FH
FH (fumarate hydratase, also known as FUM or fumarase) is a tricarboxylic acid cycle enzyme that interconverts fumarate and L-malate. It also contributes to amino-acid and urea cycle metabolism and to DNA double-strand break repair. Browse Assay Genie's current range of FH research reagents below, or read on for the biology behind the target.
FH is an enzymatic component of the tricarboxylic acid (TCA) cycle, also called the Krebs cycle. It catalyses the reversible hydration of fumarate to L-malate, and UniProt describes the dehydration of L-malate to fumarate. In the cytosol, fumarate metabolism plays a role in the urea cycle and in arginine metabolism, because fumarate is a by-product of both the urea cycle and amino-acid catabolism.
FH also has a role outside classical metabolism. It promotes DNA repair by non-homologous end-joining (NHEJ). After DNA damage, and following phosphorylation by PRKDC, the enzyme translocates to the nucleus and accumulates at DNA double-strand breaks. There it catalyses the formation of fumarate, which inhibits the histone demethylase KDM2B. This results in enhanced dimethylation of histone H3 lysine 36 (H3K36me2).
The FH gene produces a cytosolic form and an N-terminal extended form, which differ only in the translation start site used. The extended form is targeted to the mitochondrion, where removal of the extension gives the same mature protein as in the cytoplasm. The enzyme functions as a homotetramer. It belongs to the class-II fumarase/aspartase family, fumarase subfamily, and is similar to some thermostable class II fumarases. HGNC places it in the carbon-oxygen lyases gene group. Mutations in the FH gene can cause fumarase deficiency and lead to progressive encephalopathy, so FH protein is studied in both metabolic and neurological disease contexts.
FH catalyses the interconversion of fumarate and L-malate in the tricarboxylic acid cycle, making it a core enzyme for studies of mitochondrial energy metabolism.
Cytosolic fumarate metabolism by FH links the urea cycle and amino-acid catabolism to arginine metabolism.
FH supports non-homologous end-joining by producing fumarate at double-strand breaks, inhibiting KDM2B and raising H3K36me2.
Mutations in the FH gene cause fumarase deficiency and progressive encephalopathy, which makes the enzyme relevant to inherited metabolic disease.
FH is a TCA cycle enzyme that catalyses the interconversion of fumarate and L-malate. It also contributes to cytosolic urea cycle and arginine metabolism. After DNA damage it moves to the nucleus and promotes non-homologous end-joining by generating fumarate at double-strand breaks.
FH is also known as FUM, and the enzyme is commonly called fumarase. The gene produces a cytosolic form and an N-terminal extended form, differing only in translation start site. The extended form is imported into mitochondria, where the extension is removed.
Mouse and rat both have an orthologous Fh gene. In humans, mutations in FH can cause fumarase deficiency, which leads to progressive encephalopathy. The active enzyme is a homotetramer; check the datasheet of any product for its validated reactivity.
Other proteins with similar gene symbols that have pages at Assay Genie; these are not functional partners of FH.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P07954; product specifications from Assay Genie datasheets.