HPD

Protein identityUniProt · HPA

UniProt accession

P32754

Gene

HPD

Ensembl

ENSG00000158104

Chromosome

12

Canonical length

393 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nuclear speckles

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is an enzyme in the catabolic pathway of tyrosine. The encoded protein catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. Defects in this gene are a cause of tyrosinemia type 3 (TYRO3) and hawkinsinuria (HAWK). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

Canonical amino-acid sequenceUniProt

393 residues, UniProt reviewed canonical sequence.

>P32754|HPD
     1  MTTYSDKGAK PERGRFLHFH SVTFWVGNAK QATSFYCSKM GFEPLAYRGL ETGSREVVSH
    61  VIKQGKIVFV LSSALNPWNK EMGDHLVKHG DGVKDIAFEV EDCDYIVQKA RERGAKIMRE
   121  PWVEQDKFGK VKFAVLQTYG DTTHTLVEKM NYIGQFLPGY EAPAFMDPLL PKLPKCSLEM
   181  IDHIVGNQPD QEMVSASEWY LKNLQFHRFW SVDDTQVHTE YSSLRSIVVA NYEESIKMPI
   241  NEPAPGKKKS QIQEYVDYNG GAGVQHIALK TEDIITAIRH LRERGLEFLS VPSTYYKQLR
   301  EKLKTAKIKV KENIDALEEL KILVDYDEKG YLLQIFTKPV QDRPTLFLEV IQRHNHQGFG
   361  AGNFNSLFKA FEEEQNLRGN LTNMETNGVV PGM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HPD can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

2,365 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HPD.

Disease | AllUniProt

Conditions HPD is implicated in, by any mechanism.

• Tyrosinemia 3 (TYRSN3) MIM:276710
• Hawkinsinuria (HWKS) MIM:140350

Disease | GeneticClinVar

42 pathogenic / likely-pathogenic of 456 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Tyrosinemia type III
• Hawkinsinuria
• 6 conditions

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.67

gnomAD pLI

0

gnomAD missense Z

0.73

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• L-phenylalanine catabolic process
• L-tyrosine catabolic process

Molecular functions

• 4-hydroxyphenylpyruvate dioxygenase activity
• metal ion binding
• protein homodimerization activity

Cellular components

• cytosol
• endoplasmic reticulum membrane
• extracellular exosome
• Golgi membrane

Protein domainsUniProt · Pfam · InterPro

• Glyoxalase/fosfomycin resistance/dioxygenase domain
• 4-hydroxyphenylpyruvate dioxygenase
• Glyoxalase/Bleomycin resistance protein/Dihydroxybiphenyl dioxygenase
• Vicinal oxygen chelate (VOC), core domain
• 4-hydroxyphenylpyruvate dioxygenase, C-terminal
• 4-hydroxyphenylpyruvate dioxygenase, N-terminal
• Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily

KeywordsUniProt

• Acetylation
• Cytoplasm
• Dioxygenase
• Endoplasmic reticulum
• Golgi apparatus
• Intellectual disability
• Iron
• Membrane
• Metal-binding
• Oxidoreductase
• Phenylalanine catabolism
• Phosphoprotein
• Repeat
• Tyrosine catabolism