Ephx1 encodes rat microsomal epoxide hydrolase, an endoplasmic-reticulum membrane biotransformation enzyme that hydrolyzes arene and aliphatic epoxides to dihydrodiols. The review accepts epoxide hydrolase activity and direct epoxide/lipid metabolism as core or direct functions, and keeps membrane localization, oxysterol/enzyme binding, and hormone-response annotations as non-core context.
| 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 GO; GO:0004301; F:epoxide hydrolase activity; IDA:RGD. 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 GO; GO:0019369; P:arachidonate metabolic process; ISS:UniProtKB. 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 GO; GO:0097176; P:epoxide metabolic process; IDA:UniProtKB. 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 GO; GO:0004301; F:epoxide hydrolase activity; IDA:RGD. |
| 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 GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. 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 GO; GO:0033961; F:cis-stilbene-oxide hydrolase activity; IMP:UniProtKB. 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 GO; GO:0008142; F:oxysterol binding; ISS:UniProtKB. 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 GO; GO:0008142; F:oxysterol binding; ISS:UniProtKB. |
| 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 GO; GO:0008142; F:oxysterol binding; ISS:UniProtKB. |
| 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 GO; GO:0004301; F:epoxide hydrolase activity; IDA:RGD. |
| 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 GO; GO:0019369; P:arachidonate metabolic process; ISS:UniProtKB. |
| 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 GO; GO:0019369; P:arachidonate metabolic process; ISS:UniProtKB. |
| 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 GO; GO:0033961; F:cis-stilbene-oxide hydrolase activity; IMP:UniProtKB. |
| 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 GO; GO:0033961; F:cis-stilbene-oxide hydrolase activity; IMP:UniProtKB. |
| 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 GO; GO:0097176; P:epoxide metabolic process; IDA:UniProtKB. |
| 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 GO; GO:0120253; P:hydrocarbon catabolic process; ISO:RGD. |
| 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. |
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