Ceruloplasmin (CP)
The protein contains 1065 amino acids for an estimated molecular weight of 122205 Da.
Ceruloplasmin is a blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron transport across the cell membrane. Provides Cu(2+) 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). (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
(right-click above to access to more options from the contextual menu)
Biological Process
Cellular iron ion homeostasis
Cellular protein metabolic process
Copper ion transport
Iron ion homeostasis
Iron ion transport
Post-translational protein modification
Cellular Component
Blood microparticle
Endoplasmic reticulum lumen
Extracellular exosome
Extracellular region
Extracellular space
Lysosomal membrane
Obsolete cell
Plasma membrane
Molecular Function
Chaperone binding
Copper ion binding
Ferroxidase activity
Oxidoreductase activity
The reference OMIM entry for this protein is 117700
Ceruloplasmin; cp
Ferroxidase
DESCRIPTION
Ceruloplasmin (also known as ferroxidase; iron (II):oxygen oxidoreductase, EC 1.16.3.1) is a blue alpha-2-glycoprotein that binds 90 to 95% of plasma copper and has 6 or 7 cupric ions per molecule. It is involved in peroxidation of Fe(II) transferrin to form Fe(III) transferrin. Like transferrin (TF; 190000), ceruloplasmin is a plasma metalloprotein.CLONING
Human ceruloplasmin is composed of a single polypeptide chain of 1,046 amino acids, with a molecular mass of 132 kD (Takahashi et al., 1984). Koschinsky et al. (1986) reported the nucleotide sequence of human preceruloplasmin cDNA. The mRNA from human liver was found to be 3,700 nucleotides in size. Sequence homology with factor VIII was demonstrated. The protein is synthesized in hepatocytes and secreted into the serum with copper incorporated during biosynthesis. Failure to incorporate copper during synthesis results in the secretion of an apoprotein devoid of copper, termed apoceruloplasmin (Culotta and Gitlin, 2001). Yang et al. (1990) demonstrated 2 forms of CP which differed by the presence or absence of 12 nucleotide bases encoding a deduced sequence of gly-glu-tyr-pro in the C-terminal region of the molecule. Alternative splicing was the apparent explanation, and differential expression of the 2 transcripts in different tissues with production of isoforms from a single gene was demonstrated. Klomp and Gitlin (1996) analyzed ceruloplasmin gene expression in the brain. In situ hybridization utilizing ceruloplasmin cDNA clones revealed abundant expression in specific populations of glial cells within the brain microvasculature, surrounding dopaminergic melanized neurons in the substantia nigra, and within the inner nuclear layer of the retina.GENE STRUCTURE
Daimon et al. (1995) determined that the ceruloplasmin gene contains 19 exons and spans approximately 50 kb.GENE FUNCTION
Klomp and Gitlin (1996) concluded that glial cell-specific ceruloplasmin gene expression is essential for iron homeostasis and neuronal survival in the human central nervous system. Individuals with hereditary ceruloplasmin deficiency have profound iron accumulation in most tissues, suggesting that ceruloplasmin is important for normal release of cellular iron (Mukhopadhyay et al., 1998).MAPPING
Weitkamp (1983) found a peak lod score of 3.5 at theta about 0.15 for linkage of CP to TF, which is located at 3q21. Homology argues for this linkage; TF and CP are linked in cattle with a lod score of 11.3 at 20% recombination frequency in sires (Larsen, 1977). By Southern blot analysis of human-mouse somatic cell hybrids, Naylor et al. (1985) mapped the CP gene to chromosome 3. Royle et al. (1987) localized the CP gene to 3q21-q24 by analysis of somatic cell hybrid DNAs and in situ hybridization. Riddell et al. (1987) identified a ceruloplasmin pseudogene on chromosome 8. Koschinsky et al. (1987) isolated a processed gene for human ceruloplasmin and mapped it to chromosome 8 by somatic cell hybridization. Wang et al. (1988) localized the processed pseudogene further to 8q21.13-q23.1 by in situ hybridization. They pointed out that like all other processed pseudogenes described to date, the gene is located on a chromosome different from the parent gene.MOLECULAR GENETICS
Shreffler et al., 1967 identified at least 3 variants determined by codominant alleles by starch gel electrophoresis. Mohrenweiser and Decker (1982) identified sever ... More on the omim web site
Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 117700 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).