P00450 · CERU_HUMAN
- ProteinCeruloplasmin
- GeneCP
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1065 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe2+ to Fe3+ without releasing radical oxygen species. It is involved in iron transport across the cell membrane (PubMed:16150804).
Copper ions provide a large number of enzymatic activites. Oxidizes highly toxic ferrous ions to the ferric state for further incorporation onto apo-transferrins, catalyzes Cu+ oxidation and promotes the oxidation of biogenic amines such as norepinephrin and serotonin (PubMed:14623105, PubMed:4643313, PubMed:5912351).
Provides Cu2+ ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1 (By similarity).
Has glutathione peroxidase-like activity, can remove both hydrogen peroxide and lipid hydroperoxide in the presence of thiols (PubMed:10481051).
Also shows NO-oxidase and NO2 synthase activities that determine endocrine NO homeostasis (PubMed:16906150).
Copper ions provide a large number of enzymatic activites. Oxidizes highly toxic ferrous ions to the ferric state for further incorporation onto apo-transferrins, catalyzes Cu+ oxidation and promotes the oxidation of biogenic amines such as norepinephrin and serotonin (PubMed:14623105, PubMed:4643313, PubMed:5912351).
Provides Cu2+ ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1 (By similarity).
Has glutathione peroxidase-like activity, can remove both hydrogen peroxide and lipid hydroperoxide in the presence of thiols (PubMed:10481051).
Also shows NO-oxidase and NO2 synthase activities that determine endocrine NO homeostasis (PubMed:16906150).
Catalytic activity
- 4 Fe2+ + 4 H+ + O2 = 4 Fe3+ + 2 H2OThis reaction proceeds in the backward direction.
- 2 H2O + 4 nitric oxide + O2 = 4 H+ + 4 nitriteThis reaction proceeds in the forward direction.
Cofactor
Note: Binds 6 Cu2+ cations per monomer.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
36.8 μM | Cu+ | |||||
8.3 μM | Fe2+ | |||||
1.57 mM | glutathione | |||||
0.63 mM | tert-butyl hydroperoxide | |||||
0.87 mM | glutathione |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
156 nmol/min/mg | (in presence of 5 mM tert-butyl hydroperoxide) | ||||
49 nmol/min/mg | (in presence of 5 mM H2O2) |
kcat is 22.5 min-1 and 30.3 min-1 with Cu+ and Fe2+ as substrates, respectively.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 55 | Na+ 1 (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 64 | Na+ 1 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 67 | Na+ 1 (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 120 | Cu2+ 1 (UniProtKB | ChEBI); type 2 copper site | ||||
Sequence: H | ||||||
Binding site | 120 | O2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 122 | Cu2+ 2 (UniProtKB | ChEBI); type 3 copper site | ||||
Sequence: H | ||||||
Binding site | 128 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 143 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 146 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 147 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 180 | Cu2+ 2 (UniProtKB | ChEBI); type 3 copper site | ||||
Sequence: H | ||||||
Binding site | 180 | O2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 182 | Cu2+ 3 (UniProtKB | ChEBI); type 3 copper site | ||||
Sequence: H | ||||||
Binding site | 256 | Na+ 1 (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 295 | Cu2+ 4 (UniProtKB | ChEBI); type 1 copper site | ||||
Sequence: H | ||||||
Binding site | 338 | Cu2+ 4 (UniProtKB | ChEBI); type 1 copper site | ||||
Sequence: C | ||||||
Binding site | 343 | Cu2+ 4 (UniProtKB | ChEBI); type 1 copper site | ||||
Sequence: H | ||||||
Binding site | 408 | Na+ 2 (UniProtKB | ChEBI) | ||||
Sequence: F | ||||||
Binding site | 417 | Na+ 2 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 420 | Na+ 2 (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 617 | Na+ 2 (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 656 | Cu2+ 5 (UniProtKB | ChEBI); type 1 copper site | ||||
Sequence: H | ||||||
Active site | 699 | Nucleophile; for glutathione peroxidase activity | ||||
Sequence: C | ||||||
Binding site | 699 | Cu2+ 5 (UniProtKB | ChEBI); type 1 copper site | ||||
Sequence: C | ||||||
Binding site | 704 | Cu2+ 5 (UniProtKB | ChEBI); type 1 copper site | ||||
Sequence: H | ||||||
Binding site | 709 | Cu2+ 5 (UniProtKB | ChEBI); type 1 copper site | ||||
Sequence: M | ||||||
Binding site | 767 | Na+ 3 (UniProtKB | ChEBI) | ||||
Sequence: F | ||||||
Binding site | 776 | Na+ 3 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 779 | Na+ 3 (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 955 | Na+ 3 (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 994 | Cu2+ 6 (UniProtKB | ChEBI); type 1 copper site | ||||
Sequence: H | ||||||
Binding site | 997 | Cu2+ 1 (UniProtKB | ChEBI); type 2 copper site | ||||
Sequence: H | ||||||
Binding site | 997 | O2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 999 | Cu2+ 3 (UniProtKB | ChEBI); type 3 copper site | ||||
Sequence: H | ||||||
Binding site | 999 | O2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 1039 | Cu2+ 3 (UniProtKB | ChEBI); type 3 copper site | ||||
Sequence: H | ||||||
Binding site | 1040 | Cu2+ 6 (UniProtKB | ChEBI); type 1 copper site | ||||
Sequence: C | ||||||
Binding site | 1041 | Cu2+ 2 (UniProtKB | ChEBI); type 3 copper site | ||||
Sequence: H | ||||||
Binding site | 1041 | O2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 1045 | Cu2+ 6 (UniProtKB | ChEBI); type 1 copper site | ||||
Sequence: H | ||||||
Binding site | 1050 | Cu2+ 6 (UniProtKB | ChEBI); type 1 copper site | ||||
Sequence: M |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | blood microparticle | |
Cellular Component | endoplasmic reticulum lumen | |
Cellular Component | extracellular exosome | |
Cellular Component | extracellular region | |
Cellular Component | extracellular space | |
Cellular Component | lysosomal membrane | |
Cellular Component | plasma membrane | |
Molecular Function | copper ion binding | |
Molecular Function | ferroxidase activity | |
Molecular Function | glutathione peroxidase activity | |
Molecular Function | oxidoreductase activity | |
Molecular Function | oxidoreductase activity, acting on metal ions, oxygen as acceptor | |
Molecular Function | phospholipid-hydroperoxide glutathione peroxidase activity | |
Molecular Function | protein-folding chaperone binding | |
Biological Process | intracellular copper ion homeostasis | |
Biological Process | intracellular iron ion homeostasis | |
Biological Process | iron ion transport |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameCeruloplasmin
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP00450
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Colocalizes with GCP1 in secretory intracellular compartments.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Aceruloplasminemia (ACEP)
- Note
- DescriptionAn autosomal recessive disorder of iron metabolism characterized by iron accumulation in the brain as well as visceral organs. Clinical features consist of the triad of retinal degeneration, diabetes mellitus and neurological disturbances.
- See alsoMIM:604290
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_025655 | 63 | retained in the endoplasmic reticulum; dbSNP:rs759185877 | |||
Sequence: I → T | ||||||
Natural variant | VAR_032815 | 367 | in dbSNP:rs34624984 | |||
Sequence: R → C | ||||||
Natural variant | VAR_025656 | 477 | in dbSNP:rs35331711 | |||
Sequence: P → L | ||||||
Natural variant | VAR_025657 | 544 | no effect on the localization at the plasma membrane; dbSNP:rs701753 | |||
Sequence: E → D | ||||||
Natural variant | VAR_025658 | 551 | in dbSNP:rs61733458 | |||
Sequence: T → I | ||||||
Natural variant | VAR_025659 | 793 | no effect on the localization at the plasma membrane; dbSNP:rs115552500 | |||
Sequence: R → H | ||||||
Natural variant | VAR_025660 | 841 | in dbSNP:rs56033670 | |||
Sequence: T → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,238 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-19 | UniProt | |||||
Sequence: MKILILGIFLFLCSTPAWA | |||||||
Chain | PRO_0000002912 | 20-1065 | UniProt | Ceruloplasmin | |||
Sequence: KEKHYYIGIIETTWDYASDHGEKKLISVDTEHSNIYLQNGPDRIGRLYKKALYLQYTDETFRTTIEKPVWLGFLGPIIKAETGDKVYVHLKNLASRPYTFHSHGITYYKEHEGAIYPDNTTDFQRADDKVYPGEQYTYMLLATEEQSPGEGDGNCVTRIYHSHIDAPKDIASGLIGPLIICKKDSLDKEKEKHIDREFVVMFSVVDENFSWYLEDNIKTYCSEPEKVDKDNEDFQESNRMYSVNGYTFGSLPGLSMCAEDRVKWYLFGMGNEVDVHAAFFHGQALTNKNYRIDTINLFPATLFDAYMVAQNPGEWMLSCQNLNHLKAGLQAFFQVQECNKSSSKDNIRGKHVRHYYIAAEEIIWNYAPSGIDIFTKENLTAPGSDSAVFFEQGTTRIGGSYKKLVYREYTDASFTNRKERGPEEEHLGILGPVIWAEVGDTIRVTFHNKGAYPLSIEPIGVRFNKNNEGTYYSPNYNPQSRSVPPSASHVAPTETFTYEWTVPKEVGPTNADPVCLAKMYYSAVEPTKDIFTGLIGPMKICKKGSLHANGRQKDVDKEFYLFPTVFDENESLLLEDNIRMFTTAPDQVDKEDEDFQESNKMHSMNGFMYGNQPGLTMCKGDSVVWYLFSAGNEADVHGIYFSGNTYLWRGERRDTANLFPQTSLTLHMWPDTEGTFNVECLTTDHYTGGMKQKYTVNQCRRQSEDSTFYLGERTYYIAAVEVEWDYSPQREWEKELHHLQEQNVSNAFLDKGEFYIGSKYKKVVYRQYTDSTFRVPVERKAEEEHLGILGPQLHADVGDKVKIIFKNMATRPYSIHAHGVQTESSTVTPTLPGETLTYVWKIPERSGAGTEDSACIPWAYYSTVDQVKDLYSGLIGPLIVCRRPYLKVFNPRRKLEFALLFLVFDENESWYLDDNIKTYSDHPEKVNKDDEEFIESNKMHAINGRMFGNLQGLTMHVGDEVNWYLMGMGNEIDLHTVHFHGHSFQYKHRGVYSSDVFDIFPGTYQTLEMFPRTPGIWLLHCHVTDHIHAGMETTYTVLQNEDTKSG | |||||||
Glycosylation | 138 | UniProt | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 174↔200 | UniProt | |||||
Sequence: CVTRIYHSHIDAPKDIASGLIGPLIIC | |||||||
Disulfide bond | 276↔357 | UniProt | |||||
Sequence: CAEDRVKWYLFGMGNEVDVHAAFFHGQALTNKNYRIDTINLFPATLFDAYMVAQNPGEWMLSCQNLNHLKAGLQAFFQVQEC | |||||||
Glycosylation | 358 | UniProt | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 397 | UniProt | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N | |||||||
Modified residue (large scale data) | 499 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Disulfide bond | 534↔560 | UniProt | |||||
Sequence: CLAKMYYSAVEPTKDIFTGLIGPMKIC | |||||||
Glycosylation | 588 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 637↔718 | UniProt | |||||
Sequence: CKGDSVVWYLFSAGNEADVHGIYFSGNTYLWRGERRDTANLFPQTSLTLHMWPDTEGTFNVECLTTDHYTGGMKQKYTVNQC | |||||||
Modified residue | 722 | UniProt | Phosphoserine; by FAM20C | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 722 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Glycosylation | 762 | UniProt | N-linked (GlcNAc...) (complex) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 874↔900 | UniProt | |||||
Sequence: CIPWAYYSTVDQVKDLYSGLIGPLIVC | |||||||
Glycosylation | 926 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed by the liver and secreted in plasma.
Gene expression databases
Organism-specific databases
Interaction
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 20-200 | Plastocyanin-like 1 | ||||
Sequence: KEKHYYIGIIETTWDYASDHGEKKLISVDTEHSNIYLQNGPDRIGRLYKKALYLQYTDETFRTTIEKPVWLGFLGPIIKAETGDKVYVHLKNLASRPYTFHSHGITYYKEHEGAIYPDNTTDFQRADDKVYPGEQYTYMLLATEEQSPGEGDGNCVTRIYHSHIDAPKDIASGLIGPLIIC | ||||||
Domain | 209-357 | Plastocyanin-like 2 | ||||
Sequence: KEKHIDREFVVMFSVVDENFSWYLEDNIKTYCSEPEKVDKDNEDFQESNRMYSVNGYTFGSLPGLSMCAEDRVKWYLFGMGNEVDVHAAFFHGQALTNKNYRIDTINLFPATLFDAYMVAQNPGEWMLSCQNLNHLKAGLQAFFQVQEC | ||||||
Domain | 370-560 | Plastocyanin-like 3 | ||||
Sequence: HVRHYYIAAEEIIWNYAPSGIDIFTKENLTAPGSDSAVFFEQGTTRIGGSYKKLVYREYTDASFTNRKERGPEEEHLGILGPVIWAEVGDTIRVTFHNKGAYPLSIEPIGVRFNKNNEGTYYSPNYNPQSRSVPPSASHVAPTETFTYEWTVPKEVGPTNADPVCLAKMYYSAVEPTKDIFTGLIGPMKIC | ||||||
Domain | 570-718 | Plastocyanin-like 4 | ||||
Sequence: RQKDVDKEFYLFPTVFDENESLLLEDNIRMFTTAPDQVDKEDEDFQESNKMHSMNGFMYGNQPGLTMCKGDSVVWYLFSAGNEADVHGIYFSGNTYLWRGERRDTANLFPQTSLTLHMWPDTEGTFNVECLTTDHYTGGMKQKYTVNQC | ||||||
Domain | 730-900 | Plastocyanin-like 5 | ||||
Sequence: GERTYYIAAVEVEWDYSPQREWEKELHHLQEQNVSNAFLDKGEFYIGSKYKKVVYRQYTDSTFRVPVERKAEEEHLGILGPQLHADVGDKVKIIFKNMATRPYSIHAHGVQTESSTVTPTLPGETLTYVWKIPERSGAGTEDSACIPWAYYSTVDQVKDLYSGLIGPLIVC | ||||||
Domain | 908-1061 | Plastocyanin-like 6 | ||||
Sequence: FNPRRKLEFALLFLVFDENESWYLDDNIKTYSDHPEKVNKDDEEFIESNKMHAINGRMFGNLQGLTMHVGDEVNWYLMGMGNEIDLHTVHFHGHSFQYKHRGVYSSDVFDIFPGTYQTLEMFPRTPGIWLLHCHVTDHIHAGMETTYTVLQNED |
Sequence similarities
Belongs to the multicopper oxidase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length1,065
- Mass (Da)122,219
- Last updated2024-01-24 v2
- Checksum2F2F76BB47D30F58
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 1060 | in Ref. 6; AAA51975 | ||||
Sequence: E → EGEYP |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M13699 EMBL· GenBank· DDBJ | AAA51976.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ314867 EMBL· GenBank· DDBJ | ABC40726.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
D45045 EMBL· GenBank· DDBJ | BAA08085.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
D00025 EMBL· GenBank· DDBJ | BAA00019.1 EMBL· GenBank· DDBJ | mRNA | ||
X04135 EMBL· GenBank· DDBJ | CAA27752.1 EMBL· GenBank· DDBJ | mRNA | ||
X04136 EMBL· GenBank· DDBJ | CAA27753.1 EMBL· GenBank· DDBJ | mRNA | ||
X04137 EMBL· GenBank· DDBJ | CAA27754.1 EMBL· GenBank· DDBJ | mRNA | ||
X04138 EMBL· GenBank· DDBJ | CAA27755.1 EMBL· GenBank· DDBJ | mRNA | ||
AF132978 EMBL· GenBank· DDBJ | AAF02483.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M13536 EMBL· GenBank· DDBJ | AAA51975.1 EMBL· GenBank· DDBJ | mRNA | ||
J05506 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |