subsequent proteasomal degradation. Inhibits also prolactin, growth hormone and leptin signaling by preventing STAT3 and STAT5 activation, sequestering them in the cytoplasm and reducing their binding to DNA. May be a substrate recognition component of a SCF-like E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
• Tissue Specificity: Expressed in brain and leukocytes. Also in fetal lung fibroblasts and fetal brain.
• KEGG Pathway:
  JAK-STAT sig.ling pathway (hsa04630)
  Prolactin sig.ling pathway (hsa04917)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Lipid metabolism disorder	DISEOA7S	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Obesity	DIS47Y1K	Strong	Genetic Variation	[4]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[6]
Hypoglycemia	DISRCKR7	moderate	Altered Expression	[7]
Breast cancer	DIS7DPX1	Limited	Biomarker	[5]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[5]

12 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 Suppressor of cytokine signaling 7 (SOCS7).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Suppressor of cytokine signaling 7 (SOCS7).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Suppressor of cytokine signaling 7 (SOCS7).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Suppressor of cytokine signaling 7 (SOCS7).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Suppressor of cytokine signaling 7 (SOCS7).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Suppressor of cytokine signaling 7 (SOCS7).	[13]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Suppressor of cytokine signaling 7 (SOCS7).	[13]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Suppressor of cytokine signaling 7 (SOCS7).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Suppressor of cytokine signaling 7 (SOCS7).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Suppressor of cytokine signaling 7 (SOCS7).	[17]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Suppressor of cytokine signaling 7 (SOCS7).	[18]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Suppressor of cytokine signaling 7 (SOCS7).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Suppressor of cytokine signaling 7 (SOCS7).	[16]

References

• [1] Expression of suppressor of cytokine signaling genes in human elderly and Alzheimer's disease brains and human microglia.Neuroscience. 2015 Aug 27;302:121-37. doi: 10.1016/j.neuroscience.2014.09.052. Epub 2014 Oct 5.
• [2] miR-885-5p upregulation promotes colorectal cancer cell proliferation and migration by targeting suppressor of cytokine signaling.Oncol Lett. 2018 Jul;16(1):65-72. doi: 10.3892/ol.2018.8645. Epub 2018 May 7.
• [3] Downregulation of miR-145-5p in cancer cellsand theirderived exosomes may contribute tothedevelopment of ovarian cancer by targeting CT.Int J Mol Med. 2019 Jan;43(1):256-266. doi: 10.3892/ijmm.2018.3958. Epub 2018 Oct 25.
• [4] Common variants in SOCS7 gene predict obesity, disturbances in lipid metabolism and insulin resistance.Nutr Metab Cardiovasc Dis. 2013 May;23(5):424-31. doi: 10.1016/j.numecd.2011.10.005. Epub 2012 Mar 6.
• [5] In vitro and in vivo effects of suppressor of cytokine signalling 7 knockdown in breast cancer: the influence on cellular response to hepatocyte growth factor.Biomed Res Int. 2014;2014:648040. doi: 10.1155/2014/648040. Epub 2014 Aug 4.
• [6] p53 induces miR199a-3p to suppress SOCS7 for STAT3 activation and renal fibrosis in UUO.Sci Rep. 2017 Feb 27;7:43409. doi: 10.1038/srep43409.
• [7] Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans.J Clin Invest. 2005 Sep;115(9):2462-71. doi: 10.1172/JCI23853. Epub 2005 Aug 25.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] 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.
• [13] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [14] Simvastatin inhibits IL-17 secretion by targeting multiple IL-17-regulatory cytokines and by inhibiting the expression of IL-17 transcription factor RORC in CD4+ lymphocytes. J Immunol. 2008 May 15;180(10):6988-96. doi: 10.4049/jimmunol.180.10.6988.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] 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.
• [17] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [18] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [19] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.