Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4KZ5R9)

• DOT Name: Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT)
• Synonyms: EC 2.3.1.168; 52 kDa mitochondrial autoantigen of primary biliary cirrhosis; Branched chain 2-oxo-acid dehydrogenase complex component E2; BCOADC-E2; Branched-chain alpha-keto acid dehydrogenase complex component E2; BCKAD-E2; BCKADE2; BCKDH-E2; Dihydrolipoamide acetyltransferase component of branched-chain alpha-keto acid dehydrogenase complex; Dihydrolipoamide branched chain transacylase; Dihydrolipoyllysine-residue (2-methylpropanoyl)transferase
• Gene Name: DBT
• Related Disease:
  Maple syrup urine disease
  Maple syrup urine disease type 2
  Adult glioblastoma
  Cardiac disease
  Central nervous system neoplasm
  Dilated cardiomyopathy 1A
  Dystonia
  Glioblastoma multiforme
  Glioma
  Inborn disorder of branched-chain amino acid metabolism
  Melanoma
  Post-traumatic stress disorder
  Eating disorder
  Classic maple syrup urine disease
  Intermediate maple syrup urine disease
  Intermittent maple syrup urine disease
  Thiamine-responsive maple syrup urine disease
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Ductal breast carcinoma in situ
  Primary biliary cholangitis
• UniProt ID: ODB2_HUMAN
• PDB ID: 1K8M; 1K8O; 1ZWV; 2COO; 3RNM
• EC Number: 2.3.1.168
• Pfam ID: PF00198 ; PF00364 ; PF02817
• Sequence:
  MAAVRMLRTWSRNAGKLICVRYFQTCGNVHVLKPNYVCFFGYPSFKYSHPHHFLKTTAAL
  RGQVVQFKLSDIGEGIREVTVKEWYVKEGDTVSQFDSICEVQSDKASVTITSRYDGVIKK
  LYYNLDDIAYVGKPLVDIETEALKDSEEDVVETPAVSHDEHTHQEIKGRKTLATPAVRRL
  AMENNIKLSEVVGSGKDGRILKEDILNYLEKQTGAILPPSPKVEIMPPPPKPKDMTVPIL
  VSKPPVFTGKDKTEPIKGFQKAMVKTMSAALKIPHFGYCDEIDLTELVKLREELKPIAFA
  RGIKLSFMPFFLKAASLGLLQFPILNASVDENCQNITYKASHNIGIAMDTEQGLIVPNVK
  NVQICSIFDIATELNRLQKLGSVGQLSTTDLTGGTFTLSNIGSIGGTFAKPVIMPPEVAI
  GALGSIKAIPRFNQKGEVYKAQIMNVSWSADHRVIDGATMSRFSNLWKSYLENPAFMLLD
  LK
• Function: The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3). Within this complex, the catalytic function of this enzyme is to accept, and to transfer to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component.
• KEGG Pathway:
  Valine, leucine and isoleucine degradation (hsa00280)
  Propanoate metabolism (hsa00640)
  Lipoic acid metabolism (hsa00785)
  Metabolic pathways (hsa01100)
  2-Oxocarboxylic acid metabolism (hsa01210)
• Reactome Pathway:
  Branched-chain amino acid catabolism (R-HSA-70895)
  RHOH GTPase cycle (R-HSA-9013407)
  Glyoxylate metabolism and glycine degradation (R-HSA-389661)
• BioCyc Pathway: MetaCyc:MONOMER-12007

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Maple syrup urine disease	DIS61XRH	Definitive	Autosomal recessive	[1]
Maple syrup urine disease type 2	DISRB3E6	Definitive	Autosomal recessive	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Cardiac disease	DISVO1I5	Strong	Biomarker	[3]
Central nervous system neoplasm	DISFC18W	Strong	Genetic Variation	[4]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[5]
Dystonia	DISJLFGW	Strong	Genetic Variation	[6]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Genetic Variation	[4]
Inborn disorder of branched-chain amino acid metabolism	DISOGOR1	Strong	Genetic Variation	[6]
Melanoma	DIS1RRCY	Strong	Altered Expression	[7]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[8]
Eating disorder	DISVGXN0	moderate	Biomarker	[9]
Classic maple syrup urine disease	DIS848CW	Supportive	Autosomal recessive	[10]
Intermediate maple syrup urine disease	DIS5SRXS	Supportive	Autosomal recessive	[10]
Intermittent maple syrup urine disease	DISJEHB2	Supportive	Autosomal recessive	[10]
Thiamine-responsive maple syrup urine disease	DISEL4MR	Supportive	Autosomal recessive	[10]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[7]
Breast cancer	DIS7DPX1	Limited	Biomarker	[11]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[11]
Ductal breast carcinoma in situ	DISLCJY7	Limited	Biomarker	[12]
Primary biliary cholangitis	DIS43E0O	Limited	Biomarker	[13]

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 Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[25]

12 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 Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[17]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[18]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[19]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[20]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[21]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[24]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial (DBT).	[26]

References

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