HEM6_MOUSE
ID HEM6_MOUSE Reviewed; 443 AA.
AC P36552; Q7TQ36; Q8VD08;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial;
DE Short=COX;
DE Short=Coprogen oxidase;
DE Short=Coproporphyrinogenase;
DE EC=1.3.3.3 {ECO:0000305|PubMed:8407975};
DE Flags: Precursor;
GN Name=Cpox; Synonyms=Cpo;
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], CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=8407975; DOI=10.1016/s0021-9258(19)36931-5;
RA Kohno H., Furukawa T., Yoshinaga T., Tokunaga R., Taketani S.;
RT "Coproporphyrinogen oxidase. Purification, molecular cloning, and induction
RT of mRNA during erythroid differentiation.";
RL J. Biol. Chem. 268:21359-21363(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-139.
RX PubMed=15482256; DOI=10.1042/bj20040570;
RA Dailey T.A., Woodruff J.H., Dailey H.A.;
RT "Examination of mitochondrial protein targeting of haem synthetic enzymes:
RT in vivo identification of three functional haem-responsive motifs in 5-
RT aminolaevulinate synthase.";
RL Biochem. J. 386:381-386(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-144.
RX PubMed=12862310; DOI=10.1620/tjem.200.39;
RA Susa S., Daimon M., Ono H., Li S., Yoshida T., Kato T.;
RT "The long, but not the short, presequence of human coproporphyrinogen
RT oxidase is essential for its import and sorting to mitochondria.";
RL Tohoku J. Exp. Med. 200:39-45(2003).
RN [5]
RP PROTEIN SEQUENCE OF 99-125 AND 248-258.
RX PubMed=8159699; DOI=10.1073/pnas.91.8.3024;
RA Martasek P., Camadro J.-M., Delfau-Larue M.H., Dumas J.B., Montagne J.J.,
RA de Verneuil H., Labbe P., Grandchamp B.;
RT "Molecular cloning, sequencing, and functional expression of a cDNA
RT encoding human coproporphyrinogen oxidase.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:3024-3028(1994).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, 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).
RN [7]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-393, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-393, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Involved in the heme biosynthesis. Catalyzes the aerobic
CC oxidative decarboxylation of propionate groups of rings A and B of
CC coproporphyrinogen-III to yield the vinyl groups in protoporphyrinogen-
CC IX (By similarity). {ECO:0000250|UniProtKB:P36551}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=coproporphyrinogen III + 2 H(+) + O2 = 2 CO2 + 2 H2O +
CC protoporphyrinogen IX; Xref=Rhea:RHEA:18257, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57307, ChEBI:CHEBI:57309; EC=1.3.3.3;
CC Evidence={ECO:0000305|PubMed:8407975};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18258;
CC Evidence={ECO:0000305|PubMed:8407975};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; protoporphyrinogen-IX from coproporphyrinogen-III (O2
CC route): step 1/1. {ECO:0000305|PubMed:8407975}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000269|PubMed:8407975}.
CC -!- TISSUE SPECIFICITY: Expressed in erythroid cells. Expressed in liver
CC (PubMed:8407975). {ECO:0000269|PubMed:8407975}.
CC -!- PTM: Acetylation of Lys-360 is observed in liver mitochondria from
CC fasted mice but not from fed mice.
CC -!- SIMILARITY: Belongs to the aerobic coproporphyrinogen-III oxidase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH17680.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA03840.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; D16333; BAA03840.1; ALT_FRAME; mRNA.
DR EMBL; BC017680; AAH17680.2; ALT_INIT; mRNA.
DR EMBL; AY382578; AAQ88103.1; -; Genomic_DNA.
DR EMBL; AB099924; BAC79229.1; -; Genomic_DNA.
DR CCDS; CCDS49878.1; -.
DR PIR; A48049; A48049.
DR RefSeq; NP_031783.2; NM_007757.2.
DR AlphaFoldDB; P36552; -.
DR SMR; P36552; -.
DR BioGRID; 198862; 4.
DR IntAct; P36552; 3.
DR STRING; 10090.ENSMUSP00000055455; -.
DR iPTMnet; P36552; -.
DR PhosphoSitePlus; P36552; -.
DR SwissPalm; P36552; -.
DR EPD; P36552; -.
DR jPOST; P36552; -.
DR MaxQB; P36552; -.
DR PaxDb; P36552; -.
DR PeptideAtlas; P36552; -.
DR PRIDE; P36552; -.
DR ProteomicsDB; 269589; -.
DR DNASU; 12892; -.
DR Ensembl; ENSMUST00000060077; ENSMUSP00000055455; ENSMUSG00000022742.
DR GeneID; 12892; -.
DR KEGG; mmu:12892; -.
DR UCSC; uc007znz.2; mouse.
DR CTD; 1371; -.
DR MGI; MGI:104841; Cpox.
DR VEuPathDB; HostDB:ENSMUSG00000022742; -.
DR eggNOG; KOG1518; Eukaryota.
DR GeneTree; ENSGT00390000017311; -.
DR HOGENOM; CLU_026169_1_0_1; -.
DR InParanoid; P36552; -.
DR OMA; HDKGTLF; -.
DR OrthoDB; 1080991at2759; -.
DR PhylomeDB; P36552; -.
DR TreeFam; TF300703; -.
DR BRENDA; 1.3.3.3; 3474.
DR Reactome; R-MMU-189451; Heme biosynthesis.
DR UniPathway; UPA00251; UER00322.
DR BioGRID-ORCS; 12892; 6 hits in 76 CRISPR screens.
DR ChiTaRS; Cpox; mouse.
DR PRO; PR:P36552; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; P36552; protein.
DR Bgee; ENSMUSG00000022742; Expressed in late embryo and 255 other tissues.
DR Genevisible; P36552; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016020; C:membrane; IMP:ParkinsonsUK-UCL.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0004109; F:coproporphyrinogen oxidase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005391; F:P-type sodium:potassium-exchanging transporter activity; TAS:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0005212; F:structural constituent of eye lens; IMP:MGI.
DR GO; GO:0006783; P:heme biosynthetic process; IDA:MGI.
DR GO; GO:0006813; P:potassium ion transport; TAS:MGI.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; ISO:MGI.
DR GO; GO:0046685; P:response to arsenic-containing substance; IEA:Ensembl.
DR GO; GO:0017085; P:response to insecticide; IEA:Ensembl.
DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl.
DR GO; GO:0010288; P:response to lead ion; IEA:Ensembl.
DR GO; GO:0051597; P:response to methylmercury; IEA:Ensembl.
DR GO; GO:0006814; P:sodium ion transport; TAS:MGI.
DR Gene3D; 3.40.1500.10; -; 1.
DR InterPro; IPR001260; Coprogen_oxidase_aer.
DR InterPro; IPR036406; Coprogen_oxidase_aer_sf.
DR InterPro; IPR018375; Coprogen_oxidase_CS.
DR PANTHER; PTHR10755; PTHR10755; 1.
DR Pfam; PF01218; Coprogen_oxidas; 1.
DR PRINTS; PR00073; COPRGNOXDASE.
DR SUPFAM; SSF102886; SSF102886; 1.
DR PROSITE; PS01021; COPROGEN_OXIDASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Heme biosynthesis; Mitochondrion;
KW Oxidoreductase; Phosphoprotein; Porphyrin biosynthesis; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..98
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:8159699"
FT CHAIN 99..443
FT /note="Oxygen-dependent coproporphyrinogen-III oxidase,
FT mitochondrial"
FT /id="PRO_0000006030"
FT REGION 89..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..191
FT /note="Important for dimerization"
FT /evidence="ECO:0000250"
FT REGION 381..417
FT /note="Important for dimerization"
FT /evidence="ECO:0000250"
FT ACT_SITE 247
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 233
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 249..251
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 400..405
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 316
FT /note="Important for dimerization"
FT /evidence="ECO:0000250"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3B7D0"
FT MOD_RES 393
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 393
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 7
FT /note="R -> P (in Ref. 1; BAA03840)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="S -> T (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 116..117
FT /note="CS -> SD (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="S -> T (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="V -> P (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="K -> N (in Ref. 3; BAC79229)"
FT /evidence="ECO:0000305"
FT CONFLICT 275
FT /note="T -> R (in Ref. 1; BAA03840)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 443 AA; 49715 MW; 9F3D5E8E420645F0 CRC64;
MALRLGRLGS DPWWRAVLGD YAQLRAASPR CASARVCQLP GTAGPQPRRG LGYGPWARGG
SGLGTRLAAT LAGLAGLAAA AFGHVQRAEM VPKSSGARSP SPGRREEDGD ELARRCSTFM
SSPVTELREL RRRPEDMKTK MELMIMETQA QVCRALAQVD GVADFTVDRW ERKEGGGGIT
CVLQDGRVFE KAGVSISVVH GNLSEEAANQ MRGRGKTLKT KDSKLPFTAM GVSSVIHPKN
PYAPTMHFNY RYFEVEEADG NTHWWFGGGC DLTPTYLNQE DAVHFHRTLK EACDQHGPDI
YPKFKKWCDD YFFIVHRGER RGIGGIFFDD LDSPSKEEAF RFVKTCAEAV VPSYVPIVKK
HCDDSYTPRD KLWQQLRRGR YVEFNLLYDR GTKFGLFTPG SRIESILMSL PLTARWEYMH
SPPENSKEAE ILEVLRHPKD WVH
