Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBAAHL5)

• DOT Name: Peroxisomal bifunctional enzyme (EHHADH)
• Synonyms: PBE; PBFE; L-bifunctional protein; LBP; Multifunctional enzyme 1; MFE1
• Gene Name: EHHADH
• Related Disease:
  Amyloidosis
  Bipolar disorder
  Carnitine palmitoyltransferase II deficiency
  Cytochrome-c oxidase deficiency disease
  D-bifunctional protein deficiency
  Disorder of glycogen metabolism
  Drug dependence
  Familial hyperinsulinism
  Fanconi renotubular syndrome 1
  Hepatocellular carcinoma
  Hyperinsulinemia
  Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency
  Mitochondrial disease
  Mitochondrial trifunctional protein deficiency
  Prostate cancer
  Prostate neoplasm
  Proximal renal tubular acidosis
  Substance abuse
  Substance dependence
  Tuberculosis
  Primary Fanconi syndrome
  Fanconi renotubular syndrome 3
  Parkinson disease
• UniProt ID: ECHP_HUMAN
• EC Number: 1.1.1.35; 4.2.1.17; 5.3.3.8
• Pfam ID: PF00725 ; PF02737 ; PF00378
• Sequence:
  MAEYTRLHNALALIRLRNPPVNAISTTLLRDIKEGLQKAVIDHTIKAIVICGAEGKFSAG
  ADIRGFSAPRTFGLTLGHVVDEIQRNEKPVVAAIQGMAFGGGLELALGCHYRIAHAEAQV
  GLPEVTLGLLPGARGTQLLPRLTGVPAALDLITSGRRILADEALKLGILDKVVNSDPVEE
  AIRFAQRVSDQPLESRRLCNKPIQSLPNMDSIFSEALLKMRRQHPGCLAQEACVRAVQAA
  VQYPYEVGIKKEEELFLYLLQSGQARALQYAFFAERKANKWSTPSGASWKTASARPVSSV
  GVVGLGTMGRGIVISFARARIPVIAVDSDKNQLATANKMITSVLEKEASKMQQSGHPWSG
  PKPRLTSSVKELGGVDLVIEAVFEEMSLKKQVFAELSAVCKPEAFLCTNTSALDVDEIAS
  STDRPHLVIGTHFFSPAHVMKLLEVIPSQYSSPTTIATVMNLSKKIKKIGVVVGNCFGFV
  GNRMLNPYYNQAYFLLEEGSKPEEVDQVLEEFGFKMGPFRVSDLAGLDVGWKSRKGQGLT
  GPTLLPGTPARKRGNRRYCPIPDVLCELGRFGQKTGKGWYQYDKPLGRIHKPDPWLSKFL
  SRYRKTHHIEPRTISQDEILERCLYSLINEAFRILGEGIAASPEHIDVVYLHGYGWPRHK
  GGPMFYASTVGLPTVLEKLQKYYRQNPDIPQLEPSDYLKKLASQGNPPLKEWQSLAGSPS
  SKL
• Function: Peroxisomal trifunctional enzyme possessing 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-CoA isomerase activities. Catalyzes two of the four reactions of the long chain fatty acids peroxisomal beta-oxidation pathway. Can also use branched-chain fatty acids such as 2-methyl-2E-butenoyl-CoA as a substrate, which is hydrated into (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA. Optimal isomerase for 2,5 double bonds into 3,5 form isomerization in a range of enoyl-CoA species (Probable). Also able to isomerize both 3-cis and 3-trans double bonds into the 2-trans form in a range of enoyl-CoA species. With HSD17B4, catalyzes the hydration of trans-2-enoyl-CoA and the dehydrogenation of 3-hydroxyacyl-CoA, but with opposite chiral specificity. Regulates the amount of medium-chain dicarboxylic fatty acids which are essential regulators of all fatty acid oxidation pathways. Also involved in the degradation of long-chain dicarboxylic acids through peroxisomal beta-oxidation.
• Tissue Specificity: Liver and kidney. Strongly expressed in the terminal segments of the proximal tubule. Lower amounts seen in the brain.
• KEGG Pathway:
  Fatty acid degradation (hsa00071)
  Valine, leucine and isoleucine degradation (hsa00280)
  Lysine degradation (hsa00310)
  Tryptophan metabolism (hsa00380)
  beta-Alanine metabolism (hsa00410)
  Propanoate metabolism (hsa00640)
  Butanoate metabolism (hsa00650)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  PPAR sig.ling pathway (hsa03320)
  Peroxisome (hsa04146)
• Reactome Pathway:
  Peroxisomal protein import (R-HSA-9033241)
  Beta-oxidation of very long chain fatty acids (R-HSA-390247)
• BioCyc Pathway: MetaCyc:HS03720-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyloidosis	DISHTAI2	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Carnitine palmitoyltransferase II deficiency	DIS3GFD9	Strong	Genetic Variation	[3]
Cytochrome-c oxidase deficiency disease	DISK7N3G	Strong	Genetic Variation	[3]
D-bifunctional protein deficiency	DISMU0DP	Strong	GermlineCausalMutation	[4]
Disorder of glycogen metabolism	DISYGNOB	Strong	Genetic Variation	[3]
Drug dependence	DIS9IXRC	Strong	Biomarker	[5]
Familial hyperinsulinism	DISHQKQE	Strong	Genetic Variation	[6]
Fanconi renotubular syndrome 1	DIS30RYU	Strong	GermlineCausalMutation	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
Hyperinsulinemia	DISIDWT6	Strong	Genetic Variation	[9]
Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency	DIS4F710	Strong	Biomarker	[10]
Mitochondrial disease	DISKAHA3	Strong	Genetic Variation	[3]
Mitochondrial trifunctional protein deficiency	DIS2MYYR	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Biomarker	[11]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[11]
Proximal renal tubular acidosis	DIS8M3CV	Strong	Genetic Variation	[12]
Substance abuse	DIS327VW	Strong	Biomarker	[5]
Substance dependence	DISDRAAR	Strong	Biomarker	[5]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[13]
Primary Fanconi syndrome	DISR144Y	Supportive	Autosomal dominant	[7]
Fanconi renotubular syndrome 3	DISD0LGA	Limited	Autosomal dominant	[14]
Parkinson disease	DISQVHKL	Limited	Biomarker	[15]

24 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 Peroxisomal bifunctional enzyme (EHHADH).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[20]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[21]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[22]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[23]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[24]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[25]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[26]
Deoxycholic acid	DM3GYAL	Approved	Deoxycholic acid decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[26]
Tetracycline	DMZA017	Approved	Tetracycline decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[26]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[27]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[28]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[29]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[30]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[26]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Peroxisomal bifunctional enzyme (EHHADH).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[34]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Peroxisomal bifunctional enzyme (EHHADH).	[35]

1 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 decreases the phosphorylation of Peroxisomal bifunctional enzyme (EHHADH).	[32]

References

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