8qd0

Structural highlights

Disease

FLVC2_HUMAN Fowler vasculopathy. The disease is caused by variants affecting the gene represented in this entry.

Function

FLVC2_HUMAN Putative heme b importer/sensor involved in heme homeostasis in response to the metabolic state of the cell and to diet. May act as a sensor of cytosolic and/or mitochondrial heme levels to regulate mitochondrial respiration processes, ATP synthesis and thermogenesis. At low heme levels, interacts with components of electron transfer chain (ETC) complexes and ATP2A2, leading to ubiquitin-mediated degradation of ATP2A2 and inhibition of thermogenesis. Upon heme binding, dissociates from ETC complexes to allow switching from mitochondrial ATP synthesis to thermogenesis. Alternatively, in coordination with ATP2A2 may mediate calcium transport and signaling in response to heme.^{[1] [2]}

References

1. ↑ Duffy SP, Shing J, Saraon P, Berger LC, Eiden MV, Wilde A, Tailor CS. The Fowler syndrome-associated protein FLVCR2 is an importer of heme. Mol Cell Biol. 2010 Nov;30(22):5318-24. PMID:20823265 doi:10.1128/MCB.00690-10
2. ↑ Li Y, Ivica NA, Dong T, Papageorgiou DP, He Y, Brown DR, Kleyman M, Hu G, Chen WW, Sullivan LB, Del Rosario A, Hammond PT, Vander Heiden MG, Chen J. MFSD7C switches mitochondrial ATP synthesis to thermogenesis in response to heme. Nat Commun. 2020 Sep 24;11(1):4837. PMID:32973183 doi:10.1038/s41467-020-18607-1