Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 hereditary hemochromatosis (HH) or juvenile hemochromatosis is an early onset, genetically heterogeneous, autosomal recessive disorder of iron overload. Type 2A HH is caused by mutations in the recently cloned hemojuvelin gene (HJV; also called HFE2) (Papanikolaou, G., Samuels, M. E., Ludwig, E. H., MacDonald, M. L., Franchini, P. L., Dube, M. P., Andres, L., MacFarlane, J., Sakellaropoulos, N., Politou, M., Nemeth, E., Thompson, J., Risler, J. K., Zaborowska, C., Babakaiff, R., Radomski, C. C., Pape, T. D., Davidas, O., Christakis, J., Brissot, P., Lockitch, G., Ganz, T., Hayden, M. R., and Goldberg, Y. P. (2004) Nat. Genet. 36, 77-82), whereas Type 2B HH is caused by mutations in hepcidin. HJV is highly expressed in both skeletal muscle and liver. Mutations in HJV are implicated in the majority of diagnosed juvenile hemochromatosis patients. In this study, we stably transfected HJV cDNA into human embryonic kidney 293 cells and characterized the processing of HJV and its effect on iron homeostasis. Our results indicate that HJV is a glycosylphosphatidylinositol-linked protein and undergoes a partial autocatalytic cleavage during its intracellular processing. HJV co-immunoprecipitated with neogenin, a receptor involved in a variety of cellular signaling processes. It did not interact with the closely related receptor DCC (deleted in Colon Cancer). In addition, the HJV G320V mutant implicated in Type 2A HH did not co-immunoprecipitate with neogenin. Immunoblot analysis of ferritin levels and transferrin-55Fe accumulation studies indicated that the HJV-induced increase in intracellular iron levels in human embryonic kidney 293 cells is dependent on the presence of neogenin in the cells, thus linking these two proteins to intracellular iron homeostasis.
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PMID:Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells. 1610 17

Rigorous regulation of iron absorption is required to meet the requirements of the body and to limit excess iron accumulation that can produce oxidative stress. Regulation of iron absorption is controlled by hepcidin and probably by the crypt program. Hepcidin is a humoral mediator of iron absorption that interacts with the basolateral transporter, ferroportin. High levels of hepcidin reduce iron absorption by targeting ferroportin to lysosomes for destruction. It is also proposed that ferroportin is expressed on the apical membrane and coordinates with ferroportin-hepcidin derived from the basal surface to modulate the uptake phase of iron absorption. The crypt program suggests that as crypt cells differentiate and migrate into the absorptive zone they absorb iron from the diet at levels inverse to the amount of iron taken up from transferrin. Under most circumstances, intestinal iron absorption is controlled at multiple levels that lead to hepcidin/ferroportin modulation of the enterocyte labile iron pool (LIP). It is likely that transcription of iron transport proteins involved in the apical and basolateral transport of iron are differentially regulated by separate LIPs. Iron-responsive protein (IRP) 1 and IRP2 do not appear to play a significant role in the expression of iron transport proteins, although IRP2 regulates L- and H-ferritin expression. Despite the importance of hepcidin, there is evidence of hepcidin-independent regulation of iron absorption possibly involving haemojuvelin (HJV) and neogenin, which may be up-regulated during ineffective erythropoiesis.
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PMID:The relevance of the intestinal crypt and enterocyte in regulating iron absorption. 1747 33