PPOX

Protein identityUniProt · HPA

UniProt accession

P50336

Gene

PPOX

Ensembl

ENSG00000143224

Chromosome

1

Canonical length

477 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Vesicles,Mitochondria,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes the penultimate enzyme of heme biosynthesis, which catalyzes the 6-electron oxidation of protoporphyrinogen IX to form protoporphyrin IX. Mutations in this gene cause variegate porphyria, an autosomal dominant disorder of heme metabolism resulting from a deficiency in protoporphyrinogen oxidase, an enzyme located on the inner mitochondrial membrane. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

477 residues, UniProt reviewed canonical sequence.

>P50336|PPOX
     1  MGRTVVVLGG GISGLAASYH LSRAPCPPKV VLVESSERLG GWIRSVRGPN GAIFELGPRG
    61  IRPAGALGAR TLLLVSELGL DSEVLPVRGD HPAAQNRFLY VGGALHALPT GLRGLLRPSP
   121  PFSKPLFWAG LRELTKPRGK EPDETVHSFA QRRLGPEVAS LAMDSLCRGV FAGNSRELSI
   181  RSCFPSLFQA EQTHRSILLG LLLGAGRTPQ PDSALIRQAL AERWSQWSLR GGLEMLPQAL
   241  ETHLTSRGVS VLRGQPVCGL SLQAEGRWKV SLRDSSLEAD HVISAIPASV LSELLPAEAA
   301  PLARALSAIT AVSVAVVNLQ YQGAHLPVQG FGHLVPSSED PGVLGIVYDS VAFPEQDGSP
   361  PGLRVTVMLG GSWLQTLEAS GCVLSQELFQ QRAQEAAATQ LGLKEMPSHC LVHLHKNCIP
   421  QYTLGHWQKL ESARQFLTAH RLPLTLAGAS YEGVAVNDCI ESGRQAAVSV LGTEPNS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PPOX 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

24 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PPOX.

Disease | AllUniProt

Conditions PPOX is implicated in, by any mechanism.

• Variegate porphyria (VP) MIM:176200
• Variegate porphyria, childhood-onset (VPCO) MIM:620483

Disease | GeneticClinVar

67 pathogenic / likely-pathogenic of 330 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Variegate porphyria
• Variegate porphyria, childhood-onset
• See cases
• Abnormal blistering of the skin
• Porphyrinuria

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)

0.57

gnomAD pLI

0.03

gnomAD missense Z

0.98

DepMap mean gene effect

-0.17

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 11% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• heme A biosynthetic process
• heme B biosynthetic process
• heme biosynthetic process
• porphyrin-containing compound biosynthetic process
• protoporphyrinogen IX biosynthetic process
• response to xenobiotic stimulus

Molecular functions

• flavin adenine dinucleotide binding
• oxygen-dependent protoporphyrinogen oxidase activity

Cellular components

• mitochondrial inner membrane
• mitochondrial intermembrane space
• mitochondrial membrane
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Amine oxidase
• FAD/NAD(P)-binding domain superfamily
• Flavin containing amine oxidoreductase
• Protoporphyrinogen oxidase
• Zeta Carotene Desaturase and Related Oxidoreductases

KeywordsUniProt

• FAD
• Flavoprotein
• Heme biosynthesis
• Membrane
• Mitochondrion
• Mitochondrion inner membrane
• Oxidoreductase
• Porphyrin biosynthesis