Recombinant Mouse Erythroferrone (Erfe)

Function

Iron-regulatory hormone that acts as an erythroid regulator after hemorrhage: produced by erythroblasts following blood loss and mediates suppression of hepcidin (HAMP) expression in the liver, thereby promoting increased iron absorption and mobilization from stores (PubMed:24880340, PubMed:30097509, PubMed:31800957, PubMed:34002695). Promotes lipid uptake into adipocytes and hepatocytes via transcriptional up-regulation of genes involved in fatty acid uptake (PubMed:22351773). Inhibits apoptosis and inflammatory response in cardiomyocytes via promotion of sphingosine-1-phosphate (S1P) and cAMP-dependent activation of AKT signaling (PubMed:30566056). Inhibits autophagy induced by nutrient deficiency in hepatocytes via promoting the phosphorylation of IRS1, AKT, and MTOR, and thereby subsequent activation of the AKT-MTOR signaling pathway (PubMed:24187137). Negatively regulates the differentiation of osteoblasts, potentially via sequestering BMP2, and thereby inhibits the activation of SMAD signaling (PubMed:34002695). The reduction in BMP2 signaling in osteoblasts also results in an increase in expression of the osteoclastogenesis-promoting factors TNFSF11/RANKL and SOST, thereby indirectly promotes bone resorption (PubMed:34002695)

Subcellular Location

Secreted

Tissue Specificity

Expressed in the soleus muscle in the leg (at protein level) (PubMed:22351773, PubMed:30566056). Found in blood (at protein level) (PubMed:22351773, PubMed:24187137). Weakly expressed in the heart (at protein level) (PubMed:22351773, PubMed:30566056). Predominantly expressed in skeletal muscle and, at much lower levels, in other tissues, including lung, eye, smooth muscle, brain and kidney (PubMed:22351773, PubMed:24187137). Within skeletal muscles, higher expression levels in soleus as compared with plantaris (PubMed:22351773). Expressed in osteoblasts, mature osteoclasts and erythroblasts (PubMed:34002695). When fasting, females tend to have higher circulating levels than males (PubMed:22351773). Obese mice tend to have lower expression and circulating levels as compared to lean animals (PubMed:22351773). Following EPO treatment, only expressed in bone marrow and spleen (PubMed:24880340)

Subunit

Homodimer; disulfide-linked (PubMed:22351773). Forms trimer, hexamers and higher molecular weight oligomers (PubMed:32602701). May form heteromeric complexes with C1QTNF2 and C1QTNF12 and, to a lesser extent, with C1QTNF5 and C1QTNF10 (PubMed:22351773). Interacts with BMP5 and BMP7; the interaction inhibits BMP-induced transcription of HAMP (PubMed:30097509). Interacts with BMP6; the interaction inhibits BMP-induced transcription of HAMP (PubMed:30097509, PubMed:31800957). Interacts with BMP2 (PubMed:31800957). Interacts with heterodimers composed of BMP2 and BMP6 in vitro, the interaction inhibits the heterodimer binding to its receptor BMPR1A /ALK3 and thereby suppresses expression of HAMP (PubMed:31800957)

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• Kautz L. et al. Identification of erythroferrone as an erythroid regulator of iron metabolism. — Nat. Genet. (2014)
• Arezes J. et al. Erythroferrone inhibits the induction of hepcidin by BMP6. — Blood (2018)
• Otaka N. et al. Myonectin Is an Exercise-Induced Myokine That Protects the Heart From Ischemia-Reperfusion Injury. — Circ. Res. (2018)