Reviewed, UniProtKB/Swiss-Prot P50336 (PPOX_HUMAN)

Names and origin

Protein names

Recommended name:
    Protoporphyrinogen oxidase
      Short name=PPO
    EC=1.3.3.4

Gene names

Name:

PPOX

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	477 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.
Catalytic activity	Protoporphyrinogen-IX + 3 O2 = protoporphyrin-IX + 3 H2O2.
Cofactor	Binds 1 FAD per dimer.
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; protoporphyrin-IX from protoporphyrinogen-IX: step 1/1.
Subunit structure	Homodimer.
Subcellular location	Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side By similarity.
Tissue specificity	Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
Involvement in disease	Defects in PPOX are the cause of porphyria variegata (PV) [MIM:176200]. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. PV is the most common form of porphyria in South Africa. It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease. Ref.8 Ref.9 Ref.10
Sequence similarities	Belongs to the protoporphyrinogen oxidase family.

Ontologies

Keywords
Biological process	Heme biosynthesis Porphyrin biosynthesis
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	heme biosynthetic process Ref.1 Inferred from direct assay. Source: UniProtKB oxidation reduction Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	intrinsic to mitochondrial inner membrane Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial intermembrane space Ref.2 Inferred from Experiment. Source: Reactome
Molecular function	FAD binding Ref.1 Traceable author statement. Source: UniProtKB oxygen-dependent protoporphyrinogen oxidase activity Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 477	477	Protoporphyrinogen oxidase		PRO_0000135270
Regions
	Nucleotide binding	9 – 14	6	FAD Potential
Natural variations
	Natural variant	59	1	R → W in PV. Ref.9		VAR_003686
	Natural variant	152	1	R → C in PV. Ref.10		VAR_003687
	Natural variant	168	1	R → C		VAR_003688
	Natural variant	232	1	G → R in PV. Ref.8		VAR_003689
	Natural variant	256	1	P → R: dbSNP rs12735723.		VAR_034395
	Natural variant	304	1	R → H: dbSNP rs36013429. Ref.8 Ref.3		VAR_003690

Sequences

	Sequence		Length	Mass (Da)
	P50336-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 2444DEAC2E6C33EE	FASTA	477	50,765
	10 20 30 40 50 60 MGRTVVVLGG GISGLAASYH LSRAPCPPKV VLVESSERLG GWIRSVRGPN GAIFELGPRG 70 80 90 100 110 120 IRPAGALGAR TLLLVSELGL DSEVLPVRGD HPAAQNRFLY VGGALHALPT GLRGLLRPSP 130 140 150 160 170 180 PFSKPLFWAG LRELTKPRGK EPDETVHSFA QRRLGPEVAS LAMDSLCRGV FAGNSRELSI 190 200 210 220 230 240 RSCFPSLFQA EQTHRSILLG LLLGAGRTPQ PDSALIRQAL AERWSQWSLR GGLEMLPQAL 250 260 270 280 290 300 ETHLTSRGVS VLRGQPVCGL SLQAEGRWKV SLRDSSLEAD HVISAIPASV LSELLPAEAA 310 320 330 340 350 360 PLARALSAIT AVSVAVVNLQ YQGAHLPVQG FGHLVPSSED PGVLGIVYDS VAFPEQDGSP 370 380 390 400 410 420 PGLRVTVMLG GSWLQTLEAS GCVLSQELFQ QRAQEAAATQ LGLKEMPSHC LVHLHKNCIP 430 440 450 460 470 QYTLGHWQKL ESARQFLTAH RLPLTLAGAS YEGVAVNDCI ESGRQAAVSV LGTEPNS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a human cDNA for protoporphyrinogen oxidase by complementation in vivo of a hemG mutant of Escherichia coli." Nishimura K., Taketani S., Inokuchi H. J. Biol. Chem. 270:8076-8080(1995) [PubMed: 7713909] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Human protoporphyrinogen oxidase: expression, purification, and characterization of the cloned enzyme." Dailey T.A., Dailey H.A. Protein Sci. 5:98-105(1996) [PubMed: 8771201] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[3]	"Protoporphyrinogen oxidase: complete genomic sequence and polymorphisms in the human gene." Puy H., Robreau A.-M., Rosipal R., Nordmann Y., Deybach J.-C. Biochem. Biophys. Res. Commun. 226:226-230(1996) [PubMed: 8806618] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-304.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria." Deybach J.-C., Puy H., Robreau A.-M., Lamoril J., da Silva V., Grandchamp B., Nordmann Y. Hum. Mol. Genet. 5:407-410(1996) [PubMed: 8852667] [Abstract] Cited for: VARIANT PV ARG-232, VARIANT HIS-304.
[9]	"A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria." Meissner P.N., Dailey T.A., Hift R.J., Ziman M., Corrigall A.V., Roberts A.G., Meissner D.M., Kirsch R.E., Dailey H.A. Nat. Genet. 13:95-97(1996) [PubMed: 8673113] [Abstract] Cited for: VARIANT PV TRP-59, VARIANT CYS-168.
[10]	"The genetic basis of 'Scarsdale Gourmet Diet' variegate porphyria: a missense mutation in the protoporphyrinogen oxidase gene." Frank J., Poh-Fitzpatrick M.B., King L.E. Jr., Christiano A.M. Arch. Dermatol. Res. 290:441-445(1998) [PubMed: 9763307] [Abstract] Cited for: VARIANT PV CYS-152.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Protoporphyrinogen oxidase entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	D38537 mRNA. Translation: BAA07538.1. U26446 mRNA. Translation: AAA67690.1. X99450 Genomic DNA. No translation available. AL590714 Genomic DNA. Translation: CAH72144.1. CH471121 Genomic DNA. Translation: EAW52636.1. BC002357 mRNA. Translation: AAH02357.1.
IPI	IPI00031357.
PIR	A56449. JC4971.
RefSeq	NP_000300.1. NP_001116236.1.
UniGene	Hs.517373
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P50336. 3 interactions.
STRING	P50336.
Proteomic databases
PeptideAtlas	P50336.
PRIDE	P50336.
Genome annotation databases
Ensembl	ENST00000352210; ENSP00000343943; ENSG00000143224; Homo sapiens. [Genome view] ENST00000367999; ENSP00000356978; ENSG00000143224; Homo sapiens. [Genome view]
GeneID	5498.
KEGG	hsa:5498.
UCSC	uc001fyg.2. human.
Organism-specific databases
CTD	5498.
GeneCards	GC01P159402.
H-InvDB	HIX0001234.
HGNC	HGNC:9280. PPOX.
MIM	176200. phenotype. 600923. gene.
Orphanet	95157. Porphyria, acute hepatic. 79473. Porphyria, Variegata.
PharmGKB	PA33608.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P50336.
HOVERGEN	P50336.
OMA	SWPGKLR
OrthoDB	EOG9TB6WQ
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER-13844.
BRENDA	1.3.3.4. 247.
Reactome	REACT_9431. Metabolism of porphyrins.
Gene expression databases
ArrayExpress	P50336.
Bgee	P50336.
CleanEx	HS_PPOX.
Genevestigator	P50336.
GermOnline	ENSG00000143224. Homo sapiens.
Family and domain databases
InterPro	IPR002937. Amino_oxidase. IPR004572. Protoporphyrinogen_oxidase. [Graphical view]
Pfam	PF01593. Amino_oxidase. 1 hit. [Graphical view]
TIGRFAMs	TIGR00562. proto_IX_ox. 1 hit.
ProtoNet	Search...
Other Resources
NextBio	21268.
SOURCE	Search...

Entry information

Entry name

PPOX_HUMAN

Accession

Primary (citable) accession number: P50336
Secondary accession number(s): Q5VTW8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 24, 2009
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.