Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1YB54Z)

• DOT Name: N-acetylneuraminate 9-O-acetyltransferase (CASD1)
• Synonyms: EC 2.3.1.45; CAS1 domain-containing protein 1; Sialate O-acetyltransferase; SOAT
• Gene Name: CASD1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Childhood acute lymphoblastic leukemia
  Listeriosis
  Malignant glioma
  Oligospermia
• UniProt ID: CASD1_HUMAN
• EC Number: 2.3.1.45
• Pfam ID: PF07779
• Sequence:
  MAALAYNLGKREINHYFSVRSAKVLALVAVLLLAACHLASRRYRGNDSCEYLLSSGRFLG
  EKVWQPHSCMMHKYKISEAKNCLVDKHIAFIGDSRIRQLFYSFVKIINPQFKEEGNKHEN
  IPFEDKTASVKVDFLWHPEVNGSMKQCIKVWTEDSIAKPHVIVAGAATWSIKIHNGSSEA
  LSQYKMNITSIAPLLEKLAKTSDVYWVLQDPVYEDLLSENRKMITNEKIDAYNEAAVSIL
  NSSTRNSKSNVKMFSVSKLIAQETIMESLDGLHLPESSRETTAMILMNVYCNKILKPVDG
  SCCQPRPPVTLIQKLAACFFTLSIIGYLIFYIIHRNAHRKNKPCTDLESGEEKKNIINTP
  VSSLEILLQSFCKLGLIMAYFYMCDRANLFMKENKFYTHSSFFIPIIYILVLGVFYNENT
  KETKVLNREQTDEWKGWMQLVILIYHISGASTFLPVYMHIRVLVAAYLFQTGYGHFSYFW
  IKGDFGIYRVCQVLFRLNFLVVVLCIVMDRPYQFYYFVPLVTVWFMVIYVTLALWPQIIQ
  KKANGNCFWHFGLLLKLGFLLLFICFLAYSQGAFEKIFSLWPLSKCFELKGNVYEWWFRW
  RLDRYVVFHGMLFAFIYLALQKRQILSEGKGEPLFSNKISNFLLFISVVSFLTYSIWASS
  CKNKAECNELHPSVSVVQILAFILIRNIPGYARSVYSSFFAWFGKISLELFICQYHIWLA
  ADTRGILVLIPGNPMLNIIVSTFIFVCVAHEISQITNDLAQIIIPKDNSSLLKRLACIAA
  FFCGLLILSSIQDKSKH
• Function: O-acetyltransferase that catalyzes 9-O-acetylation of sialic acids. Sialic acids are sugars at the reducing end of glycoproteins and glycolipids, and are involved in various processes such as cell-cell interactions, host-pathogen recognition.
• Tissue Specificity: Highly expressed in peripheral B lymphocytes.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[2]
Listeriosis	DISKMQBM	Strong	Biomarker	[3]
Malignant glioma	DISFXKOV	Strong	Biomarker	[4]
Oligospermia	DIS6YJF3	Strong	Altered Expression	[5]

9 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 N-acetylneuraminate 9-O-acetyltransferase (CASD1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of N-acetylneuraminate 9-O-acetyltransferase (CASD1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of N-acetylneuraminate 9-O-acetyltransferase (CASD1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of N-acetylneuraminate 9-O-acetyltransferase (CASD1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of N-acetylneuraminate 9-O-acetyltransferase (CASD1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of N-acetylneuraminate 9-O-acetyltransferase (CASD1).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of N-acetylneuraminate 9-O-acetyltransferase (CASD1).	[12]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of N-acetylneuraminate 9-O-acetyltransferase (CASD1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of N-acetylneuraminate 9-O-acetyltransferase (CASD1).	[15]

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 decreases the methylation of N-acetylneuraminate 9-O-acetyltransferase (CASD1).	[14]

References

• [1] Estrone-3-Sulfate Stimulates the Proliferation of T47D Breast Cancer Cells Stably Transfected With the Sodium-Dependent Organic Anion Transporter SOAT (SLC10A6). Front Pharmacol. 2018 Aug 21;9:941. doi: 10.3389/fphar.2018.00941. eCollection 2018.
• [2] 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.
• [3] The intrinsic cephalosporin resistome of Listeria monocytogenes in the context of stress response, gene regulation, pathogenesis and therapeutics.J Appl Microbiol. 2016 Feb;120(2):251-65. doi: 10.1111/jam.12989. Epub 2015 Dec 28.
• [4] Enhanced repair of a cisplatin-damaged reporter chloramphenicol-O-acetyltransferase gene and altered activities of DNA polymerases alpha and beta, and DNA ligase in cells of a human malignant glioma following in vivo cisplatin therapy.J Cell Biochem. 1994 Jan;54(1):11-9. doi: 10.1002/jcb.240540103.
• [5] The polymorphism L204F affects transport and membrane expression of the sodium-dependent organic anion transporter SOAT (SLC10A6).J Steroid Biochem Mol Biol. 2018 May;179:36-44. doi: 10.1016/j.jsbmb.2017.09.017. Epub 2017 Sep 23.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study. BMC Med Genomics. 2011 Mar 31;4:29. doi: 10.1186/1755-8794-4-29.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [13] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [14] 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.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.