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Protein

Ceruloplasmin

Gene

CP

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

Functioni

Ceruloplasmin is a 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. Provides Cu2+ ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1. May also play a role in fetal lung development or pulmonary antioxidant defense (By similarity).By similarity

Catalytic activityi

4 Fe2+ + 4 H+ + O2 = 4 Fe3+ + 2 H2O.

Cofactori

Cu cationNote: Binds 6 Cu cations per monomer.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi120Copper 1; type 21
Metal bindingi122Copper 2; type 31
Metal bindingi180Copper 2; type 31
Metal bindingi182Copper 3; type 31
Metal bindingi295Copper 4; type 11
Metal bindingi338Copper 4; type 11
Metal bindingi343Copper 4; type 11
Metal bindingi656Copper 5; type 11
Metal bindingi699Copper 5; type 11
Metal bindingi704Copper 5; type 11
Metal bindingi709Copper 5; type 11
Metal bindingi994Copper 6; type 11
Metal bindingi997Copper 1; type 21
Metal bindingi999Copper 3; type 31
Metal bindingi1039Copper 3; type 31
Metal bindingi1040Copper 6; type 11
Metal bindingi1041Copper 2; type 31
Metal bindingi1045Copper 6; type 11
Metal bindingi1050Copper 6; type 11

GO - Molecular functioni

  • chaperone binding Source: BHF-UCL
  • copper ion binding Source: InterPro
  • ferroxidase activity Source: Reactome
  • oxidoreductase activity, oxidizing metal ions Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processCopper transport, Ion transport, Transport
LigandCopper, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS00590-MONOMER
BRENDAi1.16.3.1 2681
ReactomeiR-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-425410 Metal ion SLC transporters
R-HSA-5619060 Defective CP causes aceruloplasminemia (ACERULOP)
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-917937 Iron uptake and transport
SABIO-RKiP00450
SIGNORiP00450

Protein family/group databases

TCDBi8.A.105.1.2 the multi-copper-containing ferrooxidase (mcfo) family

Names & Taxonomyi

Protein namesi
Recommended name:
Ceruloplasmin (EC:1.16.3.1)
Alternative name(s):
Ferroxidase
Gene namesi
Name:CP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000047457.13
HGNCiHGNC:2295 CP
MIMi117700 gene
neXtProtiNX_P00450

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Aceruloplasminemia (ACERULOP)
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:604290
Ceruloplasmin levels are decreased in Wilson disease, in which copper cannot be incorporated into ceruloplasmin in liver because of defects in the copper-transporting ATPase 2.

Organism-specific databases

DisGeNETi1356
GeneReviewsiCP
MalaCardsiCP
MIMi604290 phenotype
Orphaneti48818 Aceruloplasminemia
PharmGKBiPA26815

Chemistry databases

DrugBankiDB00055 Drotrecogin alfa

Polymorphism and mutation databases

BioMutaiCP
DMDMi116117

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 191 PublicationAdd BLAST19
ChainiPRO_000000291220 – 1065CeruloplasminAdd BLAST1046

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi138N-linked (GlcNAc...) (complex) asparagine6 Publications1
Disulfide bondi174 ↔ 200Curated
Disulfide bondi276 ↔ 357Curated
Glycosylationi358N-linked (GlcNAc...) (complex) asparagine4 Publications1
Glycosylationi397N-linked (GlcNAc...) (complex) asparagine5 Publications1
Disulfide bondi534 ↔ 560Curated
Glycosylationi588N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi637 ↔ 718Curated
Modified residuei722Phosphoserine; by FAM20C1 Publication1
Glycosylationi762N-linked (GlcNAc...) (complex) asparagine4 Publications1
Disulfide bondi874 ↔ 900Curated
Glycosylationi926N-linked (GlcNAc...) asparagine1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP00450
MaxQBiP00450
PaxDbiP00450
PeptideAtlasiP00450
PRIDEiP00450
ProteomicsDBi51251

2D gel databases

DOSAC-COBS-2DPAGEiP00450
SWISS-2DPAGEiP00450

PTM databases

CarbonylDBiP00450
GlyConnecti85
iPTMnetiP00450
PhosphoSitePlusiP00450
UniCarbKBiP00450

Miscellaneous databases

PMAP-CutDBiP00450

Expressioni

Tissue specificityi

Expressed by the liver and secreted in plasma.

Gene expression databases

BgeeiENSG00000047457 Expressed in 185 organ(s), highest expression level in liver
CleanExiHS_CP
ExpressionAtlasiP00450 baseline and differential
GenevisibleiP00450 HS

Organism-specific databases

HPAiCAB008591
HPA001834

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107748, 10 interactors
CORUMiP00450
IntActiP00450, 5 interactors
STRINGi9606.ENSP00000264613

Structurei

Secondary structure

11065
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP00450
SMRiP00450
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00450

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 357F5/8 type A 1Add BLAST338
Domaini20 – 200Plastocyanin-like 1Add BLAST181
Domaini209 – 357Plastocyanin-like 2Add BLAST149
Domaini370 – 718F5/8 type A 2Add BLAST349
Domaini370 – 560Plastocyanin-like 3Add BLAST191
Domaini570 – 718Plastocyanin-like 4Add BLAST149
Domaini730 – 1061F5/8 type A 3Add BLAST332
Domaini730 – 900Plastocyanin-like 5Add BLAST171
Domaini908 – 1061Plastocyanin-like 6Add BLAST154

Sequence similaritiesi

Belongs to the multicopper oxidase family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG1263 Eukaryota
COG2132 LUCA
HOGENOMiHOG000231499
HOVERGENiHBG003674
InParanoidiP00450
KOiK13624
OrthoDBiEOG091G00QL
PhylomeDBiP00450
TreeFamiTF329807

Family and domain databases

Gene3Di2.60.40.420, 6 hits
InterProiView protein in InterPro
IPR027150 CP
IPR001117 Cu-oxidase
IPR011706 Cu-oxidase_2
IPR011707 Cu-oxidase_3
IPR033138 Cu_oxidase_CS
IPR002355 Cu_oxidase_Cu_BS
IPR008972 Cupredoxin
PANTHERiPTHR44048:SF5 PTHR44048:SF5, 1 hit
PfamiView protein in Pfam
PF00394 Cu-oxidase, 1 hit
PF07731 Cu-oxidase_2, 1 hit
PF07732 Cu-oxidase_3, 2 hits
SUPFAMiSSF49503 SSF49503, 6 hits
PROSITEiView protein in PROSITE
PS00079 MULTICOPPER_OXIDASE1, 3 hits
PS00080 MULTICOPPER_OXIDASE2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

P00450-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKILILGIFL FLCSTPAWAK EKHYYIGIIE TTWDYASDHG EKKLISVDTE
60 70 80 90 100
HSNIYLQNGP DRIGRLYKKA LYLQYTDETF RTTIEKPVWL GFLGPIIKAE
110 120 130 140 150
TGDKVYVHLK NLASRPYTFH SHGITYYKEH EGAIYPDNTT DFQRADDKVY
160 170 180 190 200
PGEQYTYMLL ATEEQSPGEG DGNCVTRIYH SHIDAPKDIA SGLIGPLIIC
210 220 230 240 250
KKDSLDKEKE KHIDREFVVM FSVVDENFSW YLEDNIKTYC SEPEKVDKDN
260 270 280 290 300
EDFQESNRMY SVNGYTFGSL PGLSMCAEDR VKWYLFGMGN EVDVHAAFFH
310 320 330 340 350
GQALTNKNYR IDTINLFPAT LFDAYMVAQN PGEWMLSCQN LNHLKAGLQA
360 370 380 390 400
FFQVQECNKS SSKDNIRGKH VRHYYIAAEE IIWNYAPSGI DIFTKENLTA
410 420 430 440 450
PGSDSAVFFE QGTTRIGGSY KKLVYREYTD ASFTNRKERG PEEEHLGILG
460 470 480 490 500
PVIWAEVGDT IRVTFHNKGA YPLSIEPIGV RFNKNNEGTY YSPNYNPQSR
510 520 530 540 550
SVPPSASHVA PTETFTYEWT VPKEVGPTNA DPVCLAKMYY SAVDPTKDIF
560 570 580 590 600
TGLIGPMKIC KKGSLHANGR QKDVDKEFYL FPTVFDENES LLLEDNIRMF
610 620 630 640 650
TTAPDQVDKE DEDFQESNKM HSMNGFMYGN QPGLTMCKGD SVVWYLFSAG
660 670 680 690 700
NEADVHGIYF SGNTYLWRGE RRDTANLFPQ TSLTLHMWPD TEGTFNVECL
710 720 730 740 750
TTDHYTGGMK QKYTVNQCRR QSEDSTFYLG ERTYYIAAVE VEWDYSPQRE
760 770 780 790 800
WEKELHHLQE QNVSNAFLDK GEFYIGSKYK KVVYRQYTDS TFRVPVERKA
810 820 830 840 850
EEEHLGILGP QLHADVGDKV KIIFKNMATR PYSIHAHGVQ TESSTVTPTL
860 870 880 890 900
PGETLTYVWK IPERSGAGTE DSACIPWAYY STVDQVKDLY SGLIGPLIVC
910 920 930 940 950
RRPYLKVFNP RRKLEFALLF LVFDENESWY LDDNIKTYSD HPEKVNKDDE
960 970 980 990 1000
EFIESNKMHA INGRMFGNLQ GLTMHVGDEV NWYLMGMGNE IDLHTVHFHG
1010 1020 1030 1040 1050
HSFQYKHRGV YSSDVFDIFP GTYQTLEMFP RTPGIWLLHC HVTDHIHAGM
1060
ETTYTVLQNE DTKSG
Length:1,065
Mass (Da):122,205
Last modified:August 13, 1987 - v1
Checksum:i2F2F1294E2D30F58
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PFZ2E9PFZ2_HUMAN
Ceruloplasmin
CP
946Annotation score:
D6RE86D6RE86_HUMAN
Ceruloplasmin
CP
178Annotation score:
H7C5R1H7C5R1_HUMAN
Ceruloplasmin
CP
852Annotation score:
H7C5N5H7C5N5_HUMAN
Ceruloplasmin
CP
225Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1060E → EGEYP in AAA51975 (PubMed:3486416).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02565563I → T Retained in the ER due to impaired N-glycosylation; may present a vulnerability factor for iron induced oxidative stress in Parkinson disease. 2 Publications1
Natural variantiVAR_032815367R → C. Corresponds to variant dbSNP:rs34624984EnsemblClinVar.1
Natural variantiVAR_025656477P → L1 PublicationCorresponds to variant dbSNP:rs35331711EnsemblClinVar.1
Natural variantiVAR_025657544D → E Reduced ferroxidase activity; may present a vulnerability factor for iron induced oxidative stress in Parkinson disease. 2 PublicationsCorresponds to variant dbSNP:rs701753EnsemblClinVar.1
Natural variantiVAR_025658551T → I1 Publication1
Natural variantiVAR_025659793R → H2 Publications1
Natural variantiVAR_025660841T → R1 PublicationCorresponds to variant dbSNP:rs56033670EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13699 mRNA Translation: AAA51976.1
DQ314867 Genomic DNA Translation: ABC40726.1
D45045 Genomic DNA Translation: BAA08085.1
D00025 mRNA Translation: BAA00019.1
X04135 mRNA Translation: CAA27752.1
X04136 mRNA Translation: CAA27753.1
X04137 mRNA Translation: CAA27754.1
X04138 mRNA Translation: CAA27755.1
AF132978 Genomic DNA Translation: AAF02483.1
M13536 mRNA Translation: AAA51975.1
J05506 Genomic DNA No translation available.
CCDSiCCDS3141.1
PIRiA25443 KUHU
RefSeqiNP_000087.1, NM_000096.3
UniGeneiHs.558314

Genome annotation databases

EnsembliENST00000264613; ENSP00000264613; ENSG00000047457
GeneIDi1356
KEGGihsa:1356
UCSCiuc003ewy.6 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Ceruloplasmin entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13699 mRNA Translation: AAA51976.1
DQ314867 Genomic DNA Translation: ABC40726.1
D45045 Genomic DNA Translation: BAA08085.1
D00025 mRNA Translation: BAA00019.1
X04135 mRNA Translation: CAA27752.1
X04136 mRNA Translation: CAA27753.1
X04137 mRNA Translation: CAA27754.1
X04138 mRNA Translation: CAA27755.1
AF132978 Genomic DNA Translation: AAF02483.1
M13536 mRNA Translation: AAA51975.1
J05506 Genomic DNA No translation available.
CCDSiCCDS3141.1
PIRiA25443 KUHU
RefSeqiNP_000087.1, NM_000096.3
UniGeneiHs.558314

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KCWX-ray3.00A20-1065[»]
2J5WX-ray2.80A1-1065[»]
4EJXX-ray4.69A1-1065[»]
4ENZX-ray2.60A1-1065[»]
ProteinModelPortaliP00450
SMRiP00450
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107748, 10 interactors
CORUMiP00450
IntActiP00450, 5 interactors
STRINGi9606.ENSP00000264613

Chemistry databases

DrugBankiDB00055 Drotrecogin alfa

Protein family/group databases

TCDBi8.A.105.1.2 the multi-copper-containing ferrooxidase (mcfo) family

PTM databases

CarbonylDBiP00450
GlyConnecti85
iPTMnetiP00450
PhosphoSitePlusiP00450
UniCarbKBiP00450

Polymorphism and mutation databases

BioMutaiCP
DMDMi116117

2D gel databases

DOSAC-COBS-2DPAGEiP00450
SWISS-2DPAGEiP00450

Proteomic databases

EPDiP00450
MaxQBiP00450
PaxDbiP00450
PeptideAtlasiP00450
PRIDEiP00450
ProteomicsDBi51251

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264613; ENSP00000264613; ENSG00000047457
GeneIDi1356
KEGGihsa:1356
UCSCiuc003ewy.6 human

Organism-specific databases

CTDi1356
DisGeNETi1356
EuPathDBiHostDB:ENSG00000047457.13
GeneCardsiCP
GeneReviewsiCP
HGNCiHGNC:2295 CP
HPAiCAB008591
HPA001834
MalaCardsiCP
MIMi117700 gene
604290 phenotype
neXtProtiNX_P00450
Orphaneti48818 Aceruloplasminemia
PharmGKBiPA26815
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1263 Eukaryota
COG2132 LUCA
HOGENOMiHOG000231499
HOVERGENiHBG003674
InParanoidiP00450
KOiK13624
OrthoDBiEOG091G00QL
PhylomeDBiP00450
TreeFamiTF329807

Enzyme and pathway databases

BioCyciMetaCyc:HS00590-MONOMER
BRENDAi1.16.3.1 2681
ReactomeiR-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-425410 Metal ion SLC transporters
R-HSA-5619060 Defective CP causes aceruloplasminemia (ACERULOP)
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-917937 Iron uptake and transport
SABIO-RKiP00450
SIGNORiP00450

Miscellaneous databases

ChiTaRSiCP human
EvolutionaryTraceiP00450
GeneWikiiCeruloplasmin
GenomeRNAii1356
PMAP-CutDBiP00450
PROiPR:P00450
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000047457 Expressed in 185 organ(s), highest expression level in liver
CleanExiHS_CP
ExpressionAtlasiP00450 baseline and differential
GenevisibleiP00450 HS

Family and domain databases

Gene3Di2.60.40.420, 6 hits
InterProiView protein in InterPro
IPR027150 CP
IPR001117 Cu-oxidase
IPR011706 Cu-oxidase_2
IPR011707 Cu-oxidase_3
IPR033138 Cu_oxidase_CS
IPR002355 Cu_oxidase_Cu_BS
IPR008972 Cupredoxin
PANTHERiPTHR44048:SF5 PTHR44048:SF5, 1 hit
PfamiView protein in Pfam
PF00394 Cu-oxidase, 1 hit
PF07731 Cu-oxidase_2, 1 hit
PF07732 Cu-oxidase_3, 2 hits
SUPFAMiSSF49503 SSF49503, 6 hits
PROSITEiView protein in PROSITE
PS00079 MULTICOPPER_OXIDASE1, 3 hits
PS00080 MULTICOPPER_OXIDASE2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCERU_HUMAN
AccessioniPrimary (citable) accession number: P00450
Secondary accession number(s): Q14063, Q2PP18, Q9UKS4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 13, 1987
Last modified: November 7, 2018
This is version 211 of the entry and version 1 of the sequence. See 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, Direct protein sequencing, Reference proteome

Documents

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