Details of Drug Off-Target (DOT)

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

• DOT Name: Sialate O-acetylesterase (SIAE)
• Synonyms: EC 3.1.1.53; H-Lse; Sialic acid-specific 9-O-acetylesterase
• Gene Name: SIAE
• Related Disease:
  Primary biliary cholangitis
  Autoimmune disease
  Childhood acute lymphoblastic leukemia
  Depression
  Juvenile idiopathic arthritis
  Major depressive disorder
  Sleep disorder
  Type-1/2 diabetes
  Autoimmune disease, susceptibility to, 6
  Insomnia
  Osteoarthritis
  Rheumatoid arthritis
• UniProt ID: SIAE_HUMAN
• EC Number: 3.1.1.53
• Pfam ID: PF03629
• Sequence:
  MVAPGLVLGLVLPLILWADRSAGIGFRFASYINNDMVLQKEPAGAVIWGFGTPGATVTVT
  LRQGQETIMKKVTSVKAHSDTWMVVLDPMKPGGPFEVMAQQTLEKINFTLRVHDVLFGDV
  WLCSGQSNMQMTVLQIFNATRELSNTAAYQSVRILSVSPIQAEQELEDLVAVDLQWSKPT
  SENLGHGYFKYMSAVCWLFGRHLYDTLQYPIGLIASSWGGTPIEAWSSGRSLKACGVPKQ
  GSIPYDSVTGPSKHSVLWNAMIHPLCNMTLKGVVWYQGESNINYNTDLYNCTFPALIEDW
  RETFHRGSQGQTERFFPFGLVQLSSDLSKKSSDDGFPQIRWHQTADFGYVPNPKMPNTFM
  AVAMDLCDRDSPFGSIHPRDKQTVAYRLHLGARALAYGEKNLTFEGPLPEKIELLAHKGL
  LNLTYYQQIQVQKKDNKIFEISCCSDHRCKWLPASMNTVSTQSLTLAIDSCHGTVVALRY
  AWTTWPCEYKQCPLYHPSSALPAPPFIAFITDQGPGHQSNVAK
• Function: Catalyzes the removal of O-acetyl ester groups from position 9 of the parent sialic acid, N-acetylneuraminic acid.
• Tissue Specificity: Widely expressed with high expression in the testis, prostate, and colon.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary biliary cholangitis	DIS43E0O	Definitive	Genetic Variation	[1]
Autoimmune disease	DISORMTM	Strong	Biomarker	[2]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[3]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Genetic Variation	[5]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[6]
Sleep disorder	DIS3JP1U	Strong	Biomarker	[7]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[6]
Autoimmune disease, susceptibility to, 6	DISHNUXI	Limited	Unknown	[8]
Insomnia	DIS0AFR7	Limited	Genetic Variation	[4]
Osteoarthritis	DIS05URM	Limited	Biomarker	[4]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Sialate O-acetylesterase (SIAE).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sialate O-acetylesterase (SIAE).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sialate O-acetylesterase (SIAE).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sialate O-acetylesterase (SIAE).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sialate O-acetylesterase (SIAE).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Sialate O-acetylesterase (SIAE).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Sialate O-acetylesterase (SIAE).	[16]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Sialate O-acetylesterase (SIAE).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Sialate O-acetylesterase (SIAE).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Sialate O-acetylesterase (SIAE).	[18]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Sialate O-acetylesterase (SIAE).	[19]

References

• [1] Association of primary biliary cirrhosis with variants in the CLEC16A, SOCS1, SPIB and SIAE immunomodulatory genes.Genes Immun. 2012 Jun;13(4):328-35. doi: 10.1038/gene.2011.89. Epub 2012 Jan 19.
• [2] Genomic and biochemical characterization of sialic acid acetylesterase (siae) in zebrafish.Glycobiology. 2017 Oct 1;27(10):938-946. doi: 10.1093/glycob/cwx068.
• [3] Regulation of O-acetylation of sialic acids by sialate-O-acetyltransferase and sialate-O-acetylesterase activities in childhood acute lymphoblastic leukemia.Glycobiology. 2012 Jan;22(1):70-83. doi: 10.1093/glycob/cwr106. Epub 2011 Jul 29.
• [4] The prevalence of depression and insomnia symptoms among patients with rheumatoid arthritis and osteoarthritis in Poland: a case control study.Psychol Health Med. 2019 Mar;24(3):333-343. doi: 10.1080/13548506.2018.1529325. Epub 2018 Oct 4.
• [5] SIAE Rare Variants in Juvenile Idiopathic Arthritis and Primary Antibody Deficiencies.J Immunol Res. 2017;2017:1514294. doi: 10.1155/2017/1514294. Epub 2017 Aug 16.
• [6] Comparative Effectiveness of a Technology-Facilitated Depression Care Management Model in Safety-Net Primary Care Patients With Type 2 Diabetes: 6-Month Outcomes of a Large Clinical Trial.J Med Internet Res. 2018 Apr 23;20(4):e147. doi: 10.2196/jmir.7692.
• [7] Sleep disturbances in advanced cancer patients admitted to a supportive/palliative care unit.Support Care Cancer. 2017 Apr;25(4):1301-1306. doi: 10.1007/s00520-016-3524-4. Epub 2016 Dec 13.
• [8] 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.
• [9] Lack of association between rare mutations of the SIAE gene and rheumatoid arthritis in a Han Chinese population.Genet Mol Res. 2015 Oct 30;14(4):14162-8. doi: 10.4238/2015.October.29.38.
• [10] 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.
• [11] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [12] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] 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.
• [15] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [16] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.