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== Structure == |
== Structure == |
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FLVCR2 adopts the canonical MFS fold consisting of 12 transmembrane alpha-helices |
FLVCR2 adopts the canonical MFS fold consisting of 12 transmembrane alpha-helices with no significant extracellular structures or glycosylation.<ref name=”:0″ /><ref>{{Cite journal |last=Brown |first=Jennifer K. |last2=Fung |first2=Claire |last3=Tailor |first3=Chetankumar S. |date=February 2006 |title=Comprehensive mapping of receptor-functioning domains in feline leukemia virus subgroup C receptor FLVCR1 |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC1367145/ |journal=Journal of Virology |volume=80 |issue=4 |pages=1742–1751 |doi=10.1128/JVI.80.4.1742-1751.2006 |issn=0022-538X |pmc=1367145 |pmid=16439531}}</ref> |
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== References == |
== References == |
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Latest revision as of 05:07, 11 February 2026
Protein-coding gene in the species Homo sapiens
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]
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.
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. [5][12] These helices are organized into two distinct pseudo-symmetrical bundles: the N-terminal and C-terminal domains—which are both oriented towards the cytosol. [5] 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.
- ^ a b c GRCh38: Ensembl release 89: ENSG00000119686 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034258 – Ensembl, May 2017
- ^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d e Cater, Rosemary J.; Mukherjee, Dibyanti; Gil-Iturbe, Eva; Erramilli, Satchal K.; Chen, Ting; Koo, Katie; Santander, Nicolás; Reckers, Andrew; Kloss, Brian; Gawda, Tomasz; Choy, Brendon C.; Zhang, Zhening; Katewa, Aditya; Larpthaveesarp, Amara; Huang, Eric J. (May 2024). “Structural and molecular basis of choline uptake into the brain by FLVCR2”. Nature. 629 (8012): 704–709. doi:10.1038/s41586-024-07326-y. ISSN 1476-4687. PMC 11168207.
- ^ Yasujima, Tomoya; Namba, Chitaka; Azuma, Yosuke; Shinoda, Yutaro; Matake, Isamu; Yamasaki, Mione; Morimoto, Haruka; Namai, Mana; Kusuhara, Hiroyuki; Inoue, Katsuhisa; Yamashiro, Takahiro; Yuasa, Hiroaki (2025-08-01). “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. ISSN 0925-4439.
- ^ Santander, Nicolas; Lizama, Carlos O.; Meky, Eman; McKinsey, Gabriel L.; Jung, Bongnam; Sheppard, Dean; Betsholtz, Christer; Arnold, Thomas D. (2020-08-03). “Lack of Flvcr2 impairs brain angiogenesis without affecting the blood-brain barrier”. The Journal of Clinical Investigation. 130 (8): 4055–4068. doi:10.1172/JCI136578. ISSN 0021-9738. PMC 7410045.
- ^ “Tissue expression of FLVCR2 – Summary – The Human Protein Atlas”. www.proteinatlas.org. Retrieved 2025-11-11.
- ^ Meyer, Esther; Ricketts, Christopher; Morgan, Neil V.; Morris, Mark R.; Pasha, Shanaz; Tee, Louise J.; Rahman, Fatimah; Bazin, Anne; Bessières, Bettina; Déchelotte, Pierre; Yacoubi, Mohamed T.; Al-Adnani, Mudher; Marton, Tamas; Tannahill, David; Trembath, Richard C. (2010-03-12). “Mutations in FLVCR2 are associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (Fowler syndrome)”. American Journal of Human Genetics. 86 (3): 471–478. doi:10.1016/j.ajhg.2010.02.004. ISSN 1537-6605. PMC 2833392. PMID 20206334.
- ^ Shalev, Zvi; Duffy, Simon P.; Adema, Karen W.; Prasad, Rati; Hussain, Naveen; Willett, Brian J.; Tailor, Chetankumar S. (July 2009). “Identification of a Feline Leukemia Virus Variant That Can Use THTR1, FLVCR1, and FLVCR2 for Infection”. Journal of Virology. 83 (13): 6706–6716. doi:10.1128/jvi.02317-08. PMC 2698567.
- ^ 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. PMC 2976379. PMID 20823265.
- ^ Brown, Jennifer K.; Fung, Claire; Tailor, Chetankumar S. (February 2006). “Comprehensive mapping of receptor-functioning domains in feline leukemia virus subgroup C receptor FLVCR1”. Journal of Virology. 80 (4): 1742–1751. doi:10.1128/JVI.80.4.1742-1751.2006. ISSN 0022-538X. PMC 1367145. PMID 16439531.
- Wimer BM (Feb 1976). “Letter: Remission of lymphoblastic leukaemia”. Lancet. 1 (7954): 316. doi:10.1016/s0140-6736(76)91461-6. PMID 55640. S2CID 54424023.
- Brasier G, Tikellis C, Xuereb L, Craigie J, Casley D, Kovacs CS, Fudge NJ, Kalnins R, Cooper ME, Wookey PJ (Feb 2004). “Novel hexad repeats conserved in a putative transporter with restricted expression in cell types associated with growth, calcium exchange and homeostasis”. Experimental Cell Research. 293 (1): 31–42. doi:10.1016/j.yexcr.2003.10.002. PMID 14729055.
- Duffy SP, Shing J, Saraon P, Berger LC, Eiden MV, Wilde A, Tailor CS (Nov 2010). “The Fowler syndrome-associated protein FLVCR2 is an importer of heme”. Molecular and Cellular Biology. 30 (22): 5318–24. doi:10.1128/MCB.00690-10. PMC 2976379. PMID 20823265.
- Meyer E, Ricketts C, Morgan NV, Morris MR, Pasha S, Tee LJ, Rahman F, Bazin A, Bessières B, Déchelotte P, Yacoubi MT, Al-Adnani M, Marton T, Tannahill D, Trembath RC, Fallet-Bianco C, Cox P, Williams D, Maher ER (Mar 2010). “Mutations in FLVCR2 are associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (Fowler syndrome)”. American Journal of Human Genetics. 86 (3): 471–8. doi:10.1016/j.ajhg.2010.02.004. PMC 2833392. PMID 20206334.
- Brown JK, Fung C, Tailor CS (Feb 2006). “Comprehensive mapping of receptor-functioning domains in feline leukemia virus subgroup C receptor FLVCR1”. Journal of Virology. 80 (4): 1742–1751. doi:10.1128/JVI.80.4.1742-1751.2006. PMC 1367145. PMID 16439531.
- Thomas S, Encha-Razavi F, Devisme L, Etchevers H, Bessieres-Grattagliano B, Goudefroye G, Elkhartoufi N, Pateau E, Ichkou A, Bonnière M, Marcorelle P, Parent P, Manouvrier S, Holder M, Laquerrière A, Loeuillet L, Roume J, Martinovic J, Mougou-Zerelli S, Gonzales M, Meyer V, Wessner M, Feysot CB, Nitschke P, Leticee N, Munnich A, Lyonnet S, Wookey P, Gyapay G, Foliguet B, Vekemans M, Attié-Bitach T (Oct 2010). “High-throughput sequencing of a 4.1 Mb linkage interval reveals FLVCR2 deletions and mutations in lethal cerebral vasculopathy”. Human Mutation. 31 (10): 1134–41. doi:10.1002/humu.21329. PMID 20690116. S2CID 20452899.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
