ID   SC5A7_MOUSE             Reviewed;         580 AA.
AC   Q8BGY9; Q99PK3; Q9ESW5;
DT   07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   27-MAR-2024, entry version 144.
DE   RecName: Full=High affinity choline transporter 1 {ECO:0000250|UniProtKB:Q9GZV3};
DE   AltName: Full=Hemicholinium-3-sensitive choline transporter {ECO:0000303|PubMed:11709061};
DE            Short=CHT {ECO:0000303|PubMed:11709061};
DE   AltName: Full=Solute carrier family 5 member 7 {ECO:0000250|UniProtKB:Q9GZV3};
GN   Name=Slc5a7 {ECO:0000312|MGI:MGI:1927126}; Synonyms=Cht1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY
RP   REGULATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Spinal cord;
RX   PubMed=11709061; DOI=10.1042/0300-5127:0290711;
RA   Apparsundaram S., Ferguson S.M., Blakely R.D.;
RT   "Molecular cloning and characterization of a murine hemicholinium-3-
RT   sensitive choline transporter.";
RL   Biochem. Soc. Trans. 29:711-716(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ; TISSUE=Brain stem;
RA   Wieland A., Bonisch H., Bruess M.;
RT   "Molecular cloning of the human and murine high affinity choline
RT   transporters and characterization of the human gene structure.";
RL   Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Diencephalon, and Embryonic head;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Embryonic brain;
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   [5]
RP   PHOSPHORYLATION BY PKC.
RC   TISSUE=Corpus striatum, and Hippocampus;
RX   PubMed=15064333; DOI=10.1124/jpet.104.066795;
RA   Gates J. Jr., Ferguson S.M., Blakely R.D., Apparsundaram S.;
RT   "Regulation of choline transporter surface expression and phosphorylation
RT   by protein kinase C and protein phosphatase 1/2A.";
RL   J. Pharmacol. Exp. Ther. 310:536-545(2004).
RN   [6]
RP   FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP   AND DISRUPTION PHENOTYPE.
RX   PubMed=15173594; DOI=10.1073/pnas.0401667101;
RA   Ferguson S.M., Bazalakova M., Savchenko V., Tapia J.C., Wright J.,
RA   Blakely R.D.;
RT   "Lethal impairment of cholinergic neurotransmission in hemicholinium-3-
RT   sensitive choline transporter knockout mice.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:8762-8767(2004).
CC   -!- FUNCTION: High-affinity Na(+)-coupled choline transmembrane symporter
CC       (PubMed:11709061, PubMed:15173594). Functions as an electrogenic,
CC       voltage-dependent transporter with variable charge/choline
CC       stoichiometry (By similarity). Choline uptake and choline-induced
CC       current is also Cl(-)-dependent where Cl(-) is likely a regulatory ion
CC       rather than cotransported ion (By similarity). Plays a critical role in
CC       acetylcholine (ACh) synthesis by taking up the substrate choline from
CC       the synaptic cleft into the presynaptic nerve terminals after
CC       neurotransmitter release (By similarity). SLC5A7/CHT1-mediated choline
CC       high-affinity transport in cholinergic neurons is the rate-limiting
CC       step for production of ACh, thereby facilitating communication by
CC       subsequent action potentials (PubMed:11709061, PubMed:15173594).
CC       Localized predominantly in presynaptic terminal intracellular
CC       organelles, and translocated to the plasma membrane in active form in
CC       response to neuronal activity (By similarity).
CC       {ECO:0000250|UniProtKB:Q9GZV3, ECO:0000269|PubMed:11709061,
CC       ECO:0000269|PubMed:15173594}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=choline(out) + n Na(+)(out) = choline(in) + n Na(+)(in);
CC         Xref=Rhea:RHEA:76443, ChEBI:CHEBI:15354, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:11709061, ECO:0000269|PubMed:15173594};
CC   -!- ACTIVITY REGULATION: Choline uptake activity is regulated by
CC       SLC5A7/CHT1 internalization (inactive form) from the cell surface and
CC       recycling of internalized SLC5A7/CHT1 into the cell surface (active
CC       form) (By similarity). Activated by extracellular chloride ion (By
CC       similarity). Specifically inhibited by nanomolar concentrations of
CC       hemicholinium 3 (PubMed:11709061, PubMed:15173594).
CC       {ECO:0000250|UniProtKB:Q9GZV3, ECO:0000269|PubMed:11709061,
CC       ECO:0000269|PubMed:15173594}.
CC   -!- SUBUNIT: Homooligomerizes at cell surface. Interacts with SEC14L1; may
CC       regulate SLC5A7. {ECO:0000250|UniProtKB:Q9GZV3}.
CC   -!- INTERACTION:
CC       Q8BGY9; P05067: APP; Xeno; NbExp=2; IntAct=EBI-2010752, EBI-77613;
CC   -!- SUBCELLULAR LOCATION: Presynaptic cell membrane
CC       {ECO:0000269|PubMed:15173594}; Multi-pass membrane protein
CC       {ECO:0000305}. Cell projection, axon {ECO:0000269|PubMed:15173594}.
CC       Early endosome membrane {ECO:0000250|UniProtKB:Q9GZV3}; Multi-pass
CC       membrane protein {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle,
CC       synaptic vesicle membrane {ECO:0000250|UniProtKB:Q9GZV3}; Multi-pass
CC       membrane protein {ECO:0000305}. Note=Localized to motor neuron axons.
CC       {ECO:0000269|PubMed:15173594}.
CC   -!- TISSUE SPECIFICITY: Found in spinal cord, brain-stem, mid-brain and
CC       striatum (PubMed:11709061). Specific for cholinergic neurons
CC       (PubMed:11709061). {ECO:0000269|PubMed:11709061}.
CC   -!- DOMAIN: The C-terminal dileucine-like motif (DKTILV) controls
CC       SLC5A7/CHT1 internalization in clathrin-coated vesicles to early
CC       endosomes as well as choline transporter activity.
CC       {ECO:0000250|UniProtKB:Q9GZV3}.
CC   -!- PTM: Phosphorylated by PKC and dephosphorylated by PP1/PP2A.
CC       {ECO:0000269|PubMed:15064333}.
CC   -!- DISRUPTION PHENOTYPE: Although morphologically normal at birth,
CC       knockout mice become immobile, breathe irregularly, appear cyanotic,
CC       and die within an hour. Mice had developmental changes in neuromuscular
CC       junction morphology reminiscent of changes in mutant mice lacking ACh
CC       synthesis. {ECO:0000269|PubMed:15173594}.
CC   -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC       family. {ECO:0000305}.
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DR   EMBL; AF276872; AAG36945.2; -; mRNA.
DR   EMBL; AJ401467; CAC03719.1; -; mRNA.
DR   EMBL; AK034415; BAC28702.1; -; mRNA.
DR   EMBL; AK053063; BAC35253.1; -; mRNA.
DR   EMBL; BC065089; AAH65089.1; -; mRNA.
DR   CCDS; CCDS28885.1; -.
DR   RefSeq; NP_071308.2; NM_022025.4.
DR   RefSeq; XP_006524837.1; XM_006524774.3.
DR   RefSeq; XP_006524838.1; XM_006524775.2.
DR   AlphaFoldDB; Q8BGY9; -.
DR   SMR; Q8BGY9; -.
DR   DIP; DIP-46467N; -.
DR   IntAct; Q8BGY9; 3.
DR   STRING; 10090.ENSMUSP00000093379; -.
DR   BindingDB; Q8BGY9; -.
DR   ChEMBL; CHEMBL3013; -.
DR   DrugCentral; Q8BGY9; -.
DR   GlyCosmos; Q8BGY9; 1 site, No reported glycans.
DR   GlyGen; Q8BGY9; 1 site.
DR   iPTMnet; Q8BGY9; -.
DR   PhosphoSitePlus; Q8BGY9; -.
DR   PaxDb; 10090-ENSMUSP00000093379; -.
DR   ProteomicsDB; 255468; -.
DR   Antibodypedia; 33052; 97 antibodies from 22 providers.
DR   DNASU; 63993; -.
DR   Ensembl; ENSMUST00000095712.5; ENSMUSP00000093379.4; ENSMUSG00000023945.8.
DR   GeneID; 63993; -.
DR   KEGG; mmu:63993; -.
DR   UCSC; uc008czy.1; mouse.
DR   AGR; MGI:1927126; -.
DR   CTD; 60482; -.
DR   MGI; MGI:1927126; Slc5a7.
DR   VEuPathDB; HostDB:ENSMUSG00000023945; -.
DR   eggNOG; KOG3761; Eukaryota.
DR   GeneTree; ENSGT00690000101915; -.
DR   HOGENOM; CLU_018808_10_0_1; -.
DR   InParanoid; Q8BGY9; -.
DR   OMA; WKTKNTG; -.
DR   OrthoDB; 3680931at2759; -.
DR   PhylomeDB; Q8BGY9; -.
DR   TreeFam; TF314588; -.
DR   Reactome; R-MMU-264642; Acetylcholine Neurotransmitter Release Cycle.
DR   Reactome; R-MMU-425366; Transport of bile salts and organic acids, metal ions and amine compounds.
DR   BioGRID-ORCS; 63993; 1 hit in 76 CRISPR screens.
DR   ChiTaRS; Slc5a7; mouse.
DR   PRO; PR:Q8BGY9; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   RNAct; Q8BGY9; Protein.
DR   Bgee; ENSMUSG00000023945; Expressed in lumbar subsegment of spinal cord and 41 other cell types or tissues.
DR   ExpressionAtlas; Q8BGY9; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR   GO; GO:0030424; C:axon; ISO:MGI.
DR   GO; GO:0045334; C:clathrin-coated endocytic vesicle; ISO:MGI.
DR   GO; GO:0030425; C:dendrite; ISO:MGI.
DR   GO; GO:0005769; C:early endosome; ISO:MGI.
DR   GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISO:MGI.
DR   GO; GO:0031594; C:neuromuscular junction; ISO:MGI.
DR   GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR   GO; GO:0043204; C:perikaryon; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0044853; C:plasma membrane raft; ISO:MGI.
DR   GO; GO:0042734; C:presynaptic membrane; IMP:UniProtKB.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR   GO; GO:0030672; C:synaptic vesicle membrane; ISS:UniProtKB.
DR   GO; GO:0033265; F:choline binding; IDA:MGI.
DR   GO; GO:0015220; F:choline transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0005307; F:choline:sodium symporter activity; ISS:UniProtKB.
DR   GO; GO:0008292; P:acetylcholine biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0015871; P:choline transport; IDA:UniProtKB.
DR   GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR   GO; GO:0007274; P:neuromuscular synaptic transmission; IMP:MGI.
DR   GO; GO:0007271; P:synaptic transmission, cholinergic; IMP:MGI.
DR   CDD; cd11474; SLC5sbd_CHT; 1.
DR   Gene3D; 1.20.1730.10; Sodium/glucose cotransporter; 1.
DR   InterPro; IPR038377; Na/Glc_symporter_sf.
DR   InterPro; IPR001734; Na/solute_symporter.
DR   PANTHER; PTHR45897:SF2; HIGH AFFINITY CHOLINE TRANSPORTER 1; 1.
DR   PANTHER; PTHR45897; HIGH-AFFINITY CHOLINE TRANSPORTER 1; 1.
DR   Pfam; PF00474; SSF; 1.
DR   PROSITE; PS50283; NA_SOLUT_SYMP_3; 1.
DR   Genevisible; Q8BGY9; MM.
PE   1: Evidence at protein level;
KW   Cell membrane; Cell projection; Cytoplasmic vesicle; Endosome;
KW   Glycoprotein; Ion transport; Membrane; Neurotransmitter biosynthesis;
KW   Phosphoprotein; Reference proteome; Sodium; Sodium transport; Symport;
KW   Synapse; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..580
FT                   /note="High affinity choline transporter 1"
FT                   /id="PRO_0000105392"
FT   TOPO_DOM        1..6
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        7..27
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        28..48
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        49..69
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        70..81
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        82..102
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        103..125
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        126..146
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        147..164
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        165..185
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        186..191
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        192..212
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        213..237
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        238..258
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        259..274
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        275..295
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        296..317
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        318..338
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        339..376
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        377..397
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        398..406
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        407..427
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        428..435
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        436..456
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        457..481
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        482..502
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        503..580
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          502..580
FT                   /note="Mediates interaction with SEC14L1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JMD7"
FT   MOTIF           527..532
FT                   /note="Dileucine-like motif"
FT                   /evidence="ECO:0000250|UniProtKB:Q9GZV3"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        2
FT                   /note="S -> P (in Ref. 1; AAG36945)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        38
FT                   /note="R -> H (in Ref. 2; CAC03719)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        73
FT                   /note="E -> V (in Ref. 2; CAC03719)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        86
FT                   /note="Q -> H (in Ref. 1; AAG36945)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        119
FT                   /note="Q -> K (in Ref. 1; AAG36945)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        275
FT                   /note="F -> Y (in Ref. 2; CAC03719)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   580 AA;  63365 MW;  6154CE6622772A41 CRC64;
     MSFHVEGLVA IILFYLLIFL VGIWAAWKTK NSGNPEERSE AIIVGGRDIG LLVGGFTMTA
     TWVGGGYING TAEAVYGPGC GLAWAQAPIG YSLSLILGGL FFAKPMRSKG YVTMLDPFQQ
     IYGKRMGGLL FIPALMGEMF WAAAIFSALG ATISVIIDVD VNISVIVSAL IAILYTLVGG
     LYSVAYTDVV QLFCIFIGLW ISVPFALSHP AVTDIGFTAV HAKYQSPWLG TIESVEVYTW
     LDNFLLLMLG GIPWQAYFQR VLSSSSATYA QVLSFLAAFG CLVMALPAIC IGAIGASTDW
     NQTAYGYPDP KTKEEADMIL PIVLQYLCPV YISFFGLGAV SAAVMSSADS SILSASSMFA
     RNIYQLSFRQ NASDKEIVWV MRITVLVFGA SATAMALLTK TVYGLWYLSS DLVYIIIFPQ
     LLCVLFIKGT NTYGAVAGYI FGLFLRITGG EPYLYLQPLI FYPGYYSDKN GIYNQRFPFK
     TLSMVTSFFT NICVSYLAKY LFESGTLPPK LDVFDAVVAR HSEENMDKTI LVRNENIKLN
     ELAPVKPRQS LTLSSTFTNK EALLDVDSSP EGSGTEDNLQ
//