Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIZJD09)

DOT Name Pulmonary surfactant-associated protein C (SFTPC)
Synonyms SP-C; Pulmonary surfactant-associated proteolipid SPL(Val); SP5
Gene Name SFTPC
Related Disease
Lung neoplasm ( )
Respiratory failure ( )
Respiratory syncytial virus infection ( )
Surfactant metabolism dysfunction, pulmonary, 2 ( )
Alzheimer disease ( )
Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome ( )
Bacterial pneumonia ( )
Carcinoma ( )
Cerebellar ataxia, intellectual disability, and dysequilibrium ( )
Chondrosarcoma ( )
Cystic fibrosis ( )
Dementia ( )
Diphtheria ( )
Hermansky-Pudlak syndrome ( )
Herpes simplex infection ( )
High blood pressure ( )
Hydrocephalus ( )
Hyperinsulinemia ( )
Lipoid proteinosis ( )
Lung cancer ( )
Lung carcinoma ( )
Obstructive sleep apnea ( )
Pneumonia ( )
Pneumonitis ( )
Polycystic ovarian syndrome ( )
Pulmonary emphysema ( )
Pulmonary fibrosis ( )
Respiratory disease ( )
Advanced cancer ( )
Bronchopulmonary dysplasia ( )
Chronic obstructive pulmonary disease ( )
Chronic respiratory distress with surfactant metabolism deficiency ( )
Interstitial lung disease due to SP-C deficiency ( )
Adenocarcinoma ( )
Adult respiratory distress syndrome ( )
Asthma ( )
Breast cancer ( )
Breast carcinoma ( )
Congenital diaphragmatic hernia ( )
Hereditary pulmonary alveolar proteinosis ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Small-cell lung cancer ( )
Type-1/2 diabetes ( )
UniProt ID
PSPC_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2YAD
Pfam ID
PF04089 ; PF08999
Sequence
MDVGSKEVLMESPPDYSAAPRGRFGIPCCPVHLKRLLIVVVVVVLIVVVIVGALLMGLHM
SQKHTEMVLEMSIGAPEAQQRLALSEHLVTTATFSIGSTGLVVYDYQQLLIAYKPAPGTC
CYIMKIAPESIPSLEALTRKVHNFQMECSLQAKPAVPTSKLGQAEGRDAGSAPSGGDPAF
LGMAVSTLCGEVPLYYI
Function Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces.
Reactome Pathway
Defective pro-SFTPC causes SMDP2 and RDS (R-HSA-5688354 )
Defective CSF2RB causes SMDP5 (R-HSA-5688849 )
Defective CSF2RA causes SMDP4 (R-HSA-5688890 )
Surfactant metabolism (R-HSA-5683826 )

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lung neoplasm DISVARNB Definitive Genetic Variation [1]
Respiratory failure DISVMYJO Definitive Biomarker [2]
Respiratory syncytial virus infection DIS7FWHY Definitive Biomarker [3]
Surfactant metabolism dysfunction, pulmonary, 2 DIS5K18R Definitive Autosomal dominant [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome DISRVSZF Strong Genetic Variation [6]
Bacterial pneumonia DISPW7PH Strong Biomarker [7]
Carcinoma DISH9F1N Strong Altered Expression [8]
Cerebellar ataxia, intellectual disability, and dysequilibrium DIS9923V Strong Altered Expression [9]
Chondrosarcoma DIS4I7JB Strong Genetic Variation [5]
Cystic fibrosis DIS2OK1Q Strong Genetic Variation [10]
Dementia DISXL1WY Strong Genetic Variation [11]
Diphtheria DISZWM55 Strong Altered Expression [6]
Hermansky-Pudlak syndrome DISCY0HQ Strong Biomarker [2]
Herpes simplex infection DISL1SAV Strong Altered Expression [12]
High blood pressure DISY2OHH Strong Altered Expression [13]
Hydrocephalus DISIZUF7 Strong Biomarker [14]
Hyperinsulinemia DISIDWT6 Strong Biomarker [15]
Lipoid proteinosis DISHAODY Strong Genetic Variation [16]
Lung cancer DISCM4YA Strong Altered Expression [17]
Lung carcinoma DISTR26C Strong Altered Expression [17]
Obstructive sleep apnea DIS0SVD1 Strong Altered Expression [18]
Pneumonia DIS8EF3M Strong Biomarker [19]
Pneumonitis DIS88E0K Strong Biomarker [19]
Polycystic ovarian syndrome DISZ2BNG Strong Biomarker [20]
Pulmonary emphysema DIS5M7HZ Strong Biomarker [21]
Pulmonary fibrosis DISQKVLA Strong Genetic Variation [22]
Respiratory disease DISGGAGJ Strong Genetic Variation [23]
Advanced cancer DISAT1Z9 moderate Altered Expression [24]
Bronchopulmonary dysplasia DISO0BY5 moderate Altered Expression [25]
Chronic obstructive pulmonary disease DISQCIRF moderate Biomarker [26]
Chronic respiratory distress with surfactant metabolism deficiency DISWB7P1 Supportive Autosomal dominant [27]
Interstitial lung disease due to SP-C deficiency DIS91ZNC Supportive Autosomal dominant [28]
Adenocarcinoma DIS3IHTY Limited Biomarker [29]
Adult respiratory distress syndrome DISIJV47 Limited Biomarker [30]
Asthma DISW9QNS Limited Biomarker [31]
Breast cancer DIS7DPX1 Limited Biomarker [32]
Breast carcinoma DIS2UE88 Limited Biomarker [32]
Congenital diaphragmatic hernia DIS0IPVU Limited Altered Expression [33]
Hereditary pulmonary alveolar proteinosis DISQC53I Limited Genetic Variation [34]
Neoplasm DISZKGEW Limited Biomarker [35]
Non-small-cell lung cancer DIS5Y6R9 Limited Altered Expression [8]
Small-cell lung cancer DISK3LZD Limited Altered Expression [8]
Type-1/2 diabetes DISIUHAP Limited Biomarker [36]
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⏷ Show the Full List of 44 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Pulmonary surfactant-associated protein C (SFTPC). [37]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Pulmonary surfactant-associated protein C (SFTPC). [40]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Testosterone DM7HUNW Approved Testosterone increases the expression of Pulmonary surfactant-associated protein C (SFTPC). [38]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Pulmonary surfactant-associated protein C (SFTPC). [39]
Hydrocortisone DMGEMB7 Approved Hydrocortisone increases the expression of Pulmonary surfactant-associated protein C (SFTPC). [39]
Forskolin DM6ITNG Investigative Forskolin increases the expression of Pulmonary surfactant-associated protein C (SFTPC). [39]
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References

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2 Systematic review of drug effects in humans and models with surfactant-processing disease.Eur Respir Rev. 2018 Jul 11;27(149):170135. doi: 10.1183/16000617.0135-2017. Print 2018 Sep 30.
3 Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection.Am J Physiol Lung Cell Mol Physiol. 2009 Jul;297(1):L64-72. doi: 10.1152/ajplung.90640.2008. Epub 2009 Mar 20.
4 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
5 BRICHOS domain associated with lung fibrosis, dementia and cancer--a chaperone that prevents amyloid fibril formation?.FEBS J. 2011 Oct;278(20):3893-904. doi: 10.1111/j.1742-4658.2011.08209.x. Epub 2011 Jul 5.
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7 Total extracellular surfactant is increased but abnormal in a rat model of gram-negative bacterial pneumonia.Am J Physiol Lung Cell Mol Physiol. 2002 Sep;283(3):L655-63. doi: 10.1152/ajplung.00071.2002.
8 Surfactant protein gene expressions for detection of lung carcinoma cells in peripheral blood.Respir Med. 2005 Sep;99(9):1164-74. doi: 10.1016/j.rmed.2005.02.009.
9 Surfactant protein-C promoter variants associated with neonatal respiratory distress syndrome reduce transcription.Pediatr Res. 2010 Sep;68(3):216-20. doi: 10.1203/PDR.0b013e3181eb5d68.
10 Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic Fibrosis.Front Immunol. 2018 Oct 2;9:2256. doi: 10.3389/fimmu.2018.02256. eCollection 2018.
11 Surfactant protein C biosynthesis and its emerging role in conformational lung disease.Annu Rev Physiol. 2005;67:663-96. doi: 10.1146/annurev.physiol.67.040403.101937.
12 Targeted Type 2 Alveolar Cell Depletion. A Dynamic Functional Model for Lung Injury Repair.Am J Respir Cell Mol Biol. 2016 Mar;54(3):319-30. doi: 10.1165/rcmb.2014-0246OC.
13 The progression of comorbidity in IL-18 transgenic chronic obstructive pulmonary disease mice model.Biochem Biophys Res Commun. 2014 Mar 14;445(3):597-601. doi: 10.1016/j.bbrc.2014.02.052. Epub 2014 Feb 21.
14 Rheologically Essential Surfactant Proteins of the CSF Interacting with Periventricular White Matter Changes in Hydrocephalus Patients - Implications for CSF Dynamics and the Glymphatic System.Mol Neurobiol. 2019 Nov;56(11):7863-7871. doi: 10.1007/s12035-019-01648-z. Epub 2019 May 24.
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16 A nonaggregating surfactant protein C mutant is misdirected to early endosomes and disrupts phospholipid recycling.Traffic. 2011 Sep;12(9):1196-210. doi: 10.1111/j.1600-0854.2011.01223.x. Epub 2011 Jun 28.
17 MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma.Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3286-3296. doi: 10.1080/21691401.2019.1648283.
18 Pulmonary surfactant-associated proteins and inflammatory factors in obstructive sleep apnea.Sleep Breath. 2018 Mar;22(1):99-107. doi: 10.1007/s11325-017-1536-z. Epub 2017 Jul 13.
19 From the Cover: Lung-Specific Overexpression of Constitutively Active IKK2 Induces Pulmonary and Systemic Inflammations but Not Hypothalamic Inflammation and Glucose Intolerance.Toxicol Sci. 2017 Nov 1;160(1):4-14. doi: 10.1093/toxsci/kfx154.
20 Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
21 Variability in Tidal Volume Affects Lung and Cardiovascular Function Differentially in a Rat Model of Experimental Emphysema.Front Physiol. 2017 Dec 18;8:1071. doi: 10.3389/fphys.2017.01071. eCollection 2017.
22 Invitro expansion of endogenous human alveolar epithelial type II cells in fibroblast-free spheroid culture.Biochem Biophys Res Commun. 2019 Aug 6;515(4):579-585. doi: 10.1016/j.bbrc.2019.05.187. Epub 2019 Jun 6.
23 Surfactant protein C gene variation in the Finnish population - association with perinatal respiratory disease.Eur J Hum Genet. 2004 Apr;12(4):312-20. doi: 10.1038/sj.ejhg.5201137.
24 Pleiomorphic adenoma gene-like 2 expression is associated with the development of lung adenocarcinoma and emphysema.Lung Cancer. 2011 Oct;74(1):12-24. doi: 10.1016/j.lungcan.2011.02.006. Epub 2011 Mar 11.
25 Impact of Fgf10 deficiency on pulmonary vasculature formation in a mouse model of bronchopulmonary dysplasia.Hum Mol Genet. 2019 May 1;28(9):1429-1444. doi: 10.1093/hmg/ddy439.
26 Involvement of c-Jun N-Terminal Kinase in TNF--Driven Remodeling.Am J Respir Cell Mol Biol. 2017 Mar;56(3):393-401. doi: 10.1165/rcmb.2015-0195OC.
27 Surfactant dysfunction. Paediatr Respir Rev. 2011 Dec;12(4):223-9. doi: 10.1016/j.prrv.2011.01.005. Epub 2011 Mar 5.
28 Clinical and ultrastructural spectrum of diffuse lung disease associated with surfactant protein C mutations. Eur J Hum Genet. 2015 Aug;23(8):1033-41. doi: 10.1038/ejhg.2015.45. Epub 2015 Mar 18.
29 Tumor progression and cellular differentiation of pulmonary adenocarcinomas in SV40 large T antigen transgenic mice.Am J Respir Cell Mol Biol. 1997 Jun;16(6):713-23. doi: 10.1165/ajrcmb.16.6.9191473.
30 Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits.Respir Res. 2019 Nov 6;20(1):245. doi: 10.1186/s12931-019-1220-x.
31 Haplotypes of surfactant protein C are associated with common paediatric lung diseases.Pediatr Allergy Immunol. 2006 Dec;17(8):572-7. doi: 10.1111/j.1399-3038.2006.00467.x.
32 Use of lung-specific exosomes for miRNA-126 delivery in non-small cell lung cancer.Nanoscale. 2020 Jan 2;12(2):877-887. doi: 10.1039/c9nr09011h.
33 Follistatin-like 1 expression is decreased in the alveolar epithelium of hypoplastic rat lungs with nitrofen-induced congenital diaphragmatic hernia.J Pediatr Surg. 2017 May;52(5):706-709. doi: 10.1016/j.jpedsurg.2017.01.020. Epub 2017 Jan 28.
34 Genetic basis of surfactant dysfunction in Chinese children: A retrospective study.Pediatr Pulmonol. 2019 Aug;54(8):1173-1181. doi: 10.1002/ppul.24334. Epub 2019 May 12.
35 A locus on chromosome 8 controlling tumor regionality-a new type of tumor diversity in the mouse lung.Int J Cancer. 2010 Jun 1;126(11):2603-13. doi: 10.1002/ijc.24983.
36 The reduction in FOXA2 activity during lung development in fetuses from diabetic rat mothers is reversed by Akt inhibition.FEBS Open Bio. 2018 Sep 25;8(10):1594-1604. doi: 10.1002/2211-5463.12517. eCollection 2018 Oct.
37 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
38 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
39 Regulation of messenger RNAs for the hydrophobic surfactant proteins in human lung. J Clin Invest. 1989 Apr;83(4):1191-7. doi: 10.1172/JCI114000.
40 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.