HPPD_RAT
ID HPPD_RAT Reviewed; 393 AA.
AC P32755; O88655;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=4-hydroxyphenylpyruvate dioxygenase;
DE EC=1.13.11.27 {ECO:0000269|PubMed:15301540, ECO:0000269|PubMed:8814303};
DE AltName: Full=4-hydroxyphenylpyruvic acid oxidase;
DE Short=4HPPD;
DE Short=HPD;
DE Short=HPPDase;
DE AltName: Full=F Alloantigen;
DE Short=F protein;
GN Name=Hpd;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=8814303; DOI=10.1016/0014-5793(96)00902-7;
RA Lee M.H., Zhang Z.H., MacKinnon C.H., Baldwin J.E., Crouch N.P.;
RT "The C-terminal of rat 4-hydroxyphenylpyruvate dioxygenase is indispensable
RT for enzyme activity.";
RL FEBS Lett. 393:269-272(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], ACETYLATION AT THR-2, AND SUBCELLULAR LOCATION.
RX PubMed=12867153; DOI=10.1016/s1065-6995(03)00117-3;
RA Neve S., Aarenstrup L., Tornehave D., Rahbek-Nielsen H., Corydon T.J.,
RA Roepstorff P., Kristiansen K.;
RT "Tissue distribution, intracellular localization and proteolytic processing
RT of rat 4-hydroxyphenylpyruvate dioxygenase.";
RL Cell Biol. Int. 27:611-624(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-393.
RX PubMed=2445820;
RA Gershwin M.E., Coppel R.L., Bearer E., Peterson M.G., Sturgess A.,
RA McKay I.R.;
RT "Molecular cloning of the liver-specific rat F antigen.";
RL J. Immunol. 139:3828-3833(1987).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH INHIBITOR DAS869,
RP BIOPHYSICOCHEMICAL PROPERTIES, METAL-BINDING SITES, SUBUNIT, FUNCTION,
RP CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=15301540; DOI=10.1021/bi049323o;
RA Yang C., Pflugrath J.W., Camper D.L., Foster M.L., Pernich D.J.,
RA Walsh T.A.;
RT "Structural basis for herbicidal inhibitor selectivity revealed by
RT comparison of crystal structures of plant and mammalian 4-
RT hydroxyphenylpyruvate dioxygenases.";
RL Biochemistry 43:10414-10423(2004).
CC -!- FUNCTION: Catalyzes the conversion of 4-hydroxyphenylpyruvic acid to
CC homogentisic acid, one of the steps in tyrosine catabolism.
CC {ECO:0000269|PubMed:15301540, ECO:0000269|PubMed:8814303}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-(4-hydroxyphenyl)pyruvate + O2 = CO2 + homogentisate;
CC Xref=Rhea:RHEA:16189, ChEBI:CHEBI:15379, ChEBI:CHEBI:16169,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:36242; EC=1.13.11.27;
CC Evidence={ECO:0000269|PubMed:15301540, ECO:0000269|PubMed:8814303};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16190;
CC Evidence={ECO:0000305|PubMed:8814303};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:15301540};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000269|PubMed:15301540};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13 uM for 4-hydroxyphenylpyruvic acid
CC {ECO:0000269|PubMed:15301540};
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 3/6.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15301540}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12867153}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:12867153};
CC Peripheral membrane protein {ECO:0000269|PubMed:12867153}. Golgi
CC apparatus membrane {ECO:0000269|PubMed:12867153}; Peripheral membrane
CC protein {ECO:0000269|PubMed:12867153}.
CC -!- SIMILARITY: Belongs to the 4HPPD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA40740.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF082834; AAC32387.1; -; mRNA.
DR EMBL; BC081819; AAH81819.1; -; mRNA.
DR EMBL; M18405; AAA40740.1; ALT_FRAME; mRNA.
DR PIR; S32820; S32820.
DR PIR; S74178; S74178.
DR RefSeq; NP_058929.1; NM_017233.1.
DR PDB; 1SQI; X-ray; 2.15 A; A/B=1-393.
DR PDBsum; 1SQI; -.
DR AlphaFoldDB; P32755; -.
DR SMR; P32755; -.
DR STRING; 10116.ENSRNOP00000001809; -.
DR BindingDB; P32755; -.
DR ChEMBL; CHEMBL5863; -.
DR iPTMnet; P32755; -.
DR PhosphoSitePlus; P32755; -.
DR PaxDb; P32755; -.
DR PRIDE; P32755; -.
DR Ensembl; ENSRNOT00000120179; ENSRNOP00000085869; ENSRNOG00000001338.
DR GeneID; 29531; -.
DR KEGG; rno:29531; -.
DR UCSC; RGD:61974; rat.
DR CTD; 3242; -.
DR RGD; 61974; Hpd.
DR eggNOG; KOG0638; Eukaryota.
DR GeneTree; ENSGT00530000063474; -.
DR HOGENOM; CLU_034004_3_1_1; -.
DR InParanoid; P32755; -.
DR OMA; DPFPVKG; -.
DR OrthoDB; 1087836at2759; -.
DR PhylomeDB; P32755; -.
DR BRENDA; 1.13.11.27; 5301.
DR Reactome; R-RNO-8963684; Tyrosine catabolism.
DR SABIO-RK; P32755; -.
DR UniPathway; UPA00139; UER00362.
DR EvolutionaryTrace; P32755; -.
DR PRO; PR:P32755; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000001338; Expressed in liver and 18 other tissues.
DR Genevisible; P32755; RN.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0000139; C:Golgi membrane; IDA:RGD.
DR GO; GO:0003868; F:4-hydroxyphenylpyruvate dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006572; P:tyrosine catabolic process; IDA:UniProtKB.
DR CDD; cd07250; HPPD_C_like; 1.
DR CDD; cd08342; HPPD_N_like; 1.
DR Gene3D; 3.10.180.10; -; 2.
DR InterPro; IPR005956; 4OHPhenylPyrv_dOase.
DR InterPro; IPR041735; 4OHPhenylPyrv_dOase_C.
DR InterPro; IPR041736; 4OHPhenylPyrv_dOase_N.
DR InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR InterPro; IPR037523; VOC.
DR PANTHER; PTHR11959; PTHR11959; 1.
DR Pfam; PF00903; Glyoxalase; 2.
DR PIRSF; PIRSF009283; HPP_dOase; 1.
DR SUPFAM; SSF54593; SSF54593; 1.
DR TIGRFAMs; TIGR01263; 4HPPD; 1.
DR PROSITE; PS51819; VOC; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Dioxygenase; Endoplasmic reticulum;
KW Golgi apparatus; Iron; Membrane; Metal-binding; Oxidoreductase;
KW Phenylalanine catabolism; Phosphoprotein; Reference proteome; Repeat;
KW Tyrosine catabolism.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12867153"
FT CHAIN 2..393
FT /note="4-hydroxyphenylpyruvate dioxygenase"
FT /id="PRO_0000088391"
FT DOMAIN 18..149
FT /note="VOC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT DOMAIN 180..338
FT /note="VOC 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT BINDING 183
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:15301540,
FT ECO:0007744|PDB:1SQI"
FT BINDING 266
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:15301540,
FT ECO:0007744|PDB:1SQI"
FT BINDING 349
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:15301540,
FT ECO:0007744|PDB:1SQI"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000269|PubMed:12867153"
FT MOD_RES 132
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49429"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P32754"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49429"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 5..6
FT /note="SN -> WD (in Ref. 4; AAA40740)"
FT /evidence="ECO:0000305"
FT STRAND 15..25
FT /evidence="ECO:0007829|PDB:1SQI"
FT HELIX 29..40
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 43..49
FT /evidence="ECO:0007829|PDB:1SQI"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 56..64
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 67..76
FT /evidence="ECO:0007829|PDB:1SQI"
FT HELIX 80..89
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 91..101
FT /evidence="ECO:0007829|PDB:1SQI"
FT HELIX 103..113
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 117..126
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 129..137
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 143..151
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:1SQI"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 178..187
FT /evidence="ECO:0007829|PDB:1SQI"
FT HELIX 193..204
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 225..230
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 237..242
FT /evidence="ECO:0007829|PDB:1SQI"
FT HELIX 251..259
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 261..272
FT /evidence="ECO:0007829|PDB:1SQI"
FT HELIX 274..284
FT /evidence="ECO:0007829|PDB:1SQI"
FT HELIX 293..304
FT /evidence="ECO:0007829|PDB:1SQI"
FT HELIX 314..320
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 331..337
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 340..344
FT /evidence="ECO:0007829|PDB:1SQI"
FT STRAND 347..355
FT /evidence="ECO:0007829|PDB:1SQI"
FT HELIX 361..365
FT /evidence="ECO:0007829|PDB:1SQI"
SQ SEQUENCE 393 AA; 45112 MW; E8D1B7B9FC4C0EC3 CRC64;
MTTYSNKGPK PERGRFLHFH SVTFWVGNAK QAASFYCNKM GFEPLAYKGL ETGSREVVSH
VIKQGKIVFV LCSALNPWNK EMGDHLVKHG DGVKDIAFEV EDCEHIVQKA RERGAKIVRE
PWVEEDKFGK VKFAVLQTYG DTTHTLVEKI NYTGRFLPGF EAPTYKDTLL PKLPSCNLEI
IDHIVGNQPD QEMESASEWY LKNLQFHRFW SVDDTQVHTE YSSLRSIVVA NYEESIKMPI
NEPAPGRKKS QIQEYVDYNG GAGVQHIALR TEDIITTIRH LRERGMEFLA VPSSYYRLLR
ENLKTSKIQV KENMDVLEEL KILVDYDEKG YLLQIFTKPM QDRPTLFLEV IQRHNHQGFG
AGNFNSLFKA FEEEQALRGN LTDLETNGVR SGM
