Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7ZBWT1)

• DOT Name: Protein O-GlcNAcase (OGA)
• Synonyms: OGA; EC 3.2.1.169; Beta-N-acetylglucosaminidase; Beta-N-acetylhexosaminidase; Beta-hexosaminidase; Meningioma-expressed antigen 5; N-acetyl-beta-D-glucosaminidase; N-acetyl-beta-glucosaminidase; Nuclear cytoplasmic O-GlcNAcase and acetyltransferase; NCOAT
• Gene Name: OGA
• Related Disease:
  Colorectal carcinoma
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Atopic dermatitis
  Cardiac failure
  Cardiovascular disease
  Chronic kidney disease
  Colitis
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Congestive heart failure
  Diabetic kidney disease
  Epilepsy
  Epithelial ovarian cancer
  Gaucher disease
  Glioblastoma multiforme
  GM2 gangliosidosis
  Hepatocellular carcinoma
  Liver cirrhosis
  Lung carcinoma
  Lysosomal storage disease
  Matthew-Wood syndrome
  Motor neurone disease
  Myocardial infarction
  Neoplasm
  Nephropathy
  Obesity
  Ovarian cancer
  Parkinson disease
  Sandhoff disease
  Tauopathy
  Breast cancer
  Breast carcinoma
  Encephalitis
  Meningioma
  Non-insulin dependent diabetes
  Plasma cell myeloma
  Type-1/2 diabetes
  Amyotrophic lateral sclerosis
  Gangliosidosis
  Malignant soft tissue neoplasm
  Nervous system disease
  Sarcoma
  Type-1 diabetes
• UniProt ID: OGA_HUMAN
• PDB ID: 2YDQ; 5M7R; 5M7S; 5M7T; 5M7U; 5TKE; 5UHK; 5UHL; 5UHO; 5UHP; 5UN8; 5UN9; 5VVO; 5VVT; 5VVU; 5VVV; 5VVX; 6HKI; 6PM9; 7OU6; 7YEH; 8P0L
• EC Number: 3.2.1.169
• Pfam ID: PF07555
• Sequence:
  MVQKESQATLEERESELSSNPAASAGASLEPPAAPAPGEDNPAGAGGAAVAGAAGGARRF
  LCGVVEGFYGRPWVMEQRKELFRRLQKWELNTYLYAPKDDYKHRMFWREMYSVEEAEQLM
  TLISAAREYEIEFIYAISPGLDITFSNPKEVSTLKRKLDQVSQFGCRSFALLFDDIDHNM
  CAADKEVFSSFAHAQVSITNEIYQYLGEPETFLFCPTEYCGTFCYPNVSQSPYLRTVGEK
  LLPGIEVLWTGPKVVSKEIPVESIEEVSKIIKRAPVIWDNIHANDYDQKRLFLGPYKGRS
  TELIPRLKGVLTNPNCEFEANYVAIHTLATWYKSNMNGVRKDVVMTDSEDSTVSIQIKLE
  NEGSDEDIETDVLYSPQMALKLALTEWLQEFGVPHQYSSRQVAHSGAKASVVDGTPLVAA
  PSLNATTVVTTVYQEPIMSQGAALSGEPTTLTKEEEKKQPDEEPMDMVVEKQEETDHKND
  NQILSEIVEAKMAEELKPMDTDKESIAESKSPEMSMQEDCISDIAPMQTDEQTNKEQFVP
  GPNEKPLYTAEPVTLEDLQLLADLFYLPYEHGPKGAQMLREFQWLRANSSVVSVNCKGKD
  SEKIEEWRSRAAKFEEMCGLVMGMFTRLSNCANRTILYDMYSYVWDIKSIMSMVKSFVQW
  LGCRSHSSAQFLIGDQEPWAFRGGLAGEFQRLLPIDGANDLFFQPPPLTPTSKVYTIRPY
  FPKDEASVYKICREMYDDGVGLPFQSQPDLIGDKLVGGLLSLSLDYCFVLEDEDGICGYA
  LGTVDVTPFIKKCKISWIPFMQEKYTKPNGDKELSEAEKIMLSFHEEQEVLPETFLANFP
  SLIKMDIHKKVTDPSVAKSMMACLLSSLKANGSRGAFCEVRPDDKRILEFYSKLGCFEIA
  KMEGFPKDVVILGRSL
• Function: [Isoform 1]: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Deglycosylates a large and diverse number of proteins, such as CRYAB, ELK1, LMNB1 and TAB1. Can use p-nitrophenyl-beta-GlcNAc and 4-methylumbelliferone-GlcNAc as substrates but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro). Does not bind acetyl-CoA and does not have histone acetyltransferase activity ; [Isoform 3]: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc as substrate but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro), but has about six times lower specific activity than isoform 1.
• Tissue Specificity: Ubiquitous. Shows highest expression in the brain, placenta and pancreas.
• KEGG Pathway: Insulin resistance (hsa04931)
• BioCyc Pathway: MetaCyc:HS03036-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Altered Expression	[6]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[7]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[8]
Colitis	DISAF7DD	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[9]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[6]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[11]
Epilepsy	DISBB28L	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[13]
Gaucher disease	DISTW5JG	Strong	Altered Expression	[14]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[15]
GM2 gangliosidosis	DISPT716	Strong	Biomarker	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[17]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[19]
Lysosomal storage disease	DIS6QM6U	Strong	Genetic Variation	[20]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[21]
Motor neurone disease	DISUHWUI	Strong	Genetic Variation	[22]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[23]
Neoplasm	DISZKGEW	Strong	Altered Expression	[24]
Nephropathy	DISXWP4P	Strong	Altered Expression	[25]
Obesity	DIS47Y1K	Strong	Biomarker	[26]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[13]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[27]
Sandhoff disease	DISELKA4	Strong	Genetic Variation	[28]
Tauopathy	DISY2IPA	Strong	Biomarker	[29]
Breast cancer	DIS7DPX1	moderate	Biomarker	[30]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[30]
Encephalitis	DISLD1RL	moderate	Biomarker	[31]
Meningioma	DISPT4TG	moderate	Altered Expression	[32]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Altered Expression	[33]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[34]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[33]
Amyotrophic lateral sclerosis	DISF7HVM	Disputed	Biomarker	[35]
Gangliosidosis	DISIHYU4	Disputed	Altered Expression	[36]
Malignant soft tissue neoplasm	DISTC6NO	Limited	Genetic Variation	[37]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[38]
Sarcoma	DISZDG3U	Limited	Genetic Variation	[37]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[4]

21 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 Protein O-GlcNAcase (OGA).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein O-GlcNAcase (OGA).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein O-GlcNAcase (OGA).	[41]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein O-GlcNAcase (OGA).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein O-GlcNAcase (OGA).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein O-GlcNAcase (OGA).	[44]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein O-GlcNAcase (OGA).	[45]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Protein O-GlcNAcase (OGA).	[46]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein O-GlcNAcase (OGA).	[47]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Protein O-GlcNAcase (OGA).	[40]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Protein O-GlcNAcase (OGA).	[48]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein O-GlcNAcase (OGA).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Protein O-GlcNAcase (OGA).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein O-GlcNAcase (OGA).	[46]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Protein O-GlcNAcase (OGA).	[42]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Protein O-GlcNAcase (OGA).	[53]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Protein O-GlcNAcase (OGA).	[54]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Protein O-GlcNAcase (OGA).	[55]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Protein O-GlcNAcase (OGA).	[56]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Protein O-GlcNAcase (OGA).	[57]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Protein O-GlcNAcase (OGA).	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein O-GlcNAcase (OGA).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Protein O-GlcNAcase (OGA).	[51]

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