Reviewed, UniProtKB/Swiss-Prot P36551 (HEM6_HUMAN)

Names and origin

Protein names

Recommended name:
    Coproporphyrinogen-III oxidase, mitochondrial
      Short name=Coproporphyrinogenase
      Short name=Coprogen oxidase
      Short name=COX
    EC=1.3.3.3

Gene names

Name:	CPOX
Synonyms:	CPO, CPX

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	454 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	Coproporphyrinogen-III + O2 + 2 H+ = protoporphyrinogen-IX + 2 CO2 + 2 H2O.
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; protoporphyrinogen-IX from coproporphyrinogen-III (O2 route): step 1/1.
Subcellular location	Mitochondrion intermembrane space.
Involvement in disease	Defects in CPOX are the cause of hereditary coproporphyria (HCP) [MIM:121300]. HCP is an acute hepatic porphyria and an autosomal dominant disease characterized by neuropsychiatric disturbances and skin photosensitivity. Biochemically, there is an overexcretion of coproporphyrin III in the urine and in the feces. HCP is clinically characterized by attacks of abdominal pain, neurological disturbances, and psychiatric symptoms. The symptoms are generally manifested with rapid onset, and can be precipitated by drugs, alcohol, caloric deprivation, infection, endocrine factors or stress. A severe variant form is harderoporphyria, which is characterized by earlier onset attacks, massive excretion of harderoporphyrin in the feces, and a marked decrease of coproporphyrinogen IX oxidase activity. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19
Sequence similarities	Belongs to the aerobic coproporphyrinogen-III oxidase family.

Ontologies

Keywords
Biological process	Heme biosynthesis Porphyrin biosynthesis
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	heme biosynthetic process Ref.7 Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial intermembrane space Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	coproporphyrinogen oxidase activity Ref.16 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 110

110

Mitochondrion By similarity

Chain

111 – 454

344

Coproporphyrinogen-III oxidase, mitochondrial

PRO_0000006029

Amino acid modifications

Modified residue

371

1

N6-acetyllysine By similarity

Natural variations

Natural variant

135

1

V → A in HCP. Ref.18

VAR_023444

Natural variant

162 – 168

7

Missing in HCP.

VAR_002151

Natural variant

189

1

G → S in HCP; <5% of activity. Ref.11

VAR_002152

Natural variant

197

1

G → W in HCP. Ref.16

VAR_002153

Natural variant

201

1

E → K in HCP. Ref.15

VAR_002154

Natural variant

208

1

S → F in HCP. Ref.17

VAR_019067

Natural variant

214

1

L → R in HCP. Ref.18

VAR_023445

Natural variant

249

1

P → R in HCP. Ref.18

VAR_023446

Natural variant

249

1

P → S in HCP. Ref.15

VAR_002155

Natural variant

272

1

N → H: dbSNP rs1131857. Ref.11 Ref.7

VAR_002156

Natural variant

279

1

G → R in HCP; a patient carrying also the L-12 mutation in ALAD. Ref.19

VAR_058005

Natural variant

280

1

G → R in HCP. Ref.13

VAR_002157

Natural variant

294

1

V → I: dbSNP rs2228056. Ref.11 Ref.3 Ref.5

VAR_002158

Natural variant

295

1

H → D in HCP. Ref.14

VAR_002159

Natural variant

328

1

R → C in HCP. Ref.17

VAR_019068

Natural variant

331

1

R → W in HCP. Ref.10 Ref.17

VAR_002160

Natural variant

352

1

R → C: dbSNP rs11921054.

VAR_048827

Natural variant

390

1

Missing in HCP.

VAR_002161

Natural variant

404

1

K → E in HCP; harderoporphyria form. Ref.12

VAR_002162

Natural variant

427

1

W → R in HCP. Ref.16

VAR_002163

Natural variant

447

1

R → C in HCP. Ref.17

VAR_019069

Experimental info

Sequence conflict

247

1

I → T in CAA82250. Ref.7

Secondary structure

1

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454

Helix Strand Turn

Details...

Helix

122 – 128

7

Beta strand

130 – 132

3

Helix

138 – 143

6

Helix

148 – 170

23

Beta strand

177 – 183

7

Turn

184 – 186

3

Beta strand

187 – 196

10

Beta strand

198 – 213

16

Helix

216 – 224

9

Beta strand

237 – 251

15

Beta strand

256 – 267

12

Beta strand

273 – 284

12

Helix

290 – 305

16

Helix

311 – 322

12

Helix

326 – 328

3

Beta strand

330 – 342

13

Helix

347 – 359

13

Helix

361 – 372

12

Helix

379 – 399

21

Helix

406 – 408

3

Beta strand

409 – 411

3

Helix

414 – 420

7

Beta strand

423 – 426

4

Helix

438 – 447

10

Sequences

	Sequence		Length	Mass (Da)
	P36551-1 [UniParc]. Last modified June 7, 2005. Version 3. Checksum: 6EC3D15FD8FD86B5	FASTA	454	50,152
	10 20 30 40 50 60 MALQLGRLSS GPCWLVARGG CGGPRAWSQC GGGGLRAWSQ RSAAGRVCRP PGPAGTEQSR 70 80 90 100 110 120 GLGHGSTSRG GPWVGTGLAA ALAGLVGLAT AAFGHVQRAE MLPKTSGTRA TSLGRPEEEE 130 140 150 160 170 180 DELAHRCSSF MAPPVTDLGE LRRRPGDMKT KMELLILETQ AQVCQALAQV DGGANFSVDR 190 200 210 220 230 240 WERKEGGGGI SCVLQDGCVF EKAGVSISVV HGNLSEEAAK QMRSRGKVLK TKDGKLPFCA 250 260 270 280 290 300 MGVSSVIHPK NPHAPTIHFN YRYFEVEEAD GNKQWWFGGG CDLTPTYLNQ EDAVHFHRTL 310 320 330 340 350 360 KEACDQHGPD LYPKFKKWCD DYFFIAHRGE RRGIGGIFFD DLDSPSKEEV FRFVQSCARA 370 380 390 400 410 420 VVPSYIPLVK KHCDDSFTPQ EKLWQQLRRG RYVEFNLLYD RGTKFGLFTP GSRIESILMS 430 440 450 LPLTARWEYM HSPSENSKEA EILEVLRHPR DWVR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Coproporphyrinogen oxidase: gene organization and description of a mutation leading to exon 6 skipping." Delfau-Larue M.H., Martasek P., Grandchamp B. Hum. Mol. Genet. 3:1325-1330(1994) [PubMed: 7987309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thalamus.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-294.
[4]	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. , 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].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-294. Tissue: Brain, Placenta and Uterus.
[6]	"Molecular cloning, sequencing and expression of cDNA encoding human coproporphyrinogen oxidase." Taketani S., Kohno H., Furukawa T., Yoshinaga T., Tokunaga R. Biochim. Biophys. Acta 1183:547-549(1994) [PubMed: 8286403] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 73-454. Tissue: Placenta.
[7]	"Molecular cloning, sequencing, and functional expression of a cDNA encoding human coproporphyrinogen oxidase." Martasek P., Camadro J.-M., Delfau-Larue M.H., Dumas J.B., Montagne J.J., de Verneuil H., Labbe P., Grandchamp B. Proc. Natl. Acad. Sci. U.S.A. 91:3024-3028(1994) [PubMed: 8159699] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 101-454, VARIANT HIS-272. Tissue: Foreskin.
[8]	"The long, but not the short, presequence of human coproporphyrinogen oxidase is essential for its import and sorting to mitochondria." Susa S., Daimon M., Ono H., Li S., Yoshida T., Kato T. Tohoku J. Exp. Med. 200:39-45(2003) [PubMed: 12862310] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"Homozygous hereditary coproporphyria caused by an arginine to tryptophane substitution in coproporphyrinogen oxidase and common intragenic polymorphisms." Martasek P., Nordmann Y., Grandchamp B. Hum. Mol. Genet. 3:477-480(1994) [PubMed: 8012360] [Abstract] Cited for: VARIANT HCP TRP-331.
[11]	"Characterization and expression of cDNA encoding coproporphyrinogen oxidase from a patient with hereditary coproporphyria." Fujita H., Kondo M., Taketani S., Nomura N., Furuyama K., Akagi R., Nagai T., Terajima M., Galbraith R.A., Sassa S. Hum. Mol. Genet. 3:1807-1810(1994) [PubMed: 7849704] [Abstract] Cited for: VARIANT HCP SER-189, VARIANTS HIS-272 AND ILE-294.
[12]	"A molecular defect in coproporphyrinogen oxidase gene causing harderoporphyria, a variant form of hereditary coproporphyria." Lamoril J., Martasek P., Deybach J.-C., da Silva V., Grandchamp B., Nordmann Y. Hum. Mol. Genet. 4:275-278(1995) [PubMed: 7757079] [Abstract] Cited for: VARIANT HCP GLU-404.
[13]	"A novel missense mutation in exon 4 of the human coproporphyrinogen oxidase gene in two patients with hereditary coproporphyria." Daimon M., Gojyou E., Sugawara M., Yamatani K., Tominaga M., Sasaki H. Hum. Genet. 99:199-201(1997) [PubMed: 9048920] [Abstract] Cited for: VARIANT HCP ARG-280.
[14]	"Three novel mutations in the coproporphyrinogen oxidase gene." Lamoril J., Deybach J.-C., Puy H., Grandchamp B., Nordmann Y. Hum. Mutat. 9:78-80(1997) [PubMed: 8990017] [Abstract] Cited for: VARIANTS HCP 162-GLN--ALA-168 DEL AND ASP-295.
[15]	"Hereditary coproporphyria: exon screening by heteroduplex analysis detects three novel mutations in the coproporphyrinogen oxidase gene." Schreiber W.E., Zhang X., Senz J., Jamani A. Hum. Mutat. 10:196-200(1997) [PubMed: 9298818] [Abstract] Cited for: VARIANTS HCP LYS-201 AND SER-249.
[16]	"Systematic analysis of coproporphyrinogen oxidase gene defects in hereditary coproporphyria and mutation update." Rosipal R., Lamoril J., Puy H., da Silva V., Gouya L., de Rooij F.W.M., Te Velde K., Nordmann Y., Martasek P., Deybach J.-C. Hum. Mutat. 13:44-53(1999) [PubMed: 9888388] [Abstract] Cited for: VARIANTS HCP TRP-197; GLY-390 DEL AND ARG-427.
[17]	"Two novel mutations and coexistence of the 991C>T and the 1339C>T mutation on a single allele in the coproporphyrinogen oxidase gene in Swedish patients with hereditary coproporphyria." Wiman A., Floderus Y., Harper P. J. Hum. Genet. 47:407-412(2002) [PubMed: 12181641] [Abstract] Cited for: VARIANTS HCP PHE-208; CYS-328; TRP-331 AND CYS-447.
[18]	"Biochemical and genetic characterization of four cases of hereditary coproporphyria in Spain." To-Figueras J., Badenas C., Enriquez M.T., Segura S., Alvarez C., Mila M., Lecha M., Herrero C. Mol. Genet. Metab. 85:160-163(2005) [PubMed: 15896662] [Abstract] Cited for: VARIANTS HCP ALA-135; ARG-214 AND ARG-249.
[19]	"Dual gene defects involving delta-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient." Akagi R., Inoue R., Muranaka S., Tahara T., Taketani S., Anderson K.E., Phillips J.D., Sassa S. Br. J. Haematol. 132:237-243(2006) [PubMed: 16398658] [Abstract] Cited for: VARIANT HCP ARG-279.
[20]	Erratum Akagi R., Inoue R., Muranaka S., Tahara T., Taketani S., Anderson K.E., Phillips J.D., Sassa S. Br. J. Haematol. 132:662-662(2006)
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

Z34531 , Z34803, Z34804, Z34805, Z34806, Z34807, Z34808 Genomic DNA. Translation: CAA84292.1.
AK290140 mRNA. Translation: BAF82829.1.
AK223481 mRNA. Translation: BAD97201.1.
CH471052 Genomic DNA. Translation: EAW79854.1.
BC017210 mRNA. Translation: AAH17210.1.
BC023551 mRNA. Translation: AAH23551.1.
BC023554 mRNA. Translation: AAH23554.1.
D16611 mRNA. Translation: BAA04033.1. Different initiation.
Z28409 mRNA. Translation: CAA82250.1.

IPI

IPI00093057.

PIR

I52444.

RefSeq

NP_000088.3.

UniGene

Hs.476982

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AEX	X-ray	1.58	A	111-453	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P36551.

PTM databases

PhosphoSite

P36551.

Proteomic databases

PeptideAtlas

P36551.

PRIDE

P36551.

Genome annotation databases

Ensembl

ENST00000264193; ENSP00000264193; ENSG00000080819; Homo sapiens. [Genome view]

GeneID

1371.

KEGG

hsa:1371.

NMPDR

fig|9606.3.peg.22874.

UCSC

uc003dsx.1. human.

Organism-specific databases

CTD

1371.

GeneCards

GC03M099780.

H-InvDB

HIX0003491.

HGNC

HGNC:2321. CPOX.

HPA

HPA015736.

MIM

121300. phenotype.
612732. gene.

Orphanet

79273. Coproporphyria, hereditary.

PharmGKB

PA134979958.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P36551.

HOVERGEN

P36551.

OMA

VFKPWCD.

Enzyme and pathway databases

BRENDA

1.3.3.3. 247.

Reactome

REACT_9431. Metabolism of porphyrins.

Gene expression databases

ArrayExpress

P36551.

Bgee

P36551.

CleanEx

HS_CPO.
HS_CPOX.

Genevestigator

P36551.

GermOnline

ENSG00000080819. Homo sapiens.

Family and domain databases

InterPro

IPR001260. Coprogen_oxidas.
IPR018375. Coproporphyrinogen-3_ox_CS.
[Graphical view]

Gene3D

G3DSA:3.40.1500.10. Coprogen_oxidas. 1 hit.

PANTHER

PTHR10755. Coprogen_oxidas. 1 hit.

Pfam

PF01218. Coprogen_oxidas. 1 hit.
[Graphical view]

PRINTS

PR00073. COPRGNOXDASE.

PROSITE

PS01021. COPROGEN_OXIDASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

5561.

SOURCE

Search...

Entry information

Entry name

HEM6_HUMAN

Accession

Primary (citable) accession number: P36551
Secondary accession number(s): A8K275 , Q14060, Q53F08, Q8IZ45, Q96AF3

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 7, 2005
Last modified:	November 3, 2009
This is version 108 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.