P50336 (PPOX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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)

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.
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 variegate porphyria (VP) [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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	heme biosynthetic process Inferred from direct assay Ref.1. Source: UniProtKB
Cellular component	mitochondrial intermembrane space Traceable author statement. Source: Reactome
Molecular function	flavin adenine dinucleotide binding Traceable author statement Ref.1. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro oxygen-dependent protoporphyrinogen oxidase activity Inferred from direct assay Ref.1. 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 VP. Ref.9

VAR_003686

Natural variant

152

1

R → C in VP. Ref.10

VAR_003687

Natural variant

168

1

R → C. Ref.9

VAR_003688

Natural variant

232

1

G → R in VP. Ref.8

VAR_003689

Natural variant

256

1

P → R.
Corresponds to variant rs12735723 [ dbSNP | Ensembl ].

VAR_034395

Natural variant

304

1

R → H. Ref.3 Ref.8
Corresponds to variant rs36013429 [ dbSNP | Ensembl ].

VAR_003690

Secondary structure

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477

Helix Strand Turn

Details...

Beta strand

4 – 8

5

Helix

16 – 22

7

Beta strand

24 – 26

3

Beta strand

29 – 33

5

Beta strand

35 – 37

3

Helix

70 – 77

8

Helix

81 – 83

3

Beta strand

84 – 87

4

Helix

92 – 95

4

Beta strand

98 – 100

3

Beta strand

105 – 107

3

Turn

132 – 135

4

Helix

146 – 153

8

Helix

157 – 161

5

Helix

163 – 167

5

Turn

175 – 177

3

Helix

180 – 183

4

Helix

185 – 194

10

Helix

214 – 221

8

Beta strand

225 – 229

5

Helix

235 – 246

12

Beta strand

250 – 252

3

Beta strand

268 – 271

4

Beta strand

276 – 284

9

Helix

288 – 294

7

Helix

297 – 299

3

Helix

300 – 307

8

Beta strand

311 – 320

10

Turn

337 – 339

3

Helix

349 – 352

4

Helix

354 – 356

3

Beta strand

364 – 369

6

Helix

373 – 379

7

Helix

386 – 400

15

Beta strand

408 – 420

13

Helix

427 – 439

13

Beta strand

443 – 446

4

Helix

456 – 461

6

Helix

465 – 470

6

Sequences

	Sequence		Length	Mass (Da)
	P50336 [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]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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 VP 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 VP 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 VP CYS-152.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Protoporphyrinogen oxidase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
CH471121 Genomic DNA. Translation: EAW52639.1.
CH471121 Genomic DNA. Translation: EAW52641.1.
BC002357 mRNA. Translation: AAH02357.1.

IPI

IPI00031357.

PIR

A56449. JC4971.

RefSeq

NP_000300.1. NM_000309.3.
NP_001116236.1. NM_001122764.1.

UniGene

Hs.517373.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3NKS	X-ray	1.90	A	1-477	[»]

ProteinModelPortal

P50336.

SMR

P50336. Positions 2-474.

ModBase

Search...

Protein-protein interaction databases

IntAct

P50336. 3 interactions.

MINT

MINT-1402949.

STRING

P50336.

PTM databases

PhosphoSite

P50336.

Polymorphism databases

DMDM

1709742.

Proteomic databases

PeptideAtlas

P50336.

PRIDE

P50336.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000352210; ENSP00000343943; ENSG00000143224.
ENST00000367999; ENSP00000356978; ENSG00000143224.

GeneID

5498.

KEGG

hsa:5498.

UCSC

uc001fyg.2. human.

Organism-specific databases

CTD

5498.

GeneCards

GC01P161136.

H-InvDB

HIX0001234.

HGNC

HGNC:9280. PPOX.

HPA

HPA030123.

MIM

176200. phenotype.
600923. gene.

neXtProt

NX_P50336.

Orphanet

79473. Porphyria variegata.

PharmGKB

PA33608.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04374.

HOGENOM

HBG450176.

HOVERGEN

HBG001709.

InParanoid

P50336.

OMA

GAVMGIP.

OrthoDB

EOG42BX8S.

PhylomeDB

P50336.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-13844.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P50336.

Bgee

P50336.

CleanEx

HS_PPOX.

Genevestigator

P50336.

GermOnline

ENSG00000143224. Homo sapiens.

Family and domain databases

InterPro

IPR002937. Amino_oxidase.
IPR016040. NAD(P)-bd_dom.
IPR004572. Protoporphyrinogen_oxidase.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

KO

K00231.

Pfam

PF01593. Amino_oxidase. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00562. Proto_IX_ox. 1 hit.

ProtoNet

Search...

Other

NextBio

21268.

SOURCE

Search...

Entry information

Entry name

PPOX_HUMAN

Accession

Primary (citable) accession number: P50336
Secondary accession number(s): D3DVG0, Q5VTW8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.