Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT87XL1U)

DOT Name Pulmonary surfactant-associated protein A1 (SFTPA1)
Synonyms PSP-A; PSPA; SP-A; SP-A1; 35 kDa pulmonary surfactant-associated protein; Alveolar proteinosis protein; Collectin-4
Gene Name SFTPA1
Related Disease
Lung cancer ( )
Lung carcinoma ( )
Adult respiratory distress syndrome ( )
Advanced cancer ( )
Allergic rhinitis ( )
Alzheimer disease ( )
Amyloidosis ( )
Anemia ( )
Arteriosclerosis ( )
Asthma ( )
Atherosclerosis ( )
Bacillary dysentery ( )
Bacterial pneumonia ( )
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive ( )
Bronchiolitis ( )
Bronchopulmonary dysplasia ( )
Cardiovascular disease ( )
Childhood myelodysplastic syndrome ( )
Chronic kidney disease ( )
Chronic obstructive pulmonary disease ( )
Cognitive impairment ( )
Congenital alveolar dysplasia ( )
Craniosynostosis ( )
Hyperinsulinemia ( )
Inflammatory bowel disease ( )
Keratoconus ( )
Liver cirrhosis ( )
Lung adenocarcinoma ( )
Methicillin-resistant staphylococci infection ( )
Myelodysplastic syndrome ( )
Myopathy ( )
Nasal polyp ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Pneumonia ( )
Pneumonitis ( )
Pulmonary fibrosis ( )
Respiratory disease ( )
Respiratory syncytial virus infection ( )
Tuberculosis ( )
Cystic fibrosis ( )
Pulmonary disease ( )
Congenital heart disease ( )
Lung neoplasm ( )
Obesity ( )
Pulmonary tuberculosis ( )
Small-cell lung cancer ( )
Squamous cell carcinoma ( )
Stroke ( )
Type-1/2 diabetes ( )
UniProt ID
SFTA1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00059
Sequence
MWLCPLALNLILMAASGAVCEVKDVCVGSPGIPGTPGSHGLPGRDGRDGLKGDPGPPGPM
GPPGEMPCPPGNDGLPGAPGIPGECGEKGEPGERGPPGLPAHLDEELQATLHDFRHQILQ
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. Enhances the expression of MYO18A/SP-R210 on alveolar macrophages; (Microbial infection) Recognition of M.tuberculosis by dendritic cells may occur partially via this molecule. Can recognize, bind, and opsonize pathogens to enhance their elimination by alveolar macrophages ; (Microbial infection) Binds M.pneumoniae CARDS toxin, serves as one receptor for this pathogen. When SFTPA1 is down-regulated by siRNA, less toxin binds to human cells and less vacuolization (a symptom of M.pneumoniae infection) is seen.
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 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
Lung cancer DISCM4YA Definitive Biomarker [1]
Lung carcinoma DISTR26C Definitive Biomarker [1]
Adult respiratory distress syndrome DISIJV47 Strong Genetic Variation [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Allergic rhinitis DIS3U9HN Strong Altered Expression [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Amyloidosis DISHTAI2 Strong Altered Expression [5]
Anemia DISTVL0C Strong Biomarker [6]
Arteriosclerosis DISK5QGC Strong Biomarker [7]
Asthma DISW9QNS Strong Biomarker [8]
Atherosclerosis DISMN9J3 Strong Biomarker [7]
Bacillary dysentery DISFZHKN Strong Genetic Variation [9]
Bacterial pneumonia DISPW7PH Strong Biomarker [10]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive DIS3KLUX Strong Biomarker [6]
Bronchiolitis DISEE9BG Strong Biomarker [11]
Bronchopulmonary dysplasia DISO0BY5 Strong Genetic Variation [12]
Cardiovascular disease DIS2IQDX Strong Biomarker [7]
Childhood myelodysplastic syndrome DISMN80I Strong Biomarker [6]
Chronic kidney disease DISW82R7 Strong Genetic Variation [13]
Chronic obstructive pulmonary disease DISQCIRF Strong Genetic Variation [14]
Cognitive impairment DISH2ERD Strong Biomarker [5]
Congenital alveolar dysplasia DIS1IYUN Strong Genetic Variation [15]
Craniosynostosis DIS6J405 Strong Biomarker [16]
Hyperinsulinemia DISIDWT6 Strong Altered Expression [17]
Inflammatory bowel disease DISGN23E Strong Biomarker [18]
Keratoconus DISOONXH Strong Genetic Variation [19]
Liver cirrhosis DIS4G1GX Strong Biomarker [20]
Lung adenocarcinoma DISD51WR Strong Altered Expression [21]
Methicillin-resistant staphylococci infection DIS6DRDZ Strong Genetic Variation [22]
Myelodysplastic syndrome DISYHNUI Strong Biomarker [6]
Myopathy DISOWG27 Strong Biomarker [23]
Nasal polyp DISLP3XE Strong Biomarker [16]
Neoplasm DISZKGEW Strong Biomarker [24]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [25]
Pneumonia DIS8EF3M Strong Altered Expression [26]
Pneumonitis DIS88E0K Strong Altered Expression [26]
Pulmonary fibrosis DISQKVLA Strong Altered Expression [27]
Respiratory disease DISGGAGJ Strong Biomarker [3]
Respiratory syncytial virus infection DIS7FWHY Strong Genetic Variation [28]
Tuberculosis DIS2YIMD Strong Genetic Variation [29]
Cystic fibrosis DIS2OK1Q moderate Genetic Variation [30]
Pulmonary disease DIS6060I moderate Biomarker [31]
Congenital heart disease DISQBA23 Limited Altered Expression [32]
Lung neoplasm DISVARNB Limited Altered Expression [33]
Obesity DIS47Y1K Limited Biomarker [34]
Pulmonary tuberculosis DIS6FLUM Limited Genetic Variation [35]
Small-cell lung cancer DISK3LZD Limited Altered Expression [33]
Squamous cell carcinoma DISQVIFL Limited Altered Expression [36]
Stroke DISX6UHX Limited Genetic Variation [37]
Type-1/2 diabetes DISIUHAP Limited Biomarker [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 A1 (SFTPA1). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Pulmonary surfactant-associated protein A1 (SFTPA1). [42]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Pulmonary surfactant-associated protein A1 (SFTPA1). [40]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Pulmonary surfactant-associated protein A1 (SFTPA1). [41]
Paraquat DMR8O3X Investigative Paraquat increases the expression of Pulmonary surfactant-associated protein A1 (SFTPA1). [43]
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References

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3 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.
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9 Precise, direct, and rapid detection of Shigella Spa gene by a novel unmodified AuNPs-based optical genosensing system.J Microbiol Methods. 2019 Jul;162:42-49. doi: 10.1016/j.mimet.2019.05.007. Epub 2019 May 15.
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11 Human genetics and respiratory syncytial virus disease: current findings and future approaches.Curr Top Microbiol Immunol. 2013;372:121-37. doi: 10.1007/978-3-642-38919-1_6.
12 Dysplasia: a review.Pediatr Pulmonol. 2007 Oct;42(10):952-61. doi: 10.1002/ppul.20689.
13 Evaluation of the new Sebia free light chain assay using the AP22 ELITE instrument.Clin Chim Acta. 2018 Dec;487:161-167. doi: 10.1016/j.cca.2018.09.030. Epub 2018 Sep 20.
14 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.
15 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.
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17 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.
18 Management of patients with inflammatory bowel disease and spondyloarthritis.Expert Rev Clin Pharmacol. 2017 Dec;10(12):1363-1374. doi: 10.1080/17512433.2017.1377609. Epub 2017 Sep 20.
19 Repeatability and comparison of new Corvis ST parameters in normal and keratoconus eyes.Sci Rep. 2019 Oct 25;9(1):15379. doi: 10.1038/s41598-019-51502-4.
20 Systematic quantification of histological patterns shows accuracy in reflecting cirrhotic remodeling.J Gastroenterol Hepatol. 2017 Sep;32(9):1631-1639. doi: 10.1111/jgh.13722.
21 Immunohistochemical analysis and comparison of napsin A, TTF1, SPA and CK7 expression in primary lung adenocarcinoma.Biotech Histochem. 2018;93(5):364-372. doi: 10.1080/10520295.2018.1444790. Epub 2018 Jun 29.
22 Antimicrobial Resistance Patterns in Methicillin-Resistant Staphylococcus aureus from Patients Hospitalized during 2015-2017 in Hospitals in Poland.Med Princ Pract. 2020;29(1):61-68. doi: 10.1159/000501788. Epub 2019 Jul 1.
23 Inflammatory myopathy in scapulo-ilio-peroneal atrophy with cardiopathy. A study of two families.Brain. 1975 Dec;98(4):709-22. doi: 10.1093/brain/98.4.709.
24 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.
25 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.
26 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.
27 A homozygous SFTPA1 mutation drives necroptosis of type II alveolar epithelial cells in patients with idiopathic pulmonary fibrosis.J Exp Med. 2019 Dec 2;216(12):2724-2735. doi: 10.1084/jem.20182351. Epub 2019 Oct 10.
28 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.
29 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.
30 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.
31 C-proSP-B: A Possible Biomarker for Pulmonary Diseases?.Respiration. 2018;96(2):117-126. doi: 10.1159/000488245. Epub 2018 May 15.
32 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.
33 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.
34 Diminished lung compliance and elevated surfactant lipids and proteins in nutritionally obese young rats.Lung. 2004;182(2):101-17. doi: 10.1007/s00408-003-1048-4.
35 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.
36 Comprehensive investigation of clinicopathologic features, oncogenic driver mutations and immunohistochemical markers in peripheral lung squamous cell carcinoma.J Thorac Dis. 2017 Nov;9(11):4434-4440. doi: 10.21037/jtd.2017.10.43.
37 The three-dimensional shoulder pain alignment (3D-SPA) mobilization improves pain-free shoulder range, functional reach and sleep following stroke: a pilot randomized control trial.Disabil Rehabil. 2020 Oct;42(21):3072-3083. doi: 10.1080/09638288.2019.1585487. Epub 2019 Mar 23.
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40 Regulation of human pulmonary surfactant protein gene expression by 1alpha,25-dihydroxyvitamin D3. Am J Physiol Lung Cell Mol Physiol. 2005 Oct;289(4):L617-26. doi: 10.1152/ajplung.00129.2004. Epub 2005 Jun 10.
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43 Pneumoproteins as markers of paraquat lung injury: a clinical case. J Forensic Leg Med. 2008 Jan;15(1):48-52. doi: 10.1016/j.jcfm.2006.09.003. Epub 2006 Dec 14.