Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPQR0A6)

• DOT Name: Chitotriosidase-1 (CHIT1)
• Synonyms: EC 3.2.1.14; Chitinase-1
• Gene Name: CHIT1
• UniProt ID: CHIT1_HUMAN
• PDB ID: 1GUV; 1HKI; 1HKJ; 1HKK; 1HKM; 1LG1; 1LG2; 1LQ0; 1WAW; 1WB0; 4WJX; 4WK9; 4WKA; 4WKF; 4WKH; 5HBF; 5NR8; 5NRA; 5NRF; 6JJR; 6JK6; 6SO0; 6ZE8
• EC Number: 3.2.1.14
• Pfam ID: PF01607 ; PF00704
• Sequence:
  MVRSVAWAGFMVLLMIPWGSAAKLVCYFTNWAQYRQGEARFLPKDLDPSLCTHLIYAFAG
  MTNHQLSTTEWNDETLYQEFNGLKKMNPKLKTLLAIGGWNFGTQKFTDMVATANNRQTFV
  NSAIRFLRKYSFDGLDLDWEYPGSQGSPAVDKERFTTLVQDLANAFQQEAQTSGKERLLL
  SAAVPAGQTYVDAGYEVDKIAQNLDFVNLMAYDFHGSWEKVTGHNSPLYKRQEESGAAAS
  LNVDAAVQQWLQKGTPASKLILGMPTYGRSFTLASSSDTRVGAPATGSGTPGPFTKEGGM
  LAYYEVCSWKGATKQRIQDQKVPYIFRDNQWVGFDDVESFKTKVSYLKQKGLGGAMVWAL
  DLDDFAGFSCNQGRYPLIQTLRQELSLPYLPSGTPELEVPKPGQPSEPEHGPSPGQDTFC
  QGKADGLYPNPRERSSFYSCAAGRLFQQSCPTGLVFSNSCKCCTWN
• Function: Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity.
• Tissue Specificity: Detected in spleen. Secreted by cultured macrophages.
• KEGG Pathway:
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Digestion of dietary carbohydrate (R-HSA-189085)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Chitotriosidase-1 (CHIT1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Chitotriosidase-1 (CHIT1).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Chitotriosidase-1 (CHIT1).	[3]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Chitotriosidase-1 (CHIT1).	[4]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Chitotriosidase-1 (CHIT1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Chitotriosidase-1 (CHIT1).	[6]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [4] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [5] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [6] 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.