Details of Drug Off-Target (DOT)

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

• DOT Name: Arylsulfatase I (ARSI)
• Synonyms: ASI; EC 3.1.6.-
• Gene Name: ARSI
• Related Disease:
  Gastric cancer
  Panic disorder
  Stomach cancer
  Abdominal aortic aneurysm
  Anxiety
  Anxiety disorder
  Autism
  Cardiovascular disease
  Depression
  Hereditary nonpolyposis colon cancer
  Insomnia
  Neoplasm
  Syphilis
  Breast cancer
  Breast carcinoma
  Autosomal recessive spastic paraplegia type 66
  Post-traumatic stress disorder
  Retinitis pigmentosa
• UniProt ID: ARSI_HUMAN
• EC Number: 3.1.6.-
• Pfam ID: PF00884
• Sequence:
  MHTLTGFSLVSLLSFGYLSWDWAKPSFVADGPGEAGEQPSAAPPQPPHIIFILTDDQGYH
  DVGYHGSDIETPTLDRLAAKGVKLENYYIQPICTPSRSQLLTGRYQIHTGLQHSIIRPQQ
  PNCLPLDQVTLPQKLQEAGYSTHMVGKWHLGFYRKECLPTRRGFDTFLGSLTGNVDYYTY
  DNCDGPGVCGFDLHEGENVAWGLSGQYSTMLYAQRASHILASHSPQRPLFLYVAFQAVHT
  PLQSPREYLYRYRTMGNVARRKYAAMVTCMDEAVRNITWALKRYGFYNNSVIIFSSDNGG
  QTFSGGSNWPLRGRKGTYWEGGVRGLGFVHSPLLKRKQRTSRALMHITDWYPTLVGLAGG
  TTSAADGLDGYDVWPAISEGRASPRTEILHNIDPLYNHAQHGSLEGGFGIWNTAVQAAIR
  VGEWKLLTGDPGYGDWIPPQTLATFPGSWWNLERMASVRQAVWLFNISADPYEREDLAGQ
  RPDVVRTLLARLAEYNRTAIPVRYPAENPRAHPDFNGGAWGPWASDEEEEEEEGRARSFS
  RGRRKKKCKICKLRSFFRKLNTRLMSQRI
• Function: Displays arylsulfatase activity at neutral pH, when co-expressed with SUMF1; arylsulfatase activity is measured in the secretion medium of retinal cell line, but no activity is recorded when measured in cell extracts. Lacks arylsulfatase activity.
• Tissue Specificity: Expressed in placenta, in embryonic stem cells, fetal eyes and lens.
• Reactome Pathway:
  Glycosphingolipid catabolism (R-HSA-9840310)
  The activation of arylsulfatases (R-HSA-1663150)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Altered Expression	[1]
Panic disorder	DISD3VNY	Definitive	Genetic Variation	[2]
Stomach cancer	DISKIJSX	Definitive	Altered Expression	[1]
Abdominal aortic aneurysm	DISD06OF	Strong	Genetic Variation	[3]
Anxiety	DISIJDBA	Strong	Genetic Variation	[4]
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[4]
Autism	DISV4V1Z	Strong	Biomarker	[5]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[6]
Depression	DIS3XJ69	Strong	Genetic Variation	[4]
Hereditary nonpolyposis colon cancer	DISPA49R	Strong	Biomarker	[7]
Insomnia	DIS0AFR7	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[9]
Syphilis	DISJ73BS	Strong	Biomarker	[10]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[11]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[11]
Autosomal recessive spastic paraplegia type 66	DISWHXC7	Supportive	Autosomal recessive	[12]
Post-traumatic stress disorder	DISHL1EY	Limited	Genetic Variation	[13]
Retinitis pigmentosa	DISCGPY8	Limited	Biomarker	[14]

2 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 Arylsulfatase I (ARSI).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Arylsulfatase I (ARSI).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Arylsulfatase I (ARSI).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Arylsulfatase I (ARSI).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Arylsulfatase I (ARSI).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Arylsulfatase I (ARSI).	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Arylsulfatase I (ARSI).	[21]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Arylsulfatase I (ARSI).	[22]

References

• [1] Epigenetic regulation of IncRNA KCNKI5-ASI in gastric cancer.Cancer Manag Res. 2019 Sep 20;11:8589-8602. doi: 10.2147/CMAR.S186002. eCollection 2019.
• [2] White matter connectivity differences between treatment responders and non-responders in patients with panic disorder.J Affect Disord. 2020 Jan 1;260:527-535. doi: 10.1016/j.jad.2019.09.032. Epub 2019 Sep 4.
• [3] Correcting for Body Surface Area Identifies the True Prevalence of Abdominal Aortic Aneurysm in Screened Women.Eur J Vasc Endovasc Surg. 2019 Feb;57(2):221-228. doi: 10.1016/j.ejvs.2018.08.048. Epub 2018 Oct 4.
• [4] Psychological predictors of quality of life and functional outcome in patients undergoing elective surgery for degenerative lumbar spine disease.Eur Spine J. 2020 Feb;29(2):349-359. doi: 10.1007/s00586-019-06106-x. Epub 2019 Aug 14.
• [5] Development and validation of a streamlined autism case confirmation approach for use in epidemiologic risk factor research in prospective cohorts.Autism Res. 2017 Mar;10(3):485-501. doi: 10.1002/aur.1659. Epub 2016 Aug 3.
• [6] Value of the arterial stiffness index and ankle brachial index in subclinical atherosclerosis screening in healthy community-dwelling individuals.BMC Public Health. 2019 Jan 15;19(1):65. doi: 10.1186/s12889-019-6398-9.
• [7] Automated, multiplex assay for high-frequency microsatellite instability in colorectal cancer.J Clin Oncol. 2003 Aug 15;21(16):3105-12. doi: 10.1200/JCO.2003.11.133.
• [8] New Method for Insomnia Mongolian Mind-Body Interactive Psychotherapy in the Assessment of Chronic Insomnia: A Retrospective Study.Adv Ther. 2018 Jul;35(7):993-1000. doi: 10.1007/s12325-018-0726-9. Epub 2018 Jun 19.
• [9] Knockdown of long non-coding RNA TP73-AS1 inhibits cell proliferation and induces apoptosis in esophageal squamous cell carcinoma.Oncotarget. 2016 Apr 12;7(15):19960-74. doi: 10.18632/oncotarget.6963.
• [10] Comparison of Manual and Fully Automated AIX1000 Rapid Plasma Reagin Assays for Laboratory Diagnosis of Syphilis.J Clin Microbiol. 2018 Jul 26;56(8):e00214-18. doi: 10.1128/JCM.00214-18. Print 2018 Aug.
• [11] Optimism outweighs neuroticism and anxiety sensitivity to predict insomnia symptoms in women after surgery for breast cancer.Support Care Cancer. 2019 Aug;27(8):2903-2909. doi: 10.1007/s00520-018-4610-6. Epub 2018 Dec 17.
• [12] Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 2014 Jan 31;343(6170):506-511. doi: 10.1126/science.1247363.
• [13] Examining anxiety sensitivity as a mediator of the association between PTSD symptoms and suicide risk among women firefighters.J Anxiety Disord. 2017 Aug;50:94-102. doi: 10.1016/j.janxdis.2017.06.003. Epub 2017 Jun 13.
• [14] Characterization of the arylsulfatase I (ARSI) gene preferentially expressed in the human retinal pigment epithelium cell line ARPE-19.Mol Vis. 2009;15:482-94. Epub 2009 Mar 6.
• [15] 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.
• [16] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [17] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] 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.
• [20] 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.
• [21] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [22] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.