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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)DescriptionActionsGraphical viewLength
    Metal bindingi183Iron1
    Metal bindingi266Iron1
    Metal bindingi349Iron1

    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 databases

    ChEMBLiCHEMBL5863.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00000883912 – 3934-hydroxyphenylpyruvate dioxygenaseAdd BLAST392

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylthreonine1 Publication1
    Modified residuei132N6-succinyllysineBy similarity1
    Modified residuei211PhosphoserineBy similarity1
    Modified residuei226PhosphoserineBy similarity1
    Modified residuei250PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiP32755.
    PRIDEiP32755.

    PTM databases

    iPTMnetiP32755.
    PhosphoSitePlusiP32755.

    Expressioni

    Gene expression databases

    BgeeiENSRNOG00000001338.
    GenevisibleiP32755. RN.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    MINTiMINT-4568827.
    STRINGi10116.ENSRNOP00000001809.

    Chemistry databases

    BindingDBiP32755.

    Structurei

    Secondary structure

    1393
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi15 – 25Combined sources11
    Helixi29 – 40Combined sources12
    Beta strandi43 – 49Combined sources7
    Helixi50 – 52Combined sources3
    Beta strandi56 – 64Combined sources9
    Beta strandi67 – 76Combined sources10
    Helixi80 – 89Combined sources10
    Beta strandi91 – 101Combined sources11
    Helixi103 – 113Combined sources11
    Beta strandi117 – 126Combined sources10
    Beta strandi129 – 137Combined sources9
    Beta strandi143 – 151Combined sources9
    Beta strandi154 – 157Combined sources4
    Helixi170 – 172Combined sources3
    Beta strandi178 – 187Combined sources10
    Helixi193 – 204Combined sources12
    Beta strandi207 – 209Combined sources3
    Beta strandi225 – 230Combined sources6
    Beta strandi237 – 242Combined sources6
    Helixi251 – 259Combined sources9
    Beta strandi261 – 272Combined sources12
    Helixi274 – 284Combined sources11
    Helixi293 – 304Combined sources12
    Helixi314 – 320Combined sources7
    Beta strandi323 – 325Combined sources3
    Beta strandi331 – 337Combined sources7
    Beta strandi340 – 344Combined sources5
    Beta strandi347 – 355Combined sources9
    Helixi361 – 365Combined sources5

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1SQIX-ray2.15A/B1-393[»]
    ProteinModelPortaliP32755.
    SMRiP32755.
    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.
    OrthoDBiEOG091G07Y5.
    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 differs from that shown. Reason: Frameshift at position 381.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti5 – 6SN → WD in AAA40740 (PubMed:2445820).Curated2

    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
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1SQIX-ray2.15A/B1-393[»]
    ProteinModelPortaliP32755.
    SMRiP32755.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    MINTiMINT-4568827.
    STRINGi10116.ENSRNOP00000001809.

    Chemistry databases

    BindingDBiP32755.
    ChEMBLiCHEMBL5863.

    PTM databases

    iPTMnetiP32755.
    PhosphoSitePlusiP32755.

    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.
    OrthoDBiEOG091G07Y5.
    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

    BgeeiENSRNOG00000001338.
    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...

    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: November 2, 2016
    This is version 133 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.