FAAA_HUMAN
ID FAAA_HUMAN Reviewed; 419 AA.
AC P16930; B2R9X1; D3DW95; Q53XA7;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Fumarylacetoacetase;
DE Short=FAA;
DE EC=3.7.1.2 {ECO:0000250|UniProtKB:P35505};
DE AltName: Full=Beta-diketonase;
DE AltName: Full=Fumarylacetoacetate hydrolase;
GN Name=FAH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1998338;
RA Phaneuf D., Labelle Y., Berube D., Arden K., Cavenee W., Gagne R.,
RA Tanguay R.M.;
RT "Cloning and expression of the cDNA encoding human fumarylacetoacetate
RT hydrolase, the enzyme deficient in hereditary tyrosinemia: assignment of
RT the gene to chromosome 15.";
RL Am. J. Hum. Genet. 48:525-535(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-25; 32-47; 83-95 AND 195-211, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V.;
RL Submitted (JAN-2010) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 71-419 (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=2336361; DOI=10.1093/nar/18.7.1887;
RA Agsteribbe E., van Faassen H., Hartog M.V., Reversma T., Taanman J.-W.,
RA Pannekoek H., Evers R.F., Welling G.M., Berger R.;
RT "Nucleotide sequence of cDNA encoding human fumarylacetoacetase.";
RL Nucleic Acids Res. 18:1887-1887(1990).
RN [10]
RP REVIEW ON VARIANTS.
RX PubMed=9101289;
RX DOI=10.1002/(sici)1098-1004(1997)9:4<291::aid-humu1>3.0.co;2-9;
RA St Louis M., Tanguay R.M.;
RT "Mutations in the fumarylacetoacetate hydrolase gene causing hereditary
RT tyrosinemia type I: overview.";
RL Hum. Mutat. 9:291-299(1997).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309 AND TYR-395, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [14]
RP VARIANT TYRSN1 ILE-16.
RX PubMed=1401056; DOI=10.1172/jci115979;
RA Phaneuf D., Lambert M., Laframboise R., Mitchell G., Lettre F.,
RA Tanguay R.M.;
RT "Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and
RT identification of a causal mutation in a French Canadian patient.";
RL J. Clin. Invest. 90:1185-1192(1992).
RN [15]
RP VARIANT TYRSN1 ASP-134.
RX PubMed=8364576; DOI=10.1093/hmg/2.7.941;
RA Labelle Y., Phaneuf D., Leclerc B., Tanguay R.M.;
RT "Characterization of the human fumarylacetoacetate hydrolase gene and
RT identification of a missense mutation abolishing enzymatic activity.";
RL Hum. Mol. Genet. 2:941-946(1993).
RN [16]
RP VARIANT TYRSN1 GLY-166.
RX PubMed=8318997; DOI=10.1002/humu.1380020205;
RA Grompe M., Al-Dhalimy M.;
RT "Mutations of the fumarylacetoacetate hydrolase gene in four patients with
RT tyrosinemia, type I.";
RL Hum. Mutat. 2:85-93(1993).
RN [17]
RP VARIANT TYRSN1 VAL-233.
RX PubMed=7942842;
RA Rootwelt H., Berger R., Gray G., Kelly D.A., Coskun T., Kvittingen E.A.;
RT "Novel splice, missense, and nonsense mutations in the fumarylacetoacetase
RT gene causing tyrosinemia type 1.";
RL Am. J. Hum. Genet. 55:653-658(1994).
RN [18]
RP INVOLVEMENT IN TYRSN1, AND VARIANT TRP-341.
RX PubMed=7977370;
RA Rootwelt H., Brodtkorb E., Kvittingen E.A.;
RT "Identification of a frequent pseudodeficiency mutation in the
RT fumarylacetoacetase gene, with implications for diagnosis of tyrosinemia
RT type I.";
RL Am. J. Hum. Genet. 55:1122-1127(1994).
RN [19]
RP VARIANTS TYRSN1 ASP-134 AND LEU-342.
RX PubMed=8005583; DOI=10.1007/bf00201558;
RA Rootwelt H., Chou J., Gahl W.A., Berger R., Coskun T., Brodtkorb E.,
RA Kvittingen E.A.;
RT "Two missense mutations causing tyrosinemia type 1 with presence and
RT absence of immunoreactive fumarylacetoacetase.";
RL Hum. Genet. 93:615-619(1994).
RN [20]
RP VARIANTS TYRSN1 SER-337 AND GLY-381.
RX PubMed=7757089; DOI=10.1093/hmg/4.2.319;
RA St Louis M., Poudrier J., Phaneuf D., Leclerc B., Laframboise R.,
RA Tanguay R.M.;
RT "Two novel mutations involved in hereditary tyrosinemia type I.";
RL Hum. Mol. Genet. 4:319-320(1995).
RN [21]
RP VARIANT TYRSN1 GLY-234.
RX PubMed=7550234; DOI=10.1002/humu.1380060113;
RA Hahn S.H., Krasnewich D., Brantly M., Kvittingen E.A., Gahl W.A.;
RT "Heterozygosity for an exon 12 splicing mutation and a W234G missense
RT mutation in an American child with chronic tyrosinemia type 1.";
RL Hum. Mutat. 6:66-73(1995).
RN [22]
RP VARIANTS TYRSN1 ARG-193 AND VAL-369.
RX PubMed=8557261; DOI=10.1007/bf00218833;
RA Ploos van Amstel J.K., Bergman A.J.I.W., van Beurden E.A.C.M.,
RA Roijers J.F.M., Peelen T., van den Berg I.E.T., Poll-The B.T.,
RA Kvittingen E.A., Berger R.;
RT "Hereditary tyrosinemia type 1: novel missense, nonsense and splice
RT consensus mutations in the human fumarylacetoacetate hydrolase gene;
RT variability of the genotype-phenotype relationship.";
RL Hum. Genet. 97:51-59(1996).
RN [23]
RP VARIANTS TYRSN1 ASP-158; LEU-261; SER-366 DEL AND HIS-405.
RX PubMed=9633815;
RX DOI=10.1002/(sici)1098-1004(1998)12:1<19::aid-humu3>3.0.co;2-3;
RA Bergman A.J.I.W., van den Berg I.E.T., Brink W., Poll-The B.T.,
RA Ploos van Amstel J.K., Berger R.;
RT "Spectrum of mutations in the fumarylacetoacetate hydrolase gene of
RT tyrosinemia type 1 patients in northwestern Europe and Mediterranean
RT countries.";
RL Hum. Mutat. 12:19-26(1998).
RN [24]
RP VARIANT TYRSN1 ARG-279.
RX PubMed=11196105; DOI=10.1023/a:1026756501669;
RA Kim S.Z., Kupke K.G., Ierardi-Curto L., Holme E., Greter J., Tanguay R.M.,
RA Poudrier J., D'Astous M., Lettre F., Hahn S.H., Levy H.L.;
RT "Hepatocellular carcinoma despite long-term survival in chronic
RT tyrosinaemia I.";
RL J. Inherit. Metab. Dis. 23:791-804(2000).
RN [25]
RP VARIANT TYRSN1 ARG-279.
RX PubMed=11476670; DOI=10.1186/1471-2156-2-9;
RA Dreumont N., Poudrier J.A., Bergeron A., Levy H.L., Baklouti F.,
RA Tanguay R.M.;
RT "A missense mutation (Q279R) in the fumarylacetoacetate hydrolase gene,
RT responsible for hereditary tyrosinemia, acts as a splicing mutation.";
RL BMC Genet. 2:9-9(2001).
RN [26]
RP CHARACTERIZATION OF VARIANTS TYRSN1 ILE-16; CYS-62; ASP-134; ARG-193;
RP VAL-233; GLY-234 AND ARG-279, AND CHARACTERIZATION OF VARIANT TRP-341.
RX PubMed=11278491; DOI=10.1074/jbc.m009341200;
RA Bergeron A., D'Astous M., Timm D.E., Tanguay R.M.;
RT "Structural and functional analysis of missense mutations in
RT fumarylacetoacetate hydrolase, the gene deficient in hereditary tyrosinemia
RT type 1.";
RL J. Biol. Chem. 276:15225-15231(2001).
RN [27]
RP VARIANT TYRSN1 THR-35.
RX PubMed=20003495; DOI=10.1186/1750-1172-4-28;
RA Cassiman D., Zeevaert R., Holme E., Kvittingen E.A., Jaeken J.;
RT "A novel mutation causing mild, atypical fumarylacetoacetase deficiency
RT (Tyrosinemia type I): a case report.";
RL Orphanet J. Rare Dis. 4:28-28(2009).
RN [28]
RP VARIANT TRP-341.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-fumarylacetoacetate + H2O = acetoacetate + fumarate + H(+);
CC Xref=Rhea:RHEA:10244, ChEBI:CHEBI:13705, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:18034, ChEBI:CHEBI:29806; EC=3.7.1.2;
CC Evidence={ECO:0000250|UniProtKB:P35505};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P35505};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P35505};
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 6/6.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P35505}.
CC -!- INTERACTION:
CC P16930; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-4397076, EBI-10173507;
CC P16930; Q6WN34-2: CHRDL2; NbExp=3; IntAct=EBI-4397076, EBI-12593838;
CC P16930; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-4397076, EBI-10171774;
CC P16930; Q3SY46: KRTAP13-3; NbExp=3; IntAct=EBI-4397076, EBI-10241252;
CC P16930; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-4397076, EBI-3958099;
CC P16930; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-4397076, EBI-742388;
CC P16930; Q53GC0: SERTAD1; NbExp=3; IntAct=EBI-4397076, EBI-2826300;
CC P16930; P15884: TCF4; NbExp=3; IntAct=EBI-4397076, EBI-533224;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P16930-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P16930-2; Sequence=VSP_055491;
CC -!- TISSUE SPECIFICITY: Mainly expressed in liver and kidney. Lower levels
CC are also detected in many other tissues.
CC -!- DISEASE: Tyrosinemia 1 (TYRSN1) [MIM:276700]: An inborn error of
CC metabolism characterized by elevations of tyrosine in the blood and
CC urine, and hepatorenal manifestations. Typical features include hepatic
CC necrosis, renal tubular injury, episodic weakness, self-mutilation, and
CC seizures. Renal tubular dysfunction is associated with phosphate loss
CC and hypophosphataemic rickets. Progressive liver disease can lead to
CC the development of hepatocellular carcinoma. Dietary treatment with
CC restriction of tyrosine and phenylalanine alleviates the rickets, but
CC liver transplantation has so far been the only definite treatment.
CC {ECO:0000269|PubMed:11196105, ECO:0000269|PubMed:11278491,
CC ECO:0000269|PubMed:11476670, ECO:0000269|PubMed:1401056,
CC ECO:0000269|PubMed:20003495, ECO:0000269|PubMed:7550234,
CC ECO:0000269|PubMed:7757089, ECO:0000269|PubMed:7942842,
CC ECO:0000269|PubMed:7977370, ECO:0000269|PubMed:8005583,
CC ECO:0000269|PubMed:8318997, ECO:0000269|PubMed:8364576,
CC ECO:0000269|PubMed:8557261, ECO:0000269|PubMed:9633815}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the FAH family. {ECO:0000305}.
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DR EMBL; M55150; AAA52422.1; -; mRNA.
DR EMBL; BT007160; AAP35824.1; -; mRNA.
DR EMBL; AK313951; BAG36668.1; -; mRNA.
DR EMBL; BX537608; CAD97795.1; -; mRNA.
DR EMBL; AC087761; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471136; EAW99120.1; -; Genomic_DNA.
DR EMBL; CH471136; EAW99121.1; -; Genomic_DNA.
DR EMBL; BC002527; AAH02527.1; -; mRNA.
DR EMBL; X51728; CAA36016.1; -; mRNA.
DR CCDS; CCDS10314.1; -. [P16930-1]
DR PIR; A37926; A37926.
DR RefSeq; NP_000128.1; NM_000137.2. [P16930-1]
DR AlphaFoldDB; P16930; -.
DR SMR; P16930; -.
DR BioGRID; 108479; 15.
DR IntAct; P16930; 9.
DR STRING; 9606.ENSP00000385080; -.
DR DrugBank; DB01832; 4-[Hydroxy-[Methyl-Phosphinoyl]]-3-Oxo-Butanoic Acid.
DR DrugBank; DB01762; Acetoacetic acid.
DR DrugBank; DB01677; Fumaric acid.
DR iPTMnet; P16930; -.
DR MetOSite; P16930; -.
DR PhosphoSitePlus; P16930; -.
DR SwissPalm; P16930; -.
DR BioMuta; FAH; -.
DR DMDM; 119778; -.
DR OGP; P16930; -.
DR REPRODUCTION-2DPAGE; IPI00031708; -.
DR EPD; P16930; -.
DR jPOST; P16930; -.
DR MassIVE; P16930; -.
DR MaxQB; P16930; -.
DR PaxDb; P16930; -.
DR PeptideAtlas; P16930; -.
DR PRIDE; P16930; -.
DR ProteomicsDB; 53401; -. [P16930-1]
DR ProteomicsDB; 62555; -.
DR Antibodypedia; 27851; 304 antibodies from 28 providers.
DR DNASU; 2184; -.
DR Ensembl; ENST00000261755.9; ENSP00000261755.5; ENSG00000103876.14. [P16930-1]
DR Ensembl; ENST00000407106.5; ENSP00000385080.1; ENSG00000103876.14. [P16930-1]
DR Ensembl; ENST00000561421.6; ENSP00000453347.2; ENSG00000103876.14. [P16930-1]
DR GeneID; 2184; -.
DR KEGG; hsa:2184; -.
DR MANE-Select; ENST00000561421.6; ENSP00000453347.2; NM_000137.4; NP_000128.1.
DR UCSC; uc002bfm.3; human. [P16930-1]
DR CTD; 2184; -.
DR DisGeNET; 2184; -.
DR GeneCards; FAH; -.
DR HGNC; HGNC:3579; FAH.
DR HPA; ENSG00000103876; Tissue enhanced (liver).
DR MalaCards; FAH; -.
DR MIM; 276700; phenotype.
DR MIM; 613871; gene.
DR neXtProt; NX_P16930; -.
DR OpenTargets; ENSG00000103876; -.
DR Orphanet; 882; Tyrosinemia type 1.
DR PharmGKB; PA27977; -.
DR VEuPathDB; HostDB:ENSG00000103876; -.
DR eggNOG; KOG2843; Eukaryota.
DR GeneTree; ENSGT00390000008646; -.
DR HOGENOM; CLU_026207_2_0_1; -.
DR InParanoid; P16930; -.
DR OMA; YWTAAQQ; -.
DR OrthoDB; 980065at2759; -.
DR PhylomeDB; P16930; -.
DR TreeFam; TF315211; -.
DR BioCyc; MetaCyc:HS02536-MON; -.
DR BRENDA; 3.7.1.2; 2681.
DR PathwayCommons; P16930; -.
DR Reactome; R-HSA-8963684; Tyrosine catabolism.
DR SignaLink; P16930; -.
DR UniPathway; UPA00139; UER00341.
DR BioGRID-ORCS; 2184; 9 hits in 1081 CRISPR screens.
DR ChiTaRS; FAH; human.
DR GeneWiki; Fumarylacetoacetate_hydrolase; -.
DR GenomeRNAi; 2184; -.
DR Pharos; P16930; Tbio.
DR PRO; PR:P16930; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P16930; protein.
DR Bgee; ENSG00000103876; Expressed in right lobe of liver and 180 other tissues.
DR ExpressionAtlas; P16930; baseline and differential.
DR Genevisible; P16930; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0004334; F:fumarylacetoacetase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006527; P:arginine catabolic process; IEA:Ensembl.
DR GO; GO:1902000; P:homogentisate catabolic process; IBA:GO_Central.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006572; P:tyrosine catabolic process; IBA:GO_Central.
DR Gene3D; 2.30.30.230; -; 1.
DR Gene3D; 3.90.850.10; -; 1.
DR InterPro; IPR005959; Fumarylacetoacetase.
DR InterPro; IPR011234; Fumarylacetoacetase-like_C.
DR InterPro; IPR036663; Fumarylacetoacetase_C_sf.
DR InterPro; IPR015377; Fumarylacetoacetase_N.
DR InterPro; IPR036462; Fumarylacetoacetase_N_sf.
DR PANTHER; PTHR43069; PTHR43069; 1.
DR Pfam; PF01557; FAA_hydrolase; 1.
DR Pfam; PF09298; FAA_hydrolase_N; 1.
DR SUPFAM; SSF56529; SSF56529; 1.
DR SUPFAM; SSF63433; SSF63433; 1.
DR TIGRFAMs; TIGR01266; fum_ac_acetase; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Calcium; Direct protein sequencing;
KW Disease variant; Hydrolase; Lipid metabolism; Magnesium; Metal-binding;
KW Phenylalanine catabolism; Phosphoprotein; Reference proteome;
KW Tyrosine catabolism.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:25944712"
FT CHAIN 2..419
FT /note="Fumarylacetoacetase"
FT /id="PRO_0000156825"
FT ACT_SITE 133
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 126
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 128
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 142
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 233
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 240
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 244
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 253
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 257
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 350
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:25944712"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 395
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..70
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_055491"
FT VARIANT 16
FT /note="N -> I (in TYRSN1; loss of activity;
FT dbSNP:rs121965073)"
FT /evidence="ECO:0000269|PubMed:11278491,
FT ECO:0000269|PubMed:1401056"
FT /id="VAR_005205"
FT VARIANT 35
FT /note="A -> T (in TYRSN1; atypical mild phenotype)"
FT /evidence="ECO:0000269|PubMed:20003495"
FT /id="VAR_065454"
FT VARIANT 62
FT /note="F -> C (in TYRSN1; loss of activity)"
FT /evidence="ECO:0000269|PubMed:11278491"
FT /id="VAR_005206"
FT VARIANT 64
FT /note="Q -> H (in TYRSN1; dbSNP:rs80338894)"
FT /id="VAR_005207"
FT VARIANT 134
FT /note="A -> D (in TYRSN1; loss of activity;
FT dbSNP:rs121965074)"
FT /evidence="ECO:0000269|PubMed:11278491,
FT ECO:0000269|PubMed:8005583, ECO:0000269|PubMed:8364576"
FT /id="VAR_005208"
FT VARIANT 158
FT /note="G -> D (in TYRSN1)"
FT /evidence="ECO:0000269|PubMed:9633815"
FT /id="VAR_005209"
FT VARIANT 166
FT /note="V -> G (in TYRSN1; dbSNP:rs778387055)"
FT /evidence="ECO:0000269|PubMed:8318997"
FT /id="VAR_005210"
FT VARIANT 193
FT /note="C -> R (in TYRSN1; loss of activity)"
FT /evidence="ECO:0000269|PubMed:11278491,
FT ECO:0000269|PubMed:8557261"
FT /id="VAR_005211"
FT VARIANT 207
FT /note="G -> D (in TYRSN1; dbSNP:rs754196530)"
FT /id="VAR_005212"
FT VARIANT 233
FT /note="D -> V (in TYRSN1; loss of activity;
FT dbSNP:rs80338897)"
FT /evidence="ECO:0000269|PubMed:11278491,
FT ECO:0000269|PubMed:7942842"
FT /id="VAR_005213"
FT VARIANT 234
FT /note="W -> G (in TYRSN1; loss of activity;
FT dbSNP:rs1555441595)"
FT /evidence="ECO:0000269|PubMed:11278491,
FT ECO:0000269|PubMed:7550234"
FT /id="VAR_005214"
FT VARIANT 249
FT /note="P -> T (in TYRSN1)"
FT /id="VAR_005215"
FT VARIANT 261
FT /note="P -> L (in TYRSN1; dbSNP:rs80338898)"
FT /evidence="ECO:0000269|PubMed:9633815"
FT /id="VAR_005216"
FT VARIANT 279
FT /note="Q -> R (in TYRSN1; may affect splicing resulting in
FT skipping of exon 8 alone or together with exon 9; lower
FT activity as compared to wild type; dbSNP:rs121965078)"
FT /evidence="ECO:0000269|PubMed:11196105,
FT ECO:0000269|PubMed:11278491, ECO:0000269|PubMed:11476670"
FT /id="VAR_065455"
FT VARIANT 294
FT /note="T -> P (in TYRSN1; dbSNP:rs370634385)"
FT /id="VAR_005217"
FT VARIANT 337
FT /note="G -> S (in TYRSN1; dbSNP:rs80338900)"
FT /evidence="ECO:0000269|PubMed:7757089"
FT /id="VAR_005218"
FT VARIANT 341
FT /note="R -> W (does not cause a clinically relevant
FT phenotype; results in lower enzyme activity;
FT dbSNP:rs11555096)"
FT /evidence="ECO:0000269|PubMed:11278491,
FT ECO:0000269|PubMed:27535533, ECO:0000269|PubMed:7977370"
FT /id="VAR_005219"
FT VARIANT 342
FT /note="P -> L (in TYRSN1; loss of activity;
FT dbSNP:rs779040832)"
FT /evidence="ECO:0000269|PubMed:8005583"
FT /id="VAR_005220"
FT VARIANT 366
FT /note="Missing (in TYRSN1)"
FT /evidence="ECO:0000269|PubMed:9633815"
FT /id="VAR_005221"
FT VARIANT 369
FT /note="G -> V (in TYRSN1)"
FT /evidence="ECO:0000269|PubMed:8557261"
FT /id="VAR_005222"
FT VARIANT 381
FT /note="R -> G (in TYRSN1; loss of activity;
FT dbSNP:rs121965077)"
FT /evidence="ECO:0000269|PubMed:7757089"
FT /id="VAR_005223"
FT VARIANT 405
FT /note="F -> H (in TYRSN1; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:9633815"
FT /id="VAR_005224"
SQ SEQUENCE 419 AA; 46374 MW; 12EA8D8074C55BB2 CRC64;
MSFIPVAEDS DFPIHNLPYG VFSTRGDPRP RIGVAIGDQI LDLSIIKHLF TGPVLSKHQD
VFNQPTLNSF MGLGQAAWKE ARVFLQNLLS VSQARLRDDT ELRKCAFISQ ASATMHLPAT
IGDYTDFYSS RQHATNVGIM FRDKENALMP NWLHLPVGYH GRASSVVVSG TPIRRPMGQM
KPDDSKPPVY GACKLLDMEL EMAFFVGPGN RLGEPIPISK AHEHIFGMVL MNDWSARDIQ
KWEYVPLGPF LGKSFGTTVS PWVVPMDALM PFAVPNPKQD PRPLPYLCHD EPYTFDINLS
VNLKGEGMSQ AATICKSNFK YMYWTMLQQL THHSVNGCNL RPGDLLASGT ISGPEPENFG
SMLELSWKGT KPIDLGNGQT RKFLLDGDEV IITGYCQGDG YRIGFGQCAG KVLPALLPS
