GO_REF:0000002

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Echs1 annotations including catalytic activity.

"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."

GO_REF:0000024

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Echs1 annotations including fatty acid beta-oxidation.

"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."

GO_REF:0000033

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Echs1 annotations including fatty acid beta-oxidation; mitochondrion.

"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."

GO_REF:0000107

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Echs1 annotations including L-lysine catabolic process; mitochondrion.

"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."

GO_REF:0000116

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Echs1 annotations including (2E)-butenoyl-CoA hydratase activity; 3-hydroxyacyl-CoA dehydratase activity.

"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."

GO_REF:0000120

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Echs1 annotations including 3-hydroxypropionyl-CoA dehydratase activity; L-valine catabolic process; delta(3)-delta(2)-enoyl-CoA isomerase activity; enoyl-CoA hydratase activity; fatty acid beta-oxidation; and 1 other terms.

"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."

GO_REF:0000121

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Echs1 annotations including 3-hydroxypropionyl-CoA dehydratase activity; L-lysine catabolic process; L-valine catabolic process; enoyl-CoA hydratase activity; fatty acid beta-oxidation; and 2 other terms.

"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."

PMID:12379132

Effect of mutagenesis on the stereochemistry of enoyl-CoA hydratase

For Echs1, this publication supports direct annotations to enoyl-CoA hydratase activity; fatty acid beta-oxidation.

"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))."

PMID:2806264

Molecular cloning and sequence analysis of the cDNA for rat mitochondrial enoyl-CoA hydratase. Structural and evolutionary relationships linked to the bifunctional enzyme of the peroxisomal beta-oxidation system

For Echs1, this publication supports direct annotations to fatty acid beta-oxidation.

"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."

PMID:7993901

Enoyl-coenzyme A hydratase-catalyzed exchange of the alpha-protons of coenzyme A thiol esters: a model for an enolized intermediate in the enzyme-catalyzed elimination?

For Echs1, this publication supports direct annotations to enoyl-CoA hydratase activity.

"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."

file:rat/Echs1/Echs1-deep-research-falcon.md

Falcon (Edison Scientific) deep research report for rat Echs1 (P14604)

Confirms the core enoyl-CoA hydratase activity (EC 4.2.1.17) as the second step of mitochondrial fatty acid beta-oxidation, supporting the hydratase MF and fatty acid beta-oxidation process annotations.

"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."
Documents broad short-chain substrate specificity with highest activity toward crotonyl-CoA, consistent with the (2E)-butenoyl-CoA (crotonyl-CoA) hydratase activity annotation.

"ECHS1 has **broad short‑chain substrate specificity**, with highest activity commonly reported toward **crotonyl‑CoA** (C4:1‑CoA)."
Establishes a specific role in valine catabolism via hydration of methacrylyl-CoA and conversion of acryloyl-CoA to 3-hydroxypropionyl-CoA, supporting the L-valine catabolic process and 3-hydroxypropionyl-CoA dehydratase activity annotations.

"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."
Confirms mitochondrial matrix localization and precursor processing on import, supporting the mitochondrial matrix cellular component annotation.

"ECHS1 is described as a **mitochondrial matrix enzyme**. It is synthesized as a **precursor** and processed upon mitochondrial import to the mature enzyme."
Notes the homohexameric (dimer-of-trimers) crotonase-family quaternary structure, with rat liver mitochondrial ECHS1 cited as establishing the hexameric assembly and catalytic glutamate residues.

"ECHS1 forms a **homohexamer** (six identical subunits), a hallmark of crotonase‑family enzymes. Structural work explicitly references a **rat liver mitochondrial ECHS1** structure (with acetoacetyl‑CoA) showing hexameric assembly, and identifies catalytic residues (e.g., glutamates) important for proton transfer/water activation during hydration."
Records that the gathered literature emphasizes the hydratase reaction over the UniProt-listed isomerase (EC 5.3.3.8) activity, a caveat for the delta(3)-delta(2)-enoyl-CoA isomerase annotation that remains supported by experimental UniProt evidence (PubMed:10074351).

"UniProt also lists **EC 5.3.3.8**; the broader literature retrieved here mainly supports the hydratase reaction, with isomerase-related annotation not directly emphasized in the cited texts."

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models