D
IPR048236

Ceruloplasmin-like, fifth cupredoxin domain

InterPro entry
Short nameCeruloplasmin-like_CuRO_5
Overlapping
homologous
superfamilies
 
Cupredoxin (IPR008972)
domain relationships

Description

Ceruloplasmin is a serum multicopper oxidase essential for normal iron homeostasis and copper transport in blood but it is also membrane-bound via a glycosylphosphatidylinositol (GPI)-anchor in astrocytes and kidney
[4]
. It also functions in amine oxidation and as an antioxidant preventing free radicals in serum. The protein has 6 cupredoxin domains with six copper centres; three mononuclear sites in domain 2, 4 and 6 and three in the form of trinuclear clusters at the interface of domains 1 and 6. Ceruloplasmin exhibits internal sequence homology that appears to have evolved from the triplication of a sequence unit composed of two tandem cupredoxin domains. This entry represents the fifth cupredoxin domain of ceruloplasmin
[8, 12, 6, 9, 10, 11, 7]
.

This entry also includes the ceruloplasmin homologue hephaestin
[3, 2, 1, 5]
, which is involved in the metabolism and homeostasis of iron. It is a transmembrane copper-dependent ferroxidase responsible for transporting dietary iron from intestinal enterocytes into the circulatory system. The highest expression of hephaestin is found in small intestine.

References

1.Hephaestin and ceruloplasmin facilitate iron metabolism in the mouse kidney. Jiang B, Liu G, Zheng J, Chen M, Maimaitiming Z, Chen M, Liu S, Jiang R, Fuqua BK, Dunaief JL, Vulpe CD, Anderson GJ, Wang H, Chen H. Sci Rep 6, 39470, (2016). View articlePMID: 27991585

2.Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, Libina N, Gitschier J, Anderson GJ. Nat. Genet. 21, 195-9, (1999). View articlePMID: 9988272

3.Decreased hephaestin activity in the intestine of copper-deficient mice causes systemic iron deficiency. Chen H, Huang G, Su T, Gao H, Attieh ZK, McKie AT, Anderson GJ, Vulpe CD. J Nutr 136, 1236-41, (2006). View articlePMID: 16614410

4.Glycosyl phosphatidylinositol-anchored ceruloplasmin is expressed by rat Sertoli cells and is concentrated in detergent-insoluble membrane fractions. Fortna RR, Watson HA, Nyquist SE. Biol Reprod 61, 1042-9, (1999). View articlePMID: 10491642

5.Intestinal hephaestin potentiates iron absorption in weanling, adult, and pregnant mice under physiological conditions. Doguer C, Ha JH, Gulec S, Vulpe CD, Anderson GJ, Collins JF. Blood Adv 1, 1335-1346, (2017). View articlePMID: 29296776

6.Ceruloplasmin revisited: structural and functional roles of various metal cation-binding sites. Bento I, Peixoto C, Zaitsev VN, Lindley PF. Acta Crystallogr. D Biol. Crystallogr. 63, 240-8, (2007). View articlePMID: 17242517

7.Cupredoxins--a study of how proteins may evolve to use metals for bioenergetic processes. Choi M, Davidson VL. Metallomics 3, 140-51, (2011). View articlePMID: 21258692

8.Role of copper in thermal stability of human ceruloplasmin. Sedlak E, Zoldak G, Wittung-Stafshede P. Biophys J 94, 1384-91, (2008). PMID: 17965133

9.Cellular multitasking: the dual role of human Cu-ATPases in cofactor delivery and intracellular copper balance. Lutsenko S, Gupta A, Burkhead JL, Zuzel V. Arch Biochem Biophys 476, 22-32, (2008). PMID: 18534184

10.Plasma copper, iron, ceruloplasmin and ferroxidase activity in schizophrenia. Wolf TL, Kotun J, Meador-Woodruff JH. Schizophr Res 86, 167-71, (2006). PMID: 16842975

11.High ceruloplasmin levels are associated with obsessive compulsive disorder: a case control study. Virit O, Selek S, Bulut M, Savas HA, Celik H, Erel O, Herken H. Behav Brain Funct 4, 52, (2008). PMID: 19017404

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

Further reading

13. Single-chain structure of human ceruloplasmin: the complete amino acid sequence of the whole molecule. Takahashi N, Ortel TL, Putnam FW. Proc Natl Acad Sci U S A 81, 390-4, (1984). PMID: 6582496

14. Internal triplication in the structure of human ceruloplasmin. Takahashi N, Bauman RA, Ortel TL, Dwulet FE, Wang CC, Putnam FW. Proc Natl Acad Sci U S A 80, 115-9, (1983). PMID: 6571985

15. Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson's disease). SCHEINBERG IH, GITLIN D. Science 116, 484-5, (1952). PMID: 12994898

16. Ceruloplasmin metabolism and function. Hellman NE, Gitlin JD. Annu. Rev. Nutr. 22, 439-58, (2002). View articlePMID: 12055353

17. The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships. Messerschmidt A, Huber R. Eur. J. Biochem. 187, 341-52, (1990). View articlePMID: 2404764

18. Copper protein structures. Adman ET. Adv. Protein Chem. 42, 145-97, (1991). PMID: 1793005

19. Internal duplication and evolution of human ceruloplasmin. Dwulet FE, Putnam FW. Proc Natl Acad Sci U S A 78, 2805-9, (1981). PMID: 6942404

Cross References

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