Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXSJMT1)

• DOT Name: Neuroendocrine protein 7B2 (SCG5)
• Synonyms: Pituitary polypeptide; Secretogranin V; Secretogranin-5; Secretory granule endocrine protein I
• Gene Name: SCG5
• Related Disease:
  Angelman syndrome
  Small-cell lung cancer
  Adult glioblastoma
  Anaplastic astrocytoma
  Astrocytoma
  Colorectal carcinoma
  Colorectal neoplasm
  Glioblastoma multiforme
  Lung cancer
  Lung carcinoma
  Medulloblastoma
  Polyposis
  Polyposis syndrome, hereditary mixed, 1
  Thyroid gland carcinoma
  X-linked dominant hypophosphatemic rickets
  ACTH-independent macronodular adrenal hyperplasia 1
  Hyperplasia
  Type-1 diabetes
• UniProt ID: 7B2_HUMAN
• Pfam ID: PF05281
• Sequence:
  MVSRMVSTMLSGLLFWLASGWTPAFAYSPRTPDRVSEADIQRLLHGVMEQLGIARPRVEY
  PAHQAMNLVGPQSIEGGAHEGLQHLGPFGNIPNIVAELTGDNIPKDFSEDQGYPDPPNPC
  PVGKTADDGCLENTPDTAEFSREFQLHQHLFDPEHDYPGLGKWNKKLLYEKMKGGERRKR
  RSVNPYLQGQRLDNVVAKKSVPHFSDEDKDPE
• Function: Acts as a molecular chaperone for PCSK2/PC2, preventing its premature activation in the regulated secretory pathway. Binds to inactive PCSK2 in the endoplasmic reticulum and facilitates its transport from there to later compartments of the secretory pathway where it is proteolytically matured and activated. Also required for cleavage of PCSK2 but does not appear to be involved in its folding. Plays a role in regulating pituitary hormone secretion. The C-terminal peptide inhibits PCSK2 in vitro.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Angelman syndrome	DIS4QVXO	Definitive	Genetic Variation	[1]
Small-cell lung cancer	DISK3LZD	Definitive	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Anaplastic astrocytoma	DISSBE0K	Strong	Biomarker	[3]
Astrocytoma	DISL3V18	Strong	Posttranslational Modification	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[4]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[5]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[6]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[6]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[7]
Polyposis	DISZSPOK	Strong	Biomarker	[8]
Polyposis syndrome, hereditary mixed, 1	DISG6RBU	Strong	Genetic Variation	[5]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[9]
X-linked dominant hypophosphatemic rickets	DISU3OP6	Strong	Altered Expression	[10]
ACTH-independent macronodular adrenal hyperplasia 1	DISH2YV8	Limited	Biomarker	[11]
Hyperplasia	DISK4DFB	Limited	Altered Expression	[11]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[12]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Neuroendocrine protein 7B2 (SCG5) affects the response to substance of Paclitaxel.	[33]
Mitomycin	DMH0ZJE	Approved	Neuroendocrine protein 7B2 (SCG5) affects the response to substance of Mitomycin.	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Neuroendocrine protein 7B2 (SCG5).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Neuroendocrine protein 7B2 (SCG5).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neuroendocrine protein 7B2 (SCG5).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Neuroendocrine protein 7B2 (SCG5).	[16]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Neuroendocrine protein 7B2 (SCG5).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Neuroendocrine protein 7B2 (SCG5).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Neuroendocrine protein 7B2 (SCG5).	[19]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Neuroendocrine protein 7B2 (SCG5).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Neuroendocrine protein 7B2 (SCG5).	[21]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Neuroendocrine protein 7B2 (SCG5).	[22]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Neuroendocrine protein 7B2 (SCG5).	[23]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Neuroendocrine protein 7B2 (SCG5).	[24]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Neuroendocrine protein 7B2 (SCG5).	[25]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Neuroendocrine protein 7B2 (SCG5).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Neuroendocrine protein 7B2 (SCG5).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Neuroendocrine protein 7B2 (SCG5).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neuroendocrine protein 7B2 (SCG5).	[29]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Neuroendocrine protein 7B2 (SCG5).	[30]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Neuroendocrine protein 7B2 (SCG5).	[31]
Taurine	DMVW7N3	Investigative	Taurine increases the expression of Neuroendocrine protein 7B2 (SCG5).	[32]

References

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• [2] Key genes in lung cancer translational research: a meta-analysis.Pathobiology. 2010;77(2):53-63. doi: 10.1159/000278292. Epub 2010 Mar 22.
• [3] Frequent epigenetic inactivation of the chaperone SGNE1/7B2 in human gliomas.Int J Cancer. 2012 Aug 1;131(3):612-22. doi: 10.1002/ijc.26416. Epub 2011 Oct 5.
• [4] Meta-analysis of the rs4779584 polymorphism and colorectal cancer risk.PLoS One. 2014 Feb 24;9(2):e89736. doi: 10.1371/journal.pone.0089736. eCollection 2014.
• [5] Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk.Nat Genet. 2008 Jan;40(1):26-8. doi: 10.1038/ng.2007.41. Epub 2007 Dec 16.
• [6] Differential expression of the gene encoding the novel pituitary polypeptide 7B2 in human lung cancer cells.Cancer Res. 1989 Aug 1;49(15):4154-8.
• [7] SGNE1/7B2 is epigenetically altered and transcriptionally downregulated in human medulloblastomas. Oncogene. 2007 Aug 16;26(38):5662-8. doi: 10.1038/sj.onc.1210338. Epub 2007 Mar 5.
• [8] Clinicopathological features of a kindred with SCG5-GREM1-associated hereditary mixed polyposis syndrome.Hum Pathol. 2017 Feb;60:75-81. doi: 10.1016/j.humpath.2016.10.002. Epub 2016 Oct 28.
• [9] Classification of Benign and Malignant Thyroid Nodules Using a Combined Clinical Information and Gene Expression Signatures.PLoS One. 2016 Oct 24;11(10):e0164570. doi: 10.1371/journal.pone.0164570. eCollection 2016.
• [10] Hexa-D-arginine treatment increases 7B2PC2 activity in hyp-mouse osteoblasts and rescues the HYP phenotype.J Bone Miner Res. 2013 Jan;28(1):56-72. doi: 10.1002/jbmr.1738.
• [11] Gene array analysis of macronodular adrenal hyperplasia confirms clinical heterogeneity and identifies several candidate genes as molecular mediators.Oncogene. 2004 Feb 26;23(8):1575-85. doi: 10.1038/sj.onc.1207277.
• [12] Conventional and Neo-antigenic Peptides Presented by Cells Are Targeted by Circulating Nave CD8+ T Cells in Type 1 Diabetic and Healthy Donors.Cell Metab. 2018 Dec 4;28(6):946-960.e6. doi: 10.1016/j.cmet.2018.07.007. Epub 2018 Aug 2.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [15] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [16] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [17] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [18] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [19] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [20] SGNE1/7B2 is epigenetically altered and transcriptionally downregulated in human medulloblastomas. Oncogene. 2007 Aug 16;26(38):5662-8. doi: 10.1038/sj.onc.1210338. Epub 2007 Mar 5.
• [21] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [22] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [23] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [24] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [25] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [26] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [27] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [28] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [29] 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.
• [30] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [31] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [32] Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food. 2006 Spring;9(1):33-41. doi: 10.1089/jmf.2006.9.33.
• [33] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.