ID   SC6A8_MOUSE             Reviewed;         635 AA.
AC   Q8VBW1; A2ALM4; Q80YC9; Q8K4R3; Q8R1L0;
DT   07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   12-OCT-2022, sequence version 2.
DT   27-MAR-2024, entry version 149.
DE   RecName: Full=Sodium- and chloride-dependent creatine transporter 1;
DE            Short=CT1;
DE            Short=Creatine transporter 1;
DE   AltName: Full=Solute carrier family 6 member 8;
GN   Name=Slc6a8; Synonyms=Crt;
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] (ISOFORM 2), FUNCTION, TRANSPORTER ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND GLYCOSYLATION.
RX   PubMed=12439290; DOI=10.1097/01.wcb.0000033966.83623.7d;
RA   Ohtsuki S., Tachikawa M., Takanaga H., Shimizu H., Watanabe M., Hosoya K.,
RA   Terasaki T.;
RT   "The blood-brain barrier creatine transporter is a major pathway for
RT   supplying creatine to the brain.";
RL   J. Cereb. Blood Flow Metab. 22:1327-1335(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE (ISOFORM 1).
RA   Liu Q.-R., Li Q.-F.;
RT   "Cloning and expression of mouse creatine transporter gene.";
RL   Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 58-635 (ISOFORMS 2 AND 3).
RC   STRAIN=FVB/N; TISSUE=Embryo, and Kidney;
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 [LARGE SCALE ANALYSIS] AT THR-620 AND SER-623, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Creatine:sodium symporter which mediates the uptake of
CC       creatine (PubMed:12439290). Plays an important role in supplying
CC       creatine to the brain via the blood-brain barrier (PubMed:12439290).
CC       {ECO:0000269|PubMed:12439290}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(out) + creatine(out) + 2 Na(+)(out) = chloride(in) +
CC         creatine(in) + 2 Na(+)(in); Xref=Rhea:RHEA:71831, ChEBI:CHEBI:17996,
CC         ChEBI:CHEBI:29101, ChEBI:CHEBI:57947;
CC         Evidence={ECO:0000269|PubMed:12439290};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=16.2 uM for creatine {ECO:0000269|PubMed:12439290};
CC         Vmax=0.1 nmol/min/mg enzyme for creatine
CC         {ECO:0000269|PubMed:12439290};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P48029};
CC       Multi-pass membrane protein {ECO:0000255}. Apical cell membrane
CC       {ECO:0000250|UniProtKB:P48029}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=2;
CC         IsoId=Q8VBW1-2; Sequence=Displayed;
CC       Name=1;
CC         IsoId=Q8VBW1-1; Sequence=VSP_061626;
CC       Name=3;
CC         IsoId=Q8VBW1-3; Sequence=VSP_061625;
CC   -!- TISSUE SPECIFICITY: Brain. Highly expressed in brain capillaries
CC       branching in all cortical layers and moderately expressed in neuronal
CC       perikarya (at protein level). {ECO:0000269|PubMed:12439290}.
CC   -!- PTM: Glycosylated. {ECO:0000269|PubMed:12439290}.
CC   -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF)
CC       (TC 2.A.22) family. SLC6A8 subfamily. {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; AB077327; BAC11857.1; -; mRNA.
DR   EMBL; AF459435; AAL66354.1; -; mRNA.
DR   EMBL; AF459436; AAL66355.1; -; Genomic_DNA.
DR   EMBL; AL805924; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC024444; AAH24444.1; -; mRNA.
DR   EMBL; BC049801; AAH49801.1; -; mRNA.
DR   CCDS; CCDS30208.1; -. [Q8VBW1-1]
DR   CCDS; CCDS53098.1; -. [Q8VBW1-2]
DR   RefSeq; NP_001136281.1; NM_001142809.1. [Q8VBW1-2]
DR   RefSeq; NP_001136282.1; NM_001142810.1. [Q8VBW1-3]
DR   RefSeq; NP_598748.1; NM_133987.2. [Q8VBW1-1]
DR   AlphaFoldDB; Q8VBW1; -.
DR   SMR; Q8VBW1; -.
DR   BioGRID; 221964; 6.
DR   IntAct; Q8VBW1; 6.
DR   STRING; 10090.ENSMUSP00000033752; -.
DR   GlyCosmos; Q8VBW1; 3 sites, No reported glycans.
DR   GlyGen; Q8VBW1; 4 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8VBW1; -.
DR   PhosphoSitePlus; Q8VBW1; -.
DR   jPOST; Q8VBW1; -.
DR   MaxQB; Q8VBW1; -.
DR   PaxDb; 10090-ENSMUSP00000033752; -.
DR   ProteomicsDB; 255475; -. [Q8VBW1-1]
DR   ProteomicsDB; 255476; -. [Q8VBW1-2]
DR   ProteomicsDB; 255477; -. [Q8VBW1-3]
DR   Pumba; Q8VBW1; -.
DR   DNASU; 102857; -.
DR   Ensembl; ENSMUST00000033752.14; ENSMUSP00000033752.8; ENSMUSG00000019558.15. [Q8VBW1-1]
DR   Ensembl; ENSMUST00000114465.9; ENSMUSP00000110109.3; ENSMUSG00000019558.15. [Q8VBW1-2]
DR   Ensembl; ENSMUST00000114467.9; ENSMUSP00000110111.3; ENSMUSG00000019558.15. [Q8VBW1-2]
DR   GeneID; 102857; -.
DR   KEGG; mmu:102857; -.
DR   UCSC; uc009tmf.2; mouse. [Q8VBW1-2]
DR   UCSC; uc009tmg.2; mouse. [Q8VBW1-3]
DR   AGR; MGI:2147834; -.
DR   CTD; 6535; -.
DR   MGI; MGI:2147834; Slc6a8.
DR   VEuPathDB; HostDB:ENSMUSG00000019558; -.
DR   eggNOG; KOG3660; Eukaryota.
DR   GeneTree; ENSGT00940000155869; -.
DR   InParanoid; Q8VBW1; -.
DR   OMA; CVEIFRQ; -.
DR   OrthoDB; 3084493at2759; -.
DR   PhylomeDB; Q8VBW1; -.
DR   TreeFam; TF343812; -.
DR   Reactome; R-MMU-71288; Creatine metabolism.
DR   BioGRID-ORCS; 102857; 2 hits in 79 CRISPR screens.
DR   ChiTaRS; Slc6a8; mouse.
DR   PRO; PR:Q8VBW1; -.
DR   Proteomes; UP000000589; Chromosome X.
DR   RNAct; Q8VBW1; Protein.
DR   Bgee; ENSMUSG00000019558; Expressed in small intestine Peyer's patch and 257 other cell types or tissues.
DR   ExpressionAtlas; Q8VBW1; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0045211; C:postsynaptic membrane; ISO:MGI.
DR   GO; GO:0045202; C:synapse; ISO:MGI.
DR   GO; GO:0015220; F:choline transmembrane transporter activity; ISO:MGI.
DR   GO; GO:0005308; F:creatine transmembrane transporter activity; ISO:MGI.
DR   GO; GO:0005309; F:creatine:sodium symporter activity; IDA:UniProtKB.
DR   GO; GO:0005332; F:gamma-aminobutyric acid:sodium:chloride symporter activity; IBA:GO_Central.
DR   GO; GO:0015881; P:creatine transmembrane transport; ISS:UniProtKB.
DR   GO; GO:0006836; P:neurotransmitter transport; IEA:InterPro.
DR   GO; GO:0071705; P:nitrogen compound transport; ISO:MGI.
DR   GO; GO:0030163; P:protein catabolic process; ISO:MGI.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR   CDD; cd11509; SLC6sbd_CT1; 1.
DR   InterPro; IPR000175; Na/ntran_symport.
DR   InterPro; IPR002984; Na/ntran_symport_creatine.
DR   InterPro; IPR037272; SNS_sf.
DR   PANTHER; PTHR11616:SF96; SODIUM- AND CHLORIDE-DEPENDENT CREATINE TRANSPORTER 1; 1.
DR   PANTHER; PTHR11616; SODIUM/CHLORIDE DEPENDENT TRANSPORTER; 1.
DR   Pfam; PF00209; SNF; 1.
DR   PRINTS; PR01199; CRTTRANSPORT.
DR   PRINTS; PR00176; NANEUSMPORT.
DR   SUPFAM; SSF161070; SNF-like; 1.
DR   PROSITE; PS00610; NA_NEUROTRAN_SYMP_1; 1.
DR   PROSITE; PS00754; NA_NEUROTRAN_SYMP_2; 1.
DR   PROSITE; PS50267; NA_NEUROTRAN_SYMP_3; 1.
DR   Genevisible; Q8VBW1; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Glycoprotein; Ion transport; Membrane;
KW   Phosphoprotein; Reference proteome; Sodium; Sodium transport; Symport;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..635
FT                   /note="Sodium- and chloride-dependent creatine transporter
FT                   1"
FT                   /id="PRO_0000214775"
FT   TOPO_DOM        1..60
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        61..81
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        82..87
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        88..108
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        109..138
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        139..159
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        160..230
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        231..251
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        252..269
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        270..290
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        291..304
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        305..325
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        326..341
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        342..362
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        363..394
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        395..415
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        416..444
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        445..465
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        466..479
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        480..500
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        501..520
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        521..541
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        542..560
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        561..581
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        582..635
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..27
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         617
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P48029"
FT   MOD_RES         620
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         623
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   CARBOHYD        192
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        548
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         462..464
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_061625"
FT   VAR_SEQ         464
FT                   /note="D -> DVSGGK (in isoform 1)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_061626"
SQ   SEQUENCE   635 AA;  70571 MW;  FE76B1A95D2F2149 CRC64;
     MAKKSAENGI YSVSGDEKKG PLIVSGPDGA PAKGDGPAGL GAPGGRLAVP PRETWTRQMD
     FIMSCVGFAV GLGNVWRFPY LCYKNGGGVF LIPYVLIALV GGIPIFFLEI SLGQFMKAGS
     INVWNICPLF KGLGYASMVI VFYCNTYYIM VLAWGFYYLV KSFTTTLPWA TCGHTWNTPD
     CVEIFRHEDC ANASLANLTC DQLADRRSPV IEFWENKVLR LSTGLEVPGA LNWEVTLCLL
     ACWVLVYFCV WKGVKSTGKI VYFTATFPYV VLVVLLVRGV LLPGALDGII YYLKPDWSKL
     GSPQVWIDAG TQIFFSYAIG LGALTALGSY NRFNNNCYKD AIILALINSG TSFFAGFVVF
     SILGFMATEQ GVHISKVAES GPGLAFIAYP RAVTLMPVAP LWAALFFFML LLLGLDSQFV
     GVEGFITGLL DLLPASYYFR FQREISVALC CALCFVIDLS MVTDGGMYVF QLFDYYSASG
     TTLLWQAFWE CVVVAWVYGA DRFMDDIACM IGYRPCPWMK WCWSFFTPLV CMGIFIFNIV
     YYEPLVYNNT YVYPWWGEAM GWAFALSSML CVPLHLLGCL LRAKGTMAER WQHLTQPIWG
     LHHLEYRAQD ADVRGLTTLT PVSESSKVVV VESVM
//