Recombinant Human Fumarate hydratase, mitochondrial (FH)

Uniprot Id

P07954

Target Species

Human

Target Name

FH

Target Full Name

Fumarate hydratase, mitochondrial

Target Function

Catalyzes the reversible stereospecific interconversion of fumarate to L-malate. Experiments in other species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other (Probable).; Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH.; Catalyzes the dehydration of L-malate to fumarate. Fumarate metabolism in the cytosol plays a role during urea cycle and arginine metabolism; fumarate being a by-product of the urea cycle and amino-acid catabolism. Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ). In response to DNA damage and phosphorylation by PRKDC, translocates to the nucleus and accumulates at DNA double-strand breaks (DSBs): acts by catalyzing formation of fumarate, an inhibitor of KDM2B histone demethylase activity, resulting in enhanced dimethylation of histone H3 'Lys-36' (H3K36me2).

Target Involvement

Fumarase deficiency (FMRD); Hereditary leiomyomatosis and renal cell cancer (HLRCC)

Target Subcellular Location

[Isoform Mitochondrial]: Mitochondrion.; [Isoform Cytoplasmic]: Cytoplasm, cytosol. Nucleus. Chromosome.

Target Protein Families

Class-II fumarase/aspartase family, Fumarase subfamily

Target Tissue Specificity

Expressed in red blood cells; underexpressed in red blood cells (cytoplasm) of patients with hereditary non-spherocytic hemolytic anemia of unknown etiology.

Target Synonyms

FH; Fumarase; Fumarate hydratase; Fumarate hydratase mitochondrial; Fumarate hydratase; mitochondrial; FUMH_HUMAN; HLRCC; LRCC; MCL; MCUL 1; MCUL1; MS709; Multiple hereditary cutaneous leiomyomata

Target Background

The protein encoded by this gene is an enzymatic component of the tricarboxylic acid (TCA) cycle, or Krebs cycle, and catalyzes the formation of L-malate from fumarate. It exists in both a cytosolic form and an N-terminal extended form, differing only in the translation start site used. The N-terminal extended form is targeted to the mitochondrion, where the removal of the extension generates the same form as in the cytoplasm. It is similar to some thermostable class II fumarases and functions as a homotetramer. Mutations in this gene can cause fumarase deficiency and lead to progressive encephalopathy.