Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3I2G0A)

• DOT Name: Cysteine sulfinic acid decarboxylase (CSAD)
• Synonyms: EC 4.1.1.29; Aspartate 1-decarboxylase; EC 4.1.1.11; Cysteine-sulfinate decarboxylase; Sulfinoalanine decarboxylase
• Gene Name: CSAD
• Related Disease:
  Non-insulin dependent diabetes
  Type-1 diabetes
  Atrial fibrillation
  Migraine disorder
  Migraine with aura
  Migraine, familial hemiplegic, 1
  Neuromyelitis optica
  Pulmonary fibrosis
  Scleroderma
  Systemic sclerosis
  Nasopharyngeal carcinoma
  Advanced cancer
  Colon adenocarcinoma
  Familial hemiplegic migraine
  Melanoma
• UniProt ID: CSAD_HUMAN
• PDB ID: 2JIS
• EC Number: 4.1.1.11; 4.1.1.29
• Pfam ID: PF00282
• Sequence:
  MADSEALPSLAGDPVAVEALLRAVFGVVVDEAIQKGTSVSQKVCEWKEPEELKQLLDLEL
  RSQGESQKQILERCRAVIRYSVKTGHPRFFNQLFSGLDPHALAGRIITESLNTSQYTYEI
  APVFVLMEEEVLRKLRALVGWSSGDGIFCPGGSISNMYAVNLARYQRYPDCKQRGLRTLP
  PLALFTSKECHYSIQKGAAFLGLGTDSVRVVKADERGKMVPEDLERQIGMAEAEGAVPFL
  VSATSGTTVLGAFDPLEAIADVCQRHGLWLHVDAAWGGSVLLSQTHRHLLDGIQRADSVA
  WNPHKLLAAGLQCSALLLQDTSNLLKRCHGSQASYLFQQDKFYDVALDTGDKVVQCGRRV
  DCLKLWLMWKAQGDQGLERRIDQAFVLARYLVEEMKKREGFELVMEPEFVNVCFWFVPPS
  LRGKQESPDYHERLSKVAPVLKERMVKEGSMMIGYQPHGTRGNFFRVVVANSALTCADMD
  FLLNELERLGQDL
• Function: Catalyzes the decarboxylation of L-aspartate, 3-sulfino-L-alanine (cysteine sulfinic acid), and L-cysteate to beta-alanine, hypotaurine and taurine, respectively. The preferred substrate is 3-sulfino-L-alanine. Does not exhibit any decarboxylation activity toward glutamate.
• Tissue Specificity: Expressed in liver and brain. Also expressed in both astrocytes and neurons, but lower levels are expressed in astrocytes.
• KEGG Pathway:
  beta-Alanine metabolism (hsa00410)
  Taurine and hypotaurine metabolism (hsa00430)
  Pantothe.te and CoA biosynthesis (hsa00770)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Degradation of cysteine and homocysteine (R-HSA-1614558)
• BioCyc Pathway: MetaCyc:HS06642-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[2]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[3]
Migraine disorder	DISFCQTG	Strong	Biomarker	[4]
Migraine with aura	DISDM7I8	Strong	Biomarker	[4]
Migraine, familial hemiplegic, 1	DISF1GUO	Strong	Genetic Variation	[4]
Neuromyelitis optica	DISBFGKL	Strong	Biomarker	[5]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[6]
Scleroderma	DISVQ342	Strong	Altered Expression	[6]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[6]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[7]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[8]
Colon adenocarcinoma	DISDRE0J	Limited	Biomarker	[9]
Familial hemiplegic migraine	DISYVMKL	Limited	Biomarker	[10]
Melanoma	DIS1RRCY	Limited	Biomarker	[11]

7 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 Cysteine sulfinic acid decarboxylase (CSAD).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cysteine sulfinic acid decarboxylase (CSAD).	[14]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Cysteine sulfinic acid decarboxylase (CSAD).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cysteine sulfinic acid decarboxylase (CSAD).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cysteine sulfinic acid decarboxylase (CSAD).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Cysteine sulfinic acid decarboxylase (CSAD).	[18]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Cysteine sulfinic acid decarboxylase (CSAD).	[19]

1 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 Cysteine sulfinic acid decarboxylase (CSAD).	[13]

References

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• [2] Genome-Wide Association Study Confirming a Strong Effect of HLA and Identifying Variants in CSAD/lnc-ITGB7-1 on Chromosome 12q13.13 Associated With Susceptibility to Fulminant Type 1 Diabetes.Diabetes. 2019 Mar;68(3):665-675. doi: 10.2337/db18-0314. Epub 2018 Dec 14.
• [3] Cardiac Sympathetic Denervation Suppresses Atrial Fibrillation and Blood Pressure in a Chronic Intermittent Hypoxia Rat Model of Obstructive Sleep Apnea.J Am Heart Assoc. 2019 Feb 19;8(4):e010254. doi: 10.1161/JAHA.118.010254.
• [4] Familial hemiplegic migraine.Neurotherapeutics. 2007 Apr;4(2):274-84. doi: 10.1016/j.nurt.2007.01.008.
• [5] Comparison of probabilistic tractography and tract-based spatial statistics for assessing optic radiation damage in patients with autoimmune inflammatory disorders of the central nervous system.Neuroimage Clin. 2018 May 8;19:538-550. doi: 10.1016/j.nicl.2018.05.004. eCollection 2018.
• [6] Antifibrotic properties of caveolin-1 scaffolding domain in vitro and in vivo.Am J Physiol Lung Cell Mol Physiol. 2008 May;294(5):L843-61. doi: 10.1152/ajplung.00295.2007. Epub 2008 Jan 18.
• [7] Integrated analysis of multiple gene expression profiling datasets revealed novel gene signatures and molecular markers in nasopharyngeal carcinoma.Cancer Epidemiol Biomarkers Prev. 2012 Jan;21(1):166-75. doi: 10.1158/1055-9965.EPI-11-0593. Epub 2011 Nov 8.
• [8] Small-molecule binding sites to explore protein-protein interactions in the cancer proteome.Mol Biosyst. 2016 Oct 20;12(10):3067-87. doi: 10.1039/c6mb00231e. Epub 2016 Jul 25.
• [9] Investigation Of Vitamin B(12)-Modified Amphiphilic Sodium Alginate Derivatives For Enhancing The Oral Delivery Efficacy Of Peptide Drugs.Int J Nanomedicine. 2019 Sep 20;14:7743-7758. doi: 10.2147/IJN.S218944. eCollection 2019.
• [10] Migraine aura: a knockin mouse with a knockout message.Neuron. 2004 Mar 4;41(5):679-80. doi: 10.1016/s0896-6273(04)00112-6.
• [11] Prevalence of BRAF V600E mutation in Chinese melanoma patients: large scale analysis of BRAF and NRAS mutations in a 432-case cohort.Eur J Cancer. 2012 Jan;48(1):94-100. doi: 10.1016/j.ejca.2011.06.056. Epub 2011 Jul 23.
• [12] 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.
• [13] 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.
• [14] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [15] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [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] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [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] 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.