FLVCR2

Feline leukemia virus subgroup C cellular receptor family, member 2 (FLVCR2) is a choline transporter belonging to the major facilitator superfamily (MFS).^[5] It is a uniporter transmembrane protein that transports choline across the plasma membrane via a concentration gradient. FLVCR2 is highly enriched in endothelial cells of the blood-brain barrier but is also expressed in peripheral tissues such as the small intestine where it absorbs dietary choline.^[6][7][8] At the blood-brain barrier, FLVCR2 is the primary transporter of choline responsible for approximately 60% of the brains supply.^[5]

FLVCR2
Identifiers
Aliases	FLVCR2, C14orf58, CCT, EPV, FLVCRL14q, MFSD7C, PVHH, feline leukemia virus subgroup C cellular receptor family member 2, SLC49A2, FLVCR heme transporter 2
External IDs	OMIM: 610865; MGI: 2384974; HomoloGene: 9840; GeneCards: FLVCR2; OMA:FLVCR2 - orthologs
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q24.3 Start 75,578,620 bp[1] End 75,663,214 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12|12 D2 Start 85,793,313 bp[2] End 85,860,359 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte tibial nerve monocyte sperm right testis left testis right adrenal cortex left adrenal cortex mucosa of ileum right lobe of liver Top expressed in retinal pigment epithelium morula morula blastocyst yolk sac spermatid proximal tubule right kidney spermatocyte seminiferous tubule More reference expression data BioGPS n/a
Gene ontology Molecular function heme transmembrane transporter activity heme binding Cellular component integral component of membrane plasma membrane membrane Biological process transmembrane transport heme transport heme export Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55640 217721 Ensembl ENSG00000119686 ENSMUSG00000034258 UniProt Q9UPI3 Q91X85 RefSeq (mRNA) NM_017791 NM_001195283 NM_145447 RefSeq (protein) NP_001182212 NP_060261 NP_663422 Location (UCSC) Chr 14: 75.58 – 75.66 Mb Chr 12: 85.79 – 85.86 Mb PubMed search [3] [4]
Wikidata
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Mutations in FLVCR2 have been associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (Fowler syndrome).^[9]

Discovery

In 2009, the feline FLVCR2 ortholog was the first identified as a receptor of the Feline leukemia virus (FeLV) in cats.^[10] The following year, it was characterised as a heme transporter as it was shown to bind heme, increase heme transport.^[11] However, in 2024 it was shown to transport choline both in vivo and in vitro through the use of radiolabel choline transport assays and structural characterisation showing choline bound.^[5] FLVCR2's role in disease and interactions with heme remains an ongoing investigation.

Structure

FLVCR2 adopts the canonical MFS fold consisting of 12 transmembrane alpha-helices. It is a 60 kDa protein with no significant extracellular structures or glycosylation.^[5][12]