ID   PPOX_MOUSE              Reviewed;         477 AA.
AC   P51175; P97344; Q99M34;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 174.
DE   RecName: Full=Protoporphyrinogen oxidase;
DE            Short=PPO;
DE            EC=1.3.3.4;
GN   Name=Ppox;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY
RP   REGULATION.
RX   PubMed=8554330; DOI=10.1006/abbi.1995.0051;
RA   Dailey T.A., Dailey H.A., Meissner P., Prasad A.R.;
RT   "Cloning, sequence, and expression of mouse protoporphyrinogen oxidase.";
RL   Arch. Biochem. Biophys. 324:379-384(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC   TISSUE=Erythroleukemia;
RX   PubMed=7607249; DOI=10.1111/j.1432-1033.1995.0760h.x;
RA   Taketani S., Yoshinaga T., Furukawa T., Kohno H., Tokunaga R.,
RA   Nishimura K., Inokuchi H.;
RT   "Induction of terminal enzymes for heme biosynthesis during differentiation
RT   of mouse erythroleukemia cells.";
RL   Eur. J. Biochem. 230:760-765(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Mammary gland;
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   [4]
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Liver;
RX   PubMed=3346226; DOI=10.1016/s0021-9258(18)69000-3;
RA   Ferreira G.C., Andrew T.L., Karr S.W., Dailey H.A.;
RT   "Organization of the terminal two enzymes of the heme biosynthetic pathway.
RT   Orientation of protoporphyrinogen oxidase and evidence for a membrane
RT   complex.";
RL   J. Biol. Chem. 263:3835-3839(1988).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Pancreas, Spleen,
RC   and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Catalyzes the 6-electron oxidation of protoporphyrinogen-IX
CC       to form protoporphyrin-IX. {ECO:0000269|PubMed:8554330}.
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:8554330};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC       Note=Binds 1 FAD per subunit. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: Inhibited by acifluorfen.
CC       {ECO:0000269|PubMed:8554330}.
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC       biosynthesis; protoporphyrin-IX from protoporphyrinogen-IX: step 1/1.
CC   -!- SUBUNIT: Monomer. Homodimer (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000269|PubMed:3346226}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:3346226}; Intermembrane side
CC       {ECO:0000269|PubMed:3346226}.
CC   -!- INDUCTION: During erythroid differentiation.
CC       {ECO:0000269|PubMed:7607249}.
CC   -!- SIMILARITY: Belongs to the protoporphyrinogen/coproporphyrinogen
CC       oxidase family. Protoporphyrinogen oxidase subfamily. {ECO:0000305}.
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DR   EMBL; U25114; AAA96003.1; -; mRNA.
DR   EMBL; D45185; BAA08126.1; -; mRNA.
DR   EMBL; BC002047; AAH02047.1; -; mRNA.
DR   CCDS; CCDS15487.1; -.
DR   PIR; S65684; S65684.
DR   PIR; S68367; S68367.
DR   RefSeq; NP_032937.1; NM_008911.2.
DR   RefSeq; XP_006496770.1; XM_006496707.3.
DR   AlphaFoldDB; P51175; -.
DR   SMR; P51175; -.
DR   BioGRID; 202334; 2.
DR   IntAct; P51175; 4.
DR   STRING; 10090.ENSMUSP00000072863; -.
DR   iPTMnet; P51175; -.
DR   PhosphoSitePlus; P51175; -.
DR   SwissPalm; P51175; -.
DR   EPD; P51175; -.
DR   MaxQB; P51175; -.
DR   PaxDb; 10090-ENSMUSP00000072863; -.
DR   PeptideAtlas; P51175; -.
DR   ProteomicsDB; 289741; -.
DR   Pumba; P51175; -.
DR   Antibodypedia; 34299; 287 antibodies from 28 providers.
DR   DNASU; 19044; -.
DR   Ensembl; ENSMUST00000073120.11; ENSMUSP00000072863.5; ENSMUSG00000062729.13.
DR   GeneID; 19044; -.
DR   KEGG; mmu:19044; -.
DR   UCSC; uc007dns.1; mouse.
DR   AGR; MGI:104968; -.
DR   CTD; 5498; -.
DR   MGI; MGI:104968; Ppox.
DR   VEuPathDB; HostDB:ENSMUSG00000062729; -.
DR   eggNOG; KOG1276; Eukaryota.
DR   GeneTree; ENSGT00390000008744; -.
DR   HOGENOM; CLU_009629_2_1_1; -.
DR   InParanoid; P51175; -.
DR   OMA; WFDQWFG; -.
DR   OrthoDB; 65450at2759; -.
DR   PhylomeDB; P51175; -.
DR   TreeFam; TF323479; -.
DR   Reactome; R-MMU-189451; Heme biosynthesis.
DR   UniPathway; UPA00251; UER00324.
DR   BioGRID-ORCS; 19044; 6 hits in 78 CRISPR screens.
DR   ChiTaRS; Ppox; mouse.
DR   PRO; PR:P51175; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; P51175; Protein.
DR   Bgee; ENSMUSG00000062729; Expressed in fetal liver hematopoietic progenitor cell and 252 other cell types or tissues.
DR   ExpressionAtlas; P51175; baseline and differential.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR   GO; GO:0005758; C:mitochondrial intermembrane space; IDA:MGI.
DR   GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0004729; F:oxygen-dependent protoporphyrinogen oxidase activity; IDA:UniProtKB.
DR   GO; GO:0006784; P:heme A biosynthetic process; IDA:MGI.
DR   GO; GO:0006785; P:heme B biosynthetic process; IDA:MGI.
DR   GO; GO:0006783; P:heme biosynthetic process; IDA:MGI.
DR   GO; GO:0048034; P:heme O biosynthetic process; IDA:MGI.
DR   GO; GO:0006779; P:porphyrin-containing compound biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0046501; P:protoporphyrinogen IX metabolic process; ISO:MGI.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 1.
DR   InterPro; IPR002937; Amino_oxidase.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR004572; Protoporphyrinogen_oxidase.
DR   NCBIfam; TIGR00562; proto_IX_ox; 1.
DR   PANTHER; PTHR42923; PROTOPORPHYRINOGEN OXIDASE; 1.
DR   PANTHER; PTHR42923:SF3; PROTOPORPHYRINOGEN OXIDASE; 1.
DR   Pfam; PF01593; Amino_oxidase; 1.
DR   SUPFAM; SSF54373; FAD-linked reductases, C-terminal domain; 1.
DR   SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1.
DR   Genevisible; P51175; MM.
PE   1: Evidence at protein level;
KW   FAD; Flavoprotein; Heme biosynthesis; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Oxidoreductase; Porphyrin biosynthesis;
KW   Reference proteome.
FT   CHAIN           1..477
FT                   /note="Protoporphyrinogen oxidase"
FT                   /id="PRO_0000135272"
FT   BINDING         9..14
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         34..35
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         42
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         57..60
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         257
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         449
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         454..456
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        64
FT                   /note="A -> T (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        66
FT                   /note="A -> P (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        108
FT                   /note="L -> S (in Ref. 2; BAA08126)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        176
FT                   /note="R -> Q (in Ref. 3; AAH02047)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        427
FT                   /note="W -> C (in Ref. 2; BAA08126)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   477 AA;  50871 MW;  8CFB48120728DE6F CRC64;
     MGRTVIVLGG GISGLAASYH LIRGPSPPKV ILVEGSKRLG GWIRSIRGSD GAIFELGPRG
     IRPAGALGAR TLLLVSELGL ESEVLPVRGD HPAAQNRFLY VGGTLHPLPS GLRGLLRPSP
     PFSKPLFWAG LRELLKPRGK EPDETVHSFA QRRLGPEVAS LAMDSLCRGV FAGNSRELSI
     RSCFPSLFQA EQTHRSILLG LLLGAGQSPQ PDSSLIRQAR AERWSQWSLR GGLEVLPQAL
     HNHLASKGVT VLSGQPVCGL SLQPEGRWKV SLGDSSLEAD HIISAIPASE LSKLLPAEAA
     PLARILSTIK AVSVAVVNLQ YRGACLPVQG FGHLVPSSED PTVLGIVYDS VAFPEQDGNP
     PSLRVTVMLG GYWLQKLKAA GHQLSPELFQ QQAQEAAATQ LGLKEPPSHC LVHLHKNCIP
     QYTIGHWQKL DSAMQFLTAQ RLPLTLAGAS YEGVAVNDCI ESGRQAAVAV LGTESNS
//