fumC

Gene Description

Fumarate hydratase class II (fumarase C, FumC; EC 4.2.1.2), encoded by fumC (fumC-2 / PP_1755), one of three fumarase isoenzymes in Pseudomonas putida KT2440 (alongside fumA/PP_0897 and fumC1/PP_0944). It is a cytoplasmic, iron-independent homotetrameric enzyme that catalyzes the reversible, stereospecific hydration/dehydration of fumarate and (S)-malate ((S)-malate = fumarate + H2O), the step of the tricarboxylic acid (TCA) cycle that interconverts fumarate and L-malate. Unlike class I fumarases, which contain an oxygen-sensitive [4Fe-4S] cluster, class II fumarases lack a metal cofactor and are oxidant-resistant, allowing them to maintain TCA-cycle flux under oxidative/nitrosative stress. The enzyme belongs to the class-II fumarase/aspartase (fumarate lyase) family, with a conserved multi-domain fold; active sites are formed at subunit interfaces and include a catalytic A site and a non-catalytic B site.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003824 catalytic activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Root-level catalytic activity term; correct but uninformative given the specific fumarate hydratase activity is also annotated. Reason: GO:0003824 is a high-level grouping term. The more specific GO:0004333 (fumarate hydratase activity) is annotated and fully captures the molecular function, making this generic term redundant and uninformative.
GO:0004333 fumarate hydratase activity	IEA GO_REF:0000120	ACCEPT	Summary: Core molecular function. FumC is a class II fumarate hydratase (EC 4.2.1.2) catalyzing (S)-malate = fumarate + H2O. Reason: Strongly supported by HAMAP-Rule MF_00743, the class-II fumarase/aspartase family assignment, conserved active-site residues, and KT2440 evidence that FumC-type isoenzymes provide compensatory fumarase activity. This is the central function of the gene.
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: FumC is a soluble cytoplasmic enzyme, consistent with its role in the cytosolic bacterial TCA cycle. Reason: UniProt subcellular location (HAMAP-Rule MF_00743) and the soluble nature of class II fumarases support cytoplasmic localization. No signal peptide or membrane-targeting features are present.
GO:0006099 tricarboxylic acid cycle	IEA GO_REF:0000120	ACCEPT	Summary: Core biological process. The fumarate-to-malate step is a canonical reaction of the TCA cycle. Reason: Directly supported by the UniProt pathway annotation (tricarboxylic acid cycle; (S)-malate from fumarate, step 1/1) and the enzyme's well-established role in central carbon metabolism.
GO:0006106 fumarate metabolic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Correct but more general than the TCA cycle annotation; fumarate is the substrate of the catalyzed reaction. Reason: Accurate (the enzyme acts on fumarate) but a broad parent process. The TCA cycle annotation is the more informative core process; this is retained as a supporting, non-core term.
GO:0006108 malate metabolic process	IEA GO_REF:0000118	KEEP AS NON CORE	Summary: Correct but general; (S)-malate is the product/substrate of the reversible reaction. Reason: Accurate given malate is directly produced/consumed, but a broad parent process relative to the TCA cycle. Retained as supporting, non-core.
GO:0016829 lyase activity	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: High-level parent of the specific fumarate hydratase (a hydro-lyase) activity. Reason: GO:0016829 is a grouping term subsuming the specific GO:0004333 fumarate hydratase activity already annotated. It is not wrong (FumC is a hydro-lyase) but is redundant and uninformative.

Gene Description

Existing Annotations Review

Core Functions

Class II (iron-independent) fumarate hydratase catalyzing the reversible stereospecific interconversion of fumarate and (S)-malate in the TCA cycle.

References

Deep Research

Falcon

OpenScientist

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