Hephestine

Hephestine
Properties of human protein
Mass / length primary structure	1136 amino acids
Secondary to quaternary structure	Monomer; single pass type 1 membrane protein
Cofactor	6 copper
Isoforms	2
Identifier
Gene names	HEPH KIAA0698
External IDs	OMIM : 300167 ; UniProt : Q9BQS7 ;
Enzyme classification
EC, category	1.-.-.- , oxidoreductase
Response type	oxidation
Substrate	4 Fe 2+ + 4 H + + O 2
Products	4 Fe 3+ + 2 H 2 O
Occurrence
Homology family	Ferroxidase-like
Parent taxon	Newcomers
	Orthologue

Hephestine ( gene : HEPH ) is a homologous enzyme of ceruloplasmin , a membrane protein that occurs in all new mouths. In humans it is located in the breast, intestine, trabeculae of the substantia spongiosa and fibroblasts . As ferro oxidase, it oxidizes the iron (II) imported by enterocytes to iron (III) and prepares it for export through ferroportin . Together with ferroportin, Hephestine is responsible for the efflux of iron ions from the cell. It is therefore indispensable in the iron metabolism when iron is absorbed by the intestine. It may also transport copper .

The protein is named after the Greek god Hephaestus (blacksmith).

pathology

Copper is essential for the stability of Hephestine. Mice completely without ceruloplasmin and hephestine show all symptoms of macular degeneration . Increased iron concentrations in the substantia nigra in Parkinson's disease are probably due to decreased activity of hephestine and ferroportin.

regulation

Erythropoietin increases hephestine expression and iron absorption in the duodenum and from the intestinal lumen. An iron-containing diet increased the expression of ceruloplasmin and ferroportin in rats, but not of hephestine. In intestinal cells, the transition to the cancer stage is linked to increased iron import and decreased export (hephestine activity).

Hypothetical regulation of hephestine expression (Hephestine = Hp) as a reaction to different iron uptake and storage ( iron metabolism ).

Individual evidence

↑ UniProt Q9BQS7
↑ Griffiths TA, Mauk AG, MacGillivray RT: Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity . In: Biochemistry . 44, No. 45, November 2005, pp. 14725-31. doi : 10.1021 / bi051559k . PMID 16274220 .
↑ Ma Y, Yeh M, Yeh KY, Glass J: Iron Imports. V. Transport of iron through the intestinal epithelium . In: Am. J. Physiol. Gastrointest. Liver Physiol. . 290, No. 3, March 2006, pp. G417-22. doi : 10.1152 / ajpgi.00489.2005 . PMID 16474007 .
↑ Chen H, Huang G, Su T, et al : Decreased hephaestin activity in the intestine of copper-deficient mice causes systemic iron deficiency . In: J. Nutr. . 136, No. 5, May 2006, pp. 1236-41. PMID 16614410 .
↑ Hadziahmetovic M, Dentchev T, Song Y, et al : Ceruloplasmin / hephaestin knockout mice model morphologic and molecular features of AMD . In: Invest. Ophthalmol. Vis. Sci. . 49, No. 6, June 2008, pp. 2728-36. doi : 10.1167 / iovs.07-1472 . PMID 18326691 .
↑ Qian ZM, Chang YZ, Zhu L, et al : Development and iron-dependent expression of hephaestin in different brain regions of rats . In: J. Cell. Biochem. . 102, No. 5, December 2007, pp. 1225-33. doi : 10.1002 / jcb.21352 . PMID 17516501 .
↑ Wang J, Jiang H, Xie JX: Ferroportin1 and hephaestin are involved in the nigral iron accumulation of 6-OHDA-lesioned rats . In: Eur. J. Neurosci. . 25, No. 9, May 2007, pp. 2766-72. doi : 10.1111 / j.1460-9568.2007.05515.x . PMID 17561842 .
↑ Kong WN, Chang YZ, Wang SM, et al : Effect of erythropoietin on hepcidin, DMT1 with IRE, and hephaestin gene expression in duodenum of rats . In: J. Gastroenterol. . 43, No. 2, 2008, pp. 136-43. doi : 10.1007 / s00535-007-2138-5 . PMID 18306987 .
↑ Qian ZM, Chang YZ, Leung G, et al : Expression of ferroportin1, hephaestin and ceruloplasmin in rat heart . In: Biochim. Biophys. Acta . 1772, No. 5, May 2007, pp. 527-32. doi : 10.1016 / j.bbadis.2007.02.006 . PMID 17383861 .
↑ Brookes MJ, Hughes S, Turner FE, et al : Modulation of iron transport proteins in human colorectal carcinogenesis . In: Good . 55, No. 10, October 2006, pp. 1449-60. doi : 10.1136 / good 2006.094060 . PMID 16641131 .

[1] UniProt Q9BQS7

[2] Griffiths TA, Mauk AG, MacGillivray RT: Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity . In: Biochemistry . 44, No. 45, November 2005, pp. 14725-31. doi : 10.1021 / bi051559k . PMID 16274220 .

[3] Ma Y, Yeh M, Yeh KY, Glass J: Iron Imports. V. Transport of iron through the intestinal epithelium . In: Am. J. Physiol. Gastrointest. Liver Physiol. . 290, No. 3, March 2006, pp. G417-22. doi : 10.1152 / ajpgi.00489.2005 . PMID 16474007 .

[4] Chen H, Huang G, Su T, et al : Decreased hephaestin activity in the intestine of copper-deficient mice causes systemic iron deficiency . In: J. Nutr. . 136, No. 5, May 2006, pp. 1236-41. PMID 16614410 .

[5] Hadziahmetovic M, Dentchev T, Song Y, et al : Ceruloplasmin / hephaestin knockout mice model morphologic and molecular features of AMD . In: Invest. Ophthalmol. Vis. Sci. . 49, No. 6, June 2008, pp. 2728-36. doi : 10.1167 / iovs.07-1472 . PMID 18326691 .

[6] Qian ZM, Chang YZ, Zhu L, et al : Development and iron-dependent expression of hephaestin in different brain regions of rats . In: J. Cell. Biochem. . 102, No. 5, December 2007, pp. 1225-33. doi : 10.1002 / jcb.21352 . PMID 17516501 .

[7] Wang J, Jiang H, Xie JX: Ferroportin1 and hephaestin are involved in the nigral iron accumulation of 6-OHDA-lesioned rats . In: Eur. J. Neurosci. . 25, No. 9, May 2007, pp. 2766-72. doi : 10.1111 / j.1460-9568.2007.05515.x . PMID 17561842 .

[8] Kong WN, Chang YZ, Wang SM, et al : Effect of erythropoietin on hepcidin, DMT1 with IRE, and hephaestin gene expression in duodenum of rats . In: J. Gastroenterol. . 43, No. 2, 2008, pp. 136-43. doi : 10.1007 / s00535-007-2138-5 . PMID 18306987 .

[9] Qian ZM, Chang YZ, Leung G, et al : Expression of ferroportin1, hephaestin and ceruloplasmin in rat heart . In: Biochim. Biophys. Acta . 1772, No. 5, May 2007, pp. 527-32. doi : 10.1016 / j.bbadis.2007.02.006 . PMID 17383861 .

[10] Brookes MJ, Hughes S, Turner FE, et al : Modulation of iron transport proteins in human colorectal carcinogenesis . In: Good . 55, No. 10, October 2006, pp. 1449-60. doi : 10.1136 / good 2006.094060 . PMID 16641131 .