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 24-JAN-2024, entry version 212. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 22. 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 GlyGen; P16930; 1 site, 1 O-linked glycan (1 site). 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; 9606-ENSP00000385080; -. DR PeptideAtlas; P16930; -. DR ProteomicsDB; 53401; -. [P16930-1] DR ProteomicsDB; 62555; -. DR Pumba; P16930; -. DR Antibodypedia; 27851; 337 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 AGR; HGNC:3579; -. 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; 275827at2759; -. DR PhylomeDB; P16930; -. DR TreeFam; TF315211; -. DR BioCyc; MetaCyc:HS02536-MONOMER; -. 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; 12 hits in 1164 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 182 other cell types or tissues. DR ExpressionAtlas; P16930; baseline and differential. 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; Fumarylacetoacetase, N-terminal domain; 1. DR Gene3D; 3.90.850.10; Fumarylacetoacetase-like, C-terminal domain; 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 NCBIfam; TIGR01266; fum_ac_acetase; 1. DR PANTHER; PTHR43069; FUMARYLACETOACETASE; 1. DR PANTHER; PTHR43069:SF2; FUMARYLACETOACETASE; 1. DR Pfam; PF01557; FAA_hydrolase; 1. DR Pfam; PF09298; FAA_hydrolase_N; 1. DR SUPFAM; SSF56529; FAH; 1. DR SUPFAM; SSF63433; Fumarylacetoacetate hydrolase, FAH, N-terminal domain; 1. DR Genevisible; P16930; HS. 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 //