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P00450 (CERU_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 170. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ceruloplasmin

EC=1.16.3.1
Alternative name(s):
Ferroxidase
Gene names
Name:CP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1065 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

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

Cofactor

Binds 6 copper ions per monomer.

Subcellular location

Secreted. Note: Colocalizes with GCP1 in secretory intracellular compartments By similarity.

Tissue specificity

Expressed by the liver and secreted in plasma.

Involvement in disease

Aceruloplasminemia (ACERULOP) [MIM:604290]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

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.

Sequence similarities

Belongs to the multicopper oxidase family.

Contains 3 F5/8 type A domains.

Contains 6 plastocyanin-like domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Ref.7
Chain20 – 10651046Ceruloplasmin
PRO_0000002912

Regions

Domain20 – 357338F5/8 type A 1
Domain20 – 200181Plastocyanin-like 1
Domain209 – 357149Plastocyanin-like 2
Domain370 – 718349F5/8 type A 2
Domain370 – 560191Plastocyanin-like 3
Domain570 – 718149Plastocyanin-like 4
Domain730 – 1061332F5/8 type A 3
Domain730 – 900171Plastocyanin-like 5
Domain908 – 1061154Plastocyanin-like 6

Sites

Metal binding1201Copper 1; type 2
Metal binding1221Copper 2; type 3
Metal binding1801Copper 2; type 3
Metal binding1821Copper 3; type 3
Metal binding2951Copper 4; type 1
Metal binding3381Copper 4; type 1
Metal binding3431Copper 4; type 1
Metal binding6561Copper 5; type 1
Metal binding6991Copper 5; type 1
Metal binding7041Copper 5; type 1
Metal binding7091Copper 5; type 1
Metal binding9941Copper 6; type 1
Metal binding9971Copper 1; type 2
Metal binding9991Copper 3; type 3
Metal binding10391Copper 3; type 3
Metal binding10401Copper 6; type 1
Metal binding10411Copper 2; type 3
Metal binding10451Copper 6; type 1
Metal binding10501Copper 6; type 1

Amino acid modifications

Glycosylation1381N-linked (GlcNAc...) (complex) Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19
Glycosylation3581N-linked (GlcNAc...) (complex) Ref.16 Ref.17 Ref.18 Ref.19
Glycosylation3971N-linked (GlcNAc...) (complex) Ref.15 Ref.16 Ref.17 Ref.18 Ref.19
Glycosylation5881N-linked (GlcNAc...) Ref.16
Glycosylation7621N-linked (GlcNAc...) (complex) Ref.15 Ref.16 Ref.17 Ref.18
Glycosylation9261N-linked (GlcNAc...) Ref.16
Disulfide bond174 ↔ 200 Probable
Disulfide bond276 ↔ 357 Probable
Disulfide bond534 ↔ 560 Probable
Disulfide bond637 ↔ 718 Probable
Disulfide bond874 ↔ 900 Probable

Natural variations

Natural variant631I → T Retained in the ER due to impaired N-glycosylation; may present a vulnerability factor for iron induced oxidative stress in Parkinson disease. Ref.22 Ref.23
VAR_025655
Natural variant3671R → C.
Corresponds to variant rs34624984 [ dbSNP | Ensembl ].
VAR_032815
Natural variant4771P → L. Ref.22
Corresponds to variant rs35331711 [ dbSNP | Ensembl ].
VAR_025656
Natural variant5441D → E Reduced ferroxidase activity; may present a vulnerability factor for iron induced oxidative stress in Parkinson disease. Ref.22 Ref.23
Corresponds to variant rs701753 [ dbSNP | Ensembl ].
VAR_025657
Natural variant5511T → I. Ref.22
VAR_025658
Natural variant7931R → H. Ref.22 Ref.23
VAR_025659
Natural variant8411T → R. Ref.22
Corresponds to variant rs56033670 [ dbSNP | Ensembl ].
VAR_025660

Experimental info

Sequence conflict10601E → EGEYP in AAA51975. Ref.6

Secondary structure

...................................................................................................................................................................................................... 1065
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00450 [UniParc].

Last modified August 13, 1987. Version 1.
Checksum: 2F2F1294E2D30F58

FASTA1,065122,205
        10         20         30         40         50         60 
MKILILGIFL FLCSTPAWAK EKHYYIGIIE TTWDYASDHG EKKLISVDTE HSNIYLQNGP 

        70         80         90        100        110        120 
DRIGRLYKKA LYLQYTDETF RTTIEKPVWL GFLGPIIKAE TGDKVYVHLK NLASRPYTFH 

       130        140        150        160        170        180 
SHGITYYKEH EGAIYPDNTT DFQRADDKVY PGEQYTYMLL ATEEQSPGEG DGNCVTRIYH 

       190        200        210        220        230        240 
SHIDAPKDIA SGLIGPLIIC KKDSLDKEKE KHIDREFVVM FSVVDENFSW YLEDNIKTYC 

       250        260        270        280        290        300 
SEPEKVDKDN EDFQESNRMY SVNGYTFGSL PGLSMCAEDR VKWYLFGMGN EVDVHAAFFH 

       310        320        330        340        350        360 
GQALTNKNYR IDTINLFPAT LFDAYMVAQN PGEWMLSCQN LNHLKAGLQA FFQVQECNKS 

       370        380        390        400        410        420 
SSKDNIRGKH VRHYYIAAEE IIWNYAPSGI DIFTKENLTA PGSDSAVFFE QGTTRIGGSY 

       430        440        450        460        470        480 
KKLVYREYTD ASFTNRKERG PEEEHLGILG PVIWAEVGDT IRVTFHNKGA YPLSIEPIGV 

       490        500        510        520        530        540 
RFNKNNEGTY YSPNYNPQSR SVPPSASHVA PTETFTYEWT VPKEVGPTNA DPVCLAKMYY 

       550        560        570        580        590        600 
SAVDPTKDIF TGLIGPMKIC KKGSLHANGR QKDVDKEFYL FPTVFDENES LLLEDNIRMF 

       610        620        630        640        650        660 
TTAPDQVDKE DEDFQESNKM HSMNGFMYGN QPGLTMCKGD SVVWYLFSAG NEADVHGIYF 

       670        680        690        700        710        720 
SGNTYLWRGE RRDTANLFPQ TSLTLHMWPD TEGTFNVECL TTDHYTGGMK QKYTVNQCRR 

       730        740        750        760        770        780 
QSEDSTFYLG ERTYYIAAVE VEWDYSPQRE WEKELHHLQE QNVSNAFLDK GEFYIGSKYK 

       790        800        810        820        830        840 
KVVYRQYTDS TFRVPVERKA EEEHLGILGP QLHADVGDKV KIIFKNMATR PYSIHAHGVQ 

       850        860        870        880        890        900 
TESSTVTPTL PGETLTYVWK IPERSGAGTE DSACIPWAYY STVDQVKDLY SGLIGPLIVC 

       910        920        930        940        950        960 
RRPYLKVFNP RRKLEFALLF LVFDENESWY LDDNIKTYSD HPEKVNKDDE EFIESNKMHA 

       970        980        990       1000       1010       1020 
INGRMFGNLQ GLTMHVGDEV NWYLMGMGNE IDLHTVHFHG HSFQYKHRGV YSSDVFDIFP 

      1030       1040       1050       1060 
GTYQTLEMFP RTPGIWLLHC HVTDHIHAGM ETTYTVLQNE DTKSG 

« Hide

References

« Hide 'large scale' references
[1]"Complete cDNA sequence of human preceruloplasmin."
Koschinsky M.L., Funk W.D., van Oost B.A., McGillivray R.T.A.
Proc. Natl. Acad. Sci. U.S.A. 83:5086-5090(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Fine structure of the human ceruloplasmin gene."
Daimon M., Yamatani K., Igarashi M., Fukase N., Kawanami T., Kato T., Tominaga M., Sasaki H.
Biochem. Biophys. Res. Commun. 208:1028-1035(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-1006.
[4]"Isolation of a human ceruloplasmin cDNA clone that includes the N-terminal leader sequence."
Mercer J.F.B., Grimes A.
FEBS Lett. 203:185-190(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-40; 549-599; 784-829 AND 919-952.
[5]"Cloning and functional analysis of the human ceruloplasmin gene minimal promoter."
Bingle C.D.
Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
[6]"Characterization, mapping, and expression of the human ceruloplasmin gene."
Yang F., Naylor S.L., Lum J.B., Cutshaw S., McCombs J.L., Naberhaus K.H., McGill J.R., Adrian G.S., Moore C.M., Barnett D.R., Bowman B.H.
Proc. Natl. Acad. Sci. U.S.A. 83:3257-3261(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 218-1065.
[7]"Single-chain structure of human ceruloplasmin: the complete amino acid sequence of the whole molecule."
Takahashi N., Ortel T.L., Putnam F.W.
Proc. Natl. Acad. Sci. U.S.A. 81:390-394(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 20-1065.
[8]"Internal triplication in the structure of human ceruloplasmin."
Takahashi N., Bauman R.A., Ortel T.L., Dwulet F.E., Wang C.-C., Putnam F.W.
Proc. Natl. Acad. Sci. U.S.A. 80:115-119(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 158-333; 518-724 AND 858-1065.
[9]"Complete amino acid sequence of a 50,000-dalton fragment of human ceruloplasmin."
Dwulet F.E., Putnam F.W.
Proc. Natl. Acad. Sci. U.S.A. 78:790-794(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 501-905.
[10]"Primary structure of a histidine-rich proteolytic fragment of human ceruloplasmin. I. Amino acid sequence of the cyanogen bromide peptides."
Kingston I.B., Kingston B.L., Putnam F.W.
J. Biol. Chem. 255:2878-2885(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 907-1065.
[11]"Primary structure of a histidine-rich proteolytic fragment of human ceruloplasmin. II. Amino acid sequence of the tryptic peptides."
Kingston I.B., Kingston B.L., Putnam F.W.
J. Biol. Chem. 255:2886-2896(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 907-1065.
[12]"Human ceruloplasmin. Tissue-specific expression of transcripts produced by alternative splicing."
Yang F.M., Friedrichs W.E., Cupples R.L., Banifacio M.J., Sanford J.A., Horton W.A., Bowman B.H.
J. Biol. Chem. 265:10780-10785(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1007-1061.
[13]"Ceruloplasmin metabolism and function."
Hellman N.E., Gitlin J.D.
Annu. Rev. Nutr. 22:439-458(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[14]"A proteomic analysis of human bile."
Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A.
Mol. Cell. Proteomics 3:715-728(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-138.
Tissue: Bile.
[15]"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry."
Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.
Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-138; ASN-397 AND ASN-762.
Tissue: Plasma.
[16]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-138; ASN-358; ASN-397; ASN-588; ASN-762 AND ASN-926.
Tissue: Plasma.
[17]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-138; ASN-358; ASN-397 AND ASN-762.
Tissue: Liver.
[18]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-138; ASN-358; ASN-397 AND ASN-762.
[19]"Enrichment of glycopeptides for glycan structure and attachment site identification."
Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G.
Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-138; ASN-358 AND ASN-397, STRUCTURE OF CARBOHYDRATES.
Tissue: Cerebrospinal fluid.
[20]"The X-ray structure of human serum ceruloplasmin at 3.1 A: nature of the copper centres."
Zaitseva I., Zaitsev V., Card G., Moshkov K., Bax B., Ralph A., Lindley P.
J. Biol. Inorg. Chem. 1:15-23(1996)
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS), DISULFIDE BONDS, METAL-BINDING SITES.
[21]"Ceruloplasmin revisited: structural and functional roles of various metal cation-binding sites."
Bento I., Peixoto C., Zaitsev V.N., Lindley P.F.
Acta Crystallogr. D 63:240-248(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), METAL-BINDING SITES, DISULFIDE BONDS.
[22]"Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease."
Hochstrasser H., Bauer P., Walter U., Behnke S., Spiegel J., Csoti I., Zeiler B., Bornemann A., Pahnke J., Becker G., Riess O., Berg D.
Neurology 63:1912-1917(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THR-63; LEU-477; GLU-544; ILE-551; HIS-793 AND ARG-841.
[23]"Functional relevance of ceruloplasmin mutations in Parkinson's disease."
Hochstrasser H., Tomiuk J., Walter U., Behnke S., Spiegel J., Krueger R., Becker G., Riess O., Berg D.
FASEB J. 19:1851-1853(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS THR-63; GLU-544 AND HIS-793.
+Additional computationally mapped references.

Web resources

Wikipedia

Ceruloplasmin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS3141.1.
PIRKUHU. A25443.
RefSeqNP_000087.1. NM_000096.3.
UniGeneHs.558314.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KCWX-ray3.00A20-1065[»]
2J5WX-ray2.80A1-1065[»]
4EJXX-ray4.69A1-1065[»]
4ENZX-ray2.60A1-1065[»]
ProteinModelPortalP00450.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107748. 5 interactions.
IntActP00450. 5 interactions.
STRING9606.ENSP00000264613.

Chemistry

DrugBankDB00055. Drotrecogin alfa.

PTM databases

PhosphoSiteP00450.
UniCarbKBP00450.

Polymorphism databases

DMDM116117.

2D gel databases

DOSAC-COBS-2DPAGEP00450.
SWISS-2DPAGEP00450.

Proteomic databases

MaxQBP00450.
PaxDbP00450.
PeptideAtlasP00450.
PRIDEP00450.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264613; ENSP00000264613; ENSG00000047457.
GeneID1356.
KEGGhsa:1356.
UCSCuc003ewy.4. human.

Organism-specific databases

CTD1356.
GeneCardsGC03M148880.
GeneReviewsCP.
HGNCHGNC:2295. CP.
HPACAB008591.
HPA001834.
MIM117700. gene.
604290. phenotype.
neXtProtNX_P00450.
Orphanet48818. Aceruloplasminemia.
PharmGKBPA26815.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG276067.
HOGENOMHOG000231499.
HOVERGENHBG003674.
InParanoidP00450.
KOK13624.
PhylomeDBP00450.
TreeFamTF329807.

Enzyme and pathway databases

BioCycMetaCyc:HS00590-MONOMER.
ReactomeREACT_15518. Transmembrane transport of small molecules.
SABIO-RKP00450.

Gene expression databases

ArrayExpressP00450.
BgeeP00450.
CleanExHS_CP.
GenevestigatorP00450.

Family and domain databases

Gene3D2.60.40.420. 6 hits.
InterProIPR027150. CP.
IPR001117. Cu-oxidase.
IPR011706. Cu-oxidase_2.
IPR011707. Cu-oxidase_3.
IPR002355. Cu_oxidase_Cu_BS.
IPR008972. Cupredoxin.
[Graphical view]
PANTHERPTHR10127:SF294. PTHR10127:SF294. 1 hit.
PfamPF00394. Cu-oxidase. 1 hit.
PF07731. Cu-oxidase_2. 1 hit.
PF07732. Cu-oxidase_3. 2 hits.
[Graphical view]
SUPFAMSSF49503. SSF49503. 6 hits.
PROSITEPS00079. MULTICOPPER_OXIDASE1. 3 hits.
PS00080. MULTICOPPER_OXIDASE2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00450.
GeneWikiCeruloplasmin.
GenomeRNAi1356.
NextBio5493.
PMAP-CutDBP00450.
PROP00450.
SOURCESearch...

Entry information

Entry nameCERU_HUMAN
AccessionPrimary (citable) accession number: P00450
Secondary accession number(s): Q14063, Q2PP18, Q9UKS4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 13, 1987
Last modified: July 9, 2014
This is version 170 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM