ID FAAA_MOUSE Reviewed; 419 AA. AC P35505; Q3TY87; Q9QW65; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 24-JAN-2024, entry version 178. DE RecName: Full=Fumarylacetoacetase; DE Short=FAA; DE EC=3.7.1.2 {ECO:0000269|PubMed:11154690, ECO:0000269|PubMed:11209059}; DE AltName: Full=Beta-diketonase; DE AltName: Full=Fumarylacetoacetate hydrolase; GN Name=Fah; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1741389; DOI=10.1073/pnas.89.4.1363; RA Klebig M.L., Russell L.B., Rinchik E.M.; RT "Murine fumarylacetoacetate hydrolase (Fah) gene is disrupted by a RT neonatally lethal albino deletion that defines the hepatocyte-specific RT developmental regulation 1 (hsdr-1) locus."; RL Proc. Natl. Acad. Sci. U.S.A. 89:1363-1367(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J; TISSUE=Liver; RX PubMed=1524868; DOI=10.1016/0885-4505(92)90044-y; RA Grompe M., Al-Dhalimy M.; RT "Nucleotide sequence of a cDNA encoding murine fumarylacetoacetate RT hydrolase."; RL Biochem. Med. Metab. Biol. 48:26-31(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1644288; DOI=10.1101/gad.6.8.1430; RA Ruppert S., Kelsey G., Schedl A., Schmid E., Thies E., Schutz G.; RT "Deficiency of an enzyme of tyrosine metabolism underlies altered gene RT expression in newborn liver of lethal albino mice."; RL Genes Dev. 6:1430-1443(1992). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Spleen, and Visual cortex; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Kidney; 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 [6] RP MUTAGENESIS OF GLU-201, AND CATALYTIC ACTIVITY. RX PubMed=11209059; DOI=10.1073/pnas.98.2.641; RA Aponte J.L., Sega G.A., Hauser L.J., Dhar M.S., Withrow C.M., RA Carpenter D.A., Rinchik E.M., Culiat C.T., Johnson D.K.; RT "Point mutations in the murine fumarylacetoacetate hydrolase gene: animal RT models for the human genetic disorder hereditary tyrosinemia type 1."; RL Proc. Natl. Acad. Sci. U.S.A. 98:641-645(2001). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-84 AND SER-92, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [8] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH PRODUCTS AND CALCIUM, RP COFACTOR, ACTIVE SITE, AND SUBUNIT. RX PubMed=10508789; DOI=10.1016/s0969-2126(99)80170-1; RA Timm D.E., Mueller H.A., Bhanumoorthy P., Harp J.M., Bunick G.J.; RT "Crystal structure and mechanism of a carbon-carbon bond hydrolase."; RL Structure 7:1023-1033(1999). RN [9] RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) IN COMPLEX WITH INHIBITOR; CALCIUM RP AND MAGNESIUM, SUBUNIT, CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=11154690; DOI=10.1074/jbc.m007621200; RA Bateman R.L., Bhanumoorthy P., Witte J.F., McClard R.W., Grompe M., RA Timm D.E.; RT "Mechanistic inferences from the crystal structure of fumarylacetoacetate RT hydrolase with a bound phosphorus-based inhibitor."; RL J. Biol. Chem. 276:15284-15291(2001). 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:0000269|PubMed:11154690, ECO:0000269|PubMed:11209059}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:11154690, ECO:0000305|PubMed:10508789}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:11154690}; CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation; CC acetoacetate and fumarate from L-phenylalanine: step 6/6. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10508789, CC ECO:0000269|PubMed:11154690}. CC -!- TISSUE SPECIFICITY: Mainly in liver and kidney. 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; M84145; AAA37591.1; -; mRNA. DR EMBL; Z11774; CAA77819.1; -; mRNA. DR EMBL; AK143759; BAE25527.1; -; mRNA. DR EMBL; AK158808; BAE34676.1; -; mRNA. DR EMBL; BC010767; AAH10767.1; -; mRNA. DR CCDS; CCDS21418.1; -. DR PIR; A40219; A40219. DR PIR; A56825; A56825. DR RefSeq; NP_034306.2; NM_010176.4. DR PDB; 1HYO; X-ray; 1.30 A; A/B=1-419. DR PDB; 1QCN; X-ray; 1.90 A; A/B=1-419. DR PDB; 1QCO; X-ray; 1.90 A; A/B=1-419. DR PDB; 1QQJ; X-ray; 1.55 A; A/B=1-419. DR PDB; 2HZY; X-ray; 1.35 A; A/B=1-419. DR PDBsum; 1HYO; -. DR PDBsum; 1QCN; -. DR PDBsum; 1QCO; -. DR PDBsum; 1QQJ; -. DR PDBsum; 2HZY; -. DR AlphaFoldDB; P35505; -. DR SMR; P35505; -. DR BioGRID; 199589; 1. DR IntAct; P35505; 1. DR STRING; 10090.ENSMUSP00000032865; -. DR iPTMnet; P35505; -. DR PhosphoSitePlus; P35505; -. DR SwissPalm; P35505; -. DR CPTAC; non-CPTAC-3643; -. DR CPTAC; non-CPTAC-3803; -. DR EPD; P35505; -. DR jPOST; P35505; -. DR MaxQB; P35505; -. DR PaxDb; 10090-ENSMUSP00000032865; -. DR PeptideAtlas; P35505; -. DR ProteomicsDB; 267702; -. DR Pumba; P35505; -. DR Antibodypedia; 27851; 337 antibodies from 28 providers. DR DNASU; 14085; -. DR Ensembl; ENSMUST00000032865.17; ENSMUSP00000032865.9; ENSMUSG00000030630.17. DR GeneID; 14085; -. DR KEGG; mmu:14085; -. DR UCSC; uc009iej.3; mouse. DR AGR; MGI:95482; -. DR CTD; 2184; -. DR MGI; MGI:95482; Fah. DR VEuPathDB; HostDB:ENSMUSG00000030630; -. DR eggNOG; KOG2843; Eukaryota. DR GeneTree; ENSGT00390000008646; -. DR HOGENOM; CLU_026207_2_0_1; -. DR InParanoid; P35505; -. DR OMA; YWTAAQQ; -. DR OrthoDB; 275827at2759; -. DR PhylomeDB; P35505; -. DR TreeFam; TF315211; -. DR BRENDA; 3.7.1.2; 3474. DR Reactome; R-MMU-8963684; Tyrosine catabolism. DR UniPathway; UPA00139; UER00341. DR BioGRID-ORCS; 14085; 0 hits in 77 CRISPR screens. DR ChiTaRS; Fah; mouse. DR EvolutionaryTrace; P35505; -. DR PRO; PR:P35505; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; P35505; Protein. DR Bgee; ENSMUSG00000030630; Expressed in left lobe of liver and 238 other cell types or tissues. DR ExpressionAtlas; P35505; baseline and differential. DR GO; GO:0004334; F:fumarylacetoacetase activity; IMP:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006527; P:arginine catabolic process; IMP:MGI. 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 SWISS-2DPAGE; P35505; -. DR Genevisible; P35505; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Calcium; Hydrolase; Lipid metabolism; Magnesium; KW Metal-binding; Phenylalanine catabolism; Phosphoprotein; KW Reference proteome; Tyrosine catabolism. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P16930" FT CHAIN 2..419 FT /note="Fumarylacetoacetase" FT /id="PRO_0000156826" FT ACT_SITE 133 FT /note="Proton acceptor" FT /evidence="ECO:0000305|PubMed:10508789" FT BINDING 126 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:10508789, FT ECO:0000269|PubMed:11154690" FT BINDING 128 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:10508789" FT BINDING 142 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:10508789" FT BINDING 199 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:10508789, FT ECO:0000269|PubMed:11154690" FT BINDING 201 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:10508789, FT ECO:0000269|PubMed:11154690" FT BINDING 233 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:10508789, FT ECO:0000269|PubMed:11154690" FT BINDING 233 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:11154690" FT BINDING 240 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:10508789" FT BINDING 244 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:10508789" FT BINDING 253 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:11154690" FT BINDING 257 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:11154690" FT BINDING 350 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:10508789" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000250|UniProtKB:P16930" FT MOD_RES 84 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 92 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 309 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P16930" FT MOD_RES 417 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P25093" FT MUTAGEN 201 FT /note="E->G: Decrease in activity." FT /evidence="ECO:0000269|PubMed:11209059" FT CONFLICT 129..130 FT /note="SS -> PF (in Ref. 2; CAA77819)" FT /evidence="ECO:0000305" FT CONFLICT 307 FT /note="G -> R (in Ref. 3; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 376 FT /note="E -> G (in Ref. 1; AAA37591 and 5; AAH10767)" FT /evidence="ECO:0000305" FT STRAND 2..4 FT /evidence="ECO:0007829|PDB:1QQJ" FT TURN 14..16 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 19..23 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 31..36 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 39..42 FT /evidence="ECO:0007829|PDB:1HYO" FT TURN 43..46 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 47..49 FT /evidence="ECO:0007829|PDB:1HYO" FT TURN 53..57 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 59..63 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 64..67 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 68..73 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 75..89 FT /evidence="ECO:0007829|PDB:1HYO" FT TURN 90..94 FT /evidence="ECO:0007829|PDB:1QCN" FT HELIX 95..98 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 100..106 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 107..110 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 114..116 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 124..127 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 131..142 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 144..146 FT /evidence="ECO:0007829|PDB:1HYO" FT TURN 150..154 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 158..160 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 166..168 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 177..180 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 189..192 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 199..206 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 218..221 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 222..224 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 225..232 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 237..243 FT /evidence="ECO:0007829|PDB:1HYO" FT TURN 245..247 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 251..254 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 257..259 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 263..265 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 266..269 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 270..272 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 285..287 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 298..304 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 312..318 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 319..321 FT /evidence="ECO:0007829|PDB:2HZY" FT HELIX 326..334 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 345..347 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 356..358 FT /evidence="ECO:0007829|PDB:1HYO" FT HELIX 362..365 FT /evidence="ECO:0007829|PDB:1HYO" FT TURN 366..370 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 373..376 FT /evidence="ECO:0007829|PDB:2HZY" FT STRAND 380..383 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 389..397 FT /evidence="ECO:0007829|PDB:1HYO" FT STRAND 402..413 FT /evidence="ECO:0007829|PDB:1HYO" SQ SEQUENCE 419 AA; 46176 MW; 771C247377B59102 CRC64; MSFIPVAEDS DFPIQNLPYG VFSTQSNPKP RIGVAIGDQI LDLSVIKHLF TGPALSKHQH VFDETTLNNF MGLGQAAWKE ARASLQNLLS ASQARLRDDK ELRQRAFTSQ ASATMHLPAT IGDYTDFYSS RQHATNVGIM FRGKENALLP NWLHLPVGYH GRASSIVVSG TPIRRPMGQM RPDNSKPPVY GACRLLDMEL EMAFFVGPGN RFGEPIPISK AHEHIFGMVL MNDWSARDIQ QWEYVPLGPF LGKSFGTTIS PWVVPMDALM PFVVPNPKQD PKPLPYLCHS QPYTFDINLS VSLKGEGMSQ AATICRSNFK HMYWTMLQQL THHSVNGCNL RPGDLLASGT ISGSDPESFG SMLELSWKGT KAIDVEQGQT RTFLLDGDEV IITGHCQGDG YRVGFGQCAG KVLPALSPA //