Protein: Choline/ethanolamine transporter FLVCR2 (Q9UPI3)
Organism: Homo sapiens (Human)
Function: Choline uniporter that specifically mediates choline uptake at the blood-brain-barrier. Responsible for the majority of choline uptake across the blood-brain- barrier from the circulation into the brain (By similarity). Choline, a nutrient critical for brain development, is a precursor of phosphatidylcholine, as well as betaine (By similarity). Also mediates transport of ethanolamine. Choline and ethanolamine transport is not coupled with proton transport and is exclusively driven by the choline gradient across the plasma membrane. However, the presence of an inwardly directed proton gradient enhances choline uptake (By similarity). Also acts as a heme b transporter. Required to regulate mitochondrial respiration processes, ATP synthesis and thermogenesis. At low heme levels, interacts with components of electron transfer chain (ETC) complexes and ATP2A2, leading to ubiquitin-mediated degradation of ATP2A2 and inhibition of thermogenesis. Upon heme binding, dissociates from ETC complexes to allow switching from mitochondrial ATP synthesis to thermogenesis
Subcellular location: Cell membrane; Multi-pass membrane protein. Mitochondrion membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein. Note=Present on both luminal (blood-facing) and abluminal (brain-facing) sides of brain endothelial cell plasma membranes, with higher luminal membrane expression (By similarity). Also localizes in mitochondria where it interacts with components of the electron transfer complexes III, IV and V. Colocalizes with ATP2A2 at the mitochondrial-ER contact junction
Sequence: MVNEGPNQEESDDTPVPESALQADPSVSVHPSVSVHPSVSINPSVSVHPSSSAHPSALAQPSGLAHPSSSGPEDLSVIKVSRRRWAVVLVFSCYSMCNSFQWIQYGSINNIFMHFYGVSAFAIDWLSMCYMLTYIPLLLPVAWLLEKFGLRTIALTGSALNCLGAWVKLGSLKPHLFPVTVVGQLICSVAQVFILGMPSRIASVWFGANEVSTACSVAVFGNQLGIAIGFLVPPVLVPNIEDRDELAYHISIMFYIIGGVATLLLILVIIVFKEKPKYPPSRAQSLSYALTSPDASYLGSIARLFKNLNFVLLVITYGLNAGAFYALSTLLNRMVIWHYPGEEVNAGRIGLTIVIAGMLGAVISGIWLDRSKTYKETTLVVYIMTLVGMVVYTFTLNLGHLWVVFITAGTMGFFMTGYLPLGFEFAVELTYPESEGISSGLLNISAQVFGIIFTISQGQIIDNYGTKPGNIFLCVFLTLGAALTAFIKADLRRQKANKETLENKLQEEEEESNTSKVPTAVSEDHL
InterPro domains: - IPR049680: Choline/ethanolamine transporter FLVCR1-2/SLC49-like (family) [67-506]
- IPR036259: MFS transporter superfamily (homologous_superfamily) [72-503]
- IPR011701: Major facilitator superfamily (family) [95-453]
- IPR020846: Major facilitator superfamily domain (domain) [87-492]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005215 (transporter activity), GO:0022857 (transmembrane transporter activity), GO:0005515 (protein binding), GO:0015232 (heme transmembrane transporter activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0051179 (localization), GO:0009987 (cellular process), GO:0044237 (cellular metabolic process), GO:0055085 (transmembrane transport), GO:0044281 (small molecule metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0051234 (establishment of localization), GO:0071704 (organic substance metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:1903825 (organic acid transmembrane transport), GO:0046483 (heterocycle metabolic process), GO:0006810 (transport), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0046415 (urate metabolic process), GO:0071705 (nitrogen compound transport), GO:0071702 (organic substance transport), GO:0072521 (purine-containing compound metabolic process), GO:1905039 (carboxylic acid transmembrane transport), GO:0015697 (quaternary ammonium group transport), GO:0015711 (organic anion transport), GO:0015695 (organic cation transport), GO:0072337 (modified amino acid transport), GO:0015849 (organic acid transport), GO:0046942 (carboxylic acid transport), GO:0015879 (carnitine transport), GO:0015838 (amino-acid betaine transport), GO:0015718 (monocarboxylic acid transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0071944 (cell periphery), GO:0016020 (membrane), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)