Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6SFOMU)

DOT Name Pulmonary surfactant-associated protein A2 (SFTPA2)
Synonyms PSP-A; PSPA; SP-A; SP-A2; 35 kDa pulmonary surfactant-associated protein; Alveolar proteinosis protein; Collectin-5
Gene Name SFTPA2
Related Disease
Idiopathic pulmonary fibrosis ( )
Meningococcal disease ( )
Neoplasm ( )
Acute otitis media ( )
Advanced cancer ( )
Allergic rhinitis ( )
Ankylosing spondylitis ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Bacteremia ( )
Bronchopulmonary dysplasia ( )
Cardiovascular disease ( )
Congenital alveolar dysplasia ( )
Congenital diaphragmatic hernia ( )
Craniosynostosis ( )
Cystic fibrosis ( )
Early-onset anterior polar cataract ( )
Hydrocephalus ( )
Hyperinsulinemia ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Lymphangioleiomyomatosis ( )
Nasal polyp ( )
Non-small-cell lung cancer ( )
Otitis media ( )
Pneumococcal meningitis ( )
Pneumocystis pneumonia ( )
Pneumonia ( )
Pneumonitis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Psoriatic arthritis ( )
Pulmonary disease ( )
Pulmonary fibrosis ( )
Respiratory syncytial virus infection ( )
Rheumatoid arthritis ( )
Squamous cell carcinoma ( )
Tuberculosis ( )
Urinary tract infection ( )
Chronic obstructive pulmonary disease ( )
Lung adenocarcinoma ( )
Obsolete idiopathic pulmonary fibrosis ( )
Acute respiratory failure ( )
Adult respiratory distress syndrome ( )
Asthma ( )
Congenital heart disease ( )
Pulmonary tuberculosis ( )
Respiratory disease ( )
Small-cell lung cancer ( )
UniProt ID
SFPA2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00059
Sequence
MWLCPLALTLILMAASGAACEVKDVCVGSPGIPGTPGSHGLPGRDGRDGVKGDPGPPGPM
GPPGETPCPPGNNGLPGAPGVPGERGEKGEAGERGPPGLPAHLDEELQATLHDFRHQILQ
TRGALSLQGSIMTVGEKVFSSNGQSITFDAIQEACARAGGRIAVPRNPEENEAIASFVKK
YNTYAYVGLTEGPSPGDFRYSDGTPVNYTNWYRGEPAGRGKEQCVEMYTDGQWNDRNCLY
SRLTICEF
Function
In presence of calcium ions, it binds to surfactant phospholipids and contributes to lower the surface tension at the air-liquid interface in the alveoli of the mammalian lung and is essential for normal respiration.
KEGG Pathway
Phagosome (hsa04145 )
Pertussis (hsa05133 )
Reactome Pathway
Toll Like Receptor TLR1 (R-HSA-168179 )
Signal regulatory protein family interactions (R-HSA-391160 )
Surfactant metabolism (R-HSA-5683826 )
Regulation of TLR by endogenous ligand (R-HSA-5686938 )
Defective SFTPA2 causes IPF (R-HSA-5687868 )
Defective CSF2RB causes SMDP5 (R-HSA-5688849 )
Defective CSF2RA causes SMDP4 (R-HSA-5688890 )
Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016 )

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Idiopathic pulmonary fibrosis DISZGA69 Definitive Autosomal dominant [1]
Meningococcal disease DISGDM2Z Definitive Genetic Variation [2]
Neoplasm DISZKGEW Definitive Biomarker [3]
Acute otitis media DISL8D8G Strong Genetic Variation [4]
Advanced cancer DISAT1Z9 Strong Biomarker [5]
Allergic rhinitis DIS3U9HN Strong Altered Expression [6]
Ankylosing spondylitis DISRC6IR Strong Biomarker [7]
Arteriosclerosis DISK5QGC Strong Biomarker [8]
Atherosclerosis DISMN9J3 Strong Biomarker [8]
Bacteremia DIS6N9RZ Strong Genetic Variation [9]
Bronchopulmonary dysplasia DISO0BY5 Strong Biomarker [10]
Cardiovascular disease DIS2IQDX Strong Biomarker [8]
Congenital alveolar dysplasia DIS1IYUN Strong Genetic Variation [11]
Congenital diaphragmatic hernia DIS0IPVU Strong Altered Expression [12]
Craniosynostosis DIS6J405 Strong Genetic Variation [13]
Cystic fibrosis DIS2OK1Q Strong Biomarker [13]
Early-onset anterior polar cataract DISTOPIY Strong Genetic Variation [14]
Hydrocephalus DISIZUF7 Strong Biomarker [15]
Hyperinsulinemia DISIDWT6 Strong Altered Expression [16]
Lung cancer DISCM4YA Strong Genetic Variation [17]
Lung carcinoma DISTR26C Strong Genetic Variation [17]
Lung neoplasm DISVARNB Strong Genetic Variation [18]
Lymphangioleiomyomatosis DISR0RNB Strong Altered Expression [19]
Nasal polyp DISLP3XE Strong Biomarker [13]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [20]
Otitis media DISGZDUO Strong Genetic Variation [4]
Pneumococcal meningitis DISM5U0L Strong Biomarker [21]
Pneumocystis pneumonia DISFSOM3 Strong Altered Expression [22]
Pneumonia DIS8EF3M Strong Altered Expression [23]
Pneumonitis DIS88E0K Strong Altered Expression [23]
Prostate cancer DISF190Y Strong Biomarker [24]
Prostate carcinoma DISMJPLE Strong Biomarker [24]
Psoriatic arthritis DISLWTG2 Strong Biomarker [7]
Pulmonary disease DIS6060I Strong Biomarker [25]
Pulmonary fibrosis DISQKVLA Strong Genetic Variation [17]
Respiratory syncytial virus infection DIS7FWHY Strong Genetic Variation [26]
Rheumatoid arthritis DISTSB4J Strong Biomarker [7]
Squamous cell carcinoma DISQVIFL Strong Posttranslational Modification [5]
Tuberculosis DIS2YIMD Strong Genetic Variation [27]
Urinary tract infection DISMT6UV Strong Biomarker [28]
Chronic obstructive pulmonary disease DISQCIRF moderate Genetic Variation [29]
Lung adenocarcinoma DISD51WR moderate Genetic Variation [30]
Obsolete idiopathic pulmonary fibrosis DISU8XLT Moderate Autosomal dominant [31]
Acute respiratory failure DIS5KQ5Y Limited Genetic Variation [32]
Adult respiratory distress syndrome DISIJV47 Limited Genetic Variation [33]
Asthma DISW9QNS Limited Genetic Variation [34]
Congenital heart disease DISQBA23 Limited Altered Expression [35]
Pulmonary tuberculosis DIS6FLUM Limited Genetic Variation [36]
Respiratory disease DISGGAGJ Limited Genetic Variation [37]
Small-cell lung cancer DISK3LZD Limited Altered Expression [38]
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⏷ Show the Full List of 50 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 A2 (SFTPA2). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Pulmonary surfactant-associated protein A2 (SFTPA2). [40]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Genetic susceptibility to meningococcal infection.Expert Rev Anti Infect Ther. 2013 Feb;11(2):187-99. doi: 10.1586/eri.12.161.
3 Validity of using immunohistochemistry to predict treatment outcome in patients with non-small cell lung cancer not otherwise specified.J Cancer Res Clin Oncol. 2019 Oct;145(10):2495-2506. doi: 10.1007/s00432-019-03012-z. Epub 2019 Sep 7.
4 Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma.BMC Med Genet. 2006 Aug 2;7:68. doi: 10.1186/1471-2350-7-68.
5 DNA methylation profile and expression of surfactant protein A2 gene in lung cancer.Exp Lung Res. 2015 Mar;41(2):93-102. doi: 10.3109/01902148.2014.976298. Epub 2014 Dec 16.
6 Detection of surfactant proteins A, B, C, and D in human nasal mucosa and their regulation in chronic rhinosinusitis with polyps.Am J Rhinol Allergy. 2013 Jan;27(1):24-9. doi: 10.2500/ajra.2013.27.3838.
7 Dysregulation of interleukin-10-dependent gene expression in rheumatoid arthritis synovial macrophages.Arthritis Rheum. 2006 Sep;54(9):2711-21. doi: 10.1002/art.22055.
8 Cholesterol, lipoproteins and subclinical interstitial lung disease: the MESA study.Thorax. 2017 May;72(5):472-474. doi: 10.1136/thoraxjnl-2016-209568. Epub 2017 Jan 27.
9 Genotypes, intrafamilial transmission, and virulence potential of nasal methicillin-resistant Staphylococcus aureus from children in the community.J Infect Chemother. 2009 Apr;15(2):84-91. doi: 10.1007/s10156-009-0668-x. Epub 2009 Apr 25.
10 Data mining and multiparameter analysis of lung surfactant protein genes in bronchopulmonary dysplasia.Hum Mol Genet. 2004 Jun 1;13(11):1095-104. doi: 10.1093/hmg/ddh132. Epub 2004 Apr 21.
11 Surfactant Protein A and B Gene Polymorphisms and Risk of Respiratory Distress Syndrome in Late-Preterm Neonates.PLoS One. 2016 Nov 11;11(11):e0166516. doi: 10.1371/journal.pone.0166516. eCollection 2016.
12 Pulmonary surfactant protein A, B, and C mRNA and protein expression in the nitrofen-induced congenital diaphragmatic hernia rat model.Pediatr Res. 2003 Nov;54(5):641-52. doi: 10.1203/01.PDR.0000086906.19683.42. Epub 2003 Aug 6.
13 Sinonasal surfactant protein A1, A2, and D gene expression in cystic fibrosis: a preliminary report.Otolaryngol Head Neck Surg. 2007 Jul;137(1):34-8. doi: 10.1016/j.otohns.2007.01.025.
14 Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: a prospective, observational, genetic study.Crit Care. 2011;15(1):R57. doi: 10.1186/cc10030. Epub 2011 Feb 10.
15 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.
16 The combined effects of insulin and cortisol on surfactant protein mRNA levels.Pediatr Res. 1995 Oct;38(4):513-21. doi: 10.1203/00006450-199510000-00007.
17 Epigallocatechin-3-gallate (EGCG) inhibits aggregation of pulmonary fibrosis associated mutant surfactant protein A2 via a proteasomal degradation pathway.Int J Biochem Cell Biol. 2019 Nov;116:105612. doi: 10.1016/j.biocel.2019.105612. Epub 2019 Sep 20.
18 Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet. 2009 Jan;84(1):52-9. doi: 10.1016/j.ajhg.2008.11.010. Epub 2008 Dec 18.
19 Clinical Course of Histologically Proven Multifocal Micronodular Pneumocyte Hyperplasia in Tuberous Sclerosis Complex: A Case Series and Comparison with Lymphangiomyomatosis.Respiration. 2018;95(5):310-316. doi: 10.1159/000486101. Epub 2018 Jan 24.
20 Surfactant protein A gene deletion and prognostics for patients with stage I non-small cell lung cancer.Clin Cancer Res. 2005 Aug 1;11(15):5417-24. doi: 10.1158/1078-0432.CCR-04-2087.
21 Genetic diversity of pneumococcal surface protein A of Streptococcus pneumoniae meningitis in German children.Vaccine. 2007 Jan 22;25(6):1030-5. doi: 10.1016/j.vaccine.2006.09.061. Epub 2006 Oct 2.
22 Inhibition of lung surfactant protein B expression during Pneumocystis carinii pneumonia in mice.J Lab Clin Med. 1999 May;133(5):423-33. doi: 10.1016/s0022-2143(99)90019-7.
23 Differential severity of LPS-induced lung injury in CD26/DPP4 positive and deficient F344 rats.Histol Histopathol. 2019 Oct;34(10):1151-1171. doi: 10.14670/HH-18-117. Epub 2019 Apr 12.
24 Genome-wide screening for complete genetic loss in prostate cancer by comparative hybridization onto cDNA microarrays.Oncogene. 2003 Feb 27;22(8):1247-52. doi: 10.1038/sj.onc.1206247.
25 C-proSP-B: A Possible Biomarker for Pulmonary Diseases?.Respiration. 2018;96(2):117-126. doi: 10.1159/000488245. Epub 2018 May 15.
26 Pattern recognition receptors and genetic risk for rsv infection: value for clinical decision-making?.Pediatr Pulmonol. 2011 Feb;46(2):101-10. doi: 10.1002/ppul.21348. Epub 2010 Oct 20.
27 Functional Analysis of Genetic Variations in Surfactant Protein D in Mycobacterial Infection and Their Association With Tuberculosis.Front Immunol. 2018 Jul 2;9:1543. doi: 10.3389/fimmu.2018.01543. eCollection 2018.
28 Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli.Innate Immun. 2016 Jan;22(1):9-20. doi: 10.1177/1753425915609973. Epub 2015 Oct 28.
29 Functional polymorphisms in surfactant protein genes and chronic obstructive pulmonary disease risk: a meta-analysis.Genet Test Mol Biomarkers. 2013 Dec;17(12):910-7. doi: 10.1089/gtmb.2013.0308. Epub 2013 Oct 5.
30 Germline SFTPA1 mutation in familial idiopathic interstitial pneumonia and lung cancer.Hum Mol Genet. 2016 Apr 15;25(8):1457-67. doi: 10.1093/hmg/ddw014. Epub 2016 Jan 19.
31 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.
32 Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection.Crit Care. 2014 Jun 20;18(3):R127. doi: 10.1186/cc13934.
33 Human Surfactant Proteins A2 (SP-A2) and B (SP-B) Genes as Determinants of Respiratory Distress Syndrome.Indian Pediatr. 2015 May;52(5):391-4. doi: 10.1007/s13312-015-0643-9.
34 Genetic Variation in Surfactant Protein-A2 Delays Resolution of Eosinophilia in Asthma.J Immunol. 2019 Sep 1;203(5):1122-1130. doi: 10.4049/jimmunol.1900546. Epub 2019 Jul 26.
35 Decreased surfactant proteins in lambs with pulmonary hypertension secondary to increased blood flow.Am J Physiol Lung Cell Mol Physiol. 2001 Nov;281(5):L1264-70. doi: 10.1152/ajplung.2001.281.5.L1264.
36 Correlation analysis between single nucleotide polymorphisms of pulmonary surfactant protein A gene and pulmonary tuberculosis in the Han population in China.Int J Infect Dis. 2014 Sep;26:31-6. doi: 10.1016/j.ijid.2014.03.1395. Epub 2014 Jun 28.
37 Allelic mRNA expression imbalance in C-type lectins reveals a frequent regulatory SNP in the human surfactant protein A (SP-A) gene.Genes Immun. 2013 Mar;14(2):99-106. doi: 10.1038/gene.2012.61. Epub 2013 Jan 17.
38 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.
39 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.
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.