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FLVCR1  -  feline leukemia virus subgroup C cellular...

Homo sapiens

Synonyms: AXPC1, FLVCR, Feline leukemia virus subgroup C receptor, Feline leukemia virus subgroup C receptor-related protein 1, MFSD7B, ...
 
 
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Disease relevance of FLVCR1

 

High impact information on FLVCR1

  • FLVCR is upregulated on CFU-E, indicating that heme export is important in primary cells at this stage [1].
  • Inhibition of FLVCR in K562 cells decreases heme export, impairs their erythroid maturation and leads to apoptosis [1].
  • Studies of FLVCR expression in cell lines suggest this exporter also impacts heme trafficking in intestine and liver [1].
  • FLVCR protects developing erythroid cells from haem toxicity during the early stages of differentiation, and ABCG2 averts protoporphyrin accumulation (particularly under hypoxic conditions) [4].
  • FLVCR has significant amino acid sequence homology with members of the major facilitator superfamily and especially D-glucarate transporters described in bacteria and in C. elegans [5].
 

Biological context of FLVCR1

  • Splicing, polyadenylation, and expression patterns, as estimated by in silico analysis, differed between the two FLVCR genes despite their similar genomic structures, suggesting active and independent evolution of transcriptional and messenger RNA processing patterns after gene duplication [6].
  • In further studies, a 6-kb fragment of the human FLVCR gene was amplified by polymerase chain reaction from genomic DNA, using homologous cDNA sequences identified in the human Expressed Sequence Tags database [5].
  • To address these issues, we functionally cloned a putative cell surface receptor for FeLV-C (FLVCR) by using a human T-lymphocyte cDNA library in a retroviral vector [2].
  • Infection of cells by the highly anemogenic feline leukemia virus subgroup C (FeLV-C) is mediated by the heme exporter FLVCR1, a cell surface protein containing 12 potential transmembrane segments with six presumptive extracellular loops (ECLs) [7].
  • The upstream 1q transcribed sequences were determined to comprise a novel gene of unknown function, LQK1.Annotation of contigs centered at hFLVCR and FLVCRL14q also revealed highly conserved gene clusters on chromosomes 1 and 14, inferred to result from a duplication [6].
 

Anatomical context of FLVCR1

 

Other interactions of FLVCR1

  • The clusters contained members of the FLVCR, Angel (KIAA0759), JDP, p21SNFT, and TGF- families, as well as two uncharacterized families [6].
  • Mouse cells expressing a hybrid protein containing FLVCR2 backbone with the ECL6 sequence from FLVCR1 were highly susceptible to FeLV-C infection [7].

References

  1. Identification of a human heme exporter that is essential for erythropoiesis. Quigley, J.G., Yang, Z., Worthington, M.T., Phillips, J.D., Sabo, K.M., Sabath, D.E., Berg, C.L., Sassa, S., Wood, B.L., Abkowitz, J.L. Cell (2004) [Pubmed]
  2. A putative cell surface receptor for anemia-inducing feline leukemia virus subgroup C is a member of a transporter superfamily. Tailor, C.S., Willett, B.J., Kabat, D. J. Virol. (1999) [Pubmed]
  3. Investigation of a putative role for FLVCR, a cytoplasmic heme exporter, in Diamond-Blackfan anemia. Quigley, J.G., Gazda, H., Yang, Z., Ball, S., Sieff, C.A., Abkowitz, J.L. Blood Cells Mol. Dis. (2005) [Pubmed]
  4. Recent advances in mammalian haem transport. Latunde-Dada, G.O., Simpson, R.J., McKie, A.T. Trends Biochem. Sci. (2006) [Pubmed]
  5. Cloning of the cellular receptor for feline leukemia virus subgroup C (FeLV-C), a retrovirus that induces red cell aplasia. Quigley, J.G., Burns, C.C., Anderson, M.M., Lynch, E.D., Sabo, K.M., Overbaugh, J., Abkowitz, J.L. Blood (2000) [Pubmed]
  6. Genomic structure and evolutionary context of the human feline leukemia virus subgroup C receptor (hFLVCR) gene: evidence for block duplications and de novo gene formation within duplicons of the hFLVCR locus. Lipovich, L., Hughes, A.L., King, M.C., Abkowitz, J.L., Quigley, J.G. Gene (2002) [Pubmed]
  7. Comprehensive mapping of receptor-functioning domains in feline leukemia virus subgroup C receptor FLVCR1. Brown, J.K., Fung, C., Tailor, C.S. J. Virol. (2006) [Pubmed]
 
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