Details of Drug Off-Target (DOT)

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

• DOT Name: Pulmonary surfactant-associated protein D (SFTPD)
• Synonyms: PSP-D; SP-D; Collectin-7; Lung surfactant protein D
• Gene Name: SFTPD
• UniProt ID: SFTPD_HUMAN
• PDB ID: 1B08; 1M7L; 1PW9; 1PWB; 2GGU; 2GGX; 2ORJ; 2ORK; 2OS9; 2RIA; 2RIB; 2RIC; 2RID; 2RIE; 3DBZ; 3G81; 3G83; 3G84; 3IKN; 3IKP; 3IKQ; 3IKR; 4E52; 4M17; 4M18; 5OXR; 5OXS
• Pfam ID: PF01391 ; PF00059 ; PF09006
• Sequence:
  MLLFLLSALVLLTQPLGYLEAEMKTYSHRTMPSACTLVMCSSVESGLPGRDGRDGREGPR
  GEKGDPGLPGAAGQAGMPGQAGPVGPKGDNGSVGEPGPKGDTGPSGPPGPPGVPGPAGRE
  GPLGKQGNIGPQGKPGPKGEAGPKGEVGAPGMQGSAGARGLAGPKGERGVPGERGVPGNT
  GAAGSAGAMGPQGSPGARGPPGLKGDKGIPGDKGAKGESGLPDVASLRQQVEALQGQVQH
  LQAAFSQYKKVELFPNGQSVGEKIFKTAGFVKPFTEAQLLCTQAGGQLASPRSAAENAAL
  QQLVVAKNEAAFLSMTDSKTEGKFTYPTGESLVYSNWAPGEPNDDGGSEDCVEIFTNGKW
  NDRACGEKRLVVCEF
• Function: Contributes to the lung's defense against inhaled microorganisms, organic antigens and toxins. Interacts with compounds such as bacterial lipopolysaccharides, oligosaccharides and fatty acids and modulates leukocyte action in immune response. May participate in the extracellular reorganization or turnover of pulmonary surfactant. Binds strongly maltose residues and to a lesser extent other alpha-glucosyl moieties.
• Tissue Specificity: Expressed in lung, brain, pancreas and adipose tissue (mainly mature adipocytes).
• KEGG Pathway: Phagosome (hsa04145)
• Reactome Pathway:
  Toll Like Receptor TLR1 (R-HSA-168179)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  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)
  SARS-CoV-1 activates/modulates innate immune responses (R-HSA-9692916)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Pulmonary surfactant-associated protein D (SFTPD) increases the Traumatic lung injury ADR of Methotrexate.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Pulmonary surfactant-associated protein D (SFTPD).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pulmonary surfactant-associated protein D (SFTPD).	[2]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Pulmonary surfactant-associated protein D (SFTPD).	[3]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Pulmonary surfactant-associated protein D (SFTPD).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pulmonary surfactant-associated protein D (SFTPD).	[5]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Pulmonary surfactant-associated protein D (SFTPD).	[6]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Pulmonary surfactant-associated protein D (SFTPD).	[7]

References

• [1] 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.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray. Acta Pharmacol Sin. 2004 Oct;25(10):1327-33.
• [5] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [6] Plasma surfactant D in patients following acute paraquat intoxication. Clin Toxicol (Phila). 2007 Jun-Aug;45(5):463-7. doi: 10.1080/15563650701338138.
• [7] Imbalance in the antioxidant defence system and pro-genotoxic status induced by high glucose concentrations: In vitro testing in human liver cells. Toxicol In Vitro. 2020 Dec;69:105001. doi: 10.1016/j.tiv.2020.105001. Epub 2020 Sep 15.
• [8] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.