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Protein Page:
FH (human)

Overview
FH a metabolic enzyme that participates in the tricarboxylic acid cycle that catalyzes the conversion of (S)-malate into fumarate + H2O. There are two substrate binding sites: the catalytic A site, and the non-catalytic B site that may play a role in the transfer of substrate or product between the active site and the solvent. Alternatively, the B site may bind allosteric effectors. Fumarate accumulates in the cell when FH is inactivated. Fumarate inhibits the dioxygenases that hydroxylate the transcription factor HIF and leads to its degradation by VHL. Since HIF turns on oncogenic pathways, FH has apparent tumor suppressor activity. Defects in FH are the cause of hereditary leiomyomatosis and renal cell cancer (HLRCC), a highly metastatic form of RCC. Defects in FH are the cause of fumarase deficiency (FD) also known as fumaricaciduria. FD is characterized by progressive encephalopathy, developmental delay, hypotonia, cerebral atrophy and lactic and pyruvic acidemia. Cells derived from a patient with HLRCC exhibit compromised oxidative phosphorylation, dependence on anaerobic glycolysis, rapid glycolytic flux, and overexpression of lactate dehydrogenase A (LDHA) and GLUT1. Two human isoforms are produced by alternative initiation. The longer isoform is mitochondrial, while the shorter form, missing residues 1-43, is cytoplasmic. Note: This description may include information from UniProtKB.
Protein type: Carbohydrate Metabolism - citrate (TCA) cycle; EC 4.2.1.2; Lyase; Mitochondrial; Tumor suppressor
Chromosomal Location of Human Ortholog: 1q42.1
Cellular Component: cytoplasm; cytosol; mitochondrial matrix; mitochondrion
Molecular Function: fumarate hydratase activity; protein binding
Biological Process: malate metabolic process; protein tetramerization; tricarboxylic acid cycle
Disease: Fumarase Deficiency
Reference #:  P07954 (UniProtKB)
Alt. Names/Synonyms: FH; Fumarase; fumarate hydratase; Fumarate hydratase, mitochondrial; FUMH; HLRCC; LRCC; MCL; MCUL1
Gene Symbols: FH
Molecular weight: 54,637 Da
Basal Isoelectric point: 8.85  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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FH

Protein Structure Not Found.
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