Canmetcon
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Identification
HMDB Protein ID HMDBP00861
Secondary Accession Numbers
  • 6142
Name Fumarate hydratase, mitochondrial
Synonyms
  1. Fumarase
Gene Name FH
Protein Type Enzyme
Biological Properties
General Function Involved in fumarate hydratase activity
Specific Function Also acts as a tumor suppressor.
Pathways
  • 2-ketoglutarate dehydrogenase complex deficiency
  • Citrate cycle (TCA cycle)
  • Citric Acid Cycle
  • Congenital lactic acidosis
  • Fumarase deficiency
  • Glutaminolysis and Cancer
  • Mitochondrial complex II deficiency
  • Pyruvate dehydrogenase deficiency (E2)
  • Pyruvate dehydrogenase deficiency (E3)
  • Renal cell carcinoma
  • The oncogenic action of 2-hydroxyglutarate
  • The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria
  • The Oncogenic Action of Fumarate
  • The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria
  • The Oncogenic Action of Succinate
  • tricarboxylic acid cycle
  • Warburg Effect
Reactions
L-Malic acid → Fumaric acid + Water details
GO Classification
Biological Process
fumarate metabolic process
homeostasis of number of cells within a tissue
malate metabolic process
tricarboxylic acid cycle
Cellular Component
mitochondrial matrix
tricarboxylic acid cycle enzyme complex
Component
tricarboxylic acid cycle enzyme complex
macromolecular complex
protein complex
Function
fumarate hydratase activity
catalytic activity
lyase activity
carbon-oxygen lyase activity
hydro-lyase activity
Molecular Function
fumarate hydratase activity
Process
fumarate metabolic process
metabolic process
cellular metabolic process
organic acid metabolic process
oxoacid metabolic process
carboxylic acid metabolic process
cofactor metabolic process
coenzyme metabolic process
acetyl-coa metabolic process
acetyl-coa catabolic process
tricarboxylic acid cycle
dicarboxylic acid metabolic process
Cellular Location
  1. Isoform Cytoplasmic:Cytoplasm
Gene Properties
Chromosome Location 1
Locus 1q42.1
SNPs FH
Gene Sequence
>1533 bp
ATGTACCGAGCACTTCGGCTCCTCGCGCGCTCGCGTCCCCTCGTGCGGGCTCCAGCCGCA
GCCTTAGCTTCGGCTCCCGGCTTGGGTGGCGCGGCCGTGCCCTCGTTTTGGCCTCCGAAC
GCGGCTCGAATGGCAAGCCAAAATTCCTTCCGGATAGAATATGATACCTTTGGTGAACTA
AAGGTGCCAAATGATAAGTATTATGGCGCCCAGACCGTGAGATCTACGATGAACTTTAAG
ATTGGAGGTGTGACAGAACGCATGCCAACCCCAGTTATTAAAGCTTTTGGCATCTTGAAG
CGAGCGGCCGCTGAAGTAAACCAGGATTATGGTCTTGATCCAAAGATTGCTAATGCAATA
ATGAAGGCAGCAGATGAGGTAGCTGAAGGTAAATTAAATGATCATTTTCCTCTCGTGGTA
TGGCAGACTGGATCAGGAACTCAGACAAATATGAATGTAAATGAAGTCATTAGCAATAGA
GCAATTGAAATGTTAGGAGGTGAACTTGGCAGCAAGATACCTGTGCATCCCAACGATCAT
GTTAATAAAAGCCAGAGCTCAAATGATACTTTTCCCACAGCAATGCACATTGCTGCTGCA
ATAGAAGTTCATGAAGTACTGTTACCAGGACTACAGAAGTTACATGATGCTCTTGATGCA
AAATCCAAAGAGTTTGCACAGATCATCAAGATTGGACGTACTCATACTCAGGATGCTGTT
CCACTTACTCTTGGGCAGGAATTTAGTGGTTATGTTCAACAAGTAAAATATGCAATGACA
AGAATAAAAGCTGCCATGCCAAGAATCTATGAGCTCGCAGCTGGAGGCACTGCTGTTGGT
ACAGGTTTAAATACTAGAATTGGCTTTGCAGAAAAGGTTGCTGCAAAAGTGGCTGCACTT
ACAGGCTTGCCTTTTGTCACTGCTCCGAATAAATTTGAAGCTCTGGCTGCTCATGACGCT
CTGGTTGAGCTCAGTGGAGCCATGAACACTACTGCCTGCAGTCTGATGAAGATAGCAAAT
GATATTCGATTTTTGGGTTCTGGTCCTCGGTCAGGTCTGGGAGAATTGATCTTGCCTGAA
AATGAACCAGGAAGCAGTATCATGCCAGGCAAGGTGAACCCTACTCAGTGTGAAGCAATG
ACCATGGTTGCAGCCCAAGTCATGGGGAACCATGTTGCTGTCACTGTCGGAGGCAGCAAT
GGACATTTTGAGTTGAATGTTTTCAAGCCAATGATGATTAAAAATGTGTTACACTCAGCC
AGGCTGCTGGGGGATGCTTCAGTTTCCTTTACAGAAAACTGCGTGGTGGGAATCCAGGCC
AATACAGAAAGGATCAACAAGCTGATGAATGAGTCTCTAATGTTGGTGACAGCTCTCAAT
CCTCATATAGGGTATGACAAGGCAGCAAAGATTGCTAAGACAGCACACAAAAATGGATCA
ACCTTAAAGGAAACTGCTATCGAACTTGGCTATCTCACAGCAGAGCAGTTTGACGAATGG
GTAAAACCTAAGGACATGCTGGGTCCAAAGTGA
Protein Properties
Number of Residues 510
Molecular Weight 54636.585
Theoretical pI 8.758
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Fumarate hydratase, mitochondrial
MYRALRLLARSRPLVRAPAAALASAPGLGGAAVPSFWPPNAARMASQNSFRIEYDTFGEL
KVPNDKYYGAQTVRSTMNFKIGGVTERMPTPVIKAFGILKRAAAEVNQDYGLDPKIANAI
MKAADEVAEGKLNDHFPLVVWQTGSGTQTNMNVNEVISNRAIEMLGGELGSKIPVHPNDH
VNKSQSSNDTFPTAMHIAAAIEVHEVLLPGLQKLHDALDAKSKEFAQIIKIGRTHTQDAV
PLTLGQEFSGYVQQVKYAMTRIKAAMPRIYELAAGGTAVGTGLNTRIGFAEKVAAKVAAL
TGLPFVTAPNKFEALAAHDALVELSGAMNTTACSLMKIANDIRFLGSGPRSGLGELILPE
NEPGSSIMPGKVNPTQCEAMTMVAAQVMGNHVAVTVGGSNGHFELNVFKPMMIKNVLHSA
RLLGDASVSFTENCVVGIQANTERINKLMNESLMLVTALNPHIGYDKAAKIAKTAHKNGS
TLKETAIELGYLTAEQFDEWVKPKDMLGPK
GenBank ID Protein 13111881
UniProtKB/Swiss-Prot ID P07954
UniProtKB/Swiss-Prot Entry Name FUMH_HUMAN
PDB IDs
GenBank Gene ID BC003108
GeneCard ID FH
GenAtlas ID FH
HGNC ID HGNC:3700
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203. [PubMed:18083107 ]
  4. Kinsella BT, Doonan S: Nucleotide sequence of a cDNA coding for mitochondrial fumarase from human liver. Biosci Rep. 1986 Oct;6(10):921-9. [PubMed:3828494 ]
  5. Coughlin EM, Christensen E, Kunz PL, Krishnamoorthy KS, Walker V, Dennis NR, Chalmers RA, Elpeleg ON, Whelan D, Pollitt RJ, Ramesh V, Mandell R, Shih VE: Molecular analysis and prenatal diagnosis of human fumarase deficiency. Mol Genet Metab. 1998 Apr;63(4):254-62. [PubMed:9635293 ]
  6. Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, Leigh I, Gorman P, Lamlum H, Rahman S, Roylance RR, Olpin S, Bevan S, Barker K, Hearle N, Houlston RS, Kiuru M, Lehtonen R, Karhu A, Vilkki S, Laiho P, Eklund C, Vierimaa O, Aittomaki K, Hietala M, Sistonen P, Paetau A, Salovaara R, Herva R, Launonen V, Aaltonen LA: Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet. 2002 Apr;30(4):406-10. Epub 2002 Feb 25. [PubMed:11865300 ]