Fumarylacetoacetase

NameFumarylacetoacetase
Synonyms
  • 3.7.1.2
  • Beta-diketonase
  • FAA
  • Fumarylacetoacetate hydrolase
Gene NameFAH
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009452|Fumarylacetoacetase
MSFIPVAEDSDFPIHNLPYGVFSTRGDPRPRIGVAIGDQILDLSIIKHLFTGPVLSKHQD
VFNQPTLNSFMGLGQAAWKEARVFLQNLLSVSQARLRDDTELRKCAFISQASATMHLPAT
IGDYTDFYSSRQHATNVGIMFRDKENALMPNWLHLPVGYHGRASSVVVSGTPIRRPMGQM
KPDDSKPPVYGACKLLDMELEMAFFVGPGNRLGEPIPISKAHEHIFGMVLMNDWSARDIQ
KWEYVPLGPFLGKSFGTTVSPWVVPMDALMPFAVPNPKQDPRPLPYLCHDEPYTFDINLS
VNLKGEGMSQAATICKSNFKYMYWTMLQQLTHHSVNGCNLRPGDLLASGTISGPEPENFG
SMLELSWKGTKPIDLGNGQTRKFLLDGDEVIITGYCQGDGYRIGFGQCAGKVLPALLPS
Number of residues419
Molecular Weight46373.97
Theoretical pINot Available
GO Classification
Functions
  • metal ion binding
  • fumarylacetoacetase activity
Processes
  • cellular nitrogen compound metabolic process
  • small molecule metabolic process
  • arginine catabolic process
  • L-phenylalanine catabolic process
  • tyrosine catabolic process
Components
  • cytosol
  • extracellular exosome
General FunctionMetal ion binding
Specific FunctionNot Available
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP16930
UniProtKB Entry NameFAAA_HUMAN
Cellular LocationNot Available
Gene sequence
>lcl|BSEQ0017463|Fumarylacetoacetase (FAH)
ATGTCCTTCATCCCGGTGGCCGAGGATTCCGACTTCCCCATCCACAACCTGCCCTACGGC
GTCTTCTCGACCAGAGGCGACCCAAGACCGAGGATAGGTGTGGCCATTGGCGACCAGATC
CTGGACCTCAGCATCATCAAGCACCTCTTTACTGGTCCTGTCCTCTCCAAACACCAGGAT
GTCTTCAATCAGCCTACACTCAACAGCTTCATGGGCCTGGGTCAGGCTGCCTGGAAGGAG
GCGAGAGTGTTCTTGCAGAACTTGCTGTCTGTGAGCCAAGCCAGGCTCAGAGATGACACC
GAACTTCGGAAGTGTGCATTCATCTCCCAGGCTTCTGCCACGATGCACCTTCCAGCCACC
ATAGGAGACTACACAGACTTCTATTCCTCTCGGCAGCATGCTACCAACGTCGGAATCATG
TTCAGGGACAAGGAGAATGCGTTGATGCCAAATTGGCTGCACTTACCAGTGGGCTACCAT
GGCCGTGCCTCCTCTGTCGTGGTGTCTGGCACCCCAATCCGAAGGCCCATGGGACAGATG
AAACCTGATGACTCTAAGCCTCCCGTATATGGTGCCTGCAAGCTCTTGGACATGGAGCTG
GAAATGGCTTTTTTTGTAGGCCCTGGAAACAGATTGGGAGAGCCGATCCCCATTTCCAAG
GCCCATGAGCACATTTTTGGAATGGTCCTTATGAACGACTGGAGTGCACGAGACATTCAG
AAGTGGGAGTATGTCCCTCTCGGGCCATTCCTTGGGAAGAGTTTTGGGACCACTGTCTCT
CCGTGGGTGGTGCCCATGGATGCTCTCATGCCCTTTGCTGTGCCCAACCCGAAGCAGGAC
CCCAGGCCCCTGCCGTATCTGTGCCATGACGAGCCCTACACATTTGACATCAACCTCTCT
GTTAACCTGAAAGGAGAAGGAATGAGCCAGGCGGCTACCATATGCAAGTCCAATTTTAAG
TACATGTACTGGACGATGCTGCAGCAGCTCACTCACCACTCTGTCAACGGCTGCAACCTG
CGGCCGGGGGACCTCCTGGCTTCTGGGACCATCAGCGGGCCGGAGCCAGAAAACTTCGGC
TCCATGTTGGAACTGTCGTGGAAGGGAACGAAGCCCATAGACCTGGGGAATGGTCAGACC
AGGAAGTTTCTGCTGGACGGGGATGAAGTCATCATAACAGGGTACTGCCAGGGGGATGGT
TACCGCATCGGCTTTGGCCAGTGTGCTGGAAAAGTGCTGCCTGCTCTCCTGCCATCATGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:3579
Chromosome Location15
LocusNot Available
References
  1. 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. 1998338
  2. 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. 14702039
  3. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. 17974005
  4. Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. 16572171
  5. 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. 15489334
  6. 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. 2336361
  7. St-Louis M, Tanguay RM: Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: overview. Hum Mutat. 1997;9(4):291-9. 9101289
  8. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  9. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  10. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  11. 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. 1401056
  12. 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. 8364576
  13. 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. 8318997
  14. 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. 7942842
  15. 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. 7977370
  16. 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. 8005583
  17. 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. 7757089
  18. 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. 7550234
  19. 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. 8557261
  20. 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. 9633815
  21. Kim SZ, Kupke KG, Ierardi-Curto L, Holme E, Greter J, Tanguay RM, Poudrier J, D'Astous M, Lettre F, Hahn SH, Levy HL: Hepatocellular carcinoma despite long-term survival in chronic tyrosinaemia I. J Inherit Metab Dis. 2000 Dec;23(8):791-804. 11196105
  22. Dreumont N, Poudrier JA, Bergeron A, Levy HL, Baklouti F, Tanguay RM: A missense mutation (Q279R) in the fumarylacetoacetate hydrolase gene, responsible for hereditary tyrosinemia, acts as a splicing mutation. BMC Genet. 2001;2:9. Epub 2001 Jun 29. 11476670
  23. 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. 11278491
  24. Cassiman D, Zeevaert R, Holme E, Kvittingen EA, Jaeken J: A novel mutation causing mild, atypical fumarylacetoacetase deficiency (Tyrosinemia type I): a case report. Orphanet J Rare Dis. 2009 Dec 15;4:28. doi: 10.1186/1750-1172-4-28. 20003495