PPOX_HUMAN
ID PPOX_HUMAN Reviewed; 477 AA.
AC P50336; D3DVG0; Q5VTW8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Protoporphyrinogen oxidase;
DE Short=PPO;
DE EC=1.3.3.4;
GN Name=PPOX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Placenta;
RX PubMed=7713909; DOI=10.1074/jbc.270.14.8076;
RA Nishimura K., Taketani S., Inokuchi H.;
RT "Cloning of a human cDNA for protoporphyrinogen oxidase by complementation
RT in vivo of a hemG mutant of Escherichia coli.";
RL J. Biol. Chem. 270:8076-8080(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=8771201; DOI=10.1002/pro.5560050112;
RA Dailey T.A., Dailey H.A.;
RT "Human protoporphyrinogen oxidase: expression, purification, and
RT characterization of the cloned enzyme.";
RL Protein Sci. 5:98-105(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-304.
RX PubMed=8806618; DOI=10.1006/bbrc.1996.1337;
RA Puy H., Robreau A.-M., Rosipal R., Nordmann Y., Deybach J.-C.;
RT "Protoporphyrinogen oxidase: complete genomic sequence and polymorphisms in
RT the human gene.";
RL Biochem. Biophys. Res. Commun. 226:226-230(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH FAD AND ACIFLUORFEN,
RP CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, CHARACTERIZATION OF VARIANTS VP
RP ASP-11; THR-12; PHE-15; PRO-20; PRO-38; ALA-40; GLU-40; TRP-59; PRO-73;
RP GLY-84; PRO-85; PRO-106; PRO-138; ASP-139; VAL-143; CYS-152; PRO-154;
RP MET-158; HIS-168; VAL-178; VAL-205; CYS-217; GLY-224; ARG-232; ASP-282;
RP ASN-283; PRO-295; ARG-330; ALA-332; GLY-335; CYS-348; ALA-349; PRO-350;
RP ARG-358; ASP-397; PHE-401; PRO-433; PRO-444; ARG-448; PRO-450 AND ARG-453,
RP AND MUTAGENESIS OF LEU-74; ARG-97; LEU-166; GLY-169; SER-284; VAL-290;
RP PHE-331; LEU-334; VAL-347 AND MET-368.
RX PubMed=21048046; DOI=10.1096/fj.10-170811;
RA Qin X., Tan Y., Wang L., Wang Z., Wang B., Wen X., Yang G., Xi Z., Shen Y.;
RT "Structural insight into human variegate porphyria disease.";
RL FASEB J. 25:653-664(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF MUTANTS GLY-59 AND GLN-59 IN
RP COMPLEXES WITH FAD AND ACIFLUORFEN, FUNCTION, CATALYTIC ACTIVITY,
RP MUTAGENESIS OF ARG-59; ARG-97; LEU-166; GLY-169; PHE-331; LEU-334; VAL-347
RP AND MET-368, AND CHARACTERIZATION OF VARIANTS VP TRP-59; HIS-168; ARG-330;
RP GLY-335; ALA-349; PHE-401 AND ARG-453.
RX PubMed=23467411; DOI=10.1074/jbc.m113.459768;
RA Wang B., Wen X., Qin X., Wang Z., Tan Y., Shen Y., Xi Z.;
RT "Quantitative structural insight into human variegate porphyria disease.";
RL J. Biol. Chem. 288:11731-11740(2013).
RN [11]
RP VARIANT VP ARG-232, AND VARIANT HIS-304.
RX PubMed=8852667; DOI=10.1093/hmg/5.3.407;
RA Deybach J.-C., Puy H., Robreau A.-M., Lamoril J., da Silva V.,
RA Grandchamp B., Nordmann Y.;
RT "Mutations in the protoporphyrinogen oxidase gene in patients with
RT variegate porphyria.";
RL Hum. Mol. Genet. 5:407-410(1996).
RN [12]
RP VARIANTS VP PRO-20; TRP-59 AND CYS-168.
RX PubMed=8817334; DOI=10.1093/hmg/5.7.981;
RA Warnich L., Kotze M.J., Groenewald I.M., Groenewald J.Z., van Brakel M.G.,
RA van Heerden C.J., de Villiers J.N., van de Ven W.J., Schoenmakers E.F.,
RA Taketani S., Retief A.E.;
RT "Identification of three mutations and associated haplotypes in the
RT protoporphyrinogen oxidase gene in South African families with variegate
RT porphyria.";
RL Hum. Mol. Genet. 5:981-984(1996).
RN [13]
RP VARIANTS VP TRP-59 AND CYS-168.
RX PubMed=8673113; DOI=10.1038/ng0596-95;
RA Meissner P.N., Dailey T.A., Hift R.J., Ziman M., Corrigall A.V.,
RA Roberts A.G., Meissner D.M., Kirsch R.E., Dailey H.A.;
RT "A R59W mutation in human protoporphyrinogen oxidase results in decreased
RT enzyme activity and is prevalent in South Africans with variegate
RT porphyria.";
RL Nat. Genet. 13:95-97(1996).
RN [14]
RP VARIANT VP CYS-152.
RX PubMed=9763307; DOI=10.1007/s004030050333;
RA Frank J., Poh-Fitzpatrick M.B., King L.E. Jr., Christiano A.M.;
RT "The genetic basis of 'Scarsdale Gourmet Diet' variegate porphyria: a
RT missense mutation in the protoporphyrinogen oxidase gene.";
RL Arch. Dermatol. Res. 290:441-445(1998).
RN [15]
RP VARIANT VP PRO-450.
RX PubMed=9541112; DOI=10.1136/jmg.35.3.244;
RA Frank J., Lam H., Zaider E., Poh-Fitzpatrick M., Christiano A.M.;
RT "Molecular basis of variegate porphyria: a missense mutation in the
RT protoporphyrinogen oxidase gene.";
RL J. Med. Genet. 35:244-247(1998).
RN [16]
RP VARIANTS VP GLU-169; ALA-349; ARG-358 AND PRO-433, AND CHARACTERIZATION OF
RP VARIANTS VP GLU-169; ALA-349; ARG-358 AND PRO-433.
RX PubMed=9811936; DOI=10.1093/hmg/7.12.1921;
RA Roberts A.G., Puy H., Dailey T.A., Morgan R.R., Whatley S.D., Dailey H.A.,
RA Martasek P., Nordmann Y., Deybach J.C., Elder G.H.;
RT "Molecular characterization of homozygous variegate porphyria.";
RL Hum. Mol. Genet. 7:1921-1925(1998).
RN [17]
RP VARIANTS ARG-256 AND HIS-304, AND VARIANTS VP PRO-38; GLU-40; PRO-73;
RP GLY-84; PRO-85; VAL-143; CYS-152; PRO-154; MET-158; HIS-168; VAL-172;
RP ARG-232; HIS-281 DEL; ASP-282; PRO-295; GLY-335; PRO-350; PRO-444; ARG-453
RP AND VAL-453.
RX PubMed=10486317; DOI=10.1086/302586;
RA Whatley S.D., Puy H., Morgan R.R., Robreau A.M., Roberts A.G., Nordmann Y.,
RA Elder G.H., Deybach J.C.;
RT "Variegate porphyria in Western Europe: identification of PPOX gene
RT mutations in 104 families, extent of allelic heterogeneity, and absence of
RT correlation between phenotype and type of mutation.";
RL Am. J. Hum. Genet. 65:984-994(1999).
RN [18]
RP VARIANT VP ARG-448.
RX PubMed=11074242; DOI=10.1016/s0009-9120(00)00142-9;
RA Maeda N., Horie Y., Sasaki Y., Adachi K., Nanba E., Nishida K., Saigo R.,
RA Nakagawa M., Kawasaki H., Kudo Y., Kondo M.;
RT "Three novel mutations in the protoporphyrinogen oxidase gene in Japanese
RT patients with variegate porphyria.";
RL Clin. Biochem. 33:495-500(2000).
RN [19]
RP VARIANTS VP PRO-106 AND VAL-178.
RX PubMed=11102990;
RX DOI=10.1002/1098-1004(200012)16:6<532::aid-humu18>3.0.co;2-s;
RA De Siervi A., Parera V.E., del C Batlle A.M., Rossetti M.V.;
RT "Two new mutations (H106P and L178V) in the protoporphyrinogen oxidase gene
RT in Argentinean patients with variegate porphyria.";
RL Hum. Mutat. 16:532-532(2000).
RN [20]
RP VARIANTS VP TRP-59; PRO-138 AND CYS-348.
RX PubMed=10870850; DOI=10.1006/mgme.2000.2975;
RA Corrigall A.V., Hift R.J., Davids L.M., Hancock V., Meissner D.,
RA Kirsch R.E., Meissner P.N.;
RT "Homozygous variegate porphyria in South Africa: genotypic analysis in two
RT cases.";
RL Mol. Genet. Metab. 69:323-330(2000).
RN [21]
RP VARIANT VP THR-12, VARIANT ARG-256, CHARACTERIZATION OF VARIANT VP THR-12,
RP AND CHARACTERIZATION OF VARIANT ARG-256.
RX PubMed=11286631; DOI=10.1046/j.1523-1747.2001.01293.x;
RA Kauppinen R., Timonen K., von und zu Fraunberg M., Laitinen E., Ahola H.,
RA Tenhunen R., Taketani S., Mustajoki P.;
RT "Homozygous variegate porphyria: 20 y follow-up and characterization of
RT molecular defect.";
RL J. Invest. Dermatol. 116:610-613(2001).
RN [22]
RP VARIANT VP SER-11.
RX PubMed=11348478; DOI=10.1046/j.1523-1747.2001.01308.x;
RA Frank J., Jugert F.K., Merk H.F., Kalka K., Goerz G., Anderson K.,
RA Bickers D.R., Poh-Fitzpatrick M.B., Christiano A.M.;
RT "A spectrum of novel mutations in the protoporphyrinogen oxidase gene in 13
RT families with variegate porphyria.";
RL J. Invest. Dermatol. 116:821-823(2001).
RN [23]
RP VARIANTS VP PHE-15 AND MET-290.
RX PubMed=11350188; DOI=10.1006/mgme.2001.3163;
RA Corrigall A.V., Hift R.J., Davids L.M., Hancock V., Meissner D.,
RA Kirsch R.E., Meissner P.N.;
RT "Identification of the first variegate porphyria mutation in an indigenous
RT black South African and further evidence for heterogeneity in variegate
RT porphyria.";
RL Mol. Genet. Metab. 73:91-96(2001).
RN [24]
RP VARIANTS VP CYS-152 AND PHE-401, AND CHARACTERIZATION OF VARIANT VP
RP CYS-152.
RX PubMed=11474578;
RA von und zu Fraunberg M., Tenhunen R., Kauppinen R.;
RT "Expression and characterization of six mutations in the protoporphyrinogen
RT oxidase gene among Finnish variegate porphyria patients.";
RL Mol. Med. 7:320-328(2001).
RN [25]
RP VARIANTS VP TRP-59; CYS-217 AND SER-236.
RX PubMed=12380696; DOI=10.1046/j.1445-5994.2002.00274.x;
RA Rossi E., Chin C.Y., Beilby J.P., Waso H.F., Warnich L.;
RT "Variegate porphyria in Western Australian Aboriginal patients.";
RL Intern. Med. J. 32:445-450(2002).
RN [26]
RP CHARACTERIZATION OF VARIANTS VP PRO-20; TRP-59; CYS-168 AND CYS-348.
RX PubMed=12922165; DOI=10.1016/s1570-9639(03)00186-9;
RA Maneli M.H., Corrigall A.V., Klump H.H., Davids L.M., Kirsch R.E.,
RA Meissner P.N.;
RT "Kinetic and physical characterisation of recombinant wild-type and mutant
RT human protoporphyrinogen oxidases.";
RL Biochim. Biophys. Acta 1650:10-21(2003).
RN [27]
RP VARIANTS VP CYS-152; LEU-158; VAL-205 AND ARG-330.
RX PubMed=12859407; DOI=10.1034/j.1399-0004.2003.00116.x;
RA Wiman A., Harper P., Floderus Y.;
RT "Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish
RT families with variegate porphyria.";
RL Clin. Genet. 64:122-130(2003).
RN [28]
RP VARIANT VP ASN-283.
RX PubMed=12655566; DOI=10.1002/humu.9125;
RA D'Amato M., Bonuglia M., Barile S., Griso D., Macri A., Biolcati G.;
RT "Genetic analysis of variegate porphyria (VP) in Italy: identification of
RT six novel mutations in the protoporphyrinogen oxidase (PPOX) gene.";
RL Hum. Mutat. 21:448-448(2003).
RN [29]
RP VARIANT VP ALA-40.
RX PubMed=14669009; DOI=10.1007/s00439-003-1059-5;
RA Gouya L., Puy H., Robreau A.-M., Lyoumi S., Lamoril J., Da Silva V.,
RA Grandchamp B., Deybach J.-C.;
RT "Modulation of penetrance by the wild-type allele in dominantly inherited
RT erythropoietic protoporphyria and acute hepatic porphyrias.";
RL Hum. Genet. 114:256-262(2004).
RN [30]
RP VARIANT VP SER-232.
RX PubMed=16433813; DOI=10.1111/j.1365-2133.2005.06978.x;
RA Poblete-Gutierrez P., Wolff C., Farias R., Frank J.;
RT "A Chilean boy with severe photosensitivity and finger shortening: the
RT first case of homozygous variegate porphyria in South America.";
RL Br. J. Dermatol. 154:368-371(2006).
RN [31]
RP CHARACTERIZATION OF VARIANTS VP PRO-20; TRP-59 AND CYS-168.
RX PubMed=16621625; DOI=10.1016/j.cellbi.2006.02.001;
RA Davids L.M., Corrigall A.V., Meissner P.N.;
RT "Mitochondrial targeting of human protoporphyrinogen oxidase.";
RL Cell Biol. Int. 30:416-426(2006).
RN [32]
RP VARIANT VP ARG-224.
RX PubMed=16922948; DOI=10.1111/j.1468-3083.2006.01705.x;
RA Lecha M., Badenas C., Puig S., Orfila J., Mila M., To-Figueras J.,
RA Munoz C., Mercader P., Herrero C.;
RT "Genetic studies in variegate porphyria in Spain. Identification of gene
RT mutations and family study for carrier detection.";
RL J. Eur. Acad. Dermatol. Venereol. 20:974-979(2006).
RN [33]
RP VARIANT VP ASP-11.
RX PubMed=16947091;
RA Schneider-Yin X., Minder E.I.;
RT "Swiss patients with variegate porphyria have unique mutations.";
RL Swiss. Med. Wkly. 136:515-519(2006).
RN [34]
RP VARIANT VP ASP-139.
RX PubMed=18350656;
RA Ausenda S., Di Pierro E., Brancaleoni V., Besana V., Cappellini M.D.;
RT "Novel human pathological mutations. Gene symbol: PPOX. Disease: porphyria,
RT variegate.";
RL Hum. Genet. 122:417-417(2007).
RN [35]
RP VARIANTS VP VAL-34; GLY-224 AND ALA-332.
RX PubMed=18570668; DOI=10.1186/1471-2350-9-54;
RA Rossetti M.V., Granata B.X., Giudice J., Parera V.E., Batlle A.;
RT "Genetic and biochemical studies in Argentinean patients with variegate
RT porphyria.";
RL BMC Med. Genet. 9:54-54(2008).
RN [36]
RP VARIANT VP ASP-397.
RX PubMed=19320019;
RA Ausenda S., Moriondo V., Marchini S., Besana V., Di Pierro E.,
RA Brancaleoni V., Ventura P., Rocchi E., Cappellini M.D.;
RT "Novel human pathological mutations. Gene symbol: PPOX. Disease: porphyria,
RT variegate.";
RL Hum. Genet. 125:344-344(2009).
RN [37]
RP VARIANTS VP VAL-34; PHE-76; GLY-224; ALA-332 AND CYS-422, AND
RP CHARACTERIZATION OF VARIANTS VP VAL-34; PHE-76; GLY-224; ALA-332 AND
RP CYS-422.
RX PubMed=23430901; DOI=10.1007/8904_2011_77;
RA Mendez M., Granata B.X., Jimenez M.J., Parera V.E., Batlle A.,
RA de Salamanca R.E., Rossetti M.V.;
RT "Functional characterization of five protoporphyrinogen oxidase missense
RT mutations found in Argentinean variegate porphyria patients.";
RL JIMD Rep. 4:91-97(2012).
RN [38]
RP VARIANTS VP ARG-57 AND ARG-420.
RX PubMed=24073655; DOI=10.1111/ced.12071;
RA Pinder V.A., Holden S.T., Deshpande C., Siddiqui A., Mellerio J.E.,
RA Wraige E., Powell A.M.;
RT "Homozygous variegate porphyria presenting with developmental and language
RT delay in childhood.";
RL Clin. Exp. Dermatol. 38:737-740(2013).
CC -!- FUNCTION: Catalyzes the 6-electron oxidation of protoporphyrinogen-IX
CC to form protoporphyrin-IX. {ECO:0000269|PubMed:21048046,
CC ECO:0000269|PubMed:23467411, ECO:0000269|PubMed:7713909}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 O2 + protoporphyrinogen IX = 3 H2O2 + protoporphyrin IX;
CC Xref=Rhea:RHEA:25576, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57306, ChEBI:CHEBI:57307; EC=1.3.3.4;
CC Evidence={ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:23467411};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Note=Binds 1 FAD per subunit.;
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; protoporphyrin-IX from protoporphyrinogen-IX: step 1/1.
CC -!- SUBUNIT: Monomer. Homodimer. {ECO:0000269|PubMed:21048046}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}; Intermembrane side
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, placenta, lung, liver,
CC skeletal muscle, kidney and pancreas.
CC -!- DISEASE: Variegate porphyria (VP) [MIM:176200]: A form of porphyria.
CC Porphyrias are inherited defects in the biosynthesis of heme, resulting
CC in the accumulation and increased excretion of porphyrins or porphyrin
CC precursors. They are classified as erythropoietic or hepatic, depending
CC on whether the enzyme deficiency occurs in red blood cells or in the
CC liver. Variegate porphyria is the most common form of porphyria in
CC South Africa. It is characterized by skin hyperpigmentation and
CC hypertrichosis, abdominal pain, tachycardia, hypertension and
CC neuromuscular disturbances. High fecal levels of protoporphyrin and
CC coproporphyrin, increased urine uroporphyrins and iron overload are
CC typical markers of the disease. {ECO:0000269|PubMed:10486317,
CC ECO:0000269|PubMed:10870850, ECO:0000269|PubMed:11074242,
CC ECO:0000269|PubMed:11102990, ECO:0000269|PubMed:11286631,
CC ECO:0000269|PubMed:11348478, ECO:0000269|PubMed:11350188,
CC ECO:0000269|PubMed:11474578, ECO:0000269|PubMed:12380696,
CC ECO:0000269|PubMed:12655566, ECO:0000269|PubMed:12859407,
CC ECO:0000269|PubMed:12922165, ECO:0000269|PubMed:14669009,
CC ECO:0000269|PubMed:16433813, ECO:0000269|PubMed:16621625,
CC ECO:0000269|PubMed:16922948, ECO:0000269|PubMed:16947091,
CC ECO:0000269|PubMed:18350656, ECO:0000269|PubMed:18570668,
CC ECO:0000269|PubMed:19320019, ECO:0000269|PubMed:21048046,
CC ECO:0000269|PubMed:23430901, ECO:0000269|PubMed:23467411,
CC ECO:0000269|PubMed:24073655, ECO:0000269|PubMed:8673113,
CC ECO:0000269|PubMed:8817334, ECO:0000269|PubMed:8852667,
CC ECO:0000269|PubMed:9541112, ECO:0000269|PubMed:9763307,
CC ECO:0000269|PubMed:9811936}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. Mutations leading to
CC severe PPOX deficiency cause the rare homozygous variant form of VP.
CC Missense mutations that preserve 10%-25% of wild-type activity may not
CC cause clinically overt VP in heterozygotes (PubMed:9811936). Mutations
CC with intermediate effect on catalytic activity may cause VP, but with a
CC low clinical penetrance (PubMed:10486317).
CC {ECO:0000269|PubMed:10486317, ECO:0000269|PubMed:9811936}.
CC -!- SIMILARITY: Belongs to the protoporphyrinogen/coproporphyrinogen
CC oxidase family. Protoporphyrinogen oxidase subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Protoporphyrinogen oxidase entry;
CC URL="https://en.wikipedia.org/wiki/Protoporphyrinogen_oxidase";
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DR EMBL; D38537; BAA07538.1; -; mRNA.
DR EMBL; U26446; AAA67690.1; -; mRNA.
DR EMBL; X99450; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590714; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52636.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52639.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52641.1; -; Genomic_DNA.
DR EMBL; BC002357; AAH02357.1; -; mRNA.
DR CCDS; CCDS1221.1; -.
DR PIR; JC4971; A56449.
DR RefSeq; NP_000300.1; NM_000309.3.
DR RefSeq; NP_001116236.1; NM_001122764.1.
DR PDB; 3NKS; X-ray; 1.90 A; A=1-477.
DR PDB; 4IVM; X-ray; 2.77 A; B=1-477.
DR PDB; 4IVO; X-ray; 2.60 A; B=1-477.
DR PDBsum; 3NKS; -.
DR PDBsum; 4IVM; -.
DR PDBsum; 4IVO; -.
DR AlphaFoldDB; P50336; -.
DR SMR; P50336; -.
DR BioGRID; 111492; 121.
DR IntAct; P50336; 34.
DR MINT; P50336; -.
DR STRING; 9606.ENSP00000356978; -.
DR BindingDB; P50336; -.
DR ChEMBL; CHEMBL1926488; -.
DR iPTMnet; P50336; -.
DR PhosphoSitePlus; P50336; -.
DR SwissPalm; P50336; -.
DR BioMuta; PPOX; -.
DR DMDM; 1709742; -.
DR EPD; P50336; -.
DR jPOST; P50336; -.
DR MassIVE; P50336; -.
DR MaxQB; P50336; -.
DR PaxDb; P50336; -.
DR PeptideAtlas; P50336; -.
DR PRIDE; P50336; -.
DR ProteomicsDB; 56214; -.
DR Antibodypedia; 34299; 270 antibodies from 28 providers.
DR DNASU; 5498; -.
DR Ensembl; ENST00000352210.9; ENSP00000343943.5; ENSG00000143224.18.
DR Ensembl; ENST00000367999.9; ENSP00000356978.4; ENSG00000143224.18.
DR GeneID; 5498; -.
DR KEGG; hsa:5498; -.
DR MANE-Select; ENST00000367999.9; ENSP00000356978.4; NM_001122764.3; NP_001116236.1.
DR UCSC; uc001fyg.3; human.
DR CTD; 5498; -.
DR DisGeNET; 5498; -.
DR GeneCards; PPOX; -.
DR GeneReviews; PPOX; -.
DR HGNC; HGNC:9280; PPOX.
DR HPA; ENSG00000143224; Low tissue specificity.
DR MalaCards; PPOX; -.
DR MIM; 176200; phenotype.
DR MIM; 600923; gene.
DR neXtProt; NX_P50336; -.
DR OpenTargets; ENSG00000143224; -.
DR Orphanet; 79473; Porphyria variegata.
DR PharmGKB; PA33608; -.
DR VEuPathDB; HostDB:ENSG00000143224; -.
DR eggNOG; KOG1276; Eukaryota.
DR GeneTree; ENSGT00390000008744; -.
DR HOGENOM; CLU_009629_2_1_1; -.
DR InParanoid; P50336; -.
DR OMA; WFDQWFG; -.
DR OrthoDB; 1578484at2759; -.
DR PhylomeDB; P50336; -.
DR TreeFam; TF323479; -.
DR BioCyc; MetaCyc:HS07011-MON; -.
DR BRENDA; 1.3.3.4; 2681.
DR PathwayCommons; P50336; -.
DR Reactome; R-HSA-189451; Heme biosynthesis.
DR SABIO-RK; P50336; -.
DR SignaLink; P50336; -.
DR UniPathway; UPA00251; UER00324.
DR BioGRID-ORCS; 5498; 23 hits in 1080 CRISPR screens.
DR GeneWiki; PPOX; -.
DR GenomeRNAi; 5498; -.
DR Pharos; P50336; Tchem.
DR PRO; PR:P50336; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P50336; protein.
DR Bgee; ENSG00000143224; Expressed in right uterine tube and 180 other tissues.
DR ExpressionAtlas; P50336; baseline and differential.
DR Genevisible; P50336; HS.
DR GO; GO:0031304; C:intrinsic component of mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; TAS:Reactome.
DR GO; GO:0031966; C:mitochondrial membrane; IMP:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; TAS:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0004729; F:oxygen-dependent protoporphyrinogen oxidase activity; IDA:UniProtKB.
DR GO; GO:0006783; P:heme biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006779; P:porphyrin-containing compound biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002937; Amino_oxidase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR004572; Protoporphyrinogen_oxidase.
DR Pfam; PF01593; Amino_oxidase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR TIGRFAMs; TIGR00562; proto_IX_ox; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; FAD; Flavoprotein; Heme biosynthesis;
KW Membrane; Mitochondrion; Mitochondrion inner membrane; Oxidoreductase;
KW Porphyrin biosynthesis; Reference proteome.
FT CHAIN 1..477
FT /note="Protoporphyrinogen oxidase"
FT /id="PRO_0000135270"
FT BINDING 9..14
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21048046"
FT BINDING 34..35
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21048046"
FT BINDING 42
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21048046"
FT BINDING 57..60
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21048046"
FT BINDING 257
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21048046"
FT BINDING 449
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21048046"
FT BINDING 454..456
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21048046"
FT VARIANT 11
FT /note="G -> D (in VP; abolishes enzyme activity; impairs
FT protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:16947091,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070378"
FT VARIANT 11
FT /note="G -> S (in VP)"
FT /evidence="ECO:0000269|PubMed:11348478"
FT /id="VAR_070377"
FT VARIANT 12
FT /note="I -> T (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability;
FT dbSNP:rs28936677)"
FT /evidence="ECO:0000269|PubMed:11286631,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070379"
FT VARIANT 15
FT /note="L -> F (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability;
FT dbSNP:rs769452432)"
FT /evidence="ECO:0000269|PubMed:11350188,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070380"
FT VARIANT 20
FT /note="H -> P (in VP; strongly decreases enzyme activity;
FT more resistant to thermal denaturation than wild-type
FT enzyme; abolishes mitochondrial protein targeting and
FT localization; dbSNP:rs121918326)"
FT /evidence="ECO:0000269|PubMed:12922165,
FT ECO:0000269|PubMed:16621625, ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:8817334"
FT /id="VAR_070381"
FT VARIANT 34
FT /note="E -> V (in VP; decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:18570668,
FT ECO:0000269|PubMed:23430901"
FT /id="VAR_070382"
FT VARIANT 38
FT /note="R -> P (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070383"
FT VARIANT 40
FT /note="G -> A (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:14669009,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070384"
FT VARIANT 40
FT /note="G -> E (in VP; abolishes enzyme activity; impairs
FT protein folding and/or stability; dbSNP:rs1317835140)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070385"
FT VARIANT 57
FT /note="G -> R (in VP; dbSNP:rs764352037)"
FT /evidence="ECO:0000269|PubMed:24073655"
FT /id="VAR_070386"
FT VARIANT 59
FT /note="R -> W (in VP; strongly decreases enzyme activity;
FT does not affect mitochondrial protein targeting and
FT localization; more resistant to thermal denaturation than
FT wild-type enzyme; dbSNP:rs121918324)"
FT /evidence="ECO:0000269|PubMed:10870850,
FT ECO:0000269|PubMed:12380696, ECO:0000269|PubMed:12922165,
FT ECO:0000269|PubMed:16621625, ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:23467411, ECO:0000269|PubMed:8673113,
FT ECO:0000269|PubMed:8817334"
FT /id="VAR_003686"
FT VARIANT 73
FT /note="L -> P (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070387"
FT VARIANT 76
FT /note="S -> F (in VP; decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:23430901"
FT /id="VAR_070388"
FT VARIANT 84
FT /note="V -> G (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070389"
FT VARIANT 85
FT /note="L -> P (in VP; abolishes enzyme activity; impairs
FT protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070390"
FT VARIANT 106
FT /note="H -> P (in VP; strongly decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:11102990,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070391"
FT VARIANT 138
FT /note="R -> P (in VP; slightly decreases enzyme activity;
FT dbSNP:rs767419411)"
FT /evidence="ECO:0000269|PubMed:10870850,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070392"
FT VARIANT 139
FT /note="G -> D (in VP; strongly decreases enzyme activity;
FT dbSNP:rs369381477)"
FT /evidence="ECO:0000269|PubMed:18350656,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070393"
FT VARIANT 143
FT /note="D -> V (in VP; strongly decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070394"
FT VARIANT 152
FT /note="R -> C (in VP; strongly decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:11474578, ECO:0000269|PubMed:12859407,
FT ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:9763307"
FT /id="VAR_003687"
FT VARIANT 154
FT /note="L -> P (in VP; strongly decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070395"
FT VARIANT 158
FT /note="V -> L (in VP)"
FT /evidence="ECO:0000269|PubMed:12859407"
FT /id="VAR_070396"
FT VARIANT 158
FT /note="V -> M (in VP; strongly decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070397"
FT VARIANT 168
FT /note="R -> C (in VP; strongly decreases enzyme activity;
FT does not affect mitochondrial protein targeting and
FT localization; dbSNP:rs121918325)"
FT /evidence="ECO:0000269|PubMed:12922165,
FT ECO:0000269|PubMed:16621625, ECO:0000269|PubMed:8673113,
FT ECO:0000269|PubMed:8817334"
FT /id="VAR_003688"
FT VARIANT 168
FT /note="R -> H (in VP; strongly decreases enzyme activity;
FT dbSNP:rs41270025)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:23467411"
FT /id="VAR_070398"
FT VARIANT 169
FT /note="G -> E (in VP; strongly decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:9811936"
FT /id="VAR_070399"
FT VARIANT 172
FT /note="A -> V (in VP)"
FT /evidence="ECO:0000269|PubMed:10486317"
FT /id="VAR_070400"
FT VARIANT 178
FT /note="L -> V (in VP; strongly decreases enzyme activity;
FT dbSNP:rs757473753)"
FT /evidence="ECO:0000269|PubMed:11102990,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070401"
FT VARIANT 205
FT /note="A -> V (in VP; no effect on enzyme activity)"
FT /evidence="ECO:0000269|PubMed:12859407,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070402"
FT VARIANT 217
FT /note="R -> C (in VP; decreases enzyme activity; impairs
FT protein folding and/or stability; dbSNP:rs751599052)"
FT /evidence="ECO:0000269|PubMed:12380696,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070403"
FT VARIANT 224
FT /note="W -> G (in VP; abolishes enzyme activity; impairs
FT protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:18570668,
FT ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:23430901"
FT /id="VAR_070404"
FT VARIANT 224
FT /note="W -> R (in VP)"
FT /evidence="ECO:0000269|PubMed:16922948"
FT /id="VAR_070405"
FT VARIANT 232
FT /note="G -> R (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability;
FT dbSNP:rs121918323)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:8852667"
FT /id="VAR_003689"
FT VARIANT 232
FT /note="G -> S (in VP)"
FT /evidence="ECO:0000269|PubMed:16433813"
FT /id="VAR_070406"
FT VARIANT 236
FT /note="L -> S (in VP)"
FT /evidence="ECO:0000269|PubMed:12380696"
FT /id="VAR_070407"
FT VARIANT 256
FT /note="P -> R (found in patients with the homozygous
FT variant of variegate porphyria; unknown pathological
FT significance; results in reduction of activity in a
FT prokariotyc expression system but has normal activity when
FT expressed in an eukaryotic system; dbSNP:rs12735723)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:11286631"
FT /id="VAR_034395"
FT VARIANT 281
FT /note="Missing (in VP)"
FT /evidence="ECO:0000269|PubMed:10486317"
FT /id="VAR_070408"
FT VARIANT 282
FT /note="V -> D (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070409"
FT VARIANT 283
FT /note="I -> N (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:12655566,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070410"
FT VARIANT 290
FT /note="V -> M (in VP)"
FT /evidence="ECO:0000269|PubMed:11350188"
FT /id="VAR_070411"
FT VARIANT 295
FT /note="L -> P (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070412"
FT VARIANT 304
FT /note="R -> H (in dbSNP:rs36013429)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:8806618, ECO:0000269|PubMed:8852667"
FT /id="VAR_003690"
FT VARIANT 330
FT /note="G -> R (in VP; strongly decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:12859407,
FT ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:23467411"
FT /id="VAR_070413"
FT VARIANT 332
FT /note="G -> A (in VP; abolishes activity; impairs protein
FT folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:18570668,
FT ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:23430901"
FT /id="VAR_070414"
FT VARIANT 335
FT /note="V -> G (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:23467411"
FT /id="VAR_070415"
FT VARIANT 348
FT /note="Y -> C (in VP; results in enzyme activity decrease;
FT impairs protein folding and/or stability; more resistant to
FT thermal denaturation than wild-type enzyme;
FT dbSNP:rs900431442)"
FT /evidence="ECO:0000269|PubMed:10870850,
FT ECO:0000269|PubMed:12922165, ECO:0000269|PubMed:21048046"
FT /id="VAR_070416"
FT VARIANT 349
FT /note="D -> A (in VP; decreases enzyme activity;
FT dbSNP:rs28936676)"
FT /evidence="ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:23467411, ECO:0000269|PubMed:9811936"
FT /id="VAR_070417"
FT VARIANT 350
FT /note="S -> P (in VP; abolishes activity; impairs protein
FT folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070418"
FT VARIANT 358
FT /note="G -> R (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability;
FT dbSNP:rs374936130)"
FT /evidence="ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:9811936"
FT /id="VAR_070419"
FT VARIANT 397
FT /note="A -> D (in VP; strongly decreases enzyme activity;
FT impairs protein folding and/or stability;
FT dbSNP:rs141274934)"
FT /evidence="ECO:0000269|PubMed:19320019,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070420"
FT VARIANT 401
FT /note="L -> F (in VP; strongly decreases enzyme activity;
FT dbSNP:rs776530007)"
FT /evidence="ECO:0000269|PubMed:11474578,
FT ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:23467411"
FT /id="VAR_070421"
FT VARIANT 420
FT /note="P -> R (in VP)"
FT /evidence="ECO:0000269|PubMed:24073655"
FT /id="VAR_070422"
FT VARIANT 422
FT /note="Y -> C (in VP; decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:23430901"
FT /id="VAR_070423"
FT VARIANT 433
FT /note="A -> P (in VP; decreases enzyme activity; impairs
FT protein folding and/or stability; dbSNP:rs1361576529)"
FT /evidence="ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:9811936"
FT /id="VAR_070424"
FT VARIANT 444
FT /note="L -> P (in VP; strongly decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070425"
FT VARIANT 448
FT /note="G -> R (in VP; abolishes enzyme activity; impairs
FT protein folding and/or stability)"
FT /evidence="ECO:0000269|PubMed:11074242,
FT ECO:0000269|PubMed:21048046"
FT /id="VAR_070426"
FT VARIANT 450
FT /note="S -> P (in VP; strongly decreases enzyme activity)"
FT /evidence="ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:9541112"
FT /id="VAR_070427"
FT VARIANT 453
FT /note="G -> R (in VP; strongly decreases enzyme activity;
FT dbSNP:rs928944841)"
FT /evidence="ECO:0000269|PubMed:10486317,
FT ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:23467411"
FT /id="VAR_070428"
FT VARIANT 453
FT /note="G -> V (in VP)"
FT /evidence="ECO:0000269|PubMed:10486317"
FT /id="VAR_070429"
FT MUTAGEN 59
FT /note="R->G: Decreases enzyme activity by 75%."
FT /evidence="ECO:0000269|PubMed:23467411"
FT MUTAGEN 59
FT /note="R->Q: Decreases enzyme activity by 90%. Strongly
FT decreases affinity for protoporphyrinogen-IX."
FT /evidence="ECO:0000269|PubMed:23467411"
FT MUTAGEN 74
FT /note="L->P: Abolishes enzyme activity. Impairs protein
FT folding and/or stability."
FT /evidence="ECO:0000269|PubMed:21048046"
FT MUTAGEN 97
FT /note="R->D: Decreases enzyme activity by 89%. Impairs
FT protein folding and/or stability."
FT /evidence="ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:23467411"
FT MUTAGEN 166
FT /note="L->N: Decreases enzyme activity by 95%."
FT /evidence="ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:23467411"
FT MUTAGEN 169
FT /note="G->A: Decreases enzyme activity by 64%."
FT /evidence="ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:23467411"
FT MUTAGEN 284
FT /note="S->I: Decreases enzyme activity by 87%. Impairs
FT protein folding and/or stability."
FT /evidence="ECO:0000269|PubMed:21048046"
FT MUTAGEN 290
FT /note="V->L: No effect on enzyme activity."
FT /evidence="ECO:0000269|PubMed:21048046"
FT MUTAGEN 331
FT /note="F->A: Decreases enzyme activity by 50%."
FT /evidence="ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:23467411"
FT MUTAGEN 334
FT /note="L->A: Decreases enzyme activity by 86%."
FT /evidence="ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:23467411"
FT MUTAGEN 347
FT /note="V->A: Decreases enzyme activity by 45%."
FT /evidence="ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:23467411"
FT MUTAGEN 368
FT /note="M->A: Decreases enzyme activity by 52%."
FT /evidence="ECO:0000269|PubMed:21048046,
FT ECO:0000269|PubMed:23467411"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 12..22
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:4IVO"
FT HELIX 65..77
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 92..95
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 104..107
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:3NKS"
FT TURN 132..135
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 146..154
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 156..161
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 163..171
FT /evidence="ECO:0007829|PDB:3NKS"
FT TURN 175..177
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 180..183
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 185..194
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 197..203
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 214..221
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 235..246
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 276..284
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 288..294
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 300..307
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 311..321
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 330..334
FT /evidence="ECO:0007829|PDB:3NKS"
FT TURN 337..339
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 341..347
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 349..352
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:3NKS"
FT TURN 358..361
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 363..369
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 371..379
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 386..401
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 408..420
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 426..439
FT /evidence="ECO:0007829|PDB:3NKS"
FT STRAND 443..446
FT /evidence="ECO:0007829|PDB:3NKS"
FT TURN 449..451
FT /evidence="ECO:0007829|PDB:3NKS"
FT HELIX 456..472
FT /evidence="ECO:0007829|PDB:3NKS"
SQ SEQUENCE 477 AA; 50765 MW; 2444DEAC2E6C33EE CRC64;
MGRTVVVLGG GISGLAASYH LSRAPCPPKV VLVESSERLG GWIRSVRGPN GAIFELGPRG
IRPAGALGAR TLLLVSELGL DSEVLPVRGD HPAAQNRFLY VGGALHALPT GLRGLLRPSP
PFSKPLFWAG LRELTKPRGK EPDETVHSFA QRRLGPEVAS LAMDSLCRGV FAGNSRELSI
RSCFPSLFQA EQTHRSILLG LLLGAGRTPQ PDSALIRQAL AERWSQWSLR GGLEMLPQAL
ETHLTSRGVS VLRGQPVCGL SLQAEGRWKV SLRDSSLEAD HVISAIPASV LSELLPAEAA
PLARALSAIT AVSVAVVNLQ YQGAHLPVQG FGHLVPSSED PGVLGIVYDS VAFPEQDGSP
PGLRVTVMLG GSWLQTLEAS GCVLSQELFQ QRAQEAAATQ LGLKEMPSHC LVHLHKNCIP
QYTLGHWQKL ESARQFLTAH RLPLTLAGAS YEGVAVNDCI ESGRQAAVSV LGTEPNS
