Feline leukemia virus subgroup C cellular receptor family, member 2 (FLVCR2) is a choline transporter belonging to the major facilitator superfamily (MFS). 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. At the blood-brain barrier, FLVCR2 is the primary transporter of choline responsible for approximately 60% of the brains supply.
Mutations in FLVCR2 have been associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (Fowler syndrome).
Discovery
In 2009, the feline FLVCR2 ortholog was the first identified as a receptor of the Feline leukemia virus (FeLV) in cats. The following year, it was characterised as a heme transporter as it was shown to bind heme, increase heme transport. 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. FLVCR2's role in disease and interactions with heme remains an ongoing investigation.
Structure
FLVCR2 is a 60 kDa protein that adopts the canonical MFS fold consisting of 12 transmembrane alpha-helices with no significant extracellular structures or glycosylation. These helices are organized into two distinct pseudo-symmetrical bundles: the N-terminal and C-terminal domains—which are both oriented towards the cytosol. Together, these domains pack against one another to create a central aqueous cavity that serves as the translocation pathway for substrates such as choline. The protein operates through an alternating-access mechanism, often described as a "rocker-switch" motion, where the helices undergo conformational shifts to transition the central pore between outward-facing, occluded, and inward-facing states.
↑Yasujima T, Namba C, Azuma Y, Shinoda Y, Matake I, Yamasaki M, etal. (August 2025). "The role of FLVCR1 and FLVCR2 in choline transport in the Caco-2 intestinal epithelial cell model and rat small intestine". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1871 (6) 167883. doi:10.1016/j.bbadis.2025.167883. PMID40320184.
