Ceruloplasmin 2

Author: Benedetta Maria Motta
Date: 05/01/2010



Alpha2-glycoprotein ceruloplasmin, also known as ferroxidase or iron(II):oxygen oxidoreductase, is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It is an enzyme which catalyzes the oxidation of ferrous iron to ferric iron. The molecular weight of human ceruloplasmin is reported to be 151kDa.





When relevant for the function

  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Protein Aminoacids Percentage
The Protein Aminoacids Percentage gives useful information on the local environment and the metabolic status of the cell (starvation, lack of essential AA, hypoxia)

Protein Aminoacids Percentage (Width 700 px)


mRNA synthesis
protein synthesis

post-translational modifications


cellular localization,
biological function

  • Enzymes
BRENDA - The Comprehensive Enzyme Information System"URL":
KEGG Pathways"URL":
Human Metabolome Database"URL":
  • Cell signaling and Ligand transport
  • Structural proteins




Structure of CP

Protein Aminoacids Percentage

Synthesis and Turnover

The gene encoding ceruloplasmin is on chromosome 3q, located in bands 3q23-q25.

It is mainly synthesized in the liver by hepatocytes and reticuloendothelial cells and it doesn’t cross the hematoencephalic barrier. It is secreted into plasma as oloceruloplasmin containing 6 atoms of copper in its structure.

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.

Cellular Functions

Ceruloplasmin is characterized from the structural point of view by presenting three types of binding sites for copper, and from the functional point of view, to catalyze the reduction of an oxygen molecule with formation of water, without releasing intermediaries potentially toxic (O2-, H2O2). Ceruloplasmin carries 95% of the copper in our plasma. CP has an oxidase activity nonspecific and is involved in oxidation reactions of various organic and inorganic substrates in vitro, eg Fe2+, benzidine, p-phenylenediamine, and others. Only the Fe2+ ion is considered a biological substrate for this enzyme. Catalyzes the conversion of iron from ferrous (Fe2+) to ferric form (Fe3+), therefore assisting in its transport in the plasma in association with transferrin, which can only carry iron in the ferric state. The copper in ceruloplasmin plays an important role in the oxidation of iron before it is transported to the plasma.
The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum. Osaki S, Johnson DA, Frieden E. J Biol Chem. 1966 Jun 25;241(12):2746-51

Ceruloplasmin is essential for the proper localization of ferroportin(MTP1),%20Ferroportin on the plasma membrane in different cell types, like astrocytes or macrophages.

In the brain, the majority of CP is localized in astrocytes in the nervous system and in the nuclei and ganglion cells that relate to the retina.
Glycosilphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system. Jeong SY, David S. J. Biol. Chem. 2003:278:27144-48


Levels drop in patients with hepatic disease due to reduced synthesizing capabilities.

In hereditary diseases of copper metabolism dependent, as in Wilson's disease and syndrome of Melk, the concentration of ceruloplasmin is greatly diminished. This becomes even more evident in homozygous carriers of these diseases. Lowering levels of ceruloplamin is also found in cases of liver failure and loss of protein. Moreover, ceruloplasmin is reduced in the case of hereditary hemochromatosis due to a mutation of the HFE gene.

In the presence of inflammation, cholestasis, and oral contraceptives is determined increased serum concentration of ceruloplasmin. Interferon γ induces the synthesis of mRNA and protein, but after about 16 hours the translation is inhibited.

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. Numerous mutations have been identified.

Some authors find that cell iron overload induced a significant decrease in CP protein content in the cells and that treatment with iron chelators led to a significant increase in CP protein level in the cells.
Ceruloplasmin expression and its role in iron transport in C6 cells. Chang, Y.Z., Qian, Z.M., Du, J.R., Zhu, L., Xu, Y., Li, L.Z., Wang, C.Y., Wang, Q., Ge, X.H., Ho, K.P., Niu, L., Ke, Y. Neurochem. Int.

Diagnostic Use

It is determined in the serum to confirm the diagnosis of Aceruloplasminemia.

Ceruloplasmin, a moonlighting protein in fish, 2018

  • Ceruloplasmin is an ancient multicopper oxidase evolved to insure a safe handling of oxygen in some metabolic pathways of vertebrates. The current knowledge of its structure provides a glimpse of its plasticity, revealing a multitude of binding sites that point to an elaborate mechanism of multifunctional activity. Ceruloplasmin is highly conserved throughout the vertebrate evolution. Cupredoxin, a multi-cupper blue protein is believed to be the evolutionary precursor of ceruloplasmin with three trinuclear and three mononuclear copper binding sites. There are 20 copper-binding residues in ceruloplasmin gene out of which 16 residues are conserved in fish. This ceruloplasmin gene is being characterized in zebrafish (Danio rerio), rohu (Labeo rohita), Indian medaka (Oryzias melastigama), catfish (Ictalurus punctatus), icefish (Chionodraco rastrospinosus), goldfish (Carassius auratus) and yellow perch (Perca flaviscens). The complete coding sequence of fish ceruloplasmin gene is around 3.2 kb which codes for 1000 to 1100 amino acid residues. The size of ceruloplasmin gene sequence in fish ranges around 13 kb containing 20 exons and 19 introns. Liver is the major site of synthesis in fish. Increased expression of this gene during bacterial infection in channel catfish and rohu suggested its potential involvement in bacterial disease response in fish. It has been found to serve as an indirect marker for selection against Aeromonas hydrophila resistance in rohu carp. Ceruloplasmin expression is also evident during parasitic infection in few fish species. The role of this gene is well studied during inflammatory response to hormonal, drug and heavy metal mediated toxicity in fish. Overall, ceruloplasmin represents an example of a 'moonlighting' protein that overcomes the one gene-one structure-one function concept to follow the changes of the organism in its physiological and pathological conditions.

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