8uc0

Structural highlights

Disease

FLVC1_HUMAN Posterior column ataxia-retinitis pigmentosa syndrome. The disease is caused by variants affecting the gene represented in this entry. Defective neuronal heme transmembrane export due to FLVCR1 mutations may abrogate the neuroprotective effects of neuroglobin and initiate an apoptotic cascade that results in the selective degeneration of photoreceptors in the neurosensory retina and sensory neurons in the posterior spinal cord. Defects in FLVCR1 are a cause of a sensory neuropathy resulting in pain insensitivity. Patients have decreased sensing of pain, temperature and touch. Self-injury, ulcers and amputations are commonly observed in affected individuals.^[1]

Function

FLVC1_HUMAN Heme b transporter that mediates heme efflux from the cytoplasm to the extracellular compartment. Heme export depends on the presence of HPX and is required to maintain intracellular free heme balance, protecting cells from heme toxicity. Heme export provides protection from heme or ferrous iron toxicities in liver, brain, sensory neurons and during erythropoiesis, a process in which heme synthesis intensifies. Possibly export coproporphyrin and protoporphyrin IX, which are both intermediate products in the heme biosynthetic pathway. Does not export bilirubin. The molecular mechanism of heme transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated.^{[2] [3] [4] [5]} (Microbial infection) Confers susceptibility to feline leukemia virus subgroup C (FeLV-C) infection in vitro.^[6] Heme b transporter that promotes heme efflux from the mitochondrion to the cytoplasm. Essential for erythroid differentiation.^[7]

References

1. ↑ Chiabrando D, Castori M, di Rocco M, Ungelenk M, Gießelmann S, Di Capua M, Madeo A, Grammatico P, Bartsch S, Hübner CA, Altruda F, Silengo L, Tolosano E, Kurth I. Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception. PLoS Genet. 2016 Dec 6;12(12):e1006461. PMID:27923065 doi:10.1371/journal.pgen.1006461
2. ↑ Quigley JG, Yang Z, Worthington MT, Phillips JD, Sabo KM, Sabath DE, Berg CL, Sassa S, Wood BL, Abkowitz JL. Identification of a human heme exporter that is essential for erythropoiesis. Cell. 2004 Sep 17;118(6):757-66. PMID:15369674 doi:10.1016/j.cell.2004.08.014
3. ↑ Yang Z, Philips JD, Doty RT, Giraudi P, Ostrow JD, Tiribelli C, Smith A, Abkowitz JL. Kinetics and specificity of feline leukemia virus subgroup C receptor (FLVCR) export function and its dependence on hemopexin. J Biol Chem. 2010 Sep 10;285(37):28874-82. PMID:20610401 doi:10.1074/jbc.M110.119131
4. ↑ Chiabrando D, Marro S, Mercurio S, Giorgi C, Petrillo S, Vinchi F, Fiorito V, Fagoonee S, Camporeale A, Turco E, Merlo GR, Silengo L, Altruda F, Pinton P, Tolosano E. The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation. J Clin Invest. 2012 Dec;122(12):4569-79. PMID:23187127 doi:10.1172/JCI62422
5. ↑ Chiabrando D, Castori M, di Rocco M, Ungelenk M, Gießelmann S, Di Capua M, Madeo A, Grammatico P, Bartsch S, Hübner CA, Altruda F, Silengo L, Tolosano E, Kurth I. Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception. PLoS Genet. 2016 Dec 6;12(12):e1006461. PMID:27923065 doi:10.1371/journal.pgen.1006461
6. ↑ Tailor CS, Willett BJ, Kabat D. A putative cell surface receptor for anemia-inducing feline leukemia virus subgroup C is a member of a transporter superfamily. J Virol. 1999 Aug;73(8):6500-5. PMID:10400745 doi:10.1128/JVI.73.8.6500-6505.1999
7. ↑ Chiabrando D, Marro S, Mercurio S, Giorgi C, Petrillo S, Vinchi F, Fiorito V, Fagoonee S, Camporeale A, Turco E, Merlo GR, Silengo L, Altruda F, Pinton P, Tolosano E. The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation. J Clin Invest. 2012 Dec;122(12):4569-79. PMID:23187127 doi:10.1172/JCI62422