Ceruloplasmin (ferroxidase)

PDB rendering based on 1kcw.
Symbols CP; CP-2
External IDs OMIM117700 MGI88476 HomoloGene75 GeneCards: CP Gene
EC number
RNA expression pattern
PBB GE CP 204846 at tn.png
More reference expression data
Species Human Mouse
Entrez 1356 12870
Ensembl ENSG00000047457 ENSMUSG00000003617
UniProt P00450 Q2F3J4
RefSeq (mRNA) NM_000096.3 NM_001042611
RefSeq (protein) NP_000087.1 NP_001036076
Location (UCSC) Chr 3:
148.88 – 148.94 Mb
Chr 3:
19.86 – 19.91 Mb
PubMed search [1] [2]

Ceruloplasmin (or caeruloplasmin) is a ferroxidase enzyme that in humans is encoded by the CP gene.[1][2][3]

Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948.[4] Another protein, hephaestin, is noted for its homology to ceruloplasmin, and also participates in iron and probably copper metabolism.



It is an enzyme (EC synthesized in the liver containing 6 atoms of copper in its structure. Ceruloplasmin carries about 70% of the total copper in human plasma while albumin carries about 15%. The rest is accounted for by macroglobulins. Albumin may be confused at times to have a greater importance as a copper carrier because it binds copper less tightly than ceruloplasmin. Ceruloplasmin exhibits a copper-dependent oxidase activity, which is associated with possible oxidation of Fe2+ (ferrous iron) into Fe3+ (ferric iron), therefore assisting in its transport in the plasma in association with transferrin, which can carry iron only in the ferric state. The molecular weight of human ceruloplasmin is reported to be 151kDa.


Like any other plasma protein, levels drop in patients with hepatic disease due to reduced synthesizing capabilities.

Mechanisms of low ceruplasmin levels:

Copper availability doesn't affect the translation of the nascent protein. However, the apoenzyme without copper is unstable. Apoceruloplasmin is largely degraded intracellularly in the hepatocyte and the small amount that is released has a short circulation half life of 5 hours as compared to the 5.5 days for the holo-ceruloplasmin.

Mutations in the ceruloplasmin gene can lead to the rare genetic human disease aceruloplasminemia, characterized by iron overload in the brain, liver, pancreas, and retina.


Decreased levels

Lower-than-normal ceruloplasmin levels may indicate:

Elevated levels

Greater-than-normal ceruloplasmin levels may indicate or be noticed in:

Reference ranges

Reference ranges for blood tests, comparing blood content of ceruloplasmin (shown in gray) with other constituents.


A cis-regulatory element called the GAIT element is involved in the selective translational silencing of the Ceruloplasmin transcript.[12] The silencing requires binding of a cytosolic inhibitor complex called IFN-gamma-activated inhibitor of translation (GAIT) to the GAIT element.[13]


  1. ^ Takahashi N, Ortel TL, Putnam FW (January 1984). "Single-chain structure of human ceruloplasmin: the complete amino acid sequence of the whole molecule". Proc. Natl. Acad. Sci. U.S.A. 81 (2): 390–4. doi:10.1073/pnas.81.2.390. PMC 344682. PMID 6582496. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=344682. 
  2. ^ Koschinsky ML, Funk WD, van Oost BA, MacGillivray RT (July 1986). "Complete cDNA sequence of human preceruloplasmin". Proc. Natl. Acad. Sci. U.S.A. 83 (14): 5086–90. doi:10.1073/pnas.83.14.5086. PMC 323895. PMID 2873574. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=323895. 
  3. ^ Royle NJ, Irwin DM, Koschinsky ML, MacGillivray RT, Hamerton JL (May 1987). "Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively". Somat. Cell Mol. Genet. 13 (3): 285–92. doi:10.1007/BF01535211. PMID 3474786. 
  4. ^ Holmberg CG, Laurell C-B (1948). "Investigations in serum copper. II. Isolation of the Copper containing protein, and a description of its properties". Acta Chem Scand 2: 550–56. doi:10.3891/acta.chem.scand.02-0550. 
  5. ^ Scheinberg IH, Gitlin D (October 1952). "Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson's disease)". Science 116 (3018): 484–5. doi:10.1126/science.116.3018.484. PMID 12994898. 
  6. ^ Gitlin JD (1998). "Aceruloplasminemia". Pediatr. Res. 44 (3): 271–6. doi:10.1203/00006450-199809000-00001. PMID 9727700. 
  7. ^ http://journals.lww.com/anesthesiology/Fulltext/2008/04000/Green_Plasma_Revisited.35.aspx
  8. ^ http://ang.sagepub.com/cgi/content/abstract/60/1/50?rss=1
  9. ^ Lutsenko S, Gupta A, Burkhead JL, Zuzel V (August 2008). "Cellular multitasking: the dual role of human Cu-ATPases in cofactor delivery and intracellular copper balance". Arch. Biochem. Biophys. 476 (1): 22–32. doi:10.1016/j.abb.2008.05.005. PMC 2556376. PMID 18534184. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2556376. 
  10. ^ Wolf TL, Kotun J, Meador-Woodruff JH (September 2006). "Plasma copper, iron, ceruloplasmin and ferroxidase activity in schizophrenia". Schizophr. Res. 86 (1–3): 167–71. doi:10.1016/j.schres.2006.05.027. PMID 16842975. 
  11. ^ Virit O, Selek S, Bulut M, Savas HA, Celik H, Erel O, Herken H (2008). "High ceruloplasmin levels are associated with obsessive compulsive disorder: a case control study". Behav Brain Funct 4: 52. doi:10.1186/1744-9081-4-52. PMC 2596773. PMID 19017404. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2596773. 
  12. ^ Sampath, P; Mazumder B, Seshadri V, Fox PL (2003). "Transcript-selective translational silencing by gamma interferon is directed by a novel structural element in the ceruloplasmin mRNA 3' untranslated region". Mol Cell Biol 23 (5): 1509–1519. doi:10.1128/MCB.23.5.1509-1519.2003. PMC 151701. PMID 12588972. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=151701. 
  13. ^ Mazumder B, Sampath P, Fox PL (2005). "Regulation of macrophage ceruloplasmin gene expression: one paradigm of 3'-UTR-mediated translational control". Mol Cells 20 (2): 167–72. PMID 16267389. 

Further reading

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  • ceruloplasmin — noun Etymology: International Scientific Vocabulary cerulo (from Latin caeruleus) + plasma + 1 in Date: circa 1952 a blue copper binding serum oxidase that is deficient in Wilson s disease …   New Collegiate Dictionary

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  • ceruloplasmin — ce·ru·lo·plas·min …   English syllables

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