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Protein

4-hydroxyphenylpyruvate dioxygenase

Gene

Hpd

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

    Keywordsi

    Molecular functionDioxygenase, Oxidoreductase
    Biological processPhenylalanine catabolism, Tyrosine catabolism
    LigandIron, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Chromosome 12

    Organism-specific databases

    RGDi61974 Hpd

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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

    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

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini18 – 149VOC 1PROSITE-ProRule annotationAdd BLAST132
    Domaini180 – 338VOC 2PROSITE-ProRule annotationAdd BLAST159

    Sequence similaritiesi

    Belongs to the 4HPPD family.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiKOG0638 Eukaryota
    COG3185 LUCA
    GeneTreeiENSGT00530000063474
    HOGENOMiHOG000188687
    HOVERGENiHBG005987
    InParanoidiP32755
    KOiK00457
    OMAiPTLFFEI
    OrthoDBiEOG091G07Y5
    PhylomeDBiP32755

    Family and domain databases

    Gene3Di3.10.180.10, 2 hits
    InterProiView protein in InterPro
    IPR005956 4OHPhenylPyrv_dOase
    IPR029068 Glyas_Bleomycin-R_OHBP_Dase
    IPR004360 Glyas_Fos-R_dOase_dom
    IPR037523 VOC
    PANTHERiPTHR11959 PTHR11959, 1 hit
    PfamiView protein in Pfam
    PF00903 Glyoxalase, 2 hits
    PIRSFiPIRSF009283 HPP_dOase, 1 hit
    SUPFAMiSSF54593 SSF54593, 1 hit
    TIGRFAMsiTIGR01263 4HPPD, 1 hit
    PROSITEiView protein in PROSITE
    PS51819 VOC, 2 hits

    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

    Similar proteinsi

    Entry informationi

    Entry nameiHPPD_RAT
    AccessioniPrimary (citable) accession number: P32755
    Secondary accession number(s): O88655
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
    Last sequence update: January 23, 2007
    Last modified: May 23, 2018
    This is version 143 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

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