MetaCyc Enzyme: ceruloplasmin

Gene: CP Accession Number: HS00590 (MetaCyc)

Species: Homo sapiens

Ceruloplasmin is a circulating copper protein found in vertebrate plasma, which belongs to the family of multicopper oxidases together with ascorbate oxidase and laccases. In humans it accounts for 95% of plasma copper.

The enzyme plays an important role in iron metabolism and homeostasis by its capacity to oxidize Fe2+ to Fe3+, which allows the subsequent incorporation of the latter into proteins such as apotransferrin and lactoferrin [Pulina02]. The protein was also shown to have an antioxidant activity because of its ability to scavenge superoxide radicals [Cogalgil02].

The enzyme contains six domains that are arranged in three pairs with a pseudo-ternary axis [Vachette02]. Incorporation of copper into newly synthesized apoceruloplasmin results in a detectable conformational change in the protein [Hellman02].

cDNA clones encoding the human enzyme have been isolated and sequenced [Mercer86, Koschinsky86], and the CP gene has been mapped and its structure studied [Daimon95, Yang86]. mRNA was detected in human liver, macrophages, and lymphocytes [Yang86].

Ceruloplasmin deficiency (aceruloplasminemia) leads to iron accumulation and cuases damages to a varieties of tissues and organs, including the brain [Mukhopadhyay98, Harris95].

Map Position: [149,776,320 <- 149,824,558]

Unification Links: ArrayExpress:P00450 , Entrez-gene:1356 , PhosphoSite:P00450 , Pride:P00450 , Protein Model Portal:P00450 , String:9606.ENSP00000264613 , UniProt:P00450

Relationship Links: InterPro:IN-FAMILY:IPR001117 , InterPro:IN-FAMILY:IPR002355 , InterPro:IN-FAMILY:IPR008972 , InterPro:IN-FAMILY:IPR011706 , InterPro:IN-FAMILY:IPR011707 , InterPro:IN-FAMILY:IPR027150 , Panther:IN-FAMILY:PTHR10127:SF294 , PDB:Structure:1KCW , PDB:Structure:2J5W , PDB:Structure:4EJX , PDB:Structure:4ENZ , Pfam:IN-FAMILY:PF00394 , Pfam:IN-FAMILY:PF07731 , Pfam:IN-FAMILY:PF07732 , Prosite:IN-FAMILY:PS00079 , Prosite:IN-FAMILY:PS00080

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Created 17-Jan-2011 by Caspi R , SRI International

Enzymatic reaction of: ferroxidase (ceruloplasmin)

EC Number:

4 Fe2+ + 4 H+ + oxygen <=> 4 Fe3+ + 2 H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Cofactors or Prosthetic Groups: Cu2+ [Vachette02]


Schematic showing introns, exons and/or isoforms of CP


Cogalgil02: Cogalgil S, Taysi S (2002). "Levels of antioxidant proteins and soluble intercellular adhesion molecule-1 in serum of patients with rheumatoid arthritis." Ann Clin Lab Sci 32(3);264-70. PMID: 12175089

Daimon95: Daimon M, Yamatani K, Igarashi M, Fukase N, Kawanami T, Kato T, Tominaga M, Sasaki H (1995). "Fine structure of the human ceruloplasmin gene." Biochem Biophys Res Commun 208(3);1028-35. PMID: 7702601

Harris95: Harris ZL, Takahashi Y, Miyajima H, Serizawa M, MacGillivray RT, Gitlin JD (1995). "Aceruloplasminemia: molecular characterization of this disorder of iron metabolism." Proc Natl Acad Sci U S A 92(7);2539-43. PMID: 7708681

Hellman02: Hellman NE, Kono S, Mancini GM, Hoogeboom AJ, De Jong GJ, Gitlin JD (2002). "Mechanisms of copper incorporation into human ceruloplasmin." J Biol Chem 277(48);46632-8. PMID: 12351628

Koschinsky86: Koschinsky ML, Funk WD, van Oost BA, MacGillivray RT (1986). "Complete cDNA sequence of human preceruloplasmin." Proc Natl Acad Sci U S A 83(14);5086-90. PMID: 2873574

Mercer86: Mercer JF, Grimes A (1986). "Isolation of a human ceruloplasmin cDNA clone that includes the N-terminal leader sequence." FEBS Lett 203(2);185-90. PMID: 3755405

Mukhopadhyay98: Mukhopadhyay CK, Attieh ZK, Fox PL (1998). "Role of ceruloplasmin in cellular iron uptake." Science 279(5351);714-7. PMID: 9445478

Pulina02: Pulina MO, Zakharova ET, Sokolov AV, Shavlovski MM, Bass MG, Solovyov KV, Kokryakov VN, Vasilyev VB (2002). "Studies of the ceruloplasmin-lactoferrin complex." Biochem Cell Biol 80(1);35-9. PMID: 11908641

Vachette02: Vachette P, Dainese E, Vasyliev VB, Di Muro P, Beltramini M, Svergun DI, De Filippis V, Salvato B (2002). "A key structural role for active site type 3 copper ions in human ceruloplasmin." J Biol Chem 277(43);40823-31. PMID: 12177070

Yang86: Yang F, Naylor SL, Lum JB, Cutshaw S, McCombs JL, Naberhaus KH, McGill JR, Adrian GS, Moore CM, Barnett DR (1986). "Characterization, mapping, and expression of the human ceruloplasmin gene." Proc Natl Acad Sci U S A 83(10);3257-61. PMID: 3486416

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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