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Protein

Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial

Gene

CPOX

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the heme biosynthesis. Catalyzes the aerobic oxidative decarboxylation of propionate groups of rings A and B of coproporphyrinogen-III to yield the vinyl groups in protoporphyrinogen-IX.

Catalytic activityi

Coproporphyrinogen-III + O2 + 2 H+ = protoporphyrinogen-IX + 2 CO2 + 2 H2O.

Pathwayi: protoporphyrin-IX biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes protoporphyrinogen-IX from coproporphyrinogen-III (O2 route).
Proteins known to be involved in this subpathway in this organism are:
  1. Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX)
This subpathway is part of the pathway protoporphyrin-IX biosynthesis, which is itself part of Porphyrin-containing compound metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes protoporphyrinogen-IX from coproporphyrinogen-III (O2 route), the pathway protoporphyrin-IX biosynthesis and in Porphyrin-containing compound metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei244SubstrateCurated1
Active sitei258Proton donor1 Publication1
Sitei327Important for dimerization1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Heme biosynthesis, Porphyrin biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:HS01369-MONOMER.
ZFISH:HS01369-MONOMER.
BRENDAi1.3.3.3. 2681.
ReactomeiR-HSA-189451. Heme biosynthesis.
UniPathwayiUPA00251; UER00322.

Names & Taxonomyi

Protein namesi
Recommended name:
Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (EC:1.3.3.3)
Short name:
COX
Short name:
Coprogen oxidase
Short name:
Coproporphyrinogenase
Gene namesi
Name:CPOX
Synonyms:CPO, CPX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:2321. CPOX.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Hereditary coproporphyria (HCP)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Hereditary coproporphyria is an acute hepatic porphyria characterized by skin photosensitivity, attacks of abdominal pain, neurological disturbances, and psychiatric symptoms. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. Hereditary coproporphyria is biochemically characterized by overexcretion of coproporphyrin III in the urine and in the feces.
See also OMIM:121300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023444135V → A in HCP. 1 PublicationCorresponds to variant rs201826432dbSNPEnsembl.1
Natural variantiVAR_002151162 – 168Missing in HCP. 1 Publication7
Natural variantiVAR_002152189G → S in HCP; <5% of activity. 1 PublicationCorresponds to variant rs759347283dbSNPEnsembl.1
Natural variantiVAR_002153197G → W in HCP. 1 Publication1
Natural variantiVAR_002154201E → K in HCP. 1 Publication1
Natural variantiVAR_019067208S → F in HCP. 1 PublicationCorresponds to variant rs28929486dbSNPEnsembl.1
Natural variantiVAR_023445214L → R in HCP. 1 Publication1
Natural variantiVAR_023446249P → R in HCP. 1 Publication1
Natural variantiVAR_002155249P → S in HCP. 1 Publication1
Natural variantiVAR_058005279G → R in HCP; a patient carrying also the L-12 mutation in ALAD. 1 PublicationCorresponds to variant rs121917874dbSNPEnsembl.1
Natural variantiVAR_002157280G → R in HCP. 1 Publication1
Natural variantiVAR_002159295H → D in HCP. 1 PublicationCorresponds to variant rs121917870dbSNPEnsembl.1
Natural variantiVAR_019068328R → C in HCP. 1 PublicationCorresponds to variant rs28929487dbSNPEnsembl.1
Natural variantiVAR_002160331R → W in HCP. 2 PublicationsCorresponds to variant rs121917866dbSNPEnsembl.1
Natural variantiVAR_002161390Missing in HCP. 1 Publication1
Natural variantiVAR_002162404K → E in HCP; harderoporphyria form. 1 PublicationCorresponds to variant rs121917868dbSNPEnsembl.1
Natural variantiVAR_002163427W → R in HCP. 1 Publication1
Natural variantiVAR_019069447R → C in HCP. 1 PublicationCorresponds to variant rs28931603dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi392 – 418Missing : Loss for dimerization. 1 PublicationAdd BLAST27

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1371.
MalaCardsiCPOX.
MIMi121300. phenotype.
OpenTargetsiENSG00000080819.
Orphaneti79273. Hereditary coproporphyria.
PharmGKBiPA134979958.

Chemistry databases

ChEMBLiCHEMBL1681618.

Polymorphism and mutation databases

BioMutaiCPOX.
DMDMi67476671.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 110MitochondrionBy similarityAdd BLAST110
ChainiPRO_0000006029111 – 454Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrialAdd BLAST344

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei112PhosphoserineBy similarity1
Modified residuei404N6-acetyllysine; alternateBy similarity1
Modified residuei404N6-succinyllysine; alternateBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP36551.
MaxQBiP36551.
PaxDbiP36551.
PeptideAtlasiP36551.
PRIDEiP36551.

PTM databases

iPTMnetiP36551.
PhosphoSitePlusiP36551.
SwissPalmiP36551.

Expressioni

Gene expression databases

BgeeiENSG00000080819.
CleanExiHS_CPO.
HS_CPOX.
ExpressionAtlasiP36551. baseline and differential.
GenevisibleiP36551. HS.

Organism-specific databases

HPAiHPA015736.
HPA054448.

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi107763. 10 interactors.
IntActiP36551. 15 interactors.
STRINGi9606.ENSP00000264193.

Structurei

Secondary structure

1454
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi122 – 128Combined sources7
Beta strandi130 – 132Combined sources3
Helixi138 – 143Combined sources6
Helixi148 – 170Combined sources23
Beta strandi177 – 183Combined sources7
Turni184 – 186Combined sources3
Beta strandi187 – 196Combined sources10
Beta strandi198 – 213Combined sources16
Helixi216 – 224Combined sources9
Beta strandi237 – 251Combined sources15
Beta strandi256 – 267Combined sources12
Beta strandi273 – 284Combined sources12
Helixi290 – 305Combined sources16
Helixi311 – 322Combined sources12
Helixi326 – 328Combined sources3
Beta strandi330 – 342Combined sources13
Helixi347 – 359Combined sources13
Helixi361 – 372Combined sources12
Helixi379 – 399Combined sources21
Helixi406 – 408Combined sources3
Beta strandi409 – 411Combined sources3
Helixi414 – 420Combined sources7
Helixi438 – 447Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AEXX-ray1.58A111-454[»]
ProteinModelPortaliP36551.
SMRiP36551.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP36551.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni193 – 202Important for dimerizationCurated10
Regioni260 – 262Substrate binding3
Regioni392 – 428Important for dimerizationAdd BLAST37
Regioni411 – 413Substrate binding3

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1518. Eukaryota.
COG0408. LUCA.
GeneTreeiENSGT00390000017311.
HOGENOMiHOG000262768.
HOVERGENiHBG051897.
InParanoidiP36551.
KOiK00228.
OMAiMELLIME.
OrthoDBiEOG091G06ZF.
PhylomeDBiP36551.
TreeFamiTF300703.

Family and domain databases

Gene3Di3.40.1500.10. 1 hit.
InterProiIPR001260. Coprogen_oxidase_aer.
IPR018375. Coprogen_oxidase_CS.
[Graphical view]
PANTHERiPTHR10755. PTHR10755. 1 hit.
PfamiPF01218. Coprogen_oxidas. 1 hit.
[Graphical view]
PRINTSiPR00073. COPRGNOXDASE.
SUPFAMiSSF102886. SSF102886. 1 hit.
PROSITEiPS01021. COPROGEN_OXIDASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P36551-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALQLGRLSS GPCWLVARGG CGGPRAWSQC GGGGLRAWSQ RSAAGRVCRP
60 70 80 90 100
PGPAGTEQSR GLGHGSTSRG GPWVGTGLAA ALAGLVGLAT AAFGHVQRAE
110 120 130 140 150
MLPKTSGTRA TSLGRPEEEE DELAHRCSSF MAPPVTDLGE LRRRPGDMKT
160 170 180 190 200
KMELLILETQ AQVCQALAQV DGGANFSVDR WERKEGGGGI SCVLQDGCVF
210 220 230 240 250
EKAGVSISVV HGNLSEEAAK QMRSRGKVLK TKDGKLPFCA MGVSSVIHPK
260 270 280 290 300
NPHAPTIHFN YRYFEVEEAD GNKQWWFGGG CDLTPTYLNQ EDAVHFHRTL
310 320 330 340 350
KEACDQHGPD LYPKFKKWCD DYFFIAHRGE RRGIGGIFFD DLDSPSKEEV
360 370 380 390 400
FRFVQSCARA VVPSYIPLVK KHCDDSFTPQ EKLWQQLRRG RYVEFNLLYD
410 420 430 440 450
RGTKFGLFTP GSRIESILMS LPLTARWEYM HSPSENSKEA EILEVLRHPR

DWVR
Length:454
Mass (Da):50,152
Last modified:June 7, 2005 - v3
Checksum:i6EC3D15FD8FD86B5
GO
Isoform 2 (identifier: P36551-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     272-287: NKQWWFGGGCDLTPTY → KGLRSYGKYCRAKCAF
     288-454: Missing.

Note: No experimental confirmation available.
Show »
Length:287
Mass (Da):30,383
Checksum:i69DFD4AC8247AE4E
GO

Sequence cautioni

The sequence BAA04033 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti247I → T in CAA82250 (PubMed:8159699).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023444135V → A in HCP. 1 PublicationCorresponds to variant rs201826432dbSNPEnsembl.1
Natural variantiVAR_002151162 – 168Missing in HCP. 1 Publication7
Natural variantiVAR_002152189G → S in HCP; <5% of activity. 1 PublicationCorresponds to variant rs759347283dbSNPEnsembl.1
Natural variantiVAR_002153197G → W in HCP. 1 Publication1
Natural variantiVAR_002154201E → K in HCP. 1 Publication1
Natural variantiVAR_019067208S → F in HCP. 1 PublicationCorresponds to variant rs28929486dbSNPEnsembl.1
Natural variantiVAR_023445214L → R in HCP. 1 Publication1
Natural variantiVAR_023446249P → R in HCP. 1 Publication1
Natural variantiVAR_002155249P → S in HCP. 1 Publication1
Natural variantiVAR_002156272N → H.2 PublicationsCorresponds to variant rs1131857dbSNPEnsembl.1
Natural variantiVAR_058005279G → R in HCP; a patient carrying also the L-12 mutation in ALAD. 1 PublicationCorresponds to variant rs121917874dbSNPEnsembl.1
Natural variantiVAR_002157280G → R in HCP. 1 Publication1
Natural variantiVAR_002158294V → I.3 PublicationsCorresponds to variant rs2228056dbSNPEnsembl.1
Natural variantiVAR_002159295H → D in HCP. 1 PublicationCorresponds to variant rs121917870dbSNPEnsembl.1
Natural variantiVAR_019068328R → C in HCP. 1 PublicationCorresponds to variant rs28929487dbSNPEnsembl.1
Natural variantiVAR_002160331R → W in HCP. 2 PublicationsCorresponds to variant rs121917866dbSNPEnsembl.1
Natural variantiVAR_048827352R → C.Corresponds to variant rs11921054dbSNPEnsembl.1
Natural variantiVAR_002161390Missing in HCP. 1 Publication1
Natural variantiVAR_002162404K → E in HCP; harderoporphyria form. 1 PublicationCorresponds to variant rs121917868dbSNPEnsembl.1
Natural variantiVAR_002163427W → R in HCP. 1 Publication1
Natural variantiVAR_019069447R → C in HCP. 1 PublicationCorresponds to variant rs28931603dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_057182272 – 287NKQWW…LTPTY → KGLRSYGKYCRAKCAF in isoform 2. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_057183288 – 454Missing in isoform 2. 1 PublicationAdd BLAST167

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z34531
, Z34803, Z34804, Z34805, Z34806, Z34807, Z34808 Genomic DNA. Translation: CAA84292.1.
AK290140 mRNA. Translation: BAF82829.1.
AK299692 mRNA. Translation: BAG61597.1.
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.
CCDSiCCDS2932.1. [P36551-1]
PIRiI52444.
RefSeqiNP_000088.3. NM_000097.5. [P36551-1]
UniGeneiHs.476982.

Genome annotation databases

EnsembliENST00000264193; ENSP00000264193; ENSG00000080819. [P36551-1]
GeneIDi1371.
KEGGihsa:1371.
UCSCiuc003dsx.4. human. [P36551-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z34531
, Z34803, Z34804, Z34805, Z34806, Z34807, Z34808 Genomic DNA. Translation: CAA84292.1.
AK290140 mRNA. Translation: BAF82829.1.
AK299692 mRNA. Translation: BAG61597.1.
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.
CCDSiCCDS2932.1. [P36551-1]
PIRiI52444.
RefSeqiNP_000088.3. NM_000097.5. [P36551-1]
UniGeneiHs.476982.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AEXX-ray1.58A111-454[»]
ProteinModelPortaliP36551.
SMRiP36551.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107763. 10 interactors.
IntActiP36551. 15 interactors.
STRINGi9606.ENSP00000264193.

Chemistry databases

ChEMBLiCHEMBL1681618.

PTM databases

iPTMnetiP36551.
PhosphoSitePlusiP36551.
SwissPalmiP36551.

Polymorphism and mutation databases

BioMutaiCPOX.
DMDMi67476671.

Proteomic databases

EPDiP36551.
MaxQBiP36551.
PaxDbiP36551.
PeptideAtlasiP36551.
PRIDEiP36551.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264193; ENSP00000264193; ENSG00000080819. [P36551-1]
GeneIDi1371.
KEGGihsa:1371.
UCSCiuc003dsx.4. human. [P36551-1]

Organism-specific databases

CTDi1371.
DisGeNETi1371.
GeneCardsiCPOX.
GeneReviewsiCPOX.
HGNCiHGNC:2321. CPOX.
HPAiHPA015736.
HPA054448.
MalaCardsiCPOX.
MIMi121300. phenotype.
612732. gene.
neXtProtiNX_P36551.
OpenTargetsiENSG00000080819.
Orphaneti79273. Hereditary coproporphyria.
PharmGKBiPA134979958.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1518. Eukaryota.
COG0408. LUCA.
GeneTreeiENSGT00390000017311.
HOGENOMiHOG000262768.
HOVERGENiHBG051897.
InParanoidiP36551.
KOiK00228.
OMAiMELLIME.
OrthoDBiEOG091G06ZF.
PhylomeDBiP36551.
TreeFamiTF300703.

Enzyme and pathway databases

UniPathwayiUPA00251; UER00322.
BioCyciMetaCyc:HS01369-MONOMER.
ZFISH:HS01369-MONOMER.
BRENDAi1.3.3.3. 2681.
ReactomeiR-HSA-189451. Heme biosynthesis.

Miscellaneous databases

EvolutionaryTraceiP36551.
GeneWikiiCoproporphyrinogen_III_oxidase.
GenomeRNAii1371.
PROiP36551.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000080819.
CleanExiHS_CPO.
HS_CPOX.
ExpressionAtlasiP36551. baseline and differential.
GenevisibleiP36551. HS.

Family and domain databases

Gene3Di3.40.1500.10. 1 hit.
InterProiIPR001260. Coprogen_oxidase_aer.
IPR018375. Coprogen_oxidase_CS.
[Graphical view]
PANTHERiPTHR10755. PTHR10755. 1 hit.
PfamiPF01218. Coprogen_oxidas. 1 hit.
[Graphical view]
PRINTSiPR00073. COPRGNOXDASE.
SUPFAMiSSF102886. SSF102886. 1 hit.
PROSITEiPS01021. COPROGEN_OXIDASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHEM6_HUMAN
AccessioniPrimary (citable) accession number: P36551
Secondary accession number(s): A8K275
, B4DSD5, Q14060, Q53F08, Q8IZ45, Q96AF3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 7, 2005
Last modified: November 2, 2016
This is version 176 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.