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P50336 (PPOX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protoporphyrinogen oxidase

Short name=PPO
EC=1.3.3.4
Gene names
Name:PPOX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length477 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX. Ref.1 Ref.8 Ref.9

Catalytic activity

Protoporphyrinogen-IX + 3 O2 = protoporphyrin-IX + 3 H2O2. Ref.8 Ref.9

Cofactor

Binds 1 FAD per subunit.

Pathway

Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; protoporphyrin-IX from protoporphyrinogen-IX: step 1/1.

Subunit structure

Monomer. Homodimer. Ref.8

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

Variegate porphyria (VP) [MIM:176200]: A form of porphyria. 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. Variegate porphyria 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Mutations leading to severe PPOX deficiency cause the rare homozygous variant form of VP. Missense mutations that preserve 10%-25% of wild-type activity may not cause clinically overt VP in heterozygotes (Ref.15). Mutations with intermediate effect on catalytic activity may cause VP, but with a low clinical penetrance (Ref.16). Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37

Sequence similarities

Belongs to the protoporphyrinogen oxidase family.

Ontologies

Keywords
   Biological processHeme biosynthesis
Porphyrin biosynthesis
   Cellular componentMembrane
Mitochondrion
Mitochondrion inner membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   LigandFAD
Flavoprotein
   Molecular functionOxidoreductase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processheme biosynthetic process

Inferred from direct assay Ref.1. Source: UniProtKB

oxidation-reduction process

Inferred from direct assay Ref.1. Source: UniProtKB

porphyrin-containing compound biosynthetic process

Inferred from direct assay Ref.1. Source: UniProtKB

porphyrin-containing compound metabolic process

Traceable author statement. Source: Reactome

protoporphyrinogen IX biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

response to drug

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentintegral component of mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

intrinsic component of mitochondrial inner membrane

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial intermembrane space

Traceable author statement. Source: Reactome

mitochondrial membrane

Inferred from mutant phenotype Ref.1. Source: UniProtKB

   Molecular_functionflavin adenine dinucleotide binding

Traceable author statement Ref.1. Source: UniProtKB

oxygen-dependent protoporphyrinogen oxidase activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 477477Protoporphyrinogen oxidase
PRO_0000135270

Regions

Nucleotide binding9 – 146FAD
Nucleotide binding34 – 352FAD
Nucleotide binding57 – 604FAD
Nucleotide binding454 – 4563FAD

Sites

Binding site421FAD; via amide nitrogen
Binding site2571FAD; via amide nitrogen and carbonyl oxygen
Binding site4491FAD; via amide nitrogen

Natural variations

Natural variant111G → D in VP; abolishes enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.32
VAR_070378
Natural variant111G → S in VP. Ref.21
VAR_070377
Natural variant121I → T in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.20
VAR_070379
Natural variant151L → F in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.22
VAR_070380
Natural variant201H → P in VP; strongly decreases enzyme activity; more resistant to thermal denaturation than wild-type enzyme; abolishes mitochondrial protein targeting and localization. Ref.8 Ref.11 Ref.25 Ref.30
VAR_070381
Natural variant341E → V in VP; decreases enzyme activity. Ref.34 Ref.36
VAR_070382
Natural variant381R → P in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.16
VAR_070383
Natural variant401G → A in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.28
VAR_070384
Natural variant401G → E in VP; abolishes enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.16
VAR_070385
Natural variant571G → R in VP. Ref.37
VAR_070386
Natural variant591R → W in VP; strongly decreases enzyme activity; does not affect mitochondrial protein targeting and localization; more resistant to thermal denaturation than wild-type enzyme. Ref.8 Ref.9 Ref.11 Ref.12 Ref.19 Ref.24 Ref.25 Ref.30
VAR_003686
Natural variant731L → P in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.16
VAR_070387
Natural variant761S → F in VP; decreases enzyme activity. Ref.36
VAR_070388
Natural variant841V → G in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.16
VAR_070389
Natural variant851L → P in VP; abolishes enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.16
VAR_070390
Natural variant1061H → P in VP; strongly decreases enzyme activity;. Ref.8 Ref.18
VAR_070391
Natural variant1381R → P in VP; slightly decreases enzyme activity. Ref.8 Ref.19
VAR_070392
Natural variant1391G → D in VP; strongly decreases enzyme activity. Ref.8 Ref.33
VAR_070393
Natural variant1431D → V in VP; strongly decreases enzyme activity. Ref.8 Ref.16
VAR_070394
Natural variant1521R → C in VP; strongly decreases enzyme activity. Ref.8 Ref.13 Ref.16 Ref.23 Ref.26
VAR_003687
Natural variant1541L → P in VP; strongly decreases enzyme activity. Ref.8 Ref.16
VAR_070395
Natural variant1581V → L in VP. Ref.26
VAR_070396
Natural variant1581V → M in VP; strongly decreases enzyme activity. Ref.8 Ref.16
VAR_070397
Natural variant1681R → C in VP; strongly decreases enzyme activity; does not affect mitochondrial protein targeting and localization. Ref.11 Ref.12 Ref.25 Ref.30
VAR_003688
Natural variant1681R → H in VP; strongly decreases enzyme activity. Ref.8 Ref.9 Ref.16
VAR_070398
Natural variant1691G → E in VP; strongly decreases enzyme activity. Ref.15
VAR_070399
Natural variant1721A → V in VP. Ref.16
VAR_070400
Natural variant1781L → V in VP; strongly decreases enzyme activity. Ref.8 Ref.18
VAR_070401
Natural variant2051A → V in VP; no effect on enzyme activity. Ref.8 Ref.26
VAR_070402
Natural variant2171R → C in VP; decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.24
VAR_070403
Natural variant2241W → G in VP; abolishes enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.34 Ref.36
VAR_070404
Natural variant2241W → R in VP. Ref.31
VAR_070405
Natural variant2321G → R in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.10 Ref.16
VAR_003689
Natural variant2321G → S in VP. Ref.29
VAR_070406
Natural variant2361L → S in VP. Ref.24
VAR_070407
Natural variant2561P → R Found in patients with the homozygous variant of variegate porphyria; unknown pathological significance; reported as a polymorphism in some Western European populations; the variant results in reduction of activity in a prokariotyc expression system but has normal activity when expressed in an eukaryotic system. Ref.16 Ref.20
Corresponds to variant rs12735723 [ dbSNP | Ensembl ].
VAR_034395
Natural variant2811Missing in VP. Ref.16
VAR_070408
Natural variant2821V → D in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.16
VAR_070409
Natural variant2831I → N in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.27
VAR_070410
Natural variant2901V → M in VP. Ref.22
VAR_070411
Natural variant2951L → P in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.16
VAR_070412
Natural variant3041R → H. Ref.3 Ref.10 Ref.16
Corresponds to variant rs36013429 [ dbSNP | Ensembl ].
VAR_003690
Natural variant3301G → R in VP; strongly decreases enzyme activity. Ref.8 Ref.9 Ref.26
VAR_070413
Natural variant3321G → A in VP; abolishes activity; impairs protein folding and/or stability. Ref.8 Ref.34 Ref.36
VAR_070414
Natural variant3351V → G in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.9 Ref.16
VAR_070415
Natural variant3481Y → C in VP; results in enzyme activity decrease; impairs protein folding and/or stability; more resistant to thermal denaturation than wild-type enzyme. Ref.8 Ref.19 Ref.25
VAR_070416
Natural variant3491D → A in VP; decreases enzyme activity. Ref.8 Ref.9 Ref.15
VAR_070417
Natural variant3501S → P in VP; abolishes activity; impairs protein folding and/or stability. Ref.8 Ref.16
VAR_070418
Natural variant3581G → R in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.15
VAR_070419
Natural variant3971A → D in VP; strongly decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.35
VAR_070420
Natural variant4011L → F in VP; strongly decreases enzyme activity. Ref.8 Ref.9 Ref.23
VAR_070421
Natural variant4201P → R in VP. Ref.37
VAR_070422
Natural variant4221Y → C in VP; decreases enzyme activity. Ref.36
VAR_070423
Natural variant4331A → P in VP; decreases enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.15
VAR_070424
Natural variant4441L → P in VP; strongly decreases enzyme activity. Ref.8 Ref.16
VAR_070425
Natural variant4481G → R in VP; abolishes enzyme activity; impairs protein folding and/or stability. Ref.8 Ref.17
VAR_070426
Natural variant4501S → P in VP; strongly decreases enzyme activity. Ref.8 Ref.14
VAR_070427
Natural variant4531G → R in VP; strongly decreases enzyme activity. Ref.8 Ref.9 Ref.16
VAR_070428
Natural variant4531G → V in VP. Ref.16
VAR_070429

Experimental info

Mutagenesis591R → G: Decreases enzyme activity by 75%. Ref.9
Mutagenesis591R → Q: Decreases enzyme activity by 90%. Strongly decreases affinity for protoporphyrinogen-IX. Ref.9
Mutagenesis741L → P: Abolishes enzyme activity. Impairs protein folding and/or stability. Ref.8
Mutagenesis971R → D: Decreases enzyme activity by 89%. Impairs protein folding and/or stability. Ref.8 Ref.9
Mutagenesis1661L → N: Decreases enzyme activity by 95%. Ref.8 Ref.9
Mutagenesis1691G → A: Decreases enzyme activity by 64%. Ref.8 Ref.9
Mutagenesis2841S → I: Decreases enzyme activity by 87%. Impairs protein folding and/or stability. Ref.8
Mutagenesis2901V → L: No effect on enzyme activity. Ref.8
Mutagenesis3311F → A: Decreases enzyme activity by 50%. Ref.8 Ref.9
Mutagenesis3341L → A: Decreases enzyme activity by 86%. Ref.8 Ref.9
Mutagenesis3471V → A: Decreases enzyme activity by 45%. Ref.8 Ref.9
Mutagenesis3681M → A: Decreases enzyme activity by 52%. Ref.8 Ref.9

Secondary structure

................................................................................................ 477
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P50336 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 2444DEAC2E6C33EE

FASTA47750,765
        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 

« Hide

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Structural insight into human variegate porphyria disease."
Qin X., Tan Y., Wang L., Wang Z., Wang B., Wen X., Yang G., Xi Z., Shen Y.
FASEB J. 25:653-664(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH FAD AND ACIFLUORFEN, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, CHARACTERIZATION OF VARIANTS VP ASP-11; THR-12; PHE-15; PRO-20; PRO-38; ALA-40; GLU-40; TRP-59; PRO-73; GLY-84; PRO-85; PRO-106; PRO-138; ASP-139; VAL-143; CYS-152; PRO-154; MET-158; HIS-168; VAL-178; VAL-205; CYS-217; GLY-224; ARG-232; ASP-282; ASN-283; PRO-295; ARG-330; ALA-332; GLY-335; CYS-348; ALA-349; PRO-350; ARG-358; ASP-397; PHE-401; PRO-433; PRO-444; ARG-448; PRO-450 AND ARG-453, MUTAGENESIS OF LEU-74; ARG-97; LEU-166; GLY-169; SER-284; VAL-290; PHE-331; LEU-334; VAL-347 AND MET-368.
[9]"Quantitative structural insight into human variegate porphyria disease."
Wang B., Wen X., Qin X., Wang Z., Tan Y., Shen Y., Xi Z.
J. Biol. Chem. 288:11731-11740(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF MUTANTS GLY-59 AND GLN-59 IN COMPLEXES WITH FAD AND ACIFLUORFEN, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-59; ARG-97; LEU-166; GLY-169; PHE-331; LEU-334; VAL-347 AND MET-368, CHARACTERIZATION OF VARIANTS VP TRP-59; HIS-168; ARG-330; GLY-335; ALA-349; PHE-401 AND ARG-453.
[10]"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] [Europe PMC] [Abstract]
Cited for: VARIANT VP ARG-232, VARIANT HIS-304.
[11]"Identification of three mutations and associated haplotypes in the protoporphyrinogen oxidase gene in South African families with variegate porphyria."
Warnich L., Kotze M.J., Groenewald I.M., Groenewald J.Z., van Brakel M.G., van Heerden C.J., de Villiers J.N., van de Ven W.J., Schoenmakers E.F., Taketani S., Retief A.E.
Hum. Mol. Genet. 5:981-984(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VP PRO-20; TRP-59 AND CYS-168.
[12]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS VP TRP-59 AND CYS-168.
[13]"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] [Europe PMC] [Abstract]
Cited for: VARIANT VP CYS-152.
[14]"Molecular basis of variegate porphyria: a missense mutation in the protoporphyrinogen oxidase gene."
Frank J., Lam H., Zaider E., Poh-Fitzpatrick M., Christiano A.M.
J. Med. Genet. 35:244-247(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VP PRO-450.
[15]"Molecular characterization of homozygous variegate porphyria."
Roberts A.G., Puy H., Dailey T.A., Morgan R.R., Whatley S.D., Dailey H.A., Martasek P., Nordmann Y., Deybach J.C., Elder G.H.
Hum. Mol. Genet. 7:1921-1925(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VP GLU-169; ALA-349; ARG-358 AND PRO-433, CHARACTERIZATION OF VARIANTS VP GLU-169; ALA-349; ARG-358 AND PRO-433.
[16]"Variegate porphyria in Western Europe: identification of PPOX gene mutations in 104 families, extent of allelic heterogeneity, and absence of correlation between phenotype and type of mutation."
Whatley S.D., Puy H., Morgan R.R., Robreau A.M., Roberts A.G., Nordmann Y., Elder G.H., Deybach J.C.
Am. J. Hum. Genet. 65:984-994(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARG-256 AND HIS-304, VARIANTS VP PRO-38; GLU-40; PRO-73; GLY-84; PRO-85; VAL-143; CYS-152; PRO-154; MET-158; HIS-168; VAL-172; ARG-232; HIS-281 DEL; ASP-282; PRO-295; GLY-335; PRO-350; PRO-444; ARG-453 AND VAL-453.
[17]"Three novel mutations in the protoporphyrinogen oxidase gene in Japanese patients with variegate porphyria."
Maeda N., Horie Y., Sasaki Y., Adachi K., Nanba E., Nishida K., Saigo R., Nakagawa M., Kawasaki H., Kudo Y., Kondo M.
Clin. Biochem. 33:495-500(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VP ARG-448.
[18]"Two new mutations (H106P and L178V) in the protoporphyrinogen oxidase gene in Argentinean patients with variegate porphyria."
De Siervi A., Parera V.E., del C Batlle A.M., Rossetti M.V.
Hum. Mutat. 16:532-532(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VP PRO-106 AND VAL-178.
[19]"Homozygous variegate porphyria in South Africa: genotypic analysis in two cases."
Corrigall A.V., Hift R.J., Davids L.M., Hancock V., Meissner D., Kirsch R.E., Meissner P.N.
Mol. Genet. Metab. 69:323-330(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VP TRP-59; PRO-138 AND CYS-348.
[20]"Homozygous variegate porphyria: 20 y follow-up and characterization of molecular defect."
Kauppinen R., Timonen K., von und zu Fraunberg M., Laitinen E., Ahola H., Tenhunen R., Taketani S., Mustajoki P.
J. Invest. Dermatol. 116:610-613(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VP THR-12, VARIANT ARG-256, CHARACTERIZATION OF VARIANT VP THR-12, CHARACTERIZATION OF VARIANT ARG-256.
[21]"A spectrum of novel mutations in the protoporphyrinogen oxidase gene in 13 families with variegate porphyria."
Frank J., Jugert F.K., Merk H.F., Kalka K., Goerz G., Anderson K., Bickers D.R., Poh-Fitzpatrick M.B., Christiano A.M.
J. Invest. Dermatol. 116:821-823(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VP SER-11.
[22]"Identification of the first variegate porphyria mutation in an indigenous black South African and further evidence for heterogeneity in variegate porphyria."
Corrigall A.V., Hift R.J., Davids L.M., Hancock V., Meissner D., Kirsch R.E., Meissner P.N.
Mol. Genet. Metab. 73:91-96(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VP PHE-15 AND MET-290.
[23]"Expression and characterization of six mutations in the protoporphyrinogen oxidase gene among Finnish variegate porphyria patients."
von und zu Fraunberg M., Tenhunen R., Kauppinen R.
Mol. Med. 7:320-328(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VP CYS-152 AND PHE-401, CHARACTERIZATION OF VARIANT VP CYS-152.
[24]"Variegate porphyria in Western Australian Aboriginal patients."
Rossi E., Chin C.Y., Beilby J.P., Waso H.F., Warnich L.
Intern. Med. J. 32:445-450(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VP TRP-59; CYS-217 AND SER-236.
[25]"Kinetic and physical characterisation of recombinant wild-type and mutant human protoporphyrinogen oxidases."
Maneli M.H., Corrigall A.V., Klump H.H., Davids L.M., Kirsch R.E., Meissner P.N.
Biochim. Biophys. Acta 1650:10-21(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS VP PRO-20; TRP-59; CYS-168 AND CYS-348.
[26]"Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria."
Wiman A., Harper P., Floderus Y.
Clin. Genet. 64:122-130(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VP CYS-152; LEU-158; VAL-205 AND ARG-330.
[27]"Genetic analysis of variegate porphyria (VP) in Italy: identification of six novel mutations in the protoporphyrinogen oxidase (PPOX) gene."
D'Amato M., Bonuglia M., Barile S., Griso D., Macri A., Biolcati G.
Hum. Mutat. 21:448-448(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VP ASN-283.
[28]"Modulation of penetrance by the wild-type allele in dominantly inherited erythropoietic protoporphyria and acute hepatic porphyrias."
Gouya L., Puy H., Robreau A.-M., Lyoumi S., Lamoril J., Da Silva V., Grandchamp B., Deybach J.-C.
Hum. Genet. 114:256-262(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VP ALA-40.
[29]"A Chilean boy with severe photosensitivity and finger shortening: the first case of homozygous variegate porphyria in South America."
Poblete-Gutierrez P., Wolff C., Farias R., Frank J.
Br. J. Dermatol. 154:368-371(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VP SER-232.
[30]"Mitochondrial targeting of human protoporphyrinogen oxidase."
Davids L.M., Corrigall A.V., Meissner P.N.
Cell Biol. Int. 30:416-426(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS VP PRO-20; TRP-59 AND CYS-168.
[31]"Genetic studies in variegate porphyria in Spain. Identification of gene mutations and family study for carrier detection."
Lecha M., Badenas C., Puig S., Orfila J., Mila M., To-Figueras J., Munoz C., Mercader P., Herrero C.
J. Eur. Acad. Dermatol. Venereol. 20:974-979(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VP ARG-224.
[32]"Swiss patients with variegate porphyria have unique mutations."
Schneider-Yin X., Minder E.I.
Swiss. Med. Wkly. 136:515-519(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VP ASP-11.
[33]"Novel human pathological mutations. Gene symbol: PPOX. Disease: porphyria, variegate."
Ausenda S., Di Pierro E., Brancaleoni V., Besana V., Cappellini M.D.
Hum. Genet. 122:417-417(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VP ASP-139.
[34]"Genetic and biochemical studies in Argentinean patients with variegate porphyria."
Rossetti M.V., Granata B.X., Giudice J., Parera V.E., Batlle A.
BMC Med. Genet. 9:54-54(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VP VAL-34; GLY-224 AND ALA-332.
[35]"Novel human pathological mutations. Gene symbol: PPOX. Disease: porphyria, variegate."
Ausenda S., Moriondo V., Marchini S., Besana V., Di Pierro E., Brancaleoni V., Ventura P., Rocchi E., Cappellini M.D.
Hum. Genet. 125:344-344(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VP ASP-397.
[36]"Functional characterization of five protoporphyrinogen oxidase missense mutations found in Argentinean variegate porphyria patients."
Mendez M., Granata B.X., Jimenez M.J., Parera V.E., Batlle A., de Salamanca R.E., Rossetti M.V.
JIMD Rep. 4:91-97(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VP VAL-34; PHE-76; GLY-224; ALA-332 AND CYS-422, CHARACTERIZATION OF VARIANTS VP VAL-34; PHE-76; GLY-224; ALA-332 AND CYS-422.
[37]"Homozygous variegate porphyria presenting with developmental and language delay in childhood."
Pinder V.A., Holden S.T., Deshpande C., Siddiqui A., Mellerio J.E., Wraige E., Powell A.M.
Clin. Exp. Dermatol. 38:737-740(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VP ARG-57 AND ARG-420.
+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.
PIRA56449. JC4971.
RefSeqNP_000300.1. NM_000309.3.
NP_001116236.1. NM_001122764.1.
UniGeneHs.517373.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3NKSX-ray1.90A1-477[»]
4IVMX-ray2.77B1-477[»]
4IVOX-ray2.60B1-477[»]
ProteinModelPortalP50336.
SMRP50336. Positions 2-474.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111492. 5 interactions.
IntActP50336. 3 interactions.
MINTMINT-1402949.
STRING9606.ENSP00000343943.

Chemistry

BindingDBP50336.
ChEMBLCHEMBL1926488.

PTM databases

PhosphoSiteP50336.

Polymorphism databases

DMDM1709742.

Proteomic databases

PaxDbP50336.
PeptideAtlasP50336.
PRIDEP50336.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000352210; ENSP00000343943; ENSG00000143224.
ENST00000367999; ENSP00000356978; ENSG00000143224.
GeneID5498.
KEGGhsa:5498.
UCSCuc001fyg.2. human.

Organism-specific databases

CTD5498.
GeneCardsGC01P161136.
HGNCHGNC:9280. PPOX.
HPAHPA030123.
MIM176200. phenotype.
600923. gene.
neXtProtNX_P50336.
Orphanet79473. Porphyria variegata.
PharmGKBPA33608.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1232.
HOGENOMHOG000269479.
HOVERGENHBG001709.
InParanoidP50336.
KOK00231.
OMAPNGFLDS.
OrthoDBEOG7DJSMB.
PhylomeDBP50336.
TreeFamTF323479.

Enzyme and pathway databases

BioCycMetaCyc:HS07011-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP50336.
UniPathwayUPA00251; UER00324.

Gene expression databases

ArrayExpressP50336.
BgeeP50336.
CleanExHS_PPOX.
GenevestigatorP50336.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
3.90.660.20. 1 hit.
InterProIPR002937. Amino_oxidase.
IPR016040. NAD(P)-bd_dom.
IPR004572. Protoporphyrinogen_oxidase.
IPR027418. Protoporphyrinogen_oxidase_C.
[Graphical view]
PfamPF01593. Amino_oxidase. 1 hit.
[Graphical view]
TIGRFAMsTIGR00562. proto_IX_ox. 1 hit.
ProtoNetSearch...

Other

ChiTaRSPPOX. human.
GeneWikiPPOX.
GenomeRNAi5498.
NextBio21268.
PROP50336.
SOURCESearch...

Entry information

Entry namePPOX_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM