FAAA_CAEEL
ID FAAA_CAEEL Reviewed; 418 AA.
AC Q94272;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Fumarylacetoacetase {ECO:0000255|RuleBase:RU366008};
DE Short=FAA {ECO:0000250|UniProtKB:P35505};
DE EC=3.7.1.2 {ECO:0000250|UniProtKB:P35505, ECO:0000255|RuleBase:RU366008};
DE AltName: Full=Beta-diketonase;
DE AltName: Full=Fumarylacetoacetate hydrolase {ECO:0000255|RuleBase:RU366008};
GN Name=fah-1 {ECO:0000312|WormBase:K10C2.4};
GN Synonyms=phi-43 {ECO:0000312|WormBase:K10C2.4};
GN ORFNames=K10C2.4 {ECO:0000312|WormBase:K10C2.4};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=18227072; DOI=10.1074/jbc.m708341200;
RA Fisher A.L., Page K.E., Lithgow G.J., Nash L.;
RT "The Caenorhabditis elegans K10C2.4 gene encodes a member of the
RT fumarylacetoacetate hydrolase family: a Caenorhabditis elegans model of
RT type I tyrosinemia.";
RL J. Biol. Chem. 283:9127-9135(2008).
CC -!- FUNCTION: Fumarylacetoacetase involved in the tyrosine degradation
CC pathway. {ECO:0000269|PubMed:18227072}.
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 ECO:0000255|RuleBase:RU366008};
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 {ECO:0000250|UniProtKB:P35505, ECO:0000255|RuleBase:RU366008}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the intestine and the
CC hypodermis. {ECO:0000269|PubMed:18227072}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown from hatching results in
CC stunted growth, reduced fertility, progressive destruction of the
CC intestine by adulthood characterized by the thinning of the intestinal
CC wall and loss of intracellular lipid droplets, which eventually
CC culminates in lethality (PubMed:18227072). RNAi-mediated knockdown
CC results in activation of cellular stress pathways, and thus the
CC intestinal damage is most likely due to activation of oxidative stress
CC responses and ER stress responses in the intestine (PubMed:18227072).
CC The reduced fertility phenotype is enhanced in response to exogenous
CC tyrosine or homogentisic acid (PubMed:18227072). RNAi-mediated
CC knockdown together with tatn-1 RNAi, hpd-1 RNAi or hgo-1 RNAi rescues
CC the impaired growth and fertility defects in the single fah-1 RNAi
CC mutant (PubMed:18227072). {ECO:0000269|PubMed:18227072}.
CC -!- SIMILARITY: Belongs to the FAH family. {ECO:0000255|RuleBase:RU366008}.
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DR EMBL; BX284606; CCD72626.1; -; Genomic_DNA.
DR PIR; T25813; T25813.
DR RefSeq; NP_509083.1; NM_076682.3.
DR AlphaFoldDB; Q94272; -.
DR SMR; Q94272; -.
DR DIP; DIP-24371N; -.
DR STRING; 6239.K10C2.4.1; -.
DR EPD; Q94272; -.
DR PaxDb; Q94272; -.
DR PeptideAtlas; Q94272; -.
DR EnsemblMetazoa; K10C2.4.1; K10C2.4.1; WBGene00019620.
DR GeneID; 180918; -.
DR KEGG; cel:CELE_K10C2.4; -.
DR UCSC; K10C2.4.1; c. elegans.
DR CTD; 180918; -.
DR WormBase; K10C2.4; CE04750; WBGene00019620; fah-1.
DR eggNOG; KOG2843; Eukaryota.
DR GeneTree; ENSGT00390000008646; -.
DR HOGENOM; CLU_026207_2_0_1; -.
DR InParanoid; Q94272; -.
DR OMA; YWTAAQQ; -.
DR OrthoDB; 980065at2759; -.
DR PhylomeDB; Q94272; -.
DR BRENDA; 3.7.1.2; 1045.
DR Reactome; R-CEL-8963684; Tyrosine catabolism.
DR UniPathway; UPA00139; UER00341.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00019620; Expressed in larva and 4 other tissues.
DR GO; GO:0004334; F:fumarylacetoacetase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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: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 2: Evidence at transcript level;
KW Calcium; Hydrolase; Magnesium; Metal-binding; Phenylalanine catabolism;
KW Reference proteome; Tyrosine catabolism.
FT CHAIN 1..418
FT /note="Fumarylacetoacetase"
FT /id="PRO_0000453177"
FT ACT_SITE 134
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 202
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 235
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 235
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 255
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 259
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P35505"
SQ SEQUENCE 418 AA; 46044 MW; A33C1B7FDE0644A9 CRC64;
MKSFVSVPQN SDFPIQNLPY GVFSTKADSS RHIGVAIGDQ ILNLAEIANL FDGPQLKAHQ
DVFKQSTLNA FMALPRPAWL EARARIQQLL SEDCAVLRDN AHLRSRALVA QSDATMHLPA
QIGDYTDFYS SIHHATNVGI MFRGKENALM PNWKWLPVGY HGRASSIVVS GTDLKRPVGQ
TKAPDAEVPS FGPSKLMDFE LEMAFFVGGP ENELGTRVPI EKAEDRIFGV VLMNDWSARD
IQAWEYVPLG PFLAKSFATT VSPWVVSIEA LRPYFVENPV QDPVPPAYLH HDDPFTLDIN
LAVSIRPEGD AVDHIVCKTN FKHLYWTLKQ QLAHHTVNGC NLRAGDLLGS GTVSGPEEGA
YGSMLELSWR GAKEVPVGSE IRKFLKDGDE VNLSGVCEKN GVRIGFGECR GKVLPADI
