Echs1 encodes mitochondrial short-chain enoyl-CoA hydratase (SCEH/ECHS1, EC 4.2.1.17), a matrix enzyme that catalyzes the reversible hydration of short- and medium-chain trans-2-enoyl-CoA thioesters (C4 to about C16) to the corresponding 3(S)-3-hydroxyacyl-CoA species, the second step of each mitochondrial fatty acid beta-oxidation cycle. It has highest activity on crotonyl-CoA and also carries a lower-rate delta(3)-delta(2)-enoyl-CoA isomerase activity that returns trans-3-enoyl-CoA intermediates to the beta-oxidation spiral. Beyond fatty acid oxidation it acts on branched-chain and amino-acid-derived enoyl-CoA intermediates, contributing to L-valine and L-lysine catabolism (for example hydrating methacrylyl-CoA and 3-methylcrotonyl-CoA). It is imported into the mitochondrial matrix with cleavage of a targeting presequence.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: mitochondrion is retained as contextual support for Echs1, but it is not the core function (IBA, GO_REF:0000033). Reason: mitochondrion records localization or complex context for Echs1, not the defining molecular function. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0006635 fatty acid beta-oxidation | IBA GO_REF:0000033 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining fatty acid beta-oxidation as a direct annotation (IBA, GO_REF:0000033). Reason: fatty acid beta-oxidation is a direct process-level consequence of Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. The IBD node is seeded in part by rat Echs1 itself, and the catalytic glutamate is verified intact on the rat enzyme (see residue claim), so the phylogenetic assertion is corroborated on the target. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000941828 · PANTHER:PTN000941828 SUPPORTS TRANSFER GO:0006635 IBD in the current PTHR11941 PAINT slice, seeded by mouse, rat (incl. rat members RGD:61892 and RGD:69330) and human ECHS1 (P30084); the target's own experimental grounding among the descendants is the expected marker, not circularity. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). PMID:12379132 Replacement of E164, one of the catalytic glutamates in the active site, with either aspartate or glutamine reduces the rate of formation of the 3(S) product enantiomer (k(S)) without affecting the rate of formation of the 3(R) product (k(R)). |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: catalytic activity captures part of Echs1 biology, but a more specific replacement better represents the direct role (IEA, GO_REF:0000002). Reason: catalytic activity is directionally related to Echs1 but should be replaced by the more specific term(s): enoyl-CoA hydratase activity, delta(3)-delta(2)-enoyl-CoA isomerase activity. Proposed replacements: enoyl-CoA hydratase activity delta(3)-delta(2)-enoyl-CoA isomerase activity Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). file:rat/Echs1/Echs1-deep-research-falcon.md ECHS1/SCEH catalyzes the **reversible hydration of trans‑2‑enoyl‑CoA thioesters to 3‑hydroxyacyl‑CoA (3(S)‑hydroxyacyl‑CoA)**—the canonical short‑chain enoyl‑CoA hydratase reaction (EC **4.2.1.17**). This hydration is the **second step of mitochondrial fatty‑acid β‑oxidation** for short‑chain enoyl‑CoA intermediates. |
| GO:0004165 delta(3)-delta(2)-enoyl-CoA isomerase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining delta(3)-delta(2)-enoyl-CoA isomerase activity as a direct annotation (IEA, GO_REF:0000120). Reason: UniProt records, from the rat enzyme study PMID:10074351, that Echs1 converts trans-3-enoyl-CoA to trans-2-enoyl-CoA (EC 5.3.3.8) at a lower rate than its hydratase reaction, so the EC-mapped isomerase term is experimentally grounded as a secondary activity of the same active site. Supporting Evidence: UniProtKB:P14604 At a lower rate than the hydratase reaction, catalyzes the isomerase reaction of trans-3-enoyl-CoA species (such as (3E)-hexenoyl-CoA) to trans-2-enoyl-CoA species |
| GO:0004300 enoyl-CoA hydratase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining enoyl-CoA hydratase activity as a direct annotation (IEA, GO_REF:0000120). Reason: enoyl-CoA hydratase activity directly matches Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). file:rat/Echs1/Echs1-deep-research-falcon.md ECHS1 has **broad short‑chain substrate specificity**, with highest activity commonly reported toward **crotonyl‑CoA** (C4:1‑CoA). |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: mitochondrial matrix is retained as contextual support for Echs1, but it is not the core function (IEA, GO_REF:0000120). Reason: mitochondrial matrix records localization or complex context for Echs1, not the defining molecular function. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). file:rat/Echs1/Echs1-deep-research-falcon.md ECHS1 is described as a **mitochondrial matrix enzyme**. It is synthesized as a **precursor** and processed upon mitochondrial import to the mature enzyme. |
| GO:0018812 3-hydroxyacyl-CoA dehydratase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining 3-hydroxyacyl-CoA dehydratase activity as a direct annotation (IEA, GO_REF:0000116). Reason: 3-hydroxyacyl-CoA dehydratase activity directly matches Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0120092 (2E)-butenoyl-CoA hydratase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining (2E)-butenoyl-CoA hydratase activity as a direct annotation (IEA, GO_REF:0000116). Reason: Crotonyl-CoA ((2E)-butenoyl-CoA) is the substrate for which Echs1 has its highest specificity, so the Rhea-mapped hydratase term is an exact, specific description of the core reaction. Supporting Evidence: UniProtKB:P14604 Has high substrate specificity for crotonyl-CoA ((2E)-butenoyl-CoA) |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: mitochondrion is retained as contextual support for Echs1, but it is not the core function (IEA, GO_REF:0000107). Reason: mitochondrion records localization or complex context for Echs1, not the defining molecular function. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0006574 L-valine catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining L-valine catabolic process as a direct annotation (IEA, GO_REF:0000120). Reason: L-valine catabolic process is a direct process-level consequence of Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). file:rat/Echs1/Echs1-deep-research-falcon.md ECHS1 is particularly important in **valine degradation**, where it detoxifies/reacts with reactive intermediates such as **methacrylyl-CoA** and **acryloyl-CoA**. Current disease-oriented literature suggests this valine pathway role is especially important to pathogenesis. |
| GO:0006635 fatty acid beta-oxidation | IEA GO_REF:0000120 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining fatty acid beta-oxidation as a direct annotation (IEA, GO_REF:0000120). Reason: fatty acid beta-oxidation is a direct process-level consequence of Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). file:rat/Echs1/Echs1-deep-research-falcon.md ECHS1 performs the hydration step in the β‑oxidation spiral within mitochondria, contributing to generation of acetyl‑CoA and reduced cofactors that feed the TCA cycle and OXPHOS. |
| GO:0019477 L-lysine catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining L-lysine catabolic process as a direct annotation (IEA, GO_REF:0000107). Reason: L-lysine catabolic process is a direct process-level consequence of Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0043956 3-hydroxypropionyl-CoA dehydratase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining 3-hydroxypropionyl-CoA dehydratase activity as a direct annotation (IEA, GO_REF:0000120). Reason: 3-hydroxypropionyl-CoA dehydratase activity directly matches Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). file:rat/Echs1/Echs1-deep-research-falcon.md It also acts on **branched‑chain and reactive intermediates** in amino‑acid catabolism, notably in the **valine pathway**: hydration of **methacrylyl‑CoA** and conversion of **acryloyl‑CoA** to 3‑hydroxypropionyl‑CoA are highlighted in mechanistic summaries. |
| GO:0019477 L-lysine catabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining L-lysine catabolic process as a direct annotation (ISO, GO_REF:0000121). Reason: L-lysine catabolic process is a direct process-level consequence of Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: mitochondrion is retained as contextual support for Echs1, but it is not the core function (ISO, GO_REF:0000121). Reason: mitochondrion records localization or complex context for Echs1, not the defining molecular function. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0005759 mitochondrial matrix | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: mitochondrial matrix is retained as contextual support for Echs1, but it is not the core function (ISO, GO_REF:0000121). Reason: mitochondrial matrix records localization or complex context for Echs1, not the defining molecular function. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0006574 L-valine catabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining L-valine catabolic process as a direct annotation (ISO, GO_REF:0000121). Reason: L-valine catabolic process is a direct process-level consequence of Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0043956 3-hydroxypropionyl-CoA dehydratase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining 3-hydroxypropionyl-CoA dehydratase activity as a direct annotation (ISO, GO_REF:0000121). Reason: 3-hydroxypropionyl-CoA dehydratase activity directly matches Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0006635 fatty acid beta-oxidation | ISS GO_REF:0000024 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining fatty acid beta-oxidation as a direct annotation (ISS, GO_REF:0000024). Reason: fatty acid beta-oxidation is a direct process-level consequence of Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0004300 enoyl-CoA hydratase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining enoyl-CoA hydratase activity as a direct annotation (ISO, GO_REF:0000121). Reason: enoyl-CoA hydratase activity directly matches Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0006635 fatty acid beta-oxidation | ISO GO_REF:0000121 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining fatty acid beta-oxidation as a direct annotation (ISO, GO_REF:0000121). Reason: fatty acid beta-oxidation is a direct process-level consequence of Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0004300 enoyl-CoA hydratase activity | IMP PMID:12379132 Effect of mutagenesis on the stereochemistry of enoyl-CoA hy... | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining enoyl-CoA hydratase activity as a direct annotation (IMP, PMID:12379132). Reason: enoyl-CoA hydratase activity directly matches Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: PMID:12379132 Replacement of E164, one of the catalytic glutamates in the active site, with either aspartate or glutamine reduces the rate of formation of the 3(S) product enantiomer (k(S)) without affecting the rate of formation of the 3(R) product (k(R)). |
| GO:0004300 enoyl-CoA hydratase activity | IDA PMID:7993901 Enoyl-coenzyme A hydratase-catalyzed exchange of the alpha-p... | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining enoyl-CoA hydratase activity as a direct annotation (IDA, PMID:7993901). Reason: enoyl-CoA hydratase activity directly matches Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: PMID:7993901 In contrast, enoyl-CoA hydratase catalyzes the stereospecific exchange of the pro-2S proton of butyryl-CoA with a maximum second-order rate constant of ca. 8 x 10(2) M-1 s-1. |
| GO:0006635 fatty acid beta-oxidation | IMP PMID:12379132 Effect of mutagenesis on the stereochemistry of enoyl-CoA hy... | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining fatty acid beta-oxidation as a direct annotation (IMP, PMID:12379132). Reason: fatty acid beta-oxidation is a direct process-level consequence of Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: PMID:12379132 Replacement of E164, one of the catalytic glutamates in the active site, with either aspartate or glutamine reduces the rate of formation of the 3(S) product enantiomer (k(S)) without affecting the rate of formation of the 3(R) product (k(R)). |
| GO:0006635 fatty acid beta-oxidation | TAS PMID:2806264 Molecular cloning and sequence analysis of the cDNA for rat ... | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining fatty acid beta-oxidation as a direct annotation (TAS, PMID:2806264). Reason: fatty acid beta-oxidation is a direct process-level consequence of Echs1's documented role in mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism. Supporting Evidence: PMID:2806264 To elucidate structural relationships between the mitochondrial and peroxisomal isozymes of beta-oxidation systems, cDNA of the mitochondrial enoyl-CoA hydratase was cloned and sequenced. |
| GO:0005759 mitochondrial matrix | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: mitochondrial matrix is retained as contextual support for Echs1, but it is not the core function (ISO, GO_REF:0000121; donor human ECHS1 UniProtKB:P30084). Reason: Donor-split of the already-reviewed GO:0005759 mitochondrial matrix rows; the human ECHS1 donor localizes Echs1 to the mitochondrial matrix, consistent with the experimental mitochondrial-matrix evidence, but localization is context, not the defining molecular function. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0006574 L-valine catabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: Echs1's mitochondrial enoyl-CoA hydration and isomerization in fatty acid and amino acid catabolism supports retaining L-valine catabolic process as a direct annotation (ISO, GO_REF:0000121; donor human ECHS1 UniProtKB:P30084). Reason: Donor-split of the already-accepted GO:0006574 rows; Echs1 hydrates methacrylyl-CoA/3-methylcrotonyl-CoA intermediates of valine catabolism, so the orthology transfer from human ECHS1 is sound. Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
| GO:0046395 carboxylic acid catabolic process | IEA GO_REF:0000117 | MODIFY | Summary: Carboxylic acid catabolic process is a broad parent of the specific fatty acid beta-oxidation and amino acid catabolic processes already accepted for Echs1 (IEA, GO_REF:0000117). Reason: GO:0046395 is a generic superclass covering the fatty acid beta-oxidation, L-valine and L-lysine catabolic processes that are independently annotated and accepted here; the broad parent adds no information beyond those, so it is replaced by the specific processes (previously KEEP_AS_NON_CORE, changed for consistency with the catalytic activity row of this gene and the broad-parent rows of the other genes in this batch). Policy applied across this re-review batch is that an uninformative broad parent of a specific activity or process the gene already carries is MODIFIED to that specific term; experimental rows stay at the curator's breadth unless the cited assay itself identifies the specific substrate. Proposed replacements: fatty acid beta-oxidation L-valine catabolic process Supporting Evidence: UniProtKB:P14604 Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:10074351, PubMed:7883013). |
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