| Property | HPD summary |
|---|---|
| Gene name | **HPD** (4-hydroxyphenylpyruvate dioxygenase) (pqac-00000008, pqac-00000020) |
| UniProt ID | **P32754** |
| Protein size | **393 aa**, ~**40–50 kDa** (~45 kDa) (pqac-00000025) |
| Chromosomal location | **12q24.31** (pqac-00000009) |
| EC number | **EC 1.13.11.27** (4-hydroxyphenylpyruvate dioxygenase) (pqac-00000007) |
| Enzyme class | **Fe(II)-dependent non-heme oxygenase**; an α-keto-acid-dependent oxygenase/dioxygenase (pqac-00000000, pqac-00000007) |
| Substrate | **4-hydroxyphenylpyruvate (4-HPP / HPP / pHPP)** (pqac-00000000, pqac-00000007) |
| Product | **Homogentisate / homogentisic acid (HGA)** (pqac-00000000, pqac-00000002) |
| Cofactors / reaction requirements | **Fe(II)** and **molecular oxygen** are required; **ascorbate** helps maintain the iron in the reduced ferrous state (pqac-00000001, pqac-00000005) |
| Active-site metal ligands / key catalytic residues | **His183, His266, Glu349** coordinate Fe(II) and are central to catalysis (pqac-00000000, pqac-00000007) |
| Oligomeric state | **Homodimer** (pqac-00000025) |
| Subcellular localization | Primarily **cytosolic** (pqac-00000008, pqac-00000009) |
| Primary tissue expression | Highest in **liver**, with smaller amounts in **kidney**; largely liver/kidney-enriched (pqac-00000008, pqac-00000010) |
| Structural family | Member of the **vicinal oxygen chelate (VOC)/glyoxalase superfamily**; shares the glyoxalase fold and divalent-metal-binding architecture (pqac-00000047, pqac-00000048) |
| Domain/architecture notes | Two VOC domains; active site formed in the conserved C-terminal region; C-terminal tail acts as a catalytic gate (pqac-00000025, pqac-00000027) |
| Pathway role | Catalyzes the **second step of tyrosine degradation**, downstream of **TAT** and upstream of **HGD** and **FAH** (pqac-00000019, pqac-00000022) |
| Associated inherited diseases | **Tyrosinemia type III** and **hawkinsinuria** (pqac-00000012, pqac-00000014) |
| Representative disease features | Tyrosinemia III: elevated tyrosine with neurologic features such as seizures/ataxia/developmental delay and typically no liver disease; Hawkinsinuria: infantile failure to thrive and metabolic acidosis, often improving after infancy (pqac-00000012, pqac-00000014) |
| Key therapeutic inhibitor | **Nitisinone (NTBC)**, a potent reversible competitive HPD inhibitor used clinically in **HT1** and used/off-label or investigational in **AKU** to reduce HGA (pqac-00000036, pqac-00000046) |
| Recent moonlighting activity | UniProt additionally annotates a recently reported **N(6)-adenosine-methyltransferase** activity (**EC 2.1.1.348**); the primary paper was not retrievable here, so this function should be regarded as **very recent and not yet independently evaluated in this report** (UniProt-provided context; see also unobtainable Wang et al. reference noted during search) |


*Table: This table summarizes the core biochemical, structural, localization, pathway, disease, and therapeutic properties of human HPD/4-hydroxyphenylpyruvate dioxygenase. It is useful as a compact reference for the main facts that support functional annotation of UniProt P32754.*