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Protein

4-hydroxyphenylpyruvate dioxygenase

Gene

Hpd

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Key enzyme in the degradation of tyrosine.By similarity

Catalytic activityi

4-hydroxyphenylpyruvate + O2 = homogentisate + CO2.

Cofactori

Fe cationBy similarityNote: Binds 1 Fe cation per subunit.By similarity

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. Homogentisate 1,2-dioxygenase (Hgd)
  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 bindingi183IronBy similarity1
Metal bindingi266IronBy similarity1
Metal bindingi349IronBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDioxygenase, Oxidoreductase
Biological processPhenylalanine catabolism, Tyrosine catabolism
LigandIron, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-71182 Phenylalanine and tyrosine catabolism
SABIO-RKiP49429
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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:96213 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, Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in Hpd are the cause of tyrosinemia type III.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000883892 – 3934-hydroxyphenylpyruvate dioxygenaseAdd BLAST392

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineBy similarity1
Modified residuei132N6-succinyllysineCombined sources1
Modified residuei211PhosphoserineCombined sources1
Modified residuei226PhosphoserineCombined sources1
Modified residuei250PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP49429
PaxDbiP49429
PeptideAtlasiP49429
PRIDEiP49429

PTM databases

iPTMnetiP49429
PhosphoSitePlusiP49429
SwissPalmiP49429

Expressioni

Gene expression databases

BgeeiENSMUSG00000029445
CleanExiMM_HPD
ExpressionAtlasiP49429 baseline and differential
GenevisibleiP49429 MM

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

IntActiP49429, 3 interactors
MINTiP49429
STRINGi10090.ENSMUSP00000031398

Structurei

3D structure databases

ProteinModelPortaliP49429
SMRiP49429
ModBaseiSearch...
MobiDBiSearch...

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
InParanoidiP49429
KOiK00457
OMAiPTLFFEI
OrthoDBiEOG091G07Y5
PhylomeDBiP49429
TreeFamiTF300622

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.

P49429-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTYNNKGPK PERGRFLHFH SVTFWVGNAK QAASFYCNKM GFEPLAYRGL
60 70 80 90 100
ETGSREVVSH VIKQGKIVFV LCSALNPWNK EMGDHLVKHG DGVKDIAFEV
110 120 130 140 150
EDCDHIVQKA RERGAKIVRE PWVEQDKFGK VKFAVLQTYG DTTHTLVEKI
160 170 180 190 200
NYTGRFLPGF EAPTYKDTLL PKLPRCNLEI IDHIVGNQPD QEMQSASEWY
210 220 230 240 250
LKNLQFHRFW SVDDTQVHTE YSSLRSIVVT NYEESIKMPI NEPAPGRKKS
260 270 280 290 300
QIQEYVDYNG GAGVQHIALK TEDIITAIRH LRERGTEFLA APSSYYKLLR
310 320 330 340 350
ENLKSAKIQV KESMDVLEEL HILVDYDEKG YLLQIFTKPM QDRPTLFLEV
360 370 380 390
IQRHNHQGFG AGNFNSLFKA FEEEQALRGN LTDLEPNGVR SGM
Length:393
Mass (Da):45,054
Last modified:January 23, 2007 - v3
Checksum:i70B42A4E4744744A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2 – 6TTYNN → VDYWD in CAA42111 (PubMed:1709870).Curated5
Sequence conflicti64Q → R in BAA06267 (PubMed:7774914).Curated1
Sequence conflicti120 – 121EP → DA in CAA42111 (PubMed:1709870).Curated2
Sequence conflicti206F → S in BAE28861 (PubMed:16141072).Curated1

Polymorphismi

There are two alleles (F1 and F2), F2 has Asp-104 and F1 has Asn-104. Mice are completely tolerant to the self form of the protein, but make a good antibody response to immunization with the non-self form.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti104D → N in allele F1. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D29987 mRNA Translation: BAA06267.1
AK149416 mRNA Translation: BAE28861.1
BC013343 mRNA Translation: AAH13343.1
X59530 mRNA Translation: CAA42111.1
CCDSiCCDS39265.1
PIRiA60236
RefSeqiNP_032303.1, NM_008277.2
UniGeneiMm.439709

Genome annotation databases

EnsembliENSMUST00000031398; ENSMUSP00000031398; ENSMUSG00000029445
GeneIDi15445
KEGGimmu:15445
UCSCiuc008znj.1 mouse

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHPPD_MOUSE
AccessioniPrimary (citable) accession number: P49429
Secondary accession number(s): P97322, Q3UEQ0, Q91WV9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 23, 2007
Last modified: March 28, 2018
This is version 147 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

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health