HEM6_HUMAN
ID HEM6_HUMAN Reviewed; 454 AA.
AC P36551; A8K275; B4DSD5; Q14060; Q53F08; Q8IZ45; Q96AF3;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 3.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial {ECO:0000305};
DE Short=COX;
DE Short=Coprogen oxidase;
DE Short=Coproporphyrinogenase;
DE EC=1.3.3.3 {ECO:0000269|PubMed:8159699};
DE Flags: Precursor;
GN Name=CPOX {ECO:0000312|HGNC:HGNC:2321}; Synonyms=CPO, CPX;
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 [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Placenta;
RX PubMed=7987309; DOI=10.1093/hmg/3.8.1325;
RA Delfau-Larue M.H., Martasek P., Grandchamp B.;
RT "Coproporphyrinogen oxidase: gene organization and description of a
RT mutation leading to exon 6 skipping.";
RL Hum. Mol. Genet. 3:1325-1330(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-294.
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-294.
RC TISSUE=Brain, Placenta, and Uterus;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 73-454 (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=8286403; DOI=10.1016/0005-2728(94)90083-3;
RA Taketani S., Kohno H., Furukawa T., Yoshinaga T., Tokunaga R.;
RT "Molecular cloning, sequencing and expression of cDNA encoding human
RT coproporphyrinogen oxidase.";
RL Biochim. Biophys. Acta 1183:547-549(1994).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 101-454 (ISOFORM 1), VARIANT HIS-272,
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Foreskin;
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 [8]
RP PROTEOLYTIC PROCESSING.
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 [9]
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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
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 [13]
RP INVOLVEMENT IN HCP, AND VARIANT HCP TRP-331.
RX PubMed=8012360; DOI=10.1093/hmg/3.3.477;
RA Martasek P., Nordmann Y., Grandchamp B.;
RT "Homozygous hereditary coproporphyria caused by an arginine to tryptophane
RT substitution in coproporphyrinogen oxidase and common intragenic
RT polymorphisms.";
RL Hum. Mol. Genet. 3:477-480(1994).
RN [14]
RP INVOLVEMENT IN HARPO, AND VARIANT HARPO ARG-327.
RX PubMed=21103937; DOI=10.1007/s10545-010-9237-9;
RA Hasanoglu A., Balwani M., Kasapkara C.S., Ezgue F.S., Okur I., Tuemer L.,
RA Cakmak A., Nazarenko I., Yu C., Clavero S., Bishop D.F., Desnick R.J.;
RT "Harderoporphyria due to homozygosity for coproporphyrinogen oxidase
RT missense mutation H327R.";
RL J. Inherit. Metab. Dis. 34:225-231(2011).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 111-453 IN COMPLEX WITH CITRATE,
RP MUTAGENESIS OF 392-TYR--LEU-418, ACTIVE SITE, AND SUBUNIT.
RX PubMed=16176984; DOI=10.1073/pnas.0506557102;
RA Lee D.-S., Flachsova E., Bodnarova M., Demeler B., Martasek P., Raman C.S.;
RT "Structural basis of hereditary coproporphyria.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:14232-14237(2005).
RN [16]
RP VARIANT HCP SER-189, AND VARIANTS HIS-272 AND ILE-294.
RX PubMed=7849704; DOI=10.1093/hmg/3.10.1807;
RA Fujita H., Kondo M., Taketani S., Nomura N., Furuyama K., Akagi R.,
RA Nagai T., Terajima M., Galbraith R.A., Sassa S.;
RT "Characterization and expression of cDNA encoding coproporphyrinogen
RT oxidase from a patient with hereditary coproporphyria.";
RL Hum. Mol. Genet. 3:1807-1810(1994).
RN [17]
RP VARIANT HARPO GLU-404.
RX PubMed=7757079; DOI=10.1093/hmg/4.2.275;
RA Lamoril J., Martasek P., Deybach J.-C., da Silva V., Grandchamp B.,
RA Nordmann Y.;
RT "A molecular defect in coproporphyrinogen oxidase gene causing
RT harderoporphyria, a variant form of hereditary coproporphyria.";
RL Hum. Mol. Genet. 4:275-278(1995).
RN [18]
RP VARIANT HCP ARG-280.
RX PubMed=9048920; DOI=10.1007/s004390050338;
RA Daimon M., Gojyou E., Sugawara M., Yamatani K., Tominaga M., Sasaki H.;
RT "A novel missense mutation in exon 4 of the human coproporphyrinogen
RT oxidase gene in two patients with hereditary coproporphyria.";
RL Hum. Genet. 99:199-201(1997).
RN [19]
RP VARIANTS HCP 162-GLN--ALA-168 DEL AND ASP-295.
RX PubMed=8990017;
RX DOI=10.1002/(sici)1098-1004(1997)9:1<78::aid-humu17>3.0.co;2-m;
RA Lamoril J., Deybach J.-C., Puy H., Grandchamp B., Nordmann Y.;
RT "Three novel mutations in the coproporphyrinogen oxidase gene.";
RL Hum. Mutat. 9:78-80(1997).
RN [20]
RP VARIANTS HCP LYS-201 AND SER-249.
RX PubMed=9298818;
RX DOI=10.1002/(sici)1098-1004(1997)10:3<196::aid-humu3>3.0.co;2-h;
RA Schreiber W.E., Zhang X., Senz J., Jamani A.;
RT "Hereditary coproporphyria: exon screening by heteroduplex analysis detects
RT three novel mutations in the coproporphyrinogen oxidase gene.";
RL Hum. Mutat. 10:196-200(1997).
RN [21]
RP VARIANT HCP 29-GLN--ARG-454 DEL.
RX PubMed=9843038;
RX DOI=10.1002/(sici)1096-8628(19981116)80:3<204::aid-ajmg4>3.0.co;2-g;
RA Susa S., Daimon M., Kondo H., Kondo M., Yamatani K., Sasaki H.;
RT "Identification of a novel mutation of the CPO gene in a Japanese
RT hereditary coproporphyria family.";
RL Am. J. Med. Genet. 80:204-206(1998).
RN [22]
RP VARIANTS HCP TRP-197; GLY-390 DEL AND ARG-427.
RX PubMed=9888388;
RX DOI=10.1002/(sici)1098-1004(1999)13:1<44::aid-humu5>3.0.co;2-q;
RA Rosipal R., Lamoril J., Puy H., da Silva V., Gouya L., de Rooij F.W.M.,
RA Te Velde K., Nordmann Y., Martasek P., Deybach J.-C.;
RT "Systematic analysis of coproporphyrinogen oxidase gene defects in
RT hereditary coproporphyria and mutation update.";
RL Hum. Mutat. 13:44-53(1999).
RN [23]
RP VARIANTS HCP PHE-208; CYS-328; TRP-331 AND CYS-447.
RX PubMed=12181641; DOI=10.1007/s100380200059;
RA Wiman A., Floderus Y., Harper P.;
RT "Two novel mutations and coexistence of the 991C>T and the 1339C>T mutation
RT on a single allele in the coproporphyrinogen oxidase gene in Swedish
RT patients with hereditary coproporphyria.";
RL J. Hum. Genet. 47:407-412(2002).
RN [24]
RP VARIANTS HCP ALA-135; ARG-214 AND ARG-249.
RX PubMed=15896662; DOI=10.1016/j.ymgme.2004.12.012;
RA To-Figueras J., Badenas C., Enriquez M.T., Segura S., Alvarez C., Mila M.,
RA Lecha M., Herrero C.;
RT "Biochemical and genetic characterization of four cases of hereditary
RT coproporphyria in Spain.";
RL Mol. Genet. Metab. 85:160-163(2005).
RN [25]
RP VARIANT HCP ARG-279.
RX PubMed=16398658; DOI=10.1111/j.1365-2141.2005.05852.x;
RA Akagi R., Inoue R., Muranaka S., Tahara T., Taketani S., Anderson K.E.,
RA Phillips J.D., Sassa S.;
RT "Dual gene defects involving delta-aminolaevulinate dehydratase and
RT coproporphyrinogen oxidase in a porphyria patient.";
RL Br. J. Haematol. 132:237-243(2006).
RN [26]
RP ERRATUM OF PUBMED:16398658.
RA Akagi R., Inoue R., Muranaka S., Tahara T., Taketani S., Anderson K.E.,
RA Phillips J.D., Sassa S.;
RL Br. J. Haematol. 132:662-662(2006).
CC -!- FUNCTION: Catalyzes the aerobic oxidative decarboxylation of propionate
CC groups of rings A and B of coproporphyrinogen-III to yield the vinyl
CC groups in protoporphyrinogen-IX and participates to the sixth step in
CC the heme biosynthetic pathway. {ECO:0000269|PubMed:8159699}.
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:0000269|PubMed:8159699};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18258;
CC Evidence={ECO:0000305|PubMed:8159699};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; protoporphyrinogen-IX from coproporphyrinogen-III (O2
CC route): step 1/1. {ECO:0000269|PubMed:8159699}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16176984}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P36551-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P36551-2; Sequence=VSP_057182, VSP_057183;
CC -!- DISEASE: Hereditary coproporphyria (HCP) [MIM:121300]: A form of
CC porphyria. Porphyrias are inherited defects in the biosynthesis of
CC heme, resulting in the accumulation and increased excretion of
CC porphyrins or porphyrin precursors. They are classified as
CC erythropoietic or hepatic, depending on whether the enzyme deficiency
CC occurs in red blood cells or in the liver. Hereditary coproporphyria is
CC an acute hepatic porphyria characterized by skin photosensitivity,
CC attacks of abdominal pain, neurological disturbances, and psychiatric
CC symptoms. Most attacks are precipitated by drugs, alcohol, caloric
CC deprivation, infections, or endocrine factors. Hereditary
CC coproporphyria is biochemically characterized by overexcretion of
CC coproporphyrin III in the urine and in the feces.
CC {ECO:0000269|PubMed:12181641, ECO:0000269|PubMed:15896662,
CC ECO:0000269|PubMed:16398658, ECO:0000269|PubMed:7849704,
CC ECO:0000269|PubMed:8012360, ECO:0000269|PubMed:8990017,
CC ECO:0000269|PubMed:9048920, ECO:0000269|PubMed:9298818,
CC ECO:0000269|PubMed:9843038, ECO:0000269|PubMed:9888388}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Harderoporphyria (HARPO) [MIM:618892]: An autosomal recessive
CC form of porphyria. Porphyrias are inherited defects in the biosynthesis
CC of heme, resulting in the accumulation and increased excretion of
CC porphyrins or porphyrin precursors. HARPO is a rare erythropoietic
CC variant form characterized by neonatal hemolytic anemia, sometimes
CC accompanied by skin lesions, and massive excretion of harderoporphyrin
CC in feces. {ECO:0000269|PubMed:21103937, ECO:0000269|PubMed:7757079}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the aerobic coproporphyrinogen-III oxidase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA04033.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Z34531; CAA84292.1; -; Genomic_DNA.
DR EMBL; Z34803; CAA84292.1; JOINED; Genomic_DNA.
DR EMBL; Z34804; CAA84292.1; JOINED; Genomic_DNA.
DR EMBL; Z34805; CAA84292.1; JOINED; Genomic_DNA.
DR EMBL; Z34806; CAA84292.1; JOINED; Genomic_DNA.
DR EMBL; Z34807; CAA84292.1; JOINED; Genomic_DNA.
DR EMBL; Z34808; CAA84292.1; JOINED; Genomic_DNA.
DR EMBL; AK290140; BAF82829.1; -; mRNA.
DR EMBL; AK299692; BAG61597.1; -; mRNA.
DR EMBL; AK223481; BAD97201.1; -; mRNA.
DR EMBL; CH471052; EAW79854.1; -; Genomic_DNA.
DR EMBL; BC017210; AAH17210.1; -; mRNA.
DR EMBL; BC023551; AAH23551.1; -; mRNA.
DR EMBL; BC023554; AAH23554.1; -; mRNA.
DR EMBL; D16611; BAA04033.1; ALT_INIT; mRNA.
DR EMBL; Z28409; CAA82250.1; -; mRNA.
DR CCDS; CCDS2932.1; -. [P36551-1]
DR PIR; I52444; I52444.
DR RefSeq; NP_000088.3; NM_000097.5. [P36551-1]
DR PDB; 2AEX; X-ray; 1.58 A; A=111-454.
DR PDBsum; 2AEX; -.
DR AlphaFoldDB; P36551; -.
DR SMR; P36551; -.
DR BioGRID; 107763; 54.
DR IntAct; P36551; 32.
DR MINT; P36551; -.
DR STRING; 9606.ENSP00000264193; -.
DR ChEMBL; CHEMBL1681618; -.
DR GlyGen; P36551; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P36551; -.
DR PhosphoSitePlus; P36551; -.
DR SwissPalm; P36551; -.
DR BioMuta; CPOX; -.
DR DMDM; 67476671; -.
DR EPD; P36551; -.
DR jPOST; P36551; -.
DR MassIVE; P36551; -.
DR MaxQB; P36551; -.
DR PaxDb; P36551; -.
DR PeptideAtlas; P36551; -.
DR PRIDE; P36551; -.
DR ProteomicsDB; 55213; -. [P36551-1]
DR Antibodypedia; 2788; 172 antibodies from 29 providers.
DR DNASU; 1371; -.
DR Ensembl; ENST00000647941.2; ENSP00000497326.1; ENSG00000080819.9. [P36551-1]
DR GeneID; 1371; -.
DR KEGG; hsa:1371; -.
DR MANE-Select; ENST00000647941.2; ENSP00000497326.1; NM_000097.7; NP_000088.3.
DR UCSC; uc003dsx.4; human. [P36551-1]
DR CTD; 1371; -.
DR DisGeNET; 1371; -.
DR GeneCards; CPOX; -.
DR GeneReviews; CPOX; -.
DR HGNC; HGNC:2321; CPOX.
DR HPA; ENSG00000080819; Low tissue specificity.
DR MalaCards; CPOX; -.
DR MIM; 121300; phenotype.
DR MIM; 612732; gene.
DR MIM; 618892; phenotype.
DR neXtProt; NX_P36551; -.
DR OpenTargets; ENSG00000080819; -.
DR Orphanet; 79273; Hereditary coproporphyria.
DR PharmGKB; PA134979958; -.
DR VEuPathDB; HostDB:ENSG00000080819; -.
DR eggNOG; KOG1518; Eukaryota.
DR GeneTree; ENSGT00390000017311; -.
DR HOGENOM; CLU_026169_1_0_1; -.
DR InParanoid; P36551; -.
DR OMA; HDKGTLF; -.
DR OrthoDB; 1080991at2759; -.
DR PhylomeDB; P36551; -.
DR TreeFam; TF300703; -.
DR BioCyc; MetaCyc:HS01369-MON; -.
DR BRENDA; 1.3.3.3; 2681.
DR PathwayCommons; P36551; -.
DR Reactome; R-HSA-189451; Heme biosynthesis.
DR SignaLink; P36551; -.
DR UniPathway; UPA00251; UER00322.
DR BioGRID-ORCS; 1371; 206 hits in 1091 CRISPR screens.
DR ChiTaRS; CPOX; human.
DR EvolutionaryTrace; P36551; -.
DR GeneWiki; Coproporphyrinogen_III_oxidase; -.
DR GenomeRNAi; 1371; -.
DR Pharos; P36551; Tbio.
DR PRO; PR:P36551; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P36551; protein.
DR Bgee; ENSG00000080819; Expressed in trabecular bone tissue and 184 other tissues.
DR ExpressionAtlas; P36551; baseline and differential.
DR Genevisible; P36551; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0004109; F:coproporphyrinogen oxidase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0005212; F:structural constituent of eye lens; IEA:Ensembl.
DR GO; GO:0006783; P:heme biosynthetic process; TAS:ProtInc.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IBA:GO_Central.
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 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 3D-structure; Acetylation; Alternative splicing; Disease variant;
KW Heme biosynthesis; Hereditary hemolytic anemia; Mitochondrion;
KW Oxidoreductase; Phosphoprotein; Porphyrin biosynthesis; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..110
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 111..454
FT /note="Oxygen-dependent coproporphyrinogen-III oxidase,
FT mitochondrial"
FT /id="PRO_0000006029"
FT REGION 43..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..202
FT /note="Important for dimerization"
FT /evidence="ECO:0000305"
FT REGION 392..428
FT /note="Important for dimerization"
FT ACT_SITE 258
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:16176984"
FT BINDING 244
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 260..262
FT /ligand="substrate"
FT BINDING 411..413
FT /ligand="substrate"
FT SITE 327
FT /note="Important for dimerization"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3B7D0"
FT MOD_RES 404
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P36552"
FT MOD_RES 404
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P36552"
FT VAR_SEQ 272..287
FT /note="NKQWWFGGGCDLTPTY -> KGLRSYGKYCRAKCAF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057182"
FT VAR_SEQ 288..454
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057183"
FT VARIANT 29..454
FT /note="Missing (in HCP)"
FT /evidence="ECO:0000269|PubMed:9843038"
FT /id="VAR_084511"
FT VARIANT 135
FT /note="V -> A (in HCP; dbSNP:rs201826432)"
FT /evidence="ECO:0000269|PubMed:15896662"
FT /id="VAR_023444"
FT VARIANT 162..168
FT /note="Missing (in HCP)"
FT /evidence="ECO:0000269|PubMed:8990017"
FT /id="VAR_002151"
FT VARIANT 189
FT /note="G -> S (in HCP; <5% of activity; dbSNP:rs759347283)"
FT /evidence="ECO:0000269|PubMed:7849704"
FT /id="VAR_002152"
FT VARIANT 197
FT /note="G -> W (in HCP)"
FT /evidence="ECO:0000269|PubMed:9888388"
FT /id="VAR_002153"
FT VARIANT 201
FT /note="E -> K (in HCP; dbSNP:rs1374394802)"
FT /evidence="ECO:0000269|PubMed:9298818"
FT /id="VAR_002154"
FT VARIANT 208
FT /note="S -> F (in HCP; dbSNP:rs121917872)"
FT /evidence="ECO:0000269|PubMed:12181641"
FT /id="VAR_019067"
FT VARIANT 214
FT /note="L -> R (in HCP)"
FT /evidence="ECO:0000269|PubMed:15896662"
FT /id="VAR_023445"
FT VARIANT 249
FT /note="P -> R (in HCP)"
FT /evidence="ECO:0000269|PubMed:15896662"
FT /id="VAR_023446"
FT VARIANT 249
FT /note="P -> S (in HCP)"
FT /evidence="ECO:0000269|PubMed:9298818"
FT /id="VAR_002155"
FT VARIANT 272
FT /note="N -> H (in dbSNP:rs1131857)"
FT /evidence="ECO:0000269|PubMed:7849704,
FT ECO:0000269|PubMed:8159699"
FT /id="VAR_002156"
FT VARIANT 279
FT /note="G -> R (in HCP; a patient carrying also the L-12
FT mutation in ALAD; dbSNP:rs121917874)"
FT /evidence="ECO:0000269|PubMed:16398658"
FT /id="VAR_058005"
FT VARIANT 280
FT /note="G -> R (in HCP)"
FT /evidence="ECO:0000269|PubMed:9048920"
FT /id="VAR_002157"
FT VARIANT 294
FT /note="V -> I (in dbSNP:rs2228056)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7849704, ECO:0000269|Ref.3"
FT /id="VAR_002158"
FT VARIANT 295
FT /note="H -> D (in HCP; dbSNP:rs121917870)"
FT /evidence="ECO:0000269|PubMed:8990017"
FT /id="VAR_002159"
FT VARIANT 327
FT /note="H -> R (in HARPO; dbSNP:rs587777271)"
FT /evidence="ECO:0000269|PubMed:21103937"
FT /id="VAR_084512"
FT VARIANT 328
FT /note="R -> C (in HCP; dbSNP:rs121917873)"
FT /evidence="ECO:0000269|PubMed:12181641"
FT /id="VAR_019068"
FT VARIANT 331
FT /note="R -> W (in HCP; dbSNP:rs121917866)"
FT /evidence="ECO:0000269|PubMed:12181641,
FT ECO:0000269|PubMed:8012360"
FT /id="VAR_002160"
FT VARIANT 352
FT /note="R -> C (in dbSNP:rs11921054)"
FT /id="VAR_048827"
FT VARIANT 390
FT /note="Missing (in HCP)"
FT /evidence="ECO:0000269|PubMed:9888388"
FT /id="VAR_002161"
FT VARIANT 404
FT /note="K -> E (in HARPO; dbSNP:rs121917868)"
FT /evidence="ECO:0000269|PubMed:7757079"
FT /id="VAR_002162"
FT VARIANT 427
FT /note="W -> R (in HCP)"
FT /evidence="ECO:0000269|PubMed:9888388"
FT /id="VAR_002163"
FT VARIANT 447
FT /note="R -> C (in HCP; dbSNP:rs28931603)"
FT /evidence="ECO:0000269|PubMed:12181641"
FT /id="VAR_019069"
FT MUTAGEN 392..418
FT /note="Missing: Loss for dimerization."
FT /evidence="ECO:0000269|PubMed:16176984"
FT CONFLICT 247
FT /note="I -> T (in Ref. 7; CAA82250)"
FT /evidence="ECO:0000305"
FT HELIX 122..128
FT /evidence="ECO:0007829|PDB:2AEX"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 138..143
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 148..170
FT /evidence="ECO:0007829|PDB:2AEX"
FT STRAND 177..183
FT /evidence="ECO:0007829|PDB:2AEX"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:2AEX"
FT STRAND 187..196
FT /evidence="ECO:0007829|PDB:2AEX"
FT STRAND 198..213
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 216..224
FT /evidence="ECO:0007829|PDB:2AEX"
FT STRAND 237..251
FT /evidence="ECO:0007829|PDB:2AEX"
FT STRAND 256..267
FT /evidence="ECO:0007829|PDB:2AEX"
FT STRAND 273..284
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 290..305
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 311..322
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 326..328
FT /evidence="ECO:0007829|PDB:2AEX"
FT STRAND 330..342
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 347..359
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 361..372
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 379..399
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:2AEX"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 414..420
FT /evidence="ECO:0007829|PDB:2AEX"
FT HELIX 438..447
FT /evidence="ECO:0007829|PDB:2AEX"
SQ SEQUENCE 454 AA; 50152 MW; 6EC3D15FD8FD86B5 CRC64;
MALQLGRLSS GPCWLVARGG CGGPRAWSQC GGGGLRAWSQ RSAAGRVCRP PGPAGTEQSR
GLGHGSTSRG GPWVGTGLAA ALAGLVGLAT AAFGHVQRAE MLPKTSGTRA TSLGRPEEEE
DELAHRCSSF MAPPVTDLGE LRRRPGDMKT KMELLILETQ AQVCQALAQV DGGANFSVDR
WERKEGGGGI SCVLQDGCVF EKAGVSISVV HGNLSEEAAK QMRSRGKVLK TKDGKLPFCA
MGVSSVIHPK NPHAPTIHFN YRYFEVEEAD GNKQWWFGGG CDLTPTYLNQ EDAVHFHRTL
KEACDQHGPD LYPKFKKWCD DYFFIAHRGE RRGIGGIFFD DLDSPSKEEV FRFVQSCARA
VVPSYIPLVK KHCDDSFTPQ EKLWQQLRRG RYVEFNLLYD RGTKFGLFTP GSRIESILMS
LPLTARWEYM HSPSENSKEA EILEVLRHPR DWVR
