| Erythroferrone | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | ERFE | ||||||
| NCBI gene | 151176 | ||||||
| HGNC | 26727 | ||||||
| OMIM | 615099 | ||||||
| RefSeq | NM_001291832.1 | ||||||
| UniProt | Q4G0M1 | ||||||
| Other data | |||||||
| Locus | Chr. 2 q37.3 | ||||||
| |||||||
Erythroferrone is a protein hormone, abbreviated as ERFE, encoded in humans by the FAM132B gene. Erythroferrone is produced by erythroblasts, inhibits the action of hepcidin, and so increases the amount of iron available for hemoglobin synthesis.[1][2]
Discovery
editIt was identified in 2014 in mice where the transcript was found in bone marrow, encoded by the mouse Fam132b gene.[2] The homologous gene in humans is FAM132B and the sequence is conserved in other species. The protein is synthesized by erythroblasts and secreted.[2] This sequence had previously been found expressed in mouse skeletal muscle, called myonectin (CTRP15), and linked to lipid homeostasis.[3]
Structure
editErythroferrone in humans is transcribed as a precursor (354 amino acids), with a signal peptide of (28 amino acids). The mouse gene encodes a 340 amino acid protein which is 71% identical.[2] Homology is greater at the C-terminal where there is a TNF-alpha-like domain.
Function
editErythroferrone is a hormone that regulates iron metabolism through its actions on hepcidin.[1] As shown in mice and humans, it is produced in erythroblasts, which proliferate when new red cells are synthesized, such as after after hemorrhage when more iron is needed (so-called stress erythropoiesis).[4] This process is governed by the renal hormone, erythropoietin.[2]
Its mechanism of action is to inhibit the expression of the liver hormone, hepcidin.[4] This process is governed by the renal hormone, erythropoietin.[2] By suppressing this, ERFE increases the function of the cellular iron export channel, ferroportin. This then results in increased iron absorption from the intestine and mobilization of iron from stores, which can then be used in the synthesis of hemoglobin in new red blood cells.[2]
Mice deficient in the gene encoding erythroferrone have transient maturational hemoglobin deficits and impaired hepcidin suppression in response to plebotomy with a delayed recovery from anemia.[2]
In its role as myonectin, it also promotes lipid uptake into adipocytes and hepatocytes.[3]
Regulation
editSynthesis of erythroferrone is regulated by erythropoietin binding to its receptor and activating the Jak2/Stat5 signaling pathway.[2]
Clinical significance
editThe clinical significance in humans is mostly unknown. From parallels in the mouse studies, there may be diseases where its function could be relevant. In a mouse model of thalassemia, its expression is increased, resulting in iron overload, which is also a feature of the human disease.[5] A role in the recovery from the anemia of inflammation in mice has been shown[6] and involvement in inherited anemias with ineffective erythropoiesis, anemia of chronic kidney diseases and iron-refractory iron-deficiency anemia has been suggested.[2][7]
References
edit- ^ a b Koury, M.J. "Erythroferrone: A Missing Link in Iron Regulation". The Hematologist. American Society of Hematology. Retrieved 26 August 2015.
- ^ a b c d e f g h i j Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T (2014). "Identification of erythroferrone as an erythroid regulator of iron metabolism". Nat Genet. 46 (7): 678–84. doi:10.1038/ng.2996. PMC 4104984. PMID 24880340.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Seldin MM, Peterson JM, Byerly MS, Wei Z, Wong GW (2012). "Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis". J Biol Chem. 287 (15): 11968–80. doi:10.1074/jbc.M111.336834. PMC 3320944. PMID 22351773.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Kim A, Nemeth E (2015). "New insights into iron regulation and erythropoiesis". Curr Opin Hematol. 22 (3): 199–205. doi:10.1097/MOH.0000000000000132. PMC 4509743. PMID 25710710.
- ^ Kautz L, Jung G, Du X, Gabayan V, Chapman J, Nasoff M; et al. (2015). "Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia". Blood. doi:10.1182/blood-2015-07-658419. PMID 26276665.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Kautz L, Jung G, Nemeth E, Ganz T (2014). "Erythroferrone contributes to recovery from anemia of inflammation". Blood. 124 (16): 2569–74. doi:10.1182/blood-2014-06-584607. PMC 199959. PMID 25193872.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Cucuianu A, Patiu M, Trifa AP, Tomuleasa C, Dima D (2014). "Redistribution of iron towards deposits in erythroblastopenic anemia as a consequence of decreased erythroferrone production". Med Hypotheses. 83 (5): 530–2. doi:10.1016/j.mehy.2014.09.008. PMID 25267320.
{{cite journal}}: CS1 maint: multiple names: authors list (link)