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fumarase (fumarate hydratase mitochondrial, FH)
Function:
- catalyzes conversion of fumarate to malate
- carbohydrate metabolism, tricarboxylic acid cycle
- acts as a tumor suppressor
(S)-malate fumarate + H2O
Structure:
- homotetramer
- belongs to the class-II fumarase/aspartase family, fumarase subfamily
- initiator Met-1 is removed
- contains a N-acetylalanine at position 2
- isoform cytoplasmic is acetylated at position 2
- 2 substrate binding sites:
a) catalytic A site
b) non-catalytic B site may play a role in transfer of substrate or product between active site & solvent; alternatively, the B site may bind allosteric effectors
Compartment: mitochondria, cytoplasm
Alternative initiation: named isoforms=2
Pathology:
- defects in FH are the cause of fumarase deficiency
- defects in FH are the cause of multiple cutaneous & uterine leiomyomata
- defects in FH are the cause of hereditary leiomyomatosis & renal cell cancer
Interactions
molecular events
Related
citric acid cycle, Krebs cycle or tricarboxylic acid [TCA] cycle
General
citric acid cycle enzyme
hydro-lyase, hydratase or dehydratase
Properties
SIZE: entity length = 510 aa
MW = 55 kD
COMPARTMENT: mitochondria
cytoplasm
MOTIF: binding site
SITE: 147-147
FOR-BINDING-OF: Substrate
B site {176-179}
Substrate binding {186-188}
Database Correlations
OMIM correlations
MORBIDMAP 136850
UniProt P07954
Pfam PF00206
ENZYME 4.2.1.2
References
- UniProt :accession P07954
- Atlas of Genetics & cytogenetics in oncology & Haematology
http://atlasgeneticsoncology.org/Genes/FHID40573ch1q42.html
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=FH