Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTALXO2A)

• DOT Name: Formylglycine-generating enzyme (SUMF1)
• Synonyms: FGE; EC 1.8.3.7; C-alpha-formylglycine-generating enzyme 1; Sulfatase-modifying factor 1
• Gene Name: SUMF1
• Related Disease:
  Mucosulfatidosis
  Narcolepsy
  Cystic fibrosis
  Inborn error of metabolism
  Lysosomal storage disease
  Mucopolysaccharidosis type 4A
  Multiple sclerosis
  Mucopolysaccharidosis type 3A
  Intellectual disability
  Schizophrenia
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Chronic obstructive pulmonary disease
• UniProt ID: SUMF1_HUMAN
• PDB ID: 1Y1E; 1Y1F; 1Y1G; 1Y1H; 1Y1I; 1Y1J; 1Z70; 2AFT; 2AFY; 2AII; 2AIJ; 2AIK; 2HI8; 2HIB; 5SSX; 5SSY; 5SSZ; 8ARU
• EC Number: 1.8.3.7
• Pfam ID: PF03781
• Sequence:
  MAAPALGLVCGRCPELGLVLLLLLLSLLCGAAGSQEAGTGAGAGSLAGSCGCGTPQRPGA
  HGSSAAAHRYSREANAPGPVPGERQLAHSKMVPIPAGVFTMGTDDPQIKQDGEAPARRVT
  IDAFYMDAYEVSNTEFEKFVNSTGYLTEAEKFGDSFVFEGMLSEQVKTNIQQAVAAAPWW
  LPVKGANWRHPEGPDSTILHRPDHPVLHVSWNDAVAYCTWAGKRLPTEAEWEYSCRGGLH
  NRLFPWGNKLQPKGQHYANIWQGEFPVTNTGEDGFQGTAPVDAFPPNGYGLYNIVGNAWE
  WTSDWWTVHHSVEETLNPKGPPSGKDRVKKGGSYMCHRSYCYRYRCAARSQNTPDSSASN
  LGFRCAADRLPTMD
• Function: Oxidase that catalyzes the conversion of cysteine to 3-oxoalanine on target proteins, using molecular oxygen and an unidentified reducing agent. 3-oxoalanine modification, which is also named formylglycine (fGly), occurs in the maturation of arylsulfatases and some alkaline phosphatases that use the hydrated form of 3-oxoalanine as a catalytic nucleophile. Known substrates include GALNS, ARSA, STS and ARSE.
• Tissue Specificity: Ubiquitous. Highly expressed in kidney, pancreas and liver. Detected at lower levels in leukocytes, lung, placenta, small intestine, skeletal muscle and heart.
• KEGG Pathway: Lysosome (hsa04142)
• Reactome Pathway:
  Glycosphingolipid catabolism (R-HSA-9840310)
  The activation of arylsulfatases (R-HSA-1663150)
• BioCyc Pathway: MetaCyc:ENSG00000144455-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mucosulfatidosis	DISWOTAK	Definitive	Autosomal recessive	[1]
Narcolepsy	DISLCNLI	Definitive	Genetic Variation	[2]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[3]
Inborn error of metabolism	DISO5FAY	Strong	Altered Expression	[4]
Lysosomal storage disease	DIS6QM6U	Strong	Genetic Variation	[5]
Mucopolysaccharidosis type 4A	DISTYFQS	Strong	Biomarker	[6]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[7]
Mucopolysaccharidosis type 3A	DIS2TLNF	moderate	Biomarker	[8]
Intellectual disability	DISMBNXP	Disputed	Biomarker	[9]
Schizophrenia	DISSRV2N	Disputed	Genetic Variation	[9]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[10]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[10]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[10]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Genetic Variation	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Formylglycine-generating enzyme (SUMF1).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Formylglycine-generating enzyme (SUMF1).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Formylglycine-generating enzyme (SUMF1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Formylglycine-generating enzyme (SUMF1).	[15]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Formylglycine-generating enzyme (SUMF1).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Formylglycine-generating enzyme (SUMF1).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Formylglycine-generating enzyme (SUMF1).	[18]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Formylglycine-generating enzyme (SUMF1).	[19]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Formylglycine-generating enzyme (SUMF1).	[20]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Formylglycine-generating enzyme (SUMF1).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Formylglycine-generating enzyme (SUMF1).	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Formylglycine-generating enzyme (SUMF1).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Formylglycine-generating enzyme (SUMF1).	[24]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Formylglycine-generating enzyme (SUMF1).	[26]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Formylglycine-generating enzyme (SUMF1).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Formylglycine-generating enzyme (SUMF1).	[25]

References

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• [17] 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.
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• [27] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.