Définitions et usages de : Ceruloplasmin - Dictionnaire de anglais sensagent

Ceruloplasmin (ferroxidase)

PDB rendering based on 1kcw.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1KCW, 2J5W

Identifiers

Symbols

CP; CP-2

External IDs

OMIM: 117700 MGI: 88476 HomoloGene: 75 GeneCards: CP Gene

EC number

1.16.3.1

Gene Ontology
Molecular function	• ferroxidase activity • copper ion binding • oxidoreductase activity • metal ion binding • chaperone binding
Cellular component	• extracellular region • extracellular region • extracellular space
Biological process	• ion transport • copper ion transport • cellular iron ion homeostasis • transmembrane transport
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

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.

1 Function
2 Pathology
3 Interpretation
4 Regulation
5 References
6 Further reading
7 External links

Function

It is an enzyme (EC 1.16.3.1) 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.

Pathology

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

Mechanisms of low ceruplasmin levels:

Gene expression genetically low (aceruloplasminemia)
Copper levels are low in general
- Malnutrition/trace metal deficiency in the food source
Copper does not cross the intestinal barrier due to ATP7A deficiency (Menkes disease)
Delivery of copper into the lumen of the ER-Golgi network is absent in hepatocytes due to absent ATP7B (Wilson's disease)

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 (CP), which are very rare, can lead to the genetic disease aceruloplasminemia, characterized by hyperferritinemia with iron overload. In the brain, this iron overload may lead to characteristic neurologic signs and symptoms, such as cerebellar ataxia, progressive dementia, and extrapyramidal signs. Excess iron may also deposit in the liver, pancreas, and retina, leading to cirrhosis, endocrine abnormalities, and loss of vision, respectively.

Interpretation

Decreased levels

Lower-than-normal ceruloplasmin levels may indicate:

Wilson disease (a rare copper storage disease)^[5]
Menkes disease (Menke kinky hair syndrome) (very rare)
Overdose of Vitamin C
Copper deficiency
Aceruloplasminemia^[6]

Elevated levels

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

pregnancy
oral contraceptive pill use ^[7]
lymphoma
acute and chronic inflammation (it is an acute-phase reactant)
rheumatoid arthritis
Angina ^[8]
Alzheimer's disease^[9]
Schizophrenia^[10]
Obsessive-compulsive disorder^[11]

Reference ranges

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

Regulation

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]

References

^ 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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=344682.
^ 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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=323895.
^ 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.
^ 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.
^ Scheinberg IH, Gitlin D (October 1952). "Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson disease)". Science 116 (3018): 484–5. DOI:10.1126/science.116.3018.484. PMID 12994898.
^ Gitlin JD (1998). "Aceruloplasminemia". Pediatr. Res. 44 (3): 271–6. DOI:10.1203/00006450-199809000-00001. PMID 9727700.
^ http://journals.lww.com/anesthesiology/Fulltext/2008/04000/Green_Plasma_Revisited.35.aspx
^ http://ang.sagepub.com/cgi/content/abstract/60/1/50?rss=1
^ 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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2556376.
^ 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.
^ 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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2596773.
^ 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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=151701.
^ 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.

External links

PDB gallery

1kcw: X-RAY CRYSTAL STRUCTURE OF HUMAN CERULOPLASMIN AT 3.0 ANGSTROMS

2j5w: CERULOPLASMIN REVISITED: STRUCTURAL AND FUNCTIONAL ROLES OF VARIOUS METAL CATION BINDING SITES

Other oxidoreductases (EC 1.15-1.21)

1.15: Acting on superoxide as acceptor

Superoxide dismutase (SOD1, SOD2, SOD3)

1.16: Oxidizing metal ions

Ceruloplasmin

1.17: Acting on CH or CH2 groups

Xanthine oxidase - Ribonucleotide reductase - 4-hydroxy-3-methylbut-2-enyl diphosphate reductase

1.18: Acting on iron-sulfur proteins as donors

Nitrogenase

1.19: Acting on reduced flavodoxin as donor

Nitrogenase (flavodoxin)

1.20: Acting on phosphorus or arsenic in donors

Glutaredoxin (GLRX, GLRX2, GLRX3, GLRX5)

1.21: Acting on X-H and Y-H to form an X-Y bond

Isopenicillin-N synthase

B
enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
2.7.10
2.7.11-12
3.1
- 2
- 3
- 4
- 5
- 6
- 7
3.1.3.48
3.4.21
- 22
- 23
- 24
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

Proteins: carrier proteins

Fatty acid	FABP1 · FABP2 · FABP3 · FABP4 · FABP5 · FABP6 · FABP7

Hormone	peptide hormone: Follistatin · Growth hormone binding protein · Insulin-like growth factor binding protein (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6, IGFBP7) · Neurophysins (Neurophysin I, II) steroid hormone: Sex hormone binding globulin/Androgen binding protein · Transcortin · Thyroxine-binding globulin · Transthyretin

Metal/element	calcium (Calcium-binding protein, Calmodulin-binding proteins) · copper (Ceruloplasmin) · iron (Iron-binding proteins, Transferrin receptor)

Vitamin	Retinol binding protein (1, 2, 3, 4) · Transcobalamin

Other	Acyl carrier protein · Adaptor protein · Cholesterylester transfer protein · F-box protein · GTP-binding protein · Latent TGF-beta binding protein · Light-harvesting complex · Major urinary proteins · Membrane transport protein · Odorant binding protein

B proteins: BY STRUCTURE: membrane, globular (en, ca, an), fibrous

Proteins: Globular proteins

Serum globulins

Alpha globulins	serpins: alpha-1 (Alpha 1-antichymotrypsin, Alpha 1-antitrypsin) · alpha-2 (Alpha 2-antiplasmin) · Antithrombin (Heparin cofactor II) carrier proteins: alpha-1 (Transcortin) · alpha-2 (Ceruloplasmin) · Retinol binding protein other: alpha-1 (Orosomucoid) · alpha-2 (alpha-2-Macroglobulin, Haptoglobin)

Beta globulins	carrier proteins: Sex hormone-binding globulin · Transferrin other: Angiostatin · Hemopexin · Beta-2 microglobulin · Factor H · Plasminogen · Properdin

Gamma globulin	Immunoglobulins

Other	Fibronectin (Fetal fibronectin) · Macroglobulin/Microglobulin · Transcobalamin

Other globulins

Beta-lactoglobulin (Lactoferrin) · Thyroglobulin · Alpha-lactalbumin

Albumins

Egg white	Conalbumin · Ovalbumin · Avidin

Serum albumin	Human serum albumin · Bovine serum albumin · Prealbumin

Other	C-reactive protein · Lactalbumin (Alpha-lactalbumin) · Parvalbumin · Ricin

see also disorders of globin and globulin proteins
B proteins: BY STRUCTURE: membrane, globular (en, ca, an), fibrous

Acute-phase proteins

Amyloid

Other positive

Negative

M: LMC

cell/phys/auag/auab/comp, igrc

imdf/ipig/hyps/tumr

proc, drug(L3/4)

Metabolism: Metal metabolism

Transition metal

Iron metabolism

Absorption in Duodenum	Iron(II) oxide: DMT1 (SLC11A2) · Ferritin · Hephaestin/Ferroportin (SLC11A3/SLC40A1) · Transferrin to Transferrin receptor (TFRC, TFR2) Iron(III) oxide: Duodenal cytochrome B · Integrin · Calreticulin/mobilferrin · Ferritin

Other	Hepcidin/HAMP · Hemojuvelin · Iron-responsive element binding protein (Aconitase) · Ceruloplasmin · HFE · Hemosiderin · Lactoferrin Iron-binding proteins: Ferritin

Copper metabolism

ATP7A · ATP7B · Ceruloplasmin · SLC31A1 · ATOX1

Zinc metabolism

TMC6 · TMC8 · SLC30A1 · SLC39A4

Electrolyte

Sodium metabolism	Na⁺/K⁺-ATPase

Phosphate metabolism	Phosphoric acids and phosphates

Magnesium metabolism	Magnesium transporter

Calcium metabolism	Calcium-sensing receptor · Calcium-binding protein

M: NUT

cof, enz, met

noco, nuvi, sysi/epon, met

drug(A8/11/12)

Significations et usages de Ceruloplasmin

Définition

Synonymes

Locutions

Dictionnaire analogique

Ceruloplasmin

Contents

Function

Pathology