Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB63PHR)

• DOT Name: Secretoglobin family 3A member 2 (SCGB3A2)
• Synonyms: Pneumo secretory protein 1; PnSP-1; Uteroglobin-related protein 1
• Gene Name: SCGB3A2
• Related Disease:
  Asthma
  Adenocarcinoma
  Advanced cancer
  Allergic asthma
  Allergic rhinitis
  Bronchopulmonary dysplasia
  Craniosynostosis
  Cystic fibrosis
  Graves disease
  Lung adenocarcinoma
  Nasal polyp
  Neoplasm
  Pneumonia
  Pneumonitis
  Pulmonary fibrosis
  Hashimoto thyroiditis
  Hypothyroidism
  Lung cancer
  Lung carcinoma
  Lung neoplasm
• UniProt ID: SG3A2_HUMAN
• Pfam ID: PF20490
• Sequence:
  MKLVTIFLLVTISLCSYSATAFLINKVPLPVDKLAPLPLDNILPFMDPLKLLLKTLGISV
  EHLVEGLRKCVNELGPEASEAVKKLLEALSHLV
• Function: Secreted cytokine-like protein. Binds to the scavenger receptor MARCO. Can also bind to pathogens including the Gram-positive bacterium L.monocytogenes, the Gram-negative bacterium P.aeruginosa, and yeast. Strongly inhibits phospholipase A2 (PLA2G1B) activity. Seems to have anti-inflammatory effects in respiratory epithelium. Also has anti-fibrotic activity in lung. May play a role in fetal lung development and maturation. Promotes branching morphogenesis during early stages of lung development. In the pituitary, may inhibit production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
• Tissue Specificity: Highly expressed in lung and trachea . Detected throughout the airway epithelium in lung, with slightly higher expression in large airways . Found in lung submucosal gland acinus where it localizes to serous-like cells . Probably expressed in club cells of the bronchioles . Not detected in other tissues tested .
• Reactome Pathway: Scavenging by Class A Receptors (R-HSA-3000480)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Genetic Variation	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Allergic asthma	DISHF0H3	Strong	Genetic Variation	[4]
Allergic rhinitis	DIS3U9HN	Strong	Genetic Variation	[5]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Biomarker	[6]
Craniosynostosis	DIS6J405	Strong	Biomarker	[7]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[8]
Graves disease	DISU4KOQ	Strong	Biomarker	[9]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[2]
Nasal polyp	DISLP3XE	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Pneumonia	DIS8EF3M	Strong	Biomarker	[5]
Pneumonitis	DIS88E0K	Strong	Biomarker	[5]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[10]
Hashimoto thyroiditis	DIS77CDF	Limited	Altered Expression	[9]
Hypothyroidism	DISR0H6D	Limited	Biomarker	[9]
Lung cancer	DISCM4YA	Limited	Biomarker	[11]
Lung carcinoma	DISTR26C	Limited	Biomarker	[11]
Lung neoplasm	DISVARNB	Limited	Altered Expression	[11]

9 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 Secretoglobin family 3A member 2 (SCGB3A2).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Secretoglobin family 3A member 2 (SCGB3A2).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Secretoglobin family 3A member 2 (SCGB3A2).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Secretoglobin family 3A member 2 (SCGB3A2).	[16]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Secretoglobin family 3A member 2 (SCGB3A2).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Secretoglobin family 3A member 2 (SCGB3A2).	[17]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Secretoglobin family 3A member 2 (SCGB3A2).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Secretoglobin family 3A member 2 (SCGB3A2).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Secretoglobin family 3A member 2 (SCGB3A2).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Secretoglobin family 3A member 2 (SCGB3A2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Secretoglobin family 3A member 2 (SCGB3A2).	[18]

References

• [1] Association Between Secretoglobin Family 3A Member 2 (SCGB3A2) Gene Polymorphisms and Asthma in a Korean Population.Med Sci Monit. 2017 Apr 19;23:1880-1885. doi: 10.12659/msm.903983.
• [2] Exploration of differentially expressed plasma proteins in patients with lung adenocarcinoma using iTRAQ-coupled 2D LC-MS/MS.Clin Respir J. 2018 Jun;12(6):2036-2045. doi: 10.1111/crj.12771. Epub 2018 Feb 21.
• [3] A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death.Elife. 2018 Dec 7;7:e37854. doi: 10.7554/eLife.37854.
• [4] The -112G>A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves' disease in subsets of patients with elevated levels of immunoglobulin E.J Appl Genet. 2011 May;52(2):201-7. doi: 10.1007/s13353-010-0022-0. Epub 2010 Dec 18.
• [5] Variation in Uteroglobin-Related Protein 1 (UGRP1) gene is associated with allergic rhinitis in Singapore Chinese.BMC Med Genet. 2011 Mar 16;12:39. doi: 10.1186/1471-2350-12-39.
• [6] Secretoglobins SCGB3A1 and SCGB3A2 define secretory cell subsets in mouse and human airways.Am J Respir Crit Care Med. 2002 Dec 1;166(11):1498-509. doi: 10.1164/rccm.200204-285OC. Epub 2002 Aug 1.
• [7] The cytokine-driven regulation of secretoglobins in normal human upper airway and their expression, particularly that of uteroglobin-related protein 1, in chronic rhinosinusitis.Respir Res. 2011 Mar 8;12(1):28. doi: 10.1186/1465-9921-12-28.
• [8] Identification of uteroglobin-related protein 1 and macrophage scavenger receptor with collagenous structure as a lung-specific ligand-receptor pair.J Immunol. 2003 Jul 15;171(2):924-30. doi: 10.4049/jimmunol.171.2.924.
• [9] Uterus globulin associated protein 1 (UGRP1) is a potential marker of progression of Graves' disease into hypothyroidism.Mol Cell Endocrinol. 2019 Aug 20;494:110492. doi: 10.1016/j.mce.2019.110492. Epub 2019 Jun 27.
• [10] Secretoglobin 3A2 suppresses bleomycin-induced pulmonary fibrosis by transforming growth factor beta signaling down-regulation.J Biol Chem. 2011 Jun 3;286(22):19682-92. doi: 10.1074/jbc.M111.239046. Epub 2011 Apr 10.
• [11] Unique roles of Akt1 and Akt2 in IGF-IR mediated lung tumorigenesis.Oncotarget. 2016 Jan 19;7(3):3297-316. doi: 10.18632/oncotarget.6489.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [14] Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
• [15] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [16] 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.
• [17] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [18] 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.
• [19] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.