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Gene_locus Report for: human-EPHX1

Homo sapiens (Human) microsomal epoxide hydrolase HYEP mEH, epoxide hydratase EPHX1

Comment
Epoxide hydrolases (EC 3.3.2.3) play an important role in both the activation and detoxification of exogenous chemicals such as polycyclic aromatic hydrocarbons. Mutant form of microsomal epoxide hydrolase is the molecular basis for abnormal reactions to phenytoin (diphenylhydantoin, dilantin) and some other drugs. Hydantoin used during pregnancy for seizure prophylaxis can result in children with the fetal hydantoin syndrome (FHS)(major birth defects including congenital heart disease, cleft lip/palate, microcephaly, and major genitourinary, eye, and limb defects) Defect in hydroxylation of diphenylhydantoin is related to a mutation in human-EPHX1 resulting in low activity. Familial hypercholanemia is characterized by elevated serum bile acid concentrations, itching, and fat malabsorption. In a patient with hypercholanemia. Zhu et al. (2003) identified compound heterozygosity for 2 mutations in the EPHX1 gene, which resulted in a significant decrease in EPHX1 promoter activity


Relationship
Family|Epoxide_hydrolase
Block| X
Position in NCBI Life Tree|Homo sapiens
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.)
> cellular organisms: N E > Eukaryota: N E > Opisthokonta: N E > Metazoa: N E > Eumetazoa: N E > Bilateria: N E > Deuterostomia: N E > Chordata: N E > Craniata: N E > Vertebrata: N E > Gnathostomata: N E > Teleostomi: N E > Euteleostomi: N E > Sarcopterygii: N E > Dipnotetrapodomorpha: N E > Tetrapoda: N E > Amniota: N E > Mammalia: N E > Theria: N E > Eutheria: N E > Boreoeutheria: N E > Euarchontoglires: N E > Primates: N E > Haplorrhini: N E > Simiiformes: N E > Catarrhini: N E > Hominoidea: N E > Hominidae: N E > Homininae: N E > Homo: N E > Homo sapiens: N E


Molecular evidence
Database
6 mutations: Table (e.g. : 4kbup_human-EPHX1, G430R, H139R_human-EPHX1 ... more)
No structure
No kinetic

Disease: Lipoatrophic diabetes - Familial hypercholanemia -

Xenobiotic sensitivity: Defect in hydroxylation of diphenylhydantoin -

5 substrates (e.g. : AZD1979, Carbamazepine-10,11-epoxide, Cis-stilbene-oxide... more)
6 inhibitors (e.g. : 62-mEH, NSPA, Progabide... more)
>3 Genbank links 30 more: J03518, X07936, Y00424
3 UniProt : P07099, Q6FGZ3, B1AQP8
>3 UniProt links 1 more: Q6FGZ3, P07099, B1AQP8
>3 Interpro links 1 more: Q6FGZ3, P07099, B1AQP8
>3 Prodom links 1 more: Q6FGZ3, P07099, B1AQP8
>3 Pfam links 1 more: Q6FGZ3, P07099, B1AQP8
>3 PIRSF links 1 more: Q6FGZ3, P07099, B1AQP8
>3 SUPERFAM links 1 more: Q6FGZ3, P07099, B1AQP8
1 EntrezGene : 2052
1 SNP : 2052
1 UniGene : 89649
1 HUGO HGNC : 3401
1 OMIM : 132810
1 Ensembl : ENSG00000143819
Sequence
Graphical view for this peptide sequence: human-EPHX1
Colored MSA for Epoxide_hydrolase (raw)
MWLEILLTSVLGFAIYWFISRDKEETLPLEDGWWGPGTRSAAREDDSIRP
FKVETSDEEIHDLHQRIDKFRFTPPLEDSCFHYGFNSNYLKKVISYWRNE
FDWKKQVEILNRYPHFKTKIEGLDIHFIHVKPPQLPAGHTPKPLLMVHGW
PGSFYEFYKIIPLLTDPKNHGLSDEHVFEVICPSIPGYGFSEASSKKGFN
SVATARIFYKLMLRLGFQEFYIQGGDWGSLICTNMAQLVPSHVKGLHLNM
ALVLSNFSTLTLLLGQRFGRFLGLTERDVELLYPVKEKVFYSLMRESGYM
HIQCTKPDTVGSALNDSPVGLAAYILEKFSTWTNTEFRYLEDGGLERKFS
LDDLLTNVMLYWTTGTIISSQRFYKENLGQGWMTQKHERMKVYVPTGFSA
FPFELLHTPEKWVRFKYPKLISYSYMVRGGHFAAFEEPELLAQDIRKFLS
VLERQ
Legend This sequence has been compared to family alignement (MSA)
red => minority aminoacid
blue => majority aminoacid
color intensity => conservation rate
title => sequence position(MSA position)aminoacid rate
Catalytic site
Catalytic site in the MSA

MWLEILLTSVLGFAIYWFISRDKEETLPLEDGWWGPGTRSAAREDDSIRP
FKVETSDEEIHDLHQRIDKFRFTPPLEDSCFHYGFNSNYLKKVISYWRNE
FDWKKQVEILNRYPHFKTKIEGLDIHFIHVKPPQLPAGHTPKPLLMVHGW
PGSFYEFYKIIPLLTDPKNHGLSDEHVFEVICPSIPGYGFSEASSKKGFN
SVATARIFYKLMLRLGFQEFYIQGGDWGSLICTNMAQLVPSHVKGLHLNM
ALVLSNFSTLTLLLGQRFGRFLGLTERDVELLYPVKEKVFYSLMRESGYM
HIQCTKPDTVGSALNDSPVGLAAYILEKFSTWTNTEFRYLEDGGLERKFS
LDDLLTNVMLYWTTGTIISSQRFYKENLGQGWMTQKHERMKVYVPTGFSA
FPFELLHTPEKWVRFKYPKLISYSYMVRGGHFAAFEEPELLAQDIRKFLS
VLERQ


References
16 more
    Title: Role of epoxide hydrolases and cytochrome P450s on metabolism of KZR-616, a first-in-class selective inhibitor of the immunoproteasome
    Fang Y, Johnson H, Anderl JL, Muchamuel T, McMinn D, Morisseau C, Hammock BD, Kirk C, Wang J
    Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, :, 2021 : PubMed

            

    Title: Development of potent inhibitors of the human microsomal epoxide hydrolase
    Barnych B, Singh N, Negrel S, Zhang Y, Magis D, Roux C, Hua X, Ding Z, Morisseau C and Hammock BD <2 more author(s)>
    Ref: Eur Journal of Medicinal Chemistry, 193:112206, 2020 : PubMed

            

    Title: Discovery of a Novel Microsomal Epoxide Hydrolase-Catalyzed Hydration of a Spiro Oxetane
    Li XQ, Hayes MA, Gronberg G, Berggren K, Castagnoli N, Jr., Weidolf L
    Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, 44:1341, 2016 : PubMed

            


Other Papers


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Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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