Ephx1

UniProt ID: P07687
Organism: Rattus norvegicus
Review Status: COMPLETE
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Gene Description

Ephx1 encodes rat microsomal epoxide hydrolase, an endoplasmic-reticulum membrane biotransformation enzyme that hydrolyzes arene and aliphatic epoxides to the corresponding, less reactive and more water-soluble dihydrodiols by trans addition of water. It acts on both xenobiotic arene oxides (central to detoxification, and in some cases bioactivation of procarcinogens) and endogenous lipid epoxides such as the arachidonate- and linoleate-derived epoxyeicosatrienoic acids and EpOMEs. Beyond epoxide hydrolysis it also hydrolyzes the endocannabinoid 2-arachidonoylglycerol to arachidonic acid and glycerol and binds 20(S)-hydroxycholesterol. It is anchored in the endoplasmic reticulum membrane and is broadly expressed, with liver among the highest-expressing tissues.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004301 epoxide hydrolase activity
IBA
GO_REF:0000033
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining epoxide hydrolase activity as a direct annotation (IBA, GO_REF:0000033).
Reason: epoxide hydrolase activity is a specific catalytic activity matching Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides. Rat Ephx1 is itself among the experimental seeds of the IBD node, so the phylogenetic assertion is grounded on the target.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN001856032 Β· PANTHER:PTN001856032 SUPPORTS TRANSFER
GO:0004301 IBD in the current PTHR21661 PAINT slice, seeded by rat Ephx1 itself (RGD:2557), human EPHX1 (P07099) and a Drosophila member; the target appearing among the seeds is the expected marker of descendant experimental grounding, not circularity. The same node anchors the GO:0097176 epoxide metabolic process IBD.
Supporting Evidence:
UniProtKB:P07687
FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
file:rat/Ephx1/Ephx1-deep-research-falcon.md
Rat **Ephx1** encodes **microsomal epoxide hydrolase 1 (EPHX1/mEH)**, a membrane-anchored **Ξ±/Ξ²-hydrolase-fold** enzyme best known for catalyzing the **hydrolysis of epoxides to the corresponding vicinal diols**. This reaction is central to **xenobiotic detoxification** (and in some cases **bioactivation**) because many epoxides are reactive intermediates generated by cytochrome P450s.
GO:0019369 arachidonate metabolic process
IBA
GO_REF:0000033
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining arachidonate metabolic process as a direct annotation (IBA, GO_REF:0000033).
Reason: arachidonate metabolic process is a direct metabolic process expected from Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
May play a role in the metabolism of endogenous lipids such as epoxide-containing fatty acids.
file:rat/Ephx1/Ephx1-deep-research-falcon.md
arachidonic-acid-derived **epoxyeicosatrienoic acids (EETs)** and linoleic-acid-derived **EpOMEs**, which are hydrolyzed to corresponding diols (**DHETs** and **DiHOMEs**).
GO:0097176 epoxide metabolic process
IBA
GO_REF:0000033
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining epoxide metabolic process as a direct annotation (IBA, GO_REF:0000033).
Reason: epoxide metabolic process is a direct metabolic process expected from Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
file:rat/Ephx1/Ephx1-deep-research-falcon.md
Rat **Ephx1** encodes **microsomal epoxide hydrolase 1 (EPHX1/mEH)**, a membrane-anchored **Ξ±/Ξ²-hydrolase-fold** enzyme best known for catalyzing the **hydrolysis of epoxides to the corresponding vicinal diols**. This reaction is central to **xenobiotic detoxification** (and in some cases **bioactivation**) because many epoxides are reactive intermediates generated by cytochrome P450s.
GO:0003824 catalytic activity
IEA
GO_REF:0000002
MODIFY
Summary: catalytic activity captures part of Ephx1 biology, but a more specific replacement better represents the direct role (IEA, GO_REF:0000002).
Reason: catalytic activity is directionally correct but less specific than the curated replacement term for Ephx1's role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Proposed replacements: epoxide hydrolase activity
Supporting Evidence:
UniProtKB:P07687
FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
GO:0004301 epoxide hydrolase activity
IEA
GO_REF:0000116
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining epoxide hydrolase activity as a direct annotation (IEA, GO_REF:0000116).
Reason: epoxide hydrolase activity is a specific catalytic activity matching Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
GO:0005789 endoplasmic reticulum membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: endoplasmic reticulum membrane is retained as useful context for Ephx1, but it is not the defining core function (IEA, GO_REF:0000044).
Reason: endoplasmic reticulum membrane records where Ephx1 has been observed, but localization does not define the gene product's primary activity.
Supporting Evidence:
UniProtKB:P07687
Endoplasmic reticulum membrane
file:rat/Ephx1/Ephx1-deep-research-falcon.md
EPHX1 is primarily localized to the **endoplasmic reticulum (microsomes)** with a single **N-terminal membrane anchor**
GO:0016803 ether hydrolase activity
IEA
GO_REF:0000002
MODIFY
Summary: ether hydrolase activity captures part of Ephx1 biology, but a more specific replacement better represents the direct role (IEA, GO_REF:0000002).
Reason: ether hydrolase activity is directionally correct but less specific than the curated replacement term for Ephx1's role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Proposed replacements: epoxide hydrolase activity
Supporting Evidence:
UniProtKB:P07687
FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
GO:0033961 cis-stilbene-oxide hydrolase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining cis-stilbene-oxide hydrolase activity as a direct annotation (IEA, GO_REF:0000120).
Reason: cis-stilbene-oxide hydrolase activity is a specific catalytic activity matching Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
Reaction=cis-stilbene oxide + H2O = (1R,2R)-hydrobenzoin
file:rat/Ephx1/Ephx1-deep-research-falcon.md
Reported xenobiotic substrates include **styrene oxide, cis-stilbene oxide, cyclohexene oxide, indene 1,2-oxide, ethylene oxide**
GO:0008142 oxysterol binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: oxysterol binding is retained as useful context for Ephx1, but it is not the defining core function (IEA, GO_REF:0000107).
Reason: oxysterol binding records substrate, cofactor, or quaternary-structure context for Ephx1, but the curated core function is microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
Binds 20(S)-hydroxycholesterol (20(S)-OHC)
file:rat/Ephx1/Ephx1-deep-research-falcon.md
**epoxysteroids** such as androstene oxide/estroxide
GO:0008142 oxysterol binding
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: oxysterol binding is retained as useful context for Ephx1, but it is not the defining core function (ISS, GO_REF:0000024).
Reason: oxysterol binding records substrate, cofactor, or quaternary-structure context for Ephx1, but the curated core function is microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
Binds 20(S)-hydroxycholesterol (20(S)-OHC)
GO:0008142 oxysterol binding
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: oxysterol binding is retained as useful context for Ephx1, but it is not the defining core function (ISO, GO_REF:0000121).
Reason: oxysterol binding records substrate, cofactor, or quaternary-structure context for Ephx1, but the curated core function is microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
Binds 20(S)-hydroxycholesterol (20(S)-OHC)
GO:0004301 epoxide hydrolase activity
ISO
GO_REF:0000121
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining epoxide hydrolase activity as a direct annotation (ISO, GO_REF:0000121).
Reason: epoxide hydrolase activity is a specific catalytic activity matching Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
GO:0019369 arachidonate metabolic process
ISS
GO_REF:0000024
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining arachidonate metabolic process as a direct annotation (ISS, GO_REF:0000024).
Reason: arachidonate metabolic process is a direct metabolic process expected from Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
May play a role in the metabolism of endogenous lipids such as epoxide-containing fatty acids.
GO:0019369 arachidonate metabolic process
ISO
GO_REF:0000121
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining arachidonate metabolic process as a direct annotation (ISO, GO_REF:0000121).
Reason: arachidonate metabolic process is a direct metabolic process expected from Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
May play a role in the metabolism of endogenous lipids such as epoxide-containing fatty acids.
GO:0033961 cis-stilbene-oxide hydrolase activity
ISS
GO_REF:0000024
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining cis-stilbene-oxide hydrolase activity as a direct annotation (ISS, GO_REF:0000024).
Reason: cis-stilbene-oxide hydrolase activity is a specific catalytic activity matching Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
Reaction=cis-stilbene oxide + H2O = (1R,2R)-hydrobenzoin
GO:0033961 cis-stilbene-oxide hydrolase activity
ISO
GO_REF:0000121
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining cis-stilbene-oxide hydrolase activity as a direct annotation (ISO, GO_REF:0000121).
Reason: cis-stilbene-oxide hydrolase activity is a specific catalytic activity matching Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
Reaction=cis-stilbene oxide + H2O = (1R,2R)-hydrobenzoin
GO:0004301 epoxide hydrolase activity
IMP
PMID:9854022
Catalytic triad of microsomal epoxide hydrolase: replacement...
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining epoxide hydrolase activity as a direct annotation (IMP, PMID:9854022).
Reason: epoxide hydrolase activity is a specific catalytic activity matching Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
PMID:9854022
Microsomal epoxide hydrolase (mEH) belongs to the superfamily of alpha/beta-hydrolase fold enzymes. A catalytic triad in the active centre of the enzyme hydrolyses the substrate molecules in a two-step reaction via the intermediate formation of an enzyme-substrate ester.
GO:0016020 membrane
IDA
PMID:22798687
EH3 (ABHD9): the first member of a new epoxide hydrolase fam...
KEEP AS NON CORE
Summary: membrane is retained as useful context for Ephx1, but it is not the defining core function (IDA, PMID:22798687).
Reason: membrane records where Ephx1 has been observed, but localization does not define the gene product's primary activity.
Supporting Evidence:
PMID:22798687
Epoxide hydrolases are a small superfamily of enzymes important for the detoxification of chemically reactive xenobiotic epoxides and for the processing of endogenous epoxides that act as signaling molecules.
GO:0016020 membrane
IDA
PMID:9245728
The membrane anchor of microsomal epoxide hydrolase from hum...
KEEP AS NON CORE
Summary: membrane is retained as useful context for Ephx1, but it is not the defining core function (IDA, PMID:9245728).
Reason: membrane records where Ephx1 has been observed, but localization does not define the gene product's primary activity.
Supporting Evidence:
PMID:9245728
Erratum in Biochem Biophys Res Commun.
GO:0016020 membrane
IDA
PMID:9854022
Catalytic triad of microsomal epoxide hydrolase: replacement...
KEEP AS NON CORE
Summary: membrane is retained as useful context for Ephx1, but it is not the defining core function (IDA, PMID:9854022).
Reason: membrane records where Ephx1 has been observed, but localization does not define the gene product's primary activity.
Supporting Evidence:
PMID:9854022
Microsomal epoxide hydrolase (mEH) belongs to the superfamily of alpha/beta-hydrolase fold enzymes. A catalytic triad in the active centre of the enzyme hydrolyses the substrate molecules in a two-step reaction via the intermediate formation of an enzyme-substrate ester.
GO:0033961 cis-stilbene-oxide hydrolase activity
IMP
PMID:9854022
Catalytic triad of microsomal epoxide hydrolase: replacement...
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining cis-stilbene-oxide hydrolase activity as a direct annotation (IMP, PMID:9854022).
Reason: cis-stilbene-oxide hydrolase activity is a specific catalytic activity matching Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
PMID:9854022
Microsomal epoxide hydrolase (mEH) belongs to the superfamily of alpha/beta-hydrolase fold enzymes. A catalytic triad in the active centre of the enzyme hydrolyses the substrate molecules in a two-step reaction via the intermediate formation of an enzyme-substrate ester.
GO:0043231 intracellular membrane-bounded organelle
IDA
PMID:22798687
EH3 (ABHD9): the first member of a new epoxide hydrolase fam...
KEEP AS NON CORE
Summary: intracellular membrane-bounded organelle is retained as useful context for Ephx1, but it is not the defining core function (IDA, PMID:22798687).
Reason: intracellular membrane-bounded organelle records where Ephx1 has been observed, but localization does not define the gene product's primary activity.
Supporting Evidence:
PMID:22798687
Epoxide hydrolases are a small superfamily of enzymes important for the detoxification of chemically reactive xenobiotic epoxides and for the processing of endogenous epoxides that act as signaling molecules.
GO:0043231 intracellular membrane-bounded organelle
IDA
PMID:9245728
The membrane anchor of microsomal epoxide hydrolase from hum...
KEEP AS NON CORE
Summary: intracellular membrane-bounded organelle is retained as useful context for Ephx1, but it is not the defining core function (IDA, PMID:9245728).
Reason: intracellular membrane-bounded organelle records where Ephx1 has been observed, but localization does not define the gene product's primary activity.
Supporting Evidence:
PMID:9245728
Erratum in Biochem Biophys Res Commun.
GO:0043231 intracellular membrane-bounded organelle
IDA
PMID:9854022
Catalytic triad of microsomal epoxide hydrolase: replacement...
KEEP AS NON CORE
Summary: intracellular membrane-bounded organelle is retained as useful context for Ephx1, but it is not the defining core function (IDA, PMID:9854022).
Reason: intracellular membrane-bounded organelle records where Ephx1 has been observed, but localization does not define the gene product's primary activity.
Supporting Evidence:
PMID:9854022
Microsomal epoxide hydrolase (mEH) belongs to the superfamily of alpha/beta-hydrolase fold enzymes. A catalytic triad in the active centre of the enzyme hydrolyses the substrate molecules in a two-step reaction via the intermediate formation of an enzyme-substrate ester.
GO:0097176 epoxide metabolic process
ISO
GO_REF:0000121
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining epoxide metabolic process as a direct annotation (ISO, GO_REF:0000121).
Reason: epoxide metabolic process is a direct metabolic process expected from Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
GO:0097176 epoxide metabolic process
IDA
PMID:9854022
Catalytic triad of microsomal epoxide hydrolase: replacement...
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining epoxide metabolic process as a direct annotation (IDA, PMID:9854022).
Reason: epoxide metabolic process is a direct metabolic process expected from Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
PMID:9854022
Microsomal epoxide hydrolase (mEH) belongs to the superfamily of alpha/beta-hydrolase fold enzymes. A catalytic triad in the active centre of the enzyme hydrolyses the substrate molecules in a two-step reaction via the intermediate formation of an enzyme-substrate ester.
GO:0034312 diol biosynthetic process
IDA
PMID:2507189
Epoxide hydratase: sex specific expression and rate-limiting...
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining diol biosynthetic process as a direct annotation (IDA, PMID:2507189).
Reason: diol biosynthetic process is a direct metabolic process expected from Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
PMID:2507189
However, the sum of products that potentially derive from the common intermediate DMBA 3,4-oxide namely, DMBA 3,4-diol, 3- and 4-hydroxy DMBA, was comparable between the two sexes (18 versus 20 pmol/mg/min).
GO:0004301 epoxide hydrolase activity
IDA
PMID:8313504
Studies on the importance of microsomal epoxide hydrolase in...
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining epoxide hydrolase activity as a direct annotation (IDA, PMID:8313504).
Reason: epoxide hydrolase activity is a specific catalytic activity matching Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
PMID:8313504
In order to investigate the role of the microsomal epoxide hydrolase (mEH) in the detoxification of arene oxides in the presence of a high endogenous glutathione S-transferase (GST) activity-a situation found in several organs--we expressed the rat mEH cDNA in BHK21 Syrian hamster cells.
GO:0001889 liver development
IEP
PMID:2469391
Quantitation of mRNAs specific for the mixed-function oxidas...
MARK AS OVER ANNOTATED
Summary: liver development is treated as over-annotation because it reflects context or consequence rather than Ephx1's direct role (IEP, PMID:2469391).
Reason: liver development reflects exposure, expression, phenotype, or downstream pathway context rather than the direct Ephx1 role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
PMID:2469391
Evaluation of ontogenetic expression of the cytochrome P450PCN and cytochrome P450b gene families as well as the NADPH-cytochrome P450 oxidoreductase and epoxide hydrolase genes in Holtzmann rats showed that basal levels of mRNAs encoding these enzymes could be detected in most tissues.
GO:0071385 cellular response to glucocorticoid stimulus
IEP
PMID:2350182
Glucocorticoid repression and basal regulation of the epoxid...
MARK AS OVER ANNOTATED
Summary: cellular response to glucocorticoid stimulus is treated as over-annotation because it reflects context or consequence rather than Ephx1's direct role (IEP, PMID:2350182).
Reason: cellular response to glucocorticoid stimulus reflects exposure, expression, phenotype, or downstream pathway context rather than the direct Ephx1 role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
PMID:2350182
Through a series of promoter deletions and gene transfer experiments we have examined the basal regulation and glucocorticoid-mediated repression of the rat epoxide hydrolase gene.
GO:0019899 enzyme binding
IPI
PMID:10891369
Interaction between cytochrome P450 and other drug-metaboliz...
KEEP AS NON CORE
Summary: enzyme binding is retained as useful context for Ephx1, but it is not the defining core function (IPI, PMID:10891369).
Reason: enzyme binding records substrate, cofactor, or quaternary-structure context for Ephx1, but the curated core function is microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
PMID:10891369
Protein-protein interactions between cytochrome P450 (P450) and other drug-metabolizing enzymes were studied by affinity chromatography using CYP1A1-, glycine-, and bovine serum albumin (BSA)-conjugated Sepharose 4B columns.
GO:0120253 hydrocarbon catabolic process
ISO
GO_REF:0000121
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining hydrocarbon catabolic process as a direct annotation (ISO, GO_REF:0000121).
Reason: hydrocarbon catabolic process is a direct metabolic process expected from Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
UniProtKB:P07687
FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
GO:0004301 epoxide hydrolase activity
IDA
PMID:8314768
Expression of rat microsomal epoxide hydrolase in Escherichi...
ACCEPT
Summary: Ephx1's microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides supports retaining epoxide hydrolase activity as a direct annotation (IDA, PMID:8314768).
Reason: epoxide hydrolase activity is a specific catalytic activity matching Ephx1's documented role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
Supporting Evidence:
PMID:8314768
The cDNA containing the complete coding region for rat microsomal epoxide hydrolase (EC 3.3.2.3) was cloned into the expression/secretion vector pIN-III-OmpA3 and expressed in Escherichia coli strain TG1.
GO:0047372 monoacylglycerol lipase activity
IEA
GO_REF:0000116
KEEP AS NON CORE
Summary: Monoacylglycerol lipase activity (IEA, GO_REF:0000116; RHEA:26132 = 2-arachidonoylglycerol + H2O -> glycerol + arachidonate). In addition to epoxide hydrolysis, rat microsomal epoxide hydrolase hydrolyzes the endocannabinoid 2-arachidonoylglycerol, so this specific MF is accepted as a genuine secondary activity rather than the core epoxide hydrolase function.
Reason: The RHEA:26132 reaction is the monoacylglycerol-lipase hydrolysis of 2-arachidonoylglycerol, which the UniProt record documents as a function of this enzyme; the activity is real for Ephx1 but secondary to its defining epoxide hydrolase activity, so it is retained as a non-core molecular function rather than as the gene's core function.
Supporting Evidence:
UniProtKB:P07687
Metabolizes the abundant endocannabinoid 2-arachidonoylglycerol (2-AG) to free arachidonic acid (AA) and glycerol (By similarity).
UniProtKB:P07687
Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)

Core Functions

Ephx1 encodes rat microsomal epoxide hydrolase 1. FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.

Supporting Evidence:
  • UniProtKB:P07687
    FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
  • file:rat/Ephx1/Ephx1-deep-research-falcon.md
    Rat **Ephx1** encodes **microsomal epoxide hydrolase 1 (EPHX1/mEH)**, a membrane-anchored **Ξ±/Ξ²-hydrolase-fold** enzyme best known for catalyzing the **hydrolysis of epoxides to the corresponding vicinal diols**. This reaction is central to **xenobiotic detoxification** (and in some cases **bioactivation**) because many epoxides are reactive intermediates generated by cytochrome P450s.
  • file:rat/Ephx1/Ephx1-deep-research-falcon.md
    arachidonic-acid-derived **epoxyeicosatrienoic acids (EETs)** and linoleic-acid-derived **EpOMEs**, which are hydrolyzed to corresponding diols (**DHETs** and **DiHOMEs**).

References

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Deep Research

Falcon

(Ephx1-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(Ephx1-notes.md)

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