Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4DIUKC)

• DOT Name: Chitinase domain-containing protein 1 (CHID1)
• Synonyms: Stabilin-1-interacting chitinase-like protein; SI-CLP
• Gene Name: CHID1
• Related Disease:
  Chronic bronchitis
  Rheumatoid arthritis
• UniProt ID: CHID1_HUMAN
• PDB ID: 3BXW
• Pfam ID: PF00704
• Sequence:
  MRTLFNLLWLALACSPVHTTLSKSDAKKAASKTLLEKSQFSDKPVQDRGLVVTDLKAESV
  VLEHRSYCSAKARDRHFAGDVLGYVTPWNSHGYDVTKVFGSKFTQISPVWLQLKRRGREM
  FEVTGLHDVDQGWMRAVRKHAKGLHIVPRLLFEDWTYDDFRNVLDSEDEIEELSKTVVQV
  AKNQHFDGFVVEVWNQLLSQKRVGLIHMLTHLAEALHQARLLALLVIPPAITPGTDQLGM
  FTHKEFEQLAPVLDGFSLMTYDYSTAHQPGPNAPLSWVRACVQVLDPKSKWRSKILLGLN
  FYGMDYATSKDAREPVVGARYIQTLKDHRPRMVWDSQASEHFFEYKKSRSGRHVVFYPTL
  KSLQVRLELARELGVGVSIWELGQGLDYFYDLL
• Function: Saccharide- and LPS-binding protein with possible roles in pathogen sensing and endotoxin neutralization. Ligand-binding specificity relates to the length of the oligosaccharides, with preference for chitotetraose (in vitro).
• Tissue Specificity: Expressed in cells of monocytic, T, B and epithelial origin.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic bronchitis	DISS8O8V	moderate	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Chitinase domain-containing protein 1 (CHID1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Chitinase domain-containing protein 1 (CHID1).	[4]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Chitinase domain-containing protein 1 (CHID1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Chitinase domain-containing protein 1 (CHID1).	[5]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Chitinase domain-containing protein 1 (CHID1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Chitinase domain-containing protein 1 (CHID1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Chitinase domain-containing protein 1 (CHID1).	[6]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Chitinase domain-containing protein 1 (CHID1).	[8]

References

• [1] Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease.Respir Res. 2014 Sep 21;15(1):113. doi: 10.1186/s12931-014-0113-2.
• [2] Human secreted stabilin-1-interacting chitinase-like protein aggravates the inflammation associated with rheumatoid arthritis and is a potential macrophage inflammatory regulator in rodents.Arthritis Rheumatol. 2014 May;66(5):1141-52. doi: 10.1002/art.38356.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [7] Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated in alternatively activated macrophages and secreted via lysosomal pathway. Blood. 2006 Apr 15;107(8):3221-8. doi: 10.1182/blood-2005-07-2843. Epub 2005 Dec 15.
• [8] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [9] 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.