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Identification
HMDB Protein ID HMDBP00713
Secondary Accession Numbers
  • 5986
Name Fumarylacetoacetase
Synonyms
  1. Beta-diketonase
  2. FAA
  3. Fumarylacetoacetate hydrolase
Gene Name FAH
Protein Type Unknown
Biological Properties
General Function Involved in fumarylacetoacetase activity
Specific Function Not Available
Pathways
  • Alkaptonuria
  • Disulfiram Action Pathway
  • Dopamine beta-hydroxylase deficiency
  • Hawkinsinuria
  • L-phenylalanine degradation
  • Monoamine oxidase-a deficiency (MAO-A)
  • Phenylalanine and Tyrosine Metabolism
  • Phenylketonuria
  • Tyrosine Metabolism
  • Tyrosine metabolism
  • Tyrosinemia Type 2 (or Richner-Hanhart syndrome)
  • Tyrosinemia Type 3 (TYRO3)
  • Tyrosinemia Type I
  • Tyrosinemia, transient, of the newborn
Reactions
4-Fumarylacetoacetic acid + Water → Acetoacetic acid + Fumaric acid details
Acetoacetic acid + Fumaric acid → 4-Fumarylacetoacetic acid + Water details
GO Classification
Biological Process
cellular nitrogen compound metabolic process
arginine catabolic process
L-phenylalanine catabolic process
tyrosine catabolic process
Cellular Component
cytosol
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on acid carbon-carbon bonds
hydrolase activity, acting on acid carbon-carbon bonds, in ketonic substances
fumarylacetoacetase activity
Molecular Function
metal ion binding
fumarylacetoacetase activity
Process
metabolic process
cellular metabolic process
cellular amino acid and derivative metabolic process
cellular amino acid metabolic process
aromatic amino acid family metabolic process
Cellular Location
  1. Cytoplasmic
Gene Properties
Chromosome Location 15
Locus 15q25.1
SNPs FAH
Gene Sequence
>1260 bp
ATGTCCTTCATCCCGGTGGCCGAGGATTCCGACTTCCCCATCCACAACCTGCCCTACGGC
GTCTTCTCGACCAGAGGCGACCCAAGACCGAGGATAGGTGTGGCCATTGGCGACCAGATC
CTGGACCTCAGCATCATCAAGCACCTCTTTACTGGTCCTGTCCTCTCCAAACACCAGGAT
GTCTTCAATCAGCCTACACTCAACAGCTTCATGGGCCTGGGTCAGGCTGCCTGGAAGGAG
GCGAGAGTGTTCTTGCAGAACTTGCTGTCTGTGAGCCAAGCCAGGCTCAGAGATGACACC
GAACTTCGGAAGTGTGCATTCATCTCCCAGGCTTCTGCCACGATGCACCTTCCAGCCACC
ATAGGAGACTACACAGACTTCTATTCCTCTCGGCAGCATGCTACCAACGTCGGAATCATG
TTCAGGGACAAGGAGAATGCGTTGATGCCAAATTGGCTGCACTTACCAGTGGGCTACCAT
GGCCGTGCCTCCTCTGTCGTGGTGTCTGGCACCCCAATCCGAAGGCCCATGGGACAGATG
AAACCTGATGACTCTAAGCCTCCCGTATATGGTGCCTGCAAGCTCTTGGACATGGAGCTG
GAAATGGCTTTTTTTGTAGGCCCTGGAAACAGATTGGGAGAGCCGATCCCCATTTCCAAG
GCCCATGAGCACATTTTTGGAATGGTCCTTATGAACGACTGGAGTGCACGAGACATTCAG
AAGTGGGAGTATGTCCCTCTCGGGCCATTCCTTGGGAAGAGTTTTGGGACCACTGTCTCT
CCGTGGGTGGTGCCCATGGATGCTCTCATGCCCTTTGCTGTGCCCAACCCGAAGCAGGAC
CCCAGGCCCCTGCCGTATCTGTGCCATGACGAGCCCTACACATTTGACATCAACCTCTCT
GTTAACCTGAAAGGAGAAGGAATGAGCCAGGCGGCTACCATATGCAAGTCCAATTTTAAG
TACATGTACTGGACGATGCTGCAGCAGCTCACTCACCACTCTGTCAACGGCTGCAACCTG
CGGCCGGGGGACCTCCTGGCTTCTGGGACCATCAGCGGGCCGGAGCCAGAAAACTTCGGC
TCCATGTTGGAACTGTCGTGGAAGGGAACGAAGCCCATAGACCTGGGGAATGGTCAGACC
AGGAAGTTTCTGCTGGACGGGGATGAAGTCATCATAACAGGGTACTGCCAGGGGGATGGT
TACCGCATCGGCTTTGGCCAGTGTGCTGGAAAAGTGCTGCCTGCTCTCCTGCCATCATGA
Protein Properties
Number of Residues 419
Molecular Weight 46373.97
Theoretical pI 6.943
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Fumarylacetoacetase
MSFIPVAEDSDFPIHNLPYGVFSTRGDPRPRIGVAIGDQILDLSIIKHLFTGPVLSKHQD
VFNQPTLNSFMGLGQAAWKEARVFLQNLLSVSQARLRDDTELRKCAFISQASATMHLPAT
IGDYTDFYSSRQHATNVGIMFRDKENALMPNWLHLPVGYHGRASSVVVSGTPIRRPMGQM
KPDDSKPPVYGACKLLDMELEMAFFVGPGNRLGEPIPISKAHEHIFGMVLMNDWSARDIQ
KWEYVPLGPFLGKSFGTTVSPWVVPMDALMPFAVPNPKQDPRPLPYLCHDEPYTFDINLS
VNLKGEGMSQAATICKSNFKYMYWTMLQQLTHHSVNGCNLRPGDLLASGTISGPEPENFG
SMLELSWKGTKPIDLGNGQTRKFLLDGDEVIITGYCQGDGYRIGFGQCAGKVLPALLPS
GenBank ID Protein 182393
UniProtKB/Swiss-Prot ID P16930
UniProtKB/Swiss-Prot Entry Name FAAA_HUMAN
PDB IDs Not Available
GenBank Gene ID M55150
GeneCard ID FAH
GenAtlas ID FAH
HGNC ID HGNC:3579
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. 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 ]
  3. Phaneuf D, Labelle Y, Berube D, Arden K, Cavenee W, Gagne R, Tanguay RM: Cloning and expression of the cDNA encoding human fumarylacetoacetate hydrolase, the enzyme deficient in hereditary tyrosinemia: assignment of the gene to chromosome 15. Am J Hum Genet. 1991 Mar;48(3):525-35. [PubMed:1998338 ]
  4. Agsteribbe E, van Faassen H, Hartog MV, Reversma T, Taanman JW, Pannekoek H, Evers RF, Welling GM, Berger R: Nucleotide sequence of cDNA encoding human fumarylacetoacetase. Nucleic Acids Res. 1990 Apr 11;18(7):1887. [PubMed:2336361 ]
  5. Bergeron A, D'Astous M, Timm DE, Tanguay RM: Structural and functional analysis of missense mutations in fumarylacetoacetate hydrolase, the gene deficient in hereditary tyrosinemia type 1. J Biol Chem. 2001 May 4;276(18):15225-31. Epub 2001 Jan 22. [PubMed:11278491 ]
  6. St-Louis M, Tanguay RM: Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: overview. Hum Mutat. 1997;9(4):291-9. [PubMed:9101289 ]
  7. Phaneuf D, Lambert M, Laframboise R, Mitchell G, Lettre F, Tanguay RM: Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and identification of a causal mutation in a French Canadian patient. J Clin Invest. 1992 Oct;90(4):1185-92. [PubMed:1401056 ]
  8. Labelle Y, Phaneuf D, Leclerc B, Tanguay RM: Characterization of the human fumarylacetoacetate hydrolase gene and identification of a missense mutation abolishing enzymatic activity. Hum Mol Genet. 1993 Jul;2(7):941-6. [PubMed:8364576 ]
  9. Grompe M, al-Dhalimy M: Mutations of the fumarylacetoacetate hydrolase gene in four patients with tyrosinemia, type I. Hum Mutat. 1993;2(2):85-93. [PubMed:8318997 ]
  10. Rootwelt H, Berger R, Gray G, Kelly DA, Coskun T, Kvittingen EA: Novel splice, missense, and nonsense mutations in the fumarylacetoacetase gene causing tyrosinemia type 1. Am J Hum Genet. 1994 Oct;55(4):653-8. [PubMed:7942842 ]
  11. Rootwelt H, Brodtkorb E, Kvittingen EA: Identification of a frequent pseudodeficiency mutation in the fumarylacetoacetase gene, with implications for diagnosis of tyrosinemia type I. Am J Hum Genet. 1994 Dec;55(6):1122-7. [PubMed:7977370 ]
  12. Rootwelt H, Chou J, Gahl WA, Berger R, Coskun T, Brodtkorb E, Kvittingen EA: Two missense mutations causing tyrosinemia type 1 with presence and absence of immunoreactive fumarylacetoacetase. Hum Genet. 1994 Jun;93(6):615-9. [PubMed:8005583 ]
  13. St-Louis M, Poudrier J, Phaneuf D, Leclerc B, Laframboise R, Tanguay RM: Two novel mutations involved in hereditary tyrosinemia type I. Hum Mol Genet. 1995 Feb;4(2):319-20. [PubMed:7757089 ]
  14. Hahn SH, Krasnewich D, Brantly M, Kvittingen EA, Gahl WA: Heterozygosity for an exon 12 splicing mutation and a W234G missense mutation in an American child with chronic tyrosinemia type 1. Hum Mutat. 1995;6(1):66-73. [PubMed:7550234 ]
  15. Ploos van Amstel JK, Bergman AJ, van Beurden EA, Roijers JF, Peelen T, van den Berg IE, Poll-The BT, Kvittingen EA, Berger R: Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship. Hum Genet. 1996 Jan;97(1):51-9. [PubMed:8557261 ]
  16. Bergman AJ, van den Berg IE, Brink W, Poll-The BT, Ploos van Amstel JK, Berger R: Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia type 1 patients in northwestern Europe and Mediterranean countries. Hum Mutat. 1998;12(1):19-26. [PubMed:9633815 ]