Disease relevance of FLVCR1

• FLVCR, a member of the major facilitator superfamily of transporter proteins, is the cell surface receptor for feline leukemia virus, subgroup C [1].
• In this report, we demonstrate that human FLVCR exports cytoplasmic heme and hypothesize that human FLVCR is required on developing erythroid cells to protect them from heme toxicity [1].
• Expression of the 2.0-kbp FLVCR cDNA in naturally resistant Swiss mouse fibroblasts and Chinese hamster ovary cells caused substantial susceptibility to FeLV-C but no change in susceptibilities to FeLV-B and other retroviruses [2].
• Investigation of a putative role for FLVCR, a cytoplasmic heme exporter, in Diamond-Blackfan anemia [3].

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

• RNA blot analyses showed that FLVCR mRNA is expressed in multiple hematopoietic lineages rather than specifically in erythroblasts [2].

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