Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9LBJVN)

• DOT Name: Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT)
• Synonyms: EC 2.3.1.12; 70 kDa mitochondrial autoantigen of primary biliary cirrhosis; PBC; Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex; M2 antigen complex 70 kDa subunit; Pyruvate dehydrogenase complex component E2; PDC-E2; PDCE2
• Gene Name: DLAT
• Related Disease:
  Pyruvate dehydrogenase E2 deficiency
  Autoimmune disease
  Autoimmune hepatitis
  Autoimmune polyendocrine syndrome type 1
  Breast cancer
  Breast carcinoma
  Cholestasis
  Head-neck squamous cell carcinoma
  Hepatitis
  Hepatitis A virus infection
  Influenza
  Leukemia
  Liver cirrhosis
  Liver failure
  Lupus
  Myocardial ischemia
  Paroxysmal dystonia
  Primary sclerosing cholangitis
  Psoriasis
  Psoriatic arthritis
  Pyruvate dehydrogenase complex deficiency
  Sjogren syndrome
  Systemic lupus erythematosus
  Systemic sclerosis
  Vascular disease
  Chronic graft versus host disease
  Fatty liver disease
  Fetal growth restriction
  Leigh syndrome
  Non-alcoholic fatty liver disease
  Type-1 diabetes
  Acute myelogenous leukaemia
  Angioimmunoblastic T-cell Lymphoma
  Ankylosing spondylitis
  Dystonia
  Hepatocellular carcinoma
  Type-1/2 diabetes
• UniProt ID: ODP2_HUMAN
• PDB ID: 1FYC; 1Y8N; 1Y8O; 1Y8P; 2DNE; 2PNR; 2Q8I; 3B8K; 3CRK; 3CRL; 6CT0; 6H55
• EC Number: 2.3.1.12
• Pfam ID: PF00198 ; PF00364 ; PF02817
• Sequence:
  MWRVCARRAQNVAPWAGLEARWTALQEVPGTPRVTSRSGPAPARRNSVTTGYGGVRALCG
  WTPSSGATPRNRLLLQLLGSPGRRYYSLPPHQKVPLPSLSPTMQAGTIARWEKKEGDKIN
  EGDLIAEVETDKATVGFESLEECYMAKILVAEGTRDVPIGAIICITVGKPEDIEAFKNYT
  LDSSAAPTPQAAPAPTPAATASPPTPSAQAPGSSYPPHMQVLLPALSPTMTMGTVQRWEK
  KVGEKLSEGDLLAEIETDKATIGFEVQEEGYLAKILVPEGTRDVPLGTPLCIIVEKEADI
  SAFADYRPTEVTDLKPQVPPPTPPPVAAVPPTPQPLAPTPSAPCPATPAGPKGRVFVSPL
  AKKLAVEKGIDLTQVKGTGPDGRITKKDIDSFVPSKVAPAPAAVVPPTGPGMAPVPTGVF
  TDIPISNIRRVIAQRLMQSKQTIPHYYLSIDVNMGEVLLVRKELNKILEGRSKISVNDFI
  IKASALACLKVPEANSSWMDTVIRQNHVVDVSVAVSTPAGLITPIVFNAHIKGVETIAND
  VVSLATKAREGKLQPHEFQGGTFTISNLGMFGIKNFSAIINPPQACILAIGASEDKLVPA
  DNEKGFDVASMMSVTLSCDHRVVDGAVGAQWLAEFRKYLEKPITMLL
• Function: As part of the pyruvate dehydrogenase complex, catalyzes the transfers of an acetyl group to a lipoic acid moiety (Probable). The pyruvate dehydrogenase complex, catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links cytoplasmic glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle (Probable).
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Citrate cycle (TCA cycle) (hsa00020)
  Pyruvate metabolism (hsa00620)
  Lipoic acid metabolism (hsa00785)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  2-Oxocarboxylic acid metabolism (hsa01210)
• Reactome Pathway:
  Glyoxylate metabolism and glycine degradation (R-HSA-389661)
  Signaling by Retinoic Acid (R-HSA-5362517)
  Pyruvate metabolism (R-HSA-70268)
  Regulation of pyruvate dehydrogenase (PDH) complex (R-HSA-204174)
• BioCyc Pathway: MetaCyc:HS07688-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pyruvate dehydrogenase E2 deficiency	DISITN4E	Definitive	Autosomal recessive	[1]
Autoimmune disease	DISORMTM	Strong	Biomarker	[2]
Autoimmune hepatitis	DISOX03Q	Strong	Biomarker	[3]
Autoimmune polyendocrine syndrome type 1	DISWJP8J	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[5]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[5]
Cholestasis	DISDJJWE	Strong	Biomarker	[6]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[7]
Hepatitis	DISXXX35	Strong	Biomarker	[4]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[4]
Influenza	DIS3PNU3	Strong	Genetic Variation	[8]
Leukemia	DISNAKFL	Strong	Genetic Variation	[9]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[10]
Liver failure	DISLGEL6	Strong	Biomarker	[11]
Lupus	DISOKJWA	Strong	Altered Expression	[12]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[13]
Paroxysmal dystonia	DISV0MSQ	Strong	Biomarker	[14]
Primary sclerosing cholangitis	DISTH5WJ	Strong	Biomarker	[15]
Psoriasis	DIS59VMN	Strong	Biomarker	[16]
Psoriatic arthritis	DISLWTG2	Strong	Altered Expression	[17]
Pyruvate dehydrogenase complex deficiency	DIS8RZP9	Strong	Biomarker	[14]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[18]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[12]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[12]
Vascular disease	DISVS67S	Strong	Altered Expression	[12]
Chronic graft versus host disease	DIS1MM9J	moderate	Biomarker	[19]
Fatty liver disease	DIS485QZ	moderate	Biomarker	[19]
Fetal growth restriction	DIS5WEJ5	moderate	Altered Expression	[20]
Leigh syndrome	DISWQU45	Moderate	Autosomal recessive	[21]
Non-alcoholic fatty liver disease	DISDG1NL	Disputed	Biomarker	[22]
Type-1 diabetes	DIS7HLUB	Disputed	Biomarker	[23]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[24]
Angioimmunoblastic T-cell Lymphoma	DISZPFTL	Limited	Biomarker	[25]
Ankylosing spondylitis	DISRC6IR	Limited	Altered Expression	[26]
Dystonia	DISJLFGW	Limited	Biomarker	[27]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[28]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[29]

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 Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[36]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[37]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[35]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[39]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[40]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[40]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[41]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[45]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[46]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[47]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT).	[48]

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