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]
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 comprised of 12 transmembrane alpha-helices. It is a 60 kDa protein with no significant extracellular structures or glycosylation.[5][12]
↑ Duffy, Simon P.; Shing, Jennifer; Saraon, Punit; Berger, Lloyd C.; Eiden, Maribeth V.; Wilde, Andrew; Tailor, Chetankumar S. (2010-11-01). "The Fowler Syndrome-Associated Protein FLVCR2 Is an Importer of Heme". Molecular and Cellular Biology. 30 (22): 5318–5324. doi:10.1128/MCB.00690-10. PMID20823265.
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