8.A.37 The Hepcidin (Hepcidin) Family

Hepcidin is known to increase intracellular iron through binding to and degrading ferroportin, which is a transmembrane protein that transports iron from the cytoplasm to the outside. Hepcidin (<100 nM/L) increases intracellular calcium when cells are exposed to high environmental iron concentrations (Li et al., 2012). L-type calcium channel, and ryanodine receptors are not involved. Antagonists of these channels inhibit abnormal calcium release from the sarco-endoplasmic reticulum. The increase of intracellular calcium induced by hepcidin is probably due to calcium release from the endoplasmic reticulum. Hepcidin is the key regulator of iron metabolism in humans through its inhibition of the iron-exporting protein ferroportin (Ehsani 2020).


 

References:

Ehsani, S. (2020). COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein. Biol Direct 15: 19.

Le Gac G., Ka C., Joubrel R., Gourlaouen I., Lehn P., Mornon JP., Ferec C. and Callebaut I. (2013). Structure-function analysis of the human ferroportin iron exporter (SLC40A1): effect of hemochromatosis type 4 disease mutations and identification of critical residues. Hum Mutat. 34(10):1371-80.

Li GF., Xu YJ., He YF., Du BC., Zhang P., Zhao DY., Yu C., Qin CH. and Li K. (2012). Effect of hepcidin on intracellular calcium in human osteoblasts. Mol Cell Biochem. 366(1-2):169-74.

Rice, A.E., M.J. Mendez, C.A. Hokanson, D.C. Rees, and P.J. Björkman. (2009). Investigation of the biophysical and cell biological properties of ferroportin, a multipass integral membrane protein iron exporter. J. Mol. Biol. 386: 717-732.

Examples:

TC#NameOrganismal TypeExample
8.A.37.1.1

Hepcidin

Animal

Hepcidin of Mus musculus (Q9EQ21)

 
8.A.37.1.2

Human hepcidin (84 aas).  Binds to and inhibits ferroportin (TC#2.A.100.1.4) (Le Gac et al. 2013).  Causes ferroportin internalization and degradation (Rice et al. 2009).

Animals

Hepcidin of Homo sapiens

 
8.A.37.1.3

Hepcidin antimicrobial peptide 4 of 95 aas.

Hepcidin peptide of Pagrus auriga

 
8.A.37.1.4

Hepcidin-like protein of 81 aas

Hepcidin-like protein of Python bivittatus

 
8.A.37.1.6

Uncharacterized protein of 111 aas.

UP of Quercus suber