ID FLVC1_HUMAN Reviewed; 555 AA. AC Q9Y5Y0; Q1HE16; Q86XY9; Q9NVR9; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 28-JAN-2026, entry version 174. DE RecName: Full=Choline/ethanolamine transporter FLVCR1 {ECO:0000305}; DE AltName: Full=Feline leukemia virus subgroup C receptor-related protein 1; DE Short=Feline leukemia virus subgroup C receptor {ECO:0000303|PubMed:11943475}; DE Short=hFLVCR {ECO:0000303|PubMed:11943475}; DE AltName: Full=Heme transporter FLVCR1 {ECO:0000303|PubMed:23187127}; GN Name=FLVCR1 {ECO:0000303|PubMed:16439531, ECO:0000312|HGNC:HGNC:24682}; GN Synonyms=FLVCR {ECO:0000303|PubMed:11943475}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION (ISOFORM 1) (MICROBIAL RP INFECTION), CHARACTERIZATION OF FELV-C RECEPTOR FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Lymphocyte; RX PubMed=10400745; DOI=10.1128/jvi.73.8.6500-6505.1999; RA Tailor C.S., Willett B.J., Kabat D.; RT "A putative cell surface receptor for anemia-inducing feline leukemia virus RT subgroup C is a member of a transporter superfamily."; RL J. Virol. 73:6500-6505(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS PRO-52 AND RP MET-544. RC TISSUE=Duodenum; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP GENE STRUCTURE. RX PubMed=11943475; DOI=10.1016/s0378-1119(02)00457-2; RA Lipovich L., Hughes A.L., King M.-C., Abkowitz J.L., Quigley J.G.; RT "Genomic structure and evolutionary context of the human feline leukemia RT virus subgroup C receptor (hFLVCR) gene: evidence for block duplications RT and de novo gene formation within duplicons of the hFLVCR locus."; RL Gene 286:203-213(2002). RN [7] RP FUNCTION (ISOFORM 1), TRANSPORTER ACTIVITY (ISOFORM 1), SUBCELLULAR RP LOCATION (ISOFORM 1), AND DEVELOPMENTAL STAGE (ISOFORM 1). RX PubMed=15369674; DOI=10.1016/j.cell.2004.08.014; RA Quigley J.G., Yang Z., Worthington M.T., Phillips J.D., Sabo K.M., RA Sabath D.E., Berg C.L., Sassa S., Wood B.L., Abkowitz J.L.; RT "Identification of a human heme exporter that is essential for RT erythropoiesis."; RL Cell 118:757-766(2004). RN [8] RP SUBCELLULAR LOCATION, TOPOLOGY, AND GLYCOSYLATION. RX PubMed=16439531; DOI=10.1128/jvi.80.4.1742-1751.2006; RA Brown J.K., Fung C., Tailor C.S.; RT "Comprehensive mapping of receptor-functioning domains in feline leukemia RT virus subgroup C receptor FLVCR1."; RL J. Virol. 80:1742-1751(2006). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [12] RP FUNCTION (ISOFORM 1), TRANSPORTER ACTIVITY (ISOFORM 1), AND INTERACTION RP WITH HPX. RX PubMed=20610401; DOI=10.1074/jbc.m110.119131; RA Yang Z., Philips J.D., Doty R.T., Giraudi P., Ostrow J.D., Tiribelli C., RA Smith A., Abkowitz J.L.; RT "Kinetics and specificity of feline leukemia virus subgroup C receptor RT (FLVCR) export function and its dependence on hemopexin."; RL J. Biol. Chem. 285:28874-28882(2010). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [15] RP ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION (ISOFORMS 1 AND 2), AND RP TRANSPORTER ACTIVITY (ISOFORMS 1 AND 2). RX PubMed=23187127; DOI=10.1172/jci62422; RA Chiabrando D., Marro S., Mercurio S., Giorgi C., Petrillo S., Vinchi F., RA Fiorito V., Fagoonee S., Camporeale A., Turco E., Merlo G.R., Silengo L., RA Altruda F., Pinton P., Tolosano E.; RT "The mitochondrial heme exporter FLVCR1b mediates erythroid RT differentiation."; RL J. Clin. Invest. 122:4569-4579(2012). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-536, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP FUNCTION (ISOFORM 1), TRANSPORTER ACTIVITY (ISOFORM 1), INVOLVEMENT IN RP RETSNS, AND VARIANTS RETSNS ARG-192 AND SER-221. RX PubMed=27923065; DOI=10.1371/journal.pgen.1006461; RA Chiabrando D., Castori M., di Rocco M., Ungelenk M., Giesselmann S., RA Di Capua M., Madeo A., Grammatico P., Bartsch S., Huebner C.A., Altruda F., RA Silengo L., Tolosano E., Kurth I.; RT "Mutations in the heme exporter FLVCR1 cause sensory neurodegeneration with RT loss of pain perception."; RL PLoS Genet. 12:E1006461-E1006461(2016). RN [18] RP FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=37100056; DOI=10.1016/j.cmet.2023.04.003; RA Kenny T.C., Khan A., Son Y., Yue L., Heissel S., Sharma A., Pasolli H.A., RA Liu Y., Gamazon E.R., Alwaseem H., Hite R.K., Birsoy K.; RT "Integrative genetic analysis identifies FLVCR1 as a plasma-membrane RT choline transporter in mammals."; RL Cell Metab. 35:1057-1071(2023). RN [19] {ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, ECO:0007744|PDB:8UBY, ECO:0007744|PDB:8UBZ, ECO:0007744|PDB:8UC0} RP STRUCTURE BY ELECTRON MICROSCOPY (2.42 ANGSTROMS) IN COMPLEX WITH CHOLINE RP AND ETHANOLAMINE, FUNCTION, TRANSPORTER ACTIVITY, AND MUTAGENESIS OF RP TRP-125; TYR-153; GLN-214; ASN-245; TYR-349 AND GLN-471. RX PubMed=38693265; DOI=10.1038/s41586-024-07374-4; RA Son Y., Kenny T.C., Khan A., Birsoy K., Hite R.K.; RT "Structural basis of lipid head group entry to the Kennedy pathway by RT FLVCR1."; RL Nature 0:0-0(2024). RN [20] {ECO:0007744|PDB:8QCS, ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T} RP STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) IN COMPLEX WITH CHOLINE, RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP SUBCELLULAR LOCATIONMUTAGENESIS OF TRP-125; GLN-214; ASN-245; TYR-349 AND RP GLN-471. RX PubMed=38778100; DOI=10.1038/s41586-024-07444-7; RA Ri K., Weng T.H., Claveras Cabezudo A., Joesting W., Zhang Y., Bazzone A., RA Leong N.C.P., Welsch S., Doty R.T., Gursu G., Lim T.J.Y., Schmidt S.L., RA Abkowitz J.L., Hummer G., Wu D., Nguyen L.N., Safarian S.; RT "Molecular mechanism of choline and ethanolamine transport in humans."; RL Nature 0:0-0(2024). RN [21] RP VARIANTS RETSNS ASP-121; ARG-192 AND THR-241. RX PubMed=21070897; DOI=10.1016/j.ajhg.2010.10.013; RA Rajadhyaksha A.M., Elemento O., Puffenberger E.G., Schierberl K.C., RA Xiang J.Z., Putorti M.L., Berciano J., Poulin C., Brais B., Michaelides M., RA Weleber R.G., Higgins J.J.; RT "Mutations in FLVCR1 cause posterior column ataxia and retinitis RT pigmentosa."; RL Am. J. Hum. Genet. 87:643-654(2010). RN [22] RP VARIANT RETSNS ARG-493. RX PubMed=21267618; DOI=10.1007/s10048-010-0271-4; RA Ishiura H., Fukuda Y., Mitsui J., Nakahara Y., Ahsan B., Takahashi Y., RA Ichikawa Y., Goto J., Sakai T., Tsuji S.; RT "Posterior column ataxia with retinitis pigmentosa in a Japanese family RT with a novel mutation in FLVCR1."; RL Neurogenetics 12:117-121(2011). RN [23] RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS RETSNS RP ASP-121; ARG-192; THR-241 AND ARG-493. RX PubMed=22483575; DOI=10.1016/j.bcmd.2012.03.004; RA Yanatori I., Yasui Y., Miura K., Kishi F.; RT "Mutations of FLVCR1 in posterior column ataxia and retinitis pigmentosa RT result in the loss of heme export activity."; RL Blood Cells Mol. Dis. 49:60-66(2012). RN [24] RP VARIANT RETSNS SER-221. RX PubMed=28766925; DOI=10.1002/ajmg.b.32570; RA Castori M., Morlino S., Ungelenk M., Pareyson D., Salsano E., RA Grammatico P., Tolosano E., Kurth I., Chiabrando D.; RT "Posterior column ataxia with retinitis pigmentosa coexisting with sensory- RT autonomic neuropathy and leukemia due to the homozygous p.Pro221Ser FLVCR1 RT mutation."; RL Am. J. Med. Genet. B Neuropsychiatr. Genet. 174:732-739(2017). RN [25] RP VARIANT RETSNS ASP-121. RX PubMed=30444160; DOI=10.1080/13816810.2018.1547913; RA Lee J., Scanga H.L., Dansingani K.K., Taubenslag K.J., Zlotcavitch L., RA Chauhan B.K., Sylvester C.L., Morton D.H., Nischal K.K.; RT "Clinical and imaging characteristics of posterior column ataxia with RT retinitis pigmentosa with a specific FLVCR1 mutation."; RL Ophthalmic Genet. 39:735-740(2018). RN [26] RP VARIANTS NEDMISH VAL-253; ARG-305; PRO-328; ILE-340; 363-TYR--ILE-555 DEL; RP 390-LEU--ILE-555 DEL; 400-GLN--ILE-555 DEL; PRO-409; ALA-412; ASN-421 AND RP SER-464, INVOLVEMENT IN NEDMISH, CHARACTERIZATION OF VARIANTS NEDMISH RP ARG-305; ILE-340; PRO-409; ALA-412; ASN-421 AND SER-464, VARIANTS RETSNS RP ASN-128 AND VAL-168, CHARACTERIZATION OF VARIANT RETSNS ASN-128, VARIANTS RP ARG-192; SER-249 AND THR-343, CHARACTERIZATION OF VARIANT THR-343, RP FUNCTION, AND MUTAGENESIS OF MET-151 AND LEU-443. RX PubMed=39306721; DOI=10.1016/j.gim.2024.101273; RA Calame D.G., Wong J.H., Panda P., Nguyen D.T., Leong N.C.P., Sangermano R., RA Patankar S.G., Abdel-Hamid M.S., AlAbdi L., Safwat S., Flannery K.P., RA Dardas Z., Fatih J.M., Murali C., Kannan V., Lotze T.E., Herman I., RA Ammouri F., Rezich B., Efthymiou S., Alavi S., Murphy D., Firoozfar Z., RA Nasab M.E., Bahreini A., Ghasemi M., Haridy N.A., Goldouzi H.R., Eghbal F., RA Karimiani E.G., Begtrup A., Elloumi H., Srinivasan V.M., Gowda V.K., Du H., RA Jhangiani S.N., Coban-Akdemir Z., Marafi D., Rodan L., Isikay S., RA Rosenfeld J.A., Ramanathan S., Staton M., Oberg K.C., Clark R.D., RA Wenman C., Loughlin S., Saad R., Ashraf T., Male A., Tadros S., RA Boostani R., Abdel-Salam G.M.H., Zaki M., Mardi A., Hashemi-Gorji F., RA Abdalla E., Manzini M.C., Pehlivan D., Posey J.E., Gibbs R.A., Houlden H., RA Alkuraya F.S., Bujakowska K., Maroofian R., Lupski J.R., Nguyen L.N.; RT "Biallelic variation in the choline and ethanolamine transporter FLVCR1 RT underlies a severe developmental disorder spectrum."; RL Genet. Med. 27:101273-101273(2025). CC -!- FUNCTION: Uniporter that mediates the transport of extracellular CC choline and ethanolamine into cells, thereby playing a key role in CC phospholipid biosynthesis (PubMed:37100056, PubMed:38693265, CC PubMed:38778100, PubMed:39306721). Choline and ethanolamine are the CC precursors of phosphatidylcholine and phosphatidylethanolamine, CC respectively, the two most abundant phospholipids (PubMed:38693265, CC PubMed:38778100). Transport is not coupled with proton transport and is CC exclusively driven by the choline (or ethanolamine) gradient across the CC plasma membrane (PubMed:38693265, PubMed:38778100). Also acts as a heme CC b transporter that mediates heme efflux from the cytoplasm to the CC extracellular compartment (PubMed:15369674, PubMed:20610401, CC PubMed:22483575, PubMed:23187127, PubMed:27923065). CC {ECO:0000269|PubMed:15369674, ECO:0000269|PubMed:20610401, CC ECO:0000269|PubMed:22483575, ECO:0000269|PubMed:23187127, CC ECO:0000269|PubMed:27923065, ECO:0000269|PubMed:37100056, CC ECO:0000269|PubMed:38693265, ECO:0000269|PubMed:38778100, CC ECO:0000269|PubMed:39306721}. CC -!- FUNCTION: [Isoform 1]: Uniporter that mediates the transport of CC extracellular choline and ethanolamine into cells (PubMed:37100056, CC PubMed:38693265). Choline and ethanolamine are the precursors of CC phosphatidylcholine and phosphatidylethanolamine, respectively, the two CC most abundant phospholipids (PubMed:38693265). Transport is not coupled CC with proton transport and is exclusively driven by the choline (or CC ethanolamine) gradient across the plasma membrane (PubMed:38693265). CC Also acts as a heme b transporter that mediates heme efflux from the CC cytoplasm to the extracellular compartment (PubMed:15369674, CC PubMed:20610401, PubMed:22483575, PubMed:23187127, PubMed:27923065). CC Heme export depends on the presence of HPX and is required to maintain CC intracellular free heme balance, protecting cells from heme toxicity CC (PubMed:20610401). Heme export provides protection from heme or ferrous CC iron toxicities in liver, brain, sensory neurons and during CC erythropoiesis, a process in which heme synthesis intensifies CC (PubMed:20610401, PubMed:23187127). Possibly export coproporphyrin and CC protoporphyrin IX, which are both intermediate products in the heme CC biosynthetic pathway (PubMed:20610401). Does not export bilirubin CC (PubMed:20610401). The molecular mechanism of heme transport, whether CC electrogenic, electroneutral or coupled to other ions, remains to be CC elucidated (PubMed:20610401, PubMed:23187127). CC {ECO:0000269|PubMed:15369674, ECO:0000269|PubMed:20610401, CC ECO:0000269|PubMed:22483575, ECO:0000269|PubMed:23187127, CC ECO:0000269|PubMed:27923065, ECO:0000269|PubMed:37100056, CC ECO:0000269|PubMed:38693265}. CC -!- FUNCTION: [Isoform 2]: Heme b transporter that promotes heme efflux CC from the mitochondrion to the cytoplasm. Essential for erythroid CC differentiation. {ECO:0000269|PubMed:23187127}. CC -!- FUNCTION: [Isoform 1]: (Microbial infection) Confers susceptibility to CC feline leukemia virus subgroup C (FeLV-C) infection in vitro. CC {ECO:0000269|PubMed:10400745}. CC -!- CATALYTIC ACTIVITY: CC Reaction=choline(out) = choline(in); Xref=Rhea:RHEA:32751, CC ChEBI:CHEBI:15354; Evidence={ECO:0000269|PubMed:37100056, CC ECO:0000269|PubMed:38693265, ECO:0000269|PubMed:38778100}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ethanolamine(in) = ethanolamine(out); Xref=Rhea:RHEA:32747, CC ChEBI:CHEBI:57603; Evidence={ECO:0000269|PubMed:38693265, CC ECO:0000269|PubMed:38778100}; CC -!- CATALYTIC ACTIVITY: CC Reaction=heme b(in) = heme b(out); Xref=Rhea:RHEA:75443, CC ChEBI:CHEBI:60344; Evidence={ECO:0000269|PubMed:15369674, CC ECO:0000269|PubMed:20610401}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: CC Reaction=choline(out) = choline(in); Xref=Rhea:RHEA:32751, CC ChEBI:CHEBI:15354; Evidence={ECO:0000269|PubMed:37100056, CC ECO:0000269|PubMed:38693265, ECO:0000269|PubMed:38778100}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: CC Reaction=ethanolamine(in) = ethanolamine(out); Xref=Rhea:RHEA:32747, CC ChEBI:CHEBI:57603; Evidence={ECO:0000269|PubMed:38693265, CC ECO:0000269|PubMed:38778100}; CC -!- CATALYTIC ACTIVITY: [Isoform 1]: CC Reaction=heme b(in) = heme b(out); Xref=Rhea:RHEA:75443, CC ChEBI:CHEBI:60344; Evidence={ECO:0000269|PubMed:15369674, CC ECO:0000269|PubMed:20610401}; CC -!- CATALYTIC ACTIVITY: [Isoform 2]: CC Reaction=heme b(in) = heme b(out); Xref=Rhea:RHEA:75443, CC ChEBI:CHEBI:60344; Evidence={ECO:0000305|PubMed:23187127}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=47.4 uM for choline {ECO:0000269|PubMed:38778100}; CC KM=8.0 uM for ethanolamine {ECO:0000269|PubMed:38778100}; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane CC {ECO:0000269|PubMed:15369674, ECO:0000269|PubMed:22483575, CC ECO:0000269|PubMed:37100056, ECO:0000269|PubMed:38778100}; Multi-pass CC membrane protein {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion membrane CC {ECO:0000269|PubMed:23187127}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=FLVCR1a {ECO:0000303|PubMed:23187127}; CC IsoId=Q9Y5Y0-1; Sequence=Displayed; CC Name=2; Synonyms=FLVCR1b, mitochondrial {ECO:0000303|PubMed:23187127}; CC IsoId=Q9Y5Y0-2; Sequence=VSP_047866; CC -!- TISSUE SPECIFICITY: Found all hematopoietic tissues including CC peripheral blood lymphocytes. Some expression is found in pancreas and CC kidney. {ECO:0000269|PubMed:10400745}. CC -!- DEVELOPMENTAL STAGE: [Isoform 1]: Down-regulated in haemopoietic CC progenitor cells undergoing differentiation and hemoglobinization. CC Abundant in fetal liver. {ECO:0000269|PubMed:15369674}. CC -!- PTM: N-Glycosylated. {ECO:0000269|PubMed:16439531}. CC -!- DISEASE: Retinopathy-sensory neuropathy syndrome (RETSNS) [MIM:609033]: CC An autosomal recessive neurodegenerative syndrome beginning in infancy CC with areflexia and retinitis pigmentosa. Nyctalopia (night blindness) CC and peripheral visual field loss are usually evident during late CC childhood or teenage years, with subsequent progressive constriction of CC the visual fields and loss of central retinal function over time. A CC sensory ataxia caused by degeneration of the posterior columns of the CC spinal cord results in a loss of proprioceptive sensation that is CC clinically evident in the second decade of life and gradually CC progresses. Scoliosis, camptodactyly, achalasia, gastrointestinal CC dysmotility, and a sensory peripheral neuropathy are variable features CC of the disease. Affected individuals have no clinical or radiological CC evidence of cerebral or cerebellar involvement. Some patients have pain CC insensitivity and commonly manifest self-injury, ulcers and CC amputations. {ECO:0000269|PubMed:21070897, ECO:0000269|PubMed:21267618, CC ECO:0000269|PubMed:22483575, ECO:0000269|PubMed:27923065, CC ECO:0000269|PubMed:28766925, ECO:0000269|PubMed:30444160, CC ECO:0000269|PubMed:39306721}. Note=The disease is caused by variants CC affecting the gene represented in this entry. Defective neuronal heme CC transmembrane export due to FLVCR1 mutations may abrogate the CC neuroprotective effects of neuroglobin and initiate an apoptotic CC cascade that results in the selective degeneration of photoreceptors in CC the neurosensory retina and sensory neurons in the posterior spinal CC cord. {ECO:0000269|PubMed:21070897}. CC -!- DISEASE: Neurodevelopmental disorder with microcephaly, absent speech, CC and hypotonia (NEDMISH) [MIM:621060]: A severe, autosomal recessive CC disorder characterized by profound global developmental delay, impaired CC intellectual development, absent speech, microcephaly, brain CC malformations, epilepsy, spasticity, and premature death. Brain CC malformations range from mild brain volume reduction to CC hydranencephaly. Additional features may include cortical visual CC impairment, sensory neuropathy, limb and digital malformations, and CC macrocytic anemia. {ECO:0000269|PubMed:39306721}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: Has a probable mitochondrial transit CC peptide at positions 1-38. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Feline CC leukemia virus subgroup C receptor (TC 2.A.1.28.1) family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF118637; AAD45243.1; -; mRNA. DR EMBL; AK001419; BAA91679.1; -; mRNA. DR EMBL; DQ496107; ABF47096.1; -; Genomic_DNA. DR EMBL; CH471100; EAW93374.1; -; Genomic_DNA. DR EMBL; BC048312; AAH48312.1; -; mRNA. DR CCDS; CCDS1510.1; -. [Q9Y5Y0-1] DR RefSeq; NP_054772.1; NM_014053.4. [Q9Y5Y0-1] DR PDB; 8QCS; EM; 2.90 A; A=1-555. DR PDB; 8QCT; EM; 2.60 A; A=1-555. DR PDB; 8R8T; EM; 2.90 A; A=1-555. DR PDB; 8UBW; EM; 2.59 A; A=1-555. DR PDB; 8UBX; EM; 2.50 A; A=1-555. DR PDB; 8UBY; EM; 2.67 A; A=1-555. DR PDB; 8UBZ; EM; 3.02 A; A=1-555. DR PDB; 8UC0; EM; 2.42 A; A=1-555. DR PDBsum; 8QCS; -. DR PDBsum; 8QCT; -. DR PDBsum; 8R8T; -. DR PDBsum; 8UBW; -. DR PDBsum; 8UBX; -. DR PDBsum; 8UBY; -. DR PDBsum; 8UBZ; -. DR PDBsum; 8UC0; -. DR AlphaFoldDB; Q9Y5Y0; -. DR EMDB; EMD-18334; -. DR EMDB; EMD-18335; -. DR EMDB; EMD-19009; -. DR EMDB; EMD-42107; -. DR EMDB; EMD-42108; -. DR EMDB; EMD-42109; -. DR EMDB; EMD-42110; -. DR EMDB; EMD-42111; -. DR SMR; Q9Y5Y0; -. DR BioGRID; 118803; 166. DR FunCoup; Q9Y5Y0; 1683. DR MINT; Q9Y5Y0; -. DR STRING; 9606.ENSP00000355938; -. DR TCDB; 2.A.1.28.1; the major facilitator superfamily (mfs). DR GlyCosmos; Q9Y5Y0; 2 sites, No reported glycans. DR GlyGen; Q9Y5Y0; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y5Y0; -. DR PhosphoSitePlus; Q9Y5Y0; -. DR SwissPalm; Q9Y5Y0; -. DR BioMuta; FLVCR1; -. DR DMDM; 46396053; -. DR jPOST; Q9Y5Y0; -. DR MassIVE; Q9Y5Y0; -. DR PaxDb; 9606-ENSP00000355938; -. DR PeptideAtlas; Q9Y5Y0; -. DR ProteomicsDB; 86537; -. [Q9Y5Y0-1] DR Pumba; Q9Y5Y0; -. DR Antibodypedia; 20720; 176 antibodies from 31 providers. DR DNASU; 28982; -. DR Ensembl; ENST00000366971.9; ENSP00000355938.4; ENSG00000162769.14. [Q9Y5Y0-1] DR GeneID; 28982; -. DR KEGG; hsa:28982; -. DR MANE-Select; ENST00000366971.9; ENSP00000355938.4; NM_014053.4; NP_054772.1. DR UCSC; uc001hjt.3; human. [Q9Y5Y0-1] DR AGR; HGNC:24682; -. DR ClinPGx; PA162388695; -. DR CTD; 28982; -. DR DisGeNET; 28982; -. DR GeneCards; FLVCR1; -. DR HGNC; HGNC:24682; FLVCR1. DR HPA; ENSG00000162769; Tissue enhanced (intestine). DR MalaCards; FLVCR1; -. DR MIM; 609033; phenotype. DR MIM; 609144; gene. DR MIM; 621060; phenotype. DR OpenTargets; ENSG00000162769; -. DR Orphanet; 88628; Posterior column ataxia-retinitis pigmentosa syndrome. DR VEuPathDB; HostDB:ENSG00000162769; -. DR eggNOG; KOG2563; Eukaryota. DR GeneTree; ENSGT01030000234625; -. DR InParanoid; Q9Y5Y0; -. DR OMA; LDLMGHN; -. DR OrthoDB; 422206at2759; -. DR PAN-GO; Q9Y5Y0; 6 GO annotations based on evolutionary models. DR PhylomeDB; Q9Y5Y0; -. DR PathwayCommons; Q9Y5Y0; -. DR Reactome; R-HSA-189451; Heme biosynthesis. DR Reactome; R-HSA-917937; Iron uptake and transport. [Q9Y5Y0-1] DR SignaLink; Q9Y5Y0; -. DR Agora; ENSG00000162769; -. DR BioGRID-ORCS; 28982; 32 hits in 1166 CRISPR screens. DR ChiTaRS; FLVCR1; human. DR GeneWiki; FLVCR1; -. DR GenomeRNAi; 28982; -. DR Pharos; Q9Y5Y0; Tbio. DR PRO; PR:Q9Y5Y0; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9Y5Y0; protein. DR Bgee; ENSG00000162769; Expressed in jejunal mucosa and 174 other cell types or tissues. DR ExpressionAtlas; Q9Y5Y0; baseline and differential. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0015220; F:choline transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0034228; F:ethanolamine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0020037; F:heme binding; IBA:GO_Central. DR GO; GO:0015232; F:heme transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0001568; P:blood vessel development; IEA:Ensembl. DR GO; GO:0015871; P:choline transport; IDA:UniProtKB. DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl. DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IEA:Ensembl. DR GO; GO:0030218; P:erythrocyte differentiation; IDA:MGI. DR GO; GO:0043249; P:erythrocyte maturation; IEA:UniProtKB-KW. DR GO; GO:0060323; P:head morphogenesis; IEA:Ensembl. DR GO; GO:0006783; P:heme biosynthetic process; TAS:Reactome. DR GO; GO:0097037; P:heme export; IMP:UniProtKB. DR GO; GO:0015886; P:heme transport; IMP:MGI. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0006879; P:intracellular iron ion homeostasis; TAS:Reactome. DR GO; GO:0006839; P:mitochondrial transport; IDA:MGI. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0008654; P:phospholipid biosynthetic process; IDA:UniProtKB. DR GO; GO:0046620; P:regulation of organ growth; IEA:Ensembl. DR GO; GO:0048536; P:spleen development; IEA:Ensembl. DR CDD; cd17455; MFS_FLVCR1; 1. DR FunFam; 1.20.1250.20:FF:000184; Feline leukemia virus subgroup C receptor-related protein 1; 1. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1. DR InterPro; IPR049680; FLVCR1-2_SLC49-like. DR InterPro; IPR011701; MFS. DR InterPro; IPR020846; MFS_dom. DR InterPro; IPR036259; MFS_trans_sf. DR PANTHER; PTHR10924:SF2; HEME TRANSPORTER FLVCR1; 1. DR PANTHER; PTHR10924; MAJOR FACILITATOR SUPERFAMILY PROTEIN-RELATED; 1. DR Pfam; PF07690; MFS_1; 1. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR PROSITE; PS50850; MFS; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Epilepsy; Erythrocyte maturation; Glycoprotein; Intellectual disability; KW Membrane; Mitochondrion; Neurodegeneration; Neuropathy; Phosphoprotein; KW Proteomics identification; Receptor; Reference proteome; KW Retinitis pigmentosa; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..555 FT /note="Choline/ethanolamine transporter FLVCR1" FT /id="PRO_0000084844" FT TOPO_DOM 1..99 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 100..124 FT /note="Helical; Name=TM1" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 125..142 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 143..170 FT /note="Helical; Name=TM2" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 171..172 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 173..192 FT /note="Helical; Name=TM3" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 193..199 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 200..228 FT /note="Helical; Name=TM4" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 229..233 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 234..259 FT /note="Helical; Name=TM5" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 260..265 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 266..295 FT /note="Helical; Name=TM6" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 296..331 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 332..362 FT /note="Helical; Name=TM7" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 363..366 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 367..395 FT /note="Helical; Name=TM8" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 396..397 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 398..420 FT /note="Helical; Name=TM9" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 421..423 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 424..453 FT /note="Helical; Name=TM10" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 454..461 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 462..487 FT /note="Helical; Name=TM11" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 488..489 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TRANSMEM 490..512 FT /note="Helical; Name=TM12" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT TOPO_DOM 513..555 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCS, FT ECO:0007744|PDB:8QCT, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBW, ECO:0007744|PDB:8UBX, FT ECO:0007744|PDB:8UBZ" FT REGION 1..52 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 535..555 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 214 FT /ligand="ethanolamine" FT /ligand_id="ChEBI:CHEBI:57603" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8R8T, FT ECO:0007744|PDB:8UBX" FT BINDING 471 FT /ligand="choline" FT /ligand_id="ChEBI:CHEBI:15354" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100, ECO:0007744|PDB:8QCT, FT ECO:0007744|PDB:8UBX, ECO:0007744|PDB:8UBZ" FT BINDING 471 FT /ligand="ethanolamine" FT /ligand_id="ChEBI:CHEBI:57603" FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0007744|PDB:8R8T, ECO:0007744|PDB:8UBX" FT MOD_RES 56 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 536 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CARBOHYD 265 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..276 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_047866" FT VARIANT 52 FT /note="A -> P (in dbSNP:rs11120047)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_050297" FT VARIANT 121 FT /note="N -> D (in RETSNS; likely pathogenic; abolished FT localization to the plasma membrane, leading to decreased FT heme exporter activity; dbSNP:rs267606820)" FT /evidence="ECO:0000269|PubMed:21070897, FT ECO:0000269|PubMed:22483575, ECO:0000269|PubMed:30444160" FT /id="VAR_065158" FT VARIANT 128 FT /note="Y -> N (in RETSNS; uncertain significance; decreased FT choline transmembrane transporter activity; decreased FT ethanolamine transmembrane transporter activity)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090360" FT VARIANT 168 FT /note="L -> V (in RETSNS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090361" FT VARIANT 192 FT /note="C -> R (in RETSNS; likely pathogenic; also found in FT a patient with mild developmental delay, hypotonia and FT sensory neuropathy without ocular clinical features; FT abolished localization to the plasma membrane, leading to FT decreased heme exporter activity; dbSNP:rs267606821)" FT /evidence="ECO:0000269|PubMed:21070897, FT ECO:0000269|PubMed:22483575, ECO:0000269|PubMed:27923065, FT ECO:0000269|PubMed:39306721" FT /id="VAR_065159" FT VARIANT 221 FT /note="P -> S (in RETSNS; uncertain significance; FT dbSNP:rs753000469)" FT /evidence="ECO:0000269|PubMed:27923065, FT ECO:0000269|PubMed:28766925" FT /id="VAR_077884" FT VARIANT 241 FT /note="A -> T (in RETSNS; likely pathogenic; abolished FT localization to the plasma membrane, leading to decreased FT heme exporter activity; dbSNP:rs267606819)" FT /evidence="ECO:0000269|PubMed:21070897, FT ECO:0000269|PubMed:22483575" FT /id="VAR_065160" FT VARIANT 249 FT /note="T -> S (found in a patient with a mild phenotype FT consisting of hypotonia and sensory and motor neuropathy; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090362" FT VARIANT 253 FT /note="F -> V (in NEDMISH; mild phenotype; uncertain FT significance)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090363" FT VARIANT 305 FT /note="S -> R (in NEDMISH; uncertain significance; FT decreased choline transmembrane transporter activity; FT severely decreased ethanolamine transmembrane transporter FT activity)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090364" FT VARIANT 328 FT /note="L -> P (in NEDMISH; uncertain significance; FT dbSNP:rs1664640662)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090365" FT VARIANT 340 FT /note="T -> I (in NEDMISH; uncertain significance; severely FT decreased choline and ethanolamine transmembrane FT transporter activity; dbSNP:rs754655924)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090366" FT VARIANT 343 FT /note="I -> T (found in patients with sensory neuropathy; FT uncertain significance; decreased choline and ethanolamine FT transmembrane transporter activity; dbSNP:rs774455543)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090367" FT VARIANT 363..555 FT /note="Missing (in NEDMISH; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090368" FT VARIANT 390..555 FT /note="Missing (in NEDMISH; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090369" FT VARIANT 400..555 FT /note="Missing (in NEDMISH; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090370" FT VARIANT 409 FT /note="S -> P (in NEDMISH; uncertain significance; FT decreased choline transmembrane transporter activity; FT severely decreased ethanolamine transmembrane transporter FT activity; dbSNP:rs2102568794)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090371" FT VARIANT 412 FT /note="G -> A (in NEDMISH; likely pathogenic; due to a FT nucleotide substitution that causes missplicing of exon 6 FT or results in missense variant A-412; loss of choline and FT ethanolamine transmembrane transporter activity; FT dbSNP:rs775587493)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090372" FT VARIANT 421 FT /note="D -> N (in NEDMISH; likely pathogenic; due to a FT nucleotide substitution that causes missplicing of exon 6 FT or results in missense variant N-421; missense variant N- FT 421 does not affect choline and ethanolamine transmembrane FT transporter activity; dbSNP:rs2102568834)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090373" FT VARIANT 464 FT /note="G -> S (in NEDMISH; uncertain significance; FT decreased choline and ethanolamine transmembrane FT transporter activity; dbSNP:rs1273394834)" FT /evidence="ECO:0000269|PubMed:39306721" FT /id="VAR_090374" FT VARIANT 493 FT /note="G -> R (in RETSNS; uncertain significance; abolished FT localization to the plasma membrane, leading to decreased FT heme exporter activity; dbSNP:rs1558121050)" FT /evidence="ECO:0000269|PubMed:21267618, FT ECO:0000269|PubMed:22483575" FT /id="VAR_065161" FT VARIANT 544 FT /note="T -> M (in dbSNP:rs3207090)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_050298" FT MUTAGEN 125 FT /note="W->A: Reduced transport of choline and FT ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100" FT MUTAGEN 151 FT /note="M->V: No effect on choline transmembrane transporter FT activity. No effect on ethanolamine transmembrane FT transporter activity." FT /evidence="ECO:0000269|PubMed:39306721" FT MUTAGEN 153 FT /note="Y->A: Reduced transport of choline and FT ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265" FT MUTAGEN 214 FT /note="Q->A: Reduced transport of choline and nearly FT abolished transport of ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100" FT MUTAGEN 245 FT /note="N->A: Slightly reduced transport of choline and FT ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100" FT MUTAGEN 349 FT /note="Y->A: Reduced transport of choline and FT ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100" FT MUTAGEN 443 FT /note="L->P: Decreased choline and ethanolamine FT transmembrane transporter activity." FT /evidence="ECO:0000269|PubMed:39306721" FT MUTAGEN 471 FT /note="Q->A: Slightly reduced transport of choline and FT ethanolamine." FT /evidence="ECO:0000269|PubMed:38693265, FT ECO:0000269|PubMed:38778100" FT HELIX 106..130 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 132..139 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 143..171 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 173..192 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 200..218 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 220..228 FT /evidence="ECO:0007829|PDB:8UC0" FT TURN 231..233 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 234..259 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 267..295 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 306..313 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 316..318 FT /evidence="ECO:0007829|PDB:8QCS" FT HELIX 321..330 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 332..362 FT /evidence="ECO:0007829|PDB:8UC0" FT STRAND 363..365 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 367..395 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 398..419 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 420..422 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 425..453 FT /evidence="ECO:0007829|PDB:8UC0" FT TURN 454..456 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 459..488 FT /evidence="ECO:0007829|PDB:8UC0" FT HELIX 490..510 FT /evidence="ECO:0007829|PDB:8UC0" SQ SEQUENCE 555 AA; 59863 MW; D0EBA9886CC8E747 CRC64; MARPDDEEGA AVAPGHPLAK GYLPLPRGAP VGKESVELQN GPKAGTFPVN GAPRDSLAAA SGVLGGPQTP LAPEEETQAR LLPAGAGAET PGAESSPLPL TALSPRRFVV LLIFSLYSLV NAFQWIQYSI ISNVFEGFYG VTLLHIDWLS MVYMLAYVPL IFPATWLLDT RGLRLTALLG SGLNCLGAWI KCGSVQQHLF WVTMLGQCLC SVAQVFILGL PSRIASVWFG PKEVSTACAT AVLGNQLGTA VGFLLPPVLV PNTQNDTNLL ACNISTMFYG TSAVATLLFI LTAIAFKEKP RYPPSQAQAA LQDSPPEEYS YKKSIRNLFK NIPFVLLLIT YGIMTGAFYS VSTLLNQMIL TYYEGEEVNA GRIGLTLVVA GMVGSILCGL WLDYTKTYKQ TTLIVYILSF IGMVIFTFTL DLRYIIIVFV TGGVLGFFMT GYLPLGFEFA VEITYPESEG TSSGLLNASA QIFGILFTLA QGKLTSDYGP KAGNIFLCVW MFIGIILTAL IKSDLRRHNI NIGITNVDVK AIPADSPTDQ EPKTVMLSKQ SESAI //