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Protein

4-hydroxyphenylpyruvate dioxygenase

Gene

Hpd

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Key enzyme in the degradation of tyrosine.

Catalytic activityi

4-hydroxyphenylpyruvate + O2 = homogentisate + CO2.1 Publication

Cofactori

Fe cationNote: Binds 1 Fe cation per subunit.

Kineticsi

  1. KM=13 µM for HPPA1 Publication

    Pathwayi: L-phenylalanine degradation

    This protein is involved in step 3 of the subpathway that synthesizes acetoacetate and fumarate from L-phenylalanine.
    Proteins known to be involved in the 6 steps of the subpathway in this organism are:
    1. Phenylalanine-4-hydroxylase (Pah)
    2. Tyrosine aminotransferase (Tat)
    3. 4-hydroxyphenylpyruvate dioxygenase (Hpd)
    4. no protein annotated in this organism
    5. Maleylacetoacetate isomerase (Gstz1)
    6. Fumarylacetoacetase (Fah)
    This subpathway is part of the pathway L-phenylalanine degradation, which is itself part of Amino-acid degradation.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes acetoacetate and fumarate from L-phenylalanine, the pathway L-phenylalanine degradation and in Amino-acid degradation.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi183 – 1831Iron
    Metal bindingi266 – 2661Iron
    Metal bindingi349 – 3491Iron

    GO - Molecular functioni

    • 4-hydroxyphenylpyruvate dioxygenase activity Source: UniProtKB
    • metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    • L-phenylalanine catabolic process Source: UniProtKB-UniPathway
    • tyrosine catabolic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Biological processi

    Phenylalanine catabolism, Tyrosine catabolism

    Keywords - Ligandi

    Iron, Metal-binding

    Enzyme and pathway databases

    BRENDAi1.13.11.27. 5301.
    ReactomeiR-RNO-71182. Phenylalanine and tyrosine catabolism.
    SABIO-RKP32755.
    UniPathwayiUPA00139; UER00362.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    4-hydroxyphenylpyruvate dioxygenase (EC:1.13.11.27)
    Alternative name(s):
    4-hydroxyphenylpyruvic acid oxidase
    Short name:
    4HPPD
    Short name:
    HPD
    Short name:
    HPPDase
    F Alloantigen
    Short name:
    F protein
    Gene namesi
    Name:Hpd
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Chromosome 12

    Organism-specific databases

    RGDi61974. Hpd.

    Subcellular locationi

    GO - Cellular componenti

    • endoplasmic reticulum Source: MGI
    • endoplasmic reticulum membrane Source: RGD
    • Golgi apparatus Source: MGI
    • Golgi membrane Source: RGD
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane

    Pathology & Biotechi

    Chemistry

    ChEMBLiCHEMBL5863.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methionineiRemoved1 Publication
    Chaini2 – 3933924-hydroxyphenylpyruvate dioxygenasePRO_0000088391Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylthreonine1 Publication
    Modified residuei132 – 1321N6-succinyllysineBy similarity
    Modified residuei211 – 2111PhosphoserineBy similarity
    Modified residuei226 – 2261PhosphoserineBy similarity
    Modified residuei250 – 2501PhosphoserineCombined sources

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiP32755.
    PRIDEiP32755.

    PTM databases

    iPTMnetiP32755.

    Expressioni

    Gene expression databases

    GenevisibleiP32755. RN.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    MINTiMINT-4568827.
    STRINGi10116.ENSRNOP00000001809.

    Chemistry

    BindingDBiP32755.

    Structurei

    Secondary structure

    1
    393
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi15 – 2511Combined sources
    Helixi29 – 4012Combined sources
    Beta strandi43 – 497Combined sources
    Helixi50 – 523Combined sources
    Beta strandi56 – 649Combined sources
    Beta strandi67 – 7610Combined sources
    Helixi80 – 8910Combined sources
    Beta strandi91 – 10111Combined sources
    Helixi103 – 11311Combined sources
    Beta strandi117 – 12610Combined sources
    Beta strandi129 – 1379Combined sources
    Beta strandi143 – 1519Combined sources
    Beta strandi154 – 1574Combined sources
    Helixi170 – 1723Combined sources
    Beta strandi178 – 18710Combined sources
    Helixi193 – 20412Combined sources
    Beta strandi207 – 2093Combined sources
    Beta strandi225 – 2306Combined sources
    Beta strandi237 – 2426Combined sources
    Helixi251 – 2599Combined sources
    Beta strandi261 – 27212Combined sources
    Helixi274 – 28411Combined sources
    Helixi293 – 30412Combined sources
    Helixi314 – 3207Combined sources
    Beta strandi323 – 3253Combined sources
    Beta strandi331 – 3377Combined sources
    Beta strandi340 – 3445Combined sources
    Beta strandi347 – 3559Combined sources
    Helixi361 – 3655Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1SQIX-ray2.15A/B1-393[»]
    ProteinModelPortaliP32755.
    SMRiP32755. Positions 8-366.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP32755.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the 4HPPD family.Curated

    Phylogenomic databases

    eggNOGiKOG0638. Eukaryota.
    COG3185. LUCA.
    GeneTreeiENSGT00530000063474.
    HOGENOMiHOG000188687.
    HOVERGENiHBG005987.
    InParanoidiP32755.
    KOiK00457.
    OMAiNGSGIQH.
    OrthoDBiEOG75F4D7.
    PhylomeDBiP32755.

    Family and domain databases

    Gene3Di3.10.180.10. 2 hits.
    InterProiIPR005956. 4OHPhenylPyrv_dOase.
    IPR029068. Glyas_Bleomycin-R_OHBP_Dase.
    IPR004360. Glyas_Fos-R_dOase_dom.
    [Graphical view]
    PANTHERiPTHR11959. PTHR11959. 1 hit.
    PfamiPF00903. Glyoxalase. 2 hits.
    [Graphical view]
    PIRSFiPIRSF009283. HPP_dOase. 1 hit.
    SUPFAMiSSF54593. SSF54593. 1 hit.
    TIGRFAMsiTIGR01263. 4HPPD. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P32755-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MTTYSNKGPK PERGRFLHFH SVTFWVGNAK QAASFYCNKM GFEPLAYKGL
    60 70 80 90 100
    ETGSREVVSH VIKQGKIVFV LCSALNPWNK EMGDHLVKHG DGVKDIAFEV
    110 120 130 140 150
    EDCEHIVQKA RERGAKIVRE PWVEEDKFGK VKFAVLQTYG DTTHTLVEKI
    160 170 180 190 200
    NYTGRFLPGF EAPTYKDTLL PKLPSCNLEI IDHIVGNQPD QEMESASEWY
    210 220 230 240 250
    LKNLQFHRFW SVDDTQVHTE YSSLRSIVVA NYEESIKMPI NEPAPGRKKS
    260 270 280 290 300
    QIQEYVDYNG GAGVQHIALR TEDIITTIRH LRERGMEFLA VPSSYYRLLR
    310 320 330 340 350
    ENLKTSKIQV KENMDVLEEL KILVDYDEKG YLLQIFTKPM QDRPTLFLEV
    360 370 380 390
    IQRHNHQGFG AGNFNSLFKA FEEEQALRGN LTDLETNGVR SGM
    Length:393
    Mass (Da):45,112
    Last modified:January 23, 2007 - v3
    Checksum:iE8D1B7B9FC4C0EC3
    GO

    Sequence cautioni

    The sequence AAA40740.1 differs from that shown. Reason: Frameshift at position 381. Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti5 – 62SN → WD in AAA40740 (PubMed:2445820).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF082834 mRNA. Translation: AAC32387.1.
    BC081819 mRNA. Translation: AAH81819.1.
    M18405 mRNA. Translation: AAA40740.1. Frameshift.
    PIRiS32820.
    S74178.
    RefSeqiNP_058929.1. NM_017233.1.
    UniGeneiRn.3664.

    Genome annotation databases

    EnsembliENSRNOT00000001809; ENSRNOP00000001809; ENSRNOG00000001338.
    GeneIDi29531.
    KEGGirno:29531.
    UCSCiRGD:61974. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF082834 mRNA. Translation: AAC32387.1.
    BC081819 mRNA. Translation: AAH81819.1.
    M18405 mRNA. Translation: AAA40740.1. Frameshift.
    PIRiS32820.
    S74178.
    RefSeqiNP_058929.1. NM_017233.1.
    UniGeneiRn.3664.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1SQIX-ray2.15A/B1-393[»]
    ProteinModelPortaliP32755.
    SMRiP32755. Positions 8-366.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    MINTiMINT-4568827.
    STRINGi10116.ENSRNOP00000001809.

    Chemistry

    BindingDBiP32755.
    ChEMBLiCHEMBL5863.

    PTM databases

    iPTMnetiP32755.

    Proteomic databases

    PaxDbiP32755.
    PRIDEiP32755.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSRNOT00000001809; ENSRNOP00000001809; ENSRNOG00000001338.
    GeneIDi29531.
    KEGGirno:29531.
    UCSCiRGD:61974. rat.

    Organism-specific databases

    CTDi3242.
    RGDi61974. Hpd.

    Phylogenomic databases

    eggNOGiKOG0638. Eukaryota.
    COG3185. LUCA.
    GeneTreeiENSGT00530000063474.
    HOGENOMiHOG000188687.
    HOVERGENiHBG005987.
    InParanoidiP32755.
    KOiK00457.
    OMAiNGSGIQH.
    OrthoDBiEOG75F4D7.
    PhylomeDBiP32755.

    Enzyme and pathway databases

    UniPathwayiUPA00139; UER00362.
    BRENDAi1.13.11.27. 5301.
    ReactomeiR-RNO-71182. Phenylalanine and tyrosine catabolism.
    SABIO-RKP32755.

    Miscellaneous databases

    EvolutionaryTraceiP32755.
    PROiP32755.

    Gene expression databases

    GenevisibleiP32755. RN.

    Family and domain databases

    Gene3Di3.10.180.10. 2 hits.
    InterProiIPR005956. 4OHPhenylPyrv_dOase.
    IPR029068. Glyas_Bleomycin-R_OHBP_Dase.
    IPR004360. Glyas_Fos-R_dOase_dom.
    [Graphical view]
    PANTHERiPTHR11959. PTHR11959. 1 hit.
    PfamiPF00903. Glyoxalase. 2 hits.
    [Graphical view]
    PIRSFiPIRSF009283. HPP_dOase. 1 hit.
    SUPFAMiSSF54593. SSF54593. 1 hit.
    TIGRFAMsiTIGR01263. 4HPPD. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "The C-terminal of rat 4-hydroxyphenylpyruvate dioxygenase is indispensable for enzyme activity."
      Lee M.H., Zhang Z.H., MacKinnon C.H., Baldwin J.E., Crouch N.P.
      FEBS Lett. 393:269-272(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY.
    2. "Tissue distribution, intracellular localization and proteolytic processing of rat 4-hydroxyphenylpyruvate dioxygenase."
      Neve S., Aarenstrup L., Tornehave D., Rahbek-Nielsen H., Corydon T.J., Roepstorff P., Kristiansen K.
      Cell Biol. Int. 27:611-624(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], ACETYLATION AT THR-2, SUBCELLULAR LOCATION.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Kidney.
    4. "Molecular cloning of the liver-specific rat F antigen."
      Gershwin M.E., Coppel R.L., Bearer E., Peterson M.G., Sturgess A., McKay I.R.
      J. Immunol. 139:3828-3833(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-393.
    5. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
      Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
      Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    6. "Structural basis for herbicidal inhibitor selectivity revealed by comparison of crystal structures of plant and mammalian 4-hydroxyphenylpyruvate dioxygenases."
      Yang C., Pflugrath J.W., Camper D.L., Foster M.L., Pernich D.J., Walsh T.A.
      Biochemistry 43:10414-10423(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH INHIBITOR DAS869, BIOPHYSICOCHEMICAL PROPERTIES, METAL-BINDING SITES, SUBUNIT.

    Entry informationi

    Entry nameiHPPD_RAT
    AccessioniPrimary (citable) accession number: P32755
    Secondary accession number(s): O88655
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1993
    Last sequence update: January 23, 2007
    Last modified: June 8, 2016
    This is version 130 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.