SC6A8_HUMAN
ID SC6A8_HUMAN Reviewed; 635 AA.
AC P48029; B2KY47; B4DIA3; E9PFC0; Q13032; Q66I36;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 196.
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;
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), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=7953292;
RA Nash S.R., Giros B., Kingsmore S.F., Rochelle J.M., Suter S.T., Gregor P.,
RA Seldin M.F., Caron M.G.;
RT "Cloning, pharmacological characterization, and genomic localization of the
RT human creatine transporter.";
RL Recept. Channels 2:165-174(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=7945388; DOI=10.1006/bbrc.1994.2475;
RA Sora I., Richman J., Santoro G., Wei H., Wang Y., Vanderah T., Horvath R.,
RA Nguyen M., Waite S., Roeske W.R.;
RT "The cloning and expression of a human creatine transporter.";
RL Biochem. Biophys. Res. Commun. 204:419-427(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8661155; DOI=10.1006/geno.1996.0373;
RA Sandoval N., Bauer D., Brenner V., Coy J.F., Drescher B., Kioschis P.,
RA Korn B., Nyakatura G., Poustka A., Reichwald K., Rosenthal A., Platzer M.;
RT "The genomic organization of a human creatine transporter (CRTR) gene
RT located in Xq28.";
RL Genomics 35:383-385(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Hippocampus;
RX PubMed=7622069; DOI=10.1016/0378-1119(95)00104-e;
RA Barnwell L.F., Chaudhuri G., Townsel J.G.;
RT "Cloning and sequencing of a cDNA encoding a novel member of the human
RT brain GABA/noradrenaline neurotransmitter transporter family.";
RL Gene 159:287-288(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=18515020; DOI=10.1016/j.gene.2008.04.003;
RA Martinez-Munoz C., Rosenberg E.H., Jakobs C., Salomons G.S.;
RT "Identification, characterization and cloning of SLC6A8C, a novel splice
RT variant of the creatine transporter gene.";
RL Gene 418:53-59(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Eichler E.E., Lu F., Shen Y., Muzny D.M., Gibbs R.A., Nelson D.L.;
RT "Genomic organization of the human creatine transporter and CDM genes.";
RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Hippocampus;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye, and Testis;
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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-42, AND IDENTIFICATION BY
RP 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-42; THR-617 AND THR-620, AND
RP IDENTIFICATION BY 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 [13]
RP VARIANT CCDS1 ARG-381.
RX PubMed=11898126; DOI=10.1086/340092;
RA Hahn K.A., Salomons G.S., Tackels-Horne D., Wood T.C., Taylor H.A.,
RA Schroer R.J., Lubs H.A., Jakobs C., Olson R.L., Holden K.R.,
RA Stevenson R.E., Schwartz C.E.;
RT "X-linked mental retardation with seizures and carrier manifestations is
RT caused by a mutation in the creatine-transporter gene (SLC6A8) located in
RT Xq28.";
RL Am. J. Hum. Genet. 70:1349-1356(2002).
RN [14]
RP VARIANT CCDS1 PHE-408 DEL.
RX PubMed=12210795; DOI=10.1002/ana.10246;
RA Bizzi A., Bugiani M., Salomons G.S., Hunneman D.H., Moroni I., Estienne M.,
RA Danesi U., Jakobs C., Uziel G.;
RT "X-linked creatine deficiency syndrome: a novel mutation in creatine
RT transporter gene SLC6A8.";
RL Ann. Neurol. 52:227-231(2002).
RN [15]
RP VARIANTS CCDS1 ARG-87; TRP-337; LEU-390 AND LEU-554, AND VARIANT VAL-560.
RX PubMed=15154114; DOI=10.1086/422102;
RA Rosenberg E.H., Almeida L.S., Kleefstra T., deGrauw R.S., Yntema H.G.,
RA Bahi N., Moraine C., Ropers H.-H., Fryns J.-P., deGrauw T.J., Jakobs C.,
RA Salomons G.S.;
RT "High prevalence of SLC6A8 deficiency in X-linked mental retardation.";
RL Am. J. Hum. Genet. 75:97-105(2004).
RN [16]
RP VARIANTS CCDS1 VAL-132 AND TRP-491.
RX PubMed=17101918; DOI=10.1212/01.wnl.0000239153.39710.81;
RA Lion-Francois L., Cheillan D., Pitelet G., Acquaviva-Bourdain C., Bussy G.,
RA Cotton F., Guibaud L., Gerard D., Rivier C., Vianey-Saban C., Jakobs C.,
RA Salomons G.S., des Portes V.;
RT "High frequency of creatine deficiency syndromes in patients with
RT unexplained mental retardation.";
RL Neurology 67:1713-1714(2006).
RN [17]
RP VARIANTS CCDS1 ARG-87; PHE-107 DEL; ASN-336 DEL; TRP-337; ILE-347 DEL;
RP LEU-390; TRP-391 AND LEU-554, VARIANTS ARG-4; ARG-26; VAL-560 AND ILE-629,
RP CHARACTERIZATION OF VARIANTS CCDS1 ARG-87; PHE-107 DEL; ASN-336 DEL;
RP TRP-337; ILE-347 DEL; LEU-390 AND TRP-391, AND CHARACTERIZATION OF VARIANTS
RP ARG-4; ARG-26; VAL-560 AND ILE-629.
RX PubMed=17465020; DOI=10.1002/humu.20532;
RA Rosenberg E.H., Martinez Munoz C., Betsalel O.T., van Dooren S.J.,
RA Fernandez M., Jakobs C., deGrauw T.J., Kleefstra T., Schwartz C.E.,
RA Salomons G.S.;
RT "Functional characterization of missense variants in the creatine
RT transporter gene (SLC6A8): improved diagnostic application.";
RL Hum. Mutat. 28:890-896(2007).
RN [18]
RP VARIANT CCDS1 ASN-336 DEL.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
RN [19]
RP VARIANT SER-550.
RX PubMed=23092983; DOI=10.1038/tp.2012.102;
RA Nava C., Lamari F., Heron D., Mignot C., Rastetter A., Keren B., Cohen D.,
RA Faudet A., Bouteiller D., Gilleron M., Jacquette A., Whalen S., Afenjar A.,
RA Perisse D., Laurent C., Dupuits C., Gautier C., Gerard M., Huguet G.,
RA Caillet S., Leheup B., Leboyer M., Gillberg C., Delorme R., Bourgeron T.,
RA Brice A., Depienne C.;
RT "Analysis of the chromosome X exome in patients with autism spectrum
RT disorders identified novel candidate genes, including TMLHE.";
RL Transl. Psychiatry 2:E179-E179(2012).
RN [20]
RP VARIANT CCDS1 ASN-336 DEL.
RX PubMed=24123876; DOI=10.1136/jmedgenet-2013-101644;
RA Schuurs-Hoeijmakers J.H., Vulto-van Silfhout A.T., Vissers L.E.,
RA van de Vondervoort I.I., van Bon B.W., de Ligt J., Gilissen C.,
RA Hehir-Kwa J.Y., Neveling K., del Rosario M., Hira G., Reitano S.,
RA Vitello A., Failla P., Greco D., Fichera M., Galesi O., Kleefstra T.,
RA Greally M.T., Ockeloen C.W., Willemsen M.H., Bongers E.M., Janssen I.M.,
RA Pfundt R., Veltman J.A., Romano C., Willemsen M.A., van Bokhoven H.,
RA Brunner H.G., de Vries B.B., de Brouwer A.P.;
RT "Identification of pathogenic gene variants in small families with
RT intellectually disabled siblings by exome sequencing.";
RL J. Med. Genet. 50:802-811(2013).
RN [21]
RP VARIANTS CCDS1 HIS-80; CYS-383; ASP-448 AND ILE-539.
RX PubMed=23660394; DOI=10.1016/j.ymgme.2013.04.006;
RA Comeaux M.S., Wang J., Wang G., Kleppe S., Zhang V.W., Schmitt E.S.,
RA Craigen W.J., Renaud D., Sun Q., Wong L.J.;
RT "Biochemical, molecular, and clinical diagnoses of patients with cerebral
RT creatine deficiency syndromes.";
RL Mol. Genet. Metab. 109:260-268(2013).
RN [22]
RP VARIANT CCDS1 LEU-552, CHARACTERIZATION OF VARIANT CCDS1 LEU-552, VARIANTS
RP HIS-186; MET-270; GLN-294; LEU-314; THR-318; SER-550; LEU-564; THR-611 AND
RP LYS-624, AND CHARACTERIZATION OF VARIANTS HIS-186; MET-270; GLN-294;
RP LEU-314; THR-318; LEU-564; THR-611 AND LYS-624.
RX PubMed=25861866; DOI=10.1016/j.gene.2015.04.011;
RA DesRoches C.L., Patel J., Wang P., Minassian B., Salomons G.S.,
RA Marshall C.R., Mercimek-Mahmutoglu S.;
RT "Estimated carrier frequency of creatine transporter deficiency in females
RT in the general population using functional characterization of novel
RT missense variants in the SLC6A8 gene.";
RL Gene 565:187-191(2015).
CC -!- FUNCTION: Required for the uptake of creatine in muscles and brain.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=CRT1;
CC IsoId=P48029-1; Sequence=Displayed;
CC Name=2; Synonyms=CRT2, SLC6A8B;
CC IsoId=P48029-2; Sequence=VSP_043917, VSP_043918, VSP_043919,
CC VSP_043920;
CC Name=3; Synonyms=SLC6A8C;
CC IsoId=P48029-3; Sequence=VSP_043916;
CC Name=4;
CC IsoId=P48029-4; Sequence=VSP_046316;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in skeletal muscle and
CC kidney. Also found in brain, heart, colon, testis and prostate.
CC {ECO:0000269|PubMed:7945388, ECO:0000269|PubMed:7953292}.
CC -!- DISEASE: Cerebral creatine deficiency syndrome 1 (CCDS1) [MIM:300352]:
CC An X-linked disorder of creatine transport characterized by
CC intellectual disability, severe speech delay, behavioral abnormalities,
CC and seizures. Carrier females may show mild neuropsychologic
CC impairment. {ECO:0000269|PubMed:11898126, ECO:0000269|PubMed:12210795,
CC ECO:0000269|PubMed:15154114, ECO:0000269|PubMed:17101918,
CC ECO:0000269|PubMed:17465020, ECO:0000269|PubMed:23033978,
CC ECO:0000269|PubMed:23660394, ECO:0000269|PubMed:24123876,
CC ECO:0000269|PubMed:25861866}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A8 subfamily. {ECO:0000305}.
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DR EMBL; L31409; AAC41688.1; -; mRNA.
DR EMBL; S74039; AAB32284.1; -; mRNA.
DR EMBL; U17986; AAA86990.1; -; mRNA.
DR EMBL; EU280316; ABZ82022.1; -; mRNA.
DR EMBL; AK295495; BAG58415.1; -; mRNA.
DR EMBL; U52111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z66539; CAA91442.1; -; Genomic_DNA.
DR EMBL; U36341; AAA79507.1; -; Genomic_DNA.
DR EMBL; BC012355; AAH12355.1; -; mRNA.
DR EMBL; BC081558; AAH81558.1; -; mRNA.
DR CCDS; CCDS14726.1; -. [P48029-1]
DR CCDS; CCDS48190.1; -. [P48029-4]
DR PIR; G02095; G02095.
DR PIR; JC2386; JC2386.
DR RefSeq; NP_001136277.1; NM_001142805.1.
DR RefSeq; NP_001136278.1; NM_001142806.1. [P48029-4]
DR RefSeq; NP_005620.1; NM_005629.3. [P48029-1]
DR AlphaFoldDB; P48029; -.
DR SMR; P48029; -.
DR BioGRID; 112426; 107.
DR IntAct; P48029; 16.
DR MINT; P48029; -.
DR STRING; 9606.ENSP00000253122; -.
DR DrugBank; DB00148; Creatine.
DR DrugBank; DB13191; Phosphocreatine.
DR TCDB; 2.A.22.3.11; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; P48029; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P48029; -.
DR PhosphoSitePlus; P48029; -.
DR SwissPalm; P48029; -.
DR BioMuta; SLC6A8; -.
DR DMDM; 1352529; -.
DR EPD; P48029; -.
DR jPOST; P48029; -.
DR MassIVE; P48029; -.
DR MaxQB; P48029; -.
DR PaxDb; P48029; -.
DR PeptideAtlas; P48029; -.
DR PRIDE; P48029; -.
DR ProteomicsDB; 20071; -.
DR ProteomicsDB; 55833; -. [P48029-1]
DR ProteomicsDB; 55834; -. [P48029-2]
DR ProteomicsDB; 55835; -. [P48029-3]
DR Antibodypedia; 1476; 208 antibodies from 32 providers.
DR DNASU; 6535; -.
DR Ensembl; ENST00000253122.10; ENSP00000253122.5; ENSG00000130821.17. [P48029-1]
DR Ensembl; ENST00000430077.6; ENSP00000403041.2; ENSG00000130821.17. [P48029-4]
DR GeneID; 6535; -.
DR KEGG; hsa:6535; -.
DR MANE-Select; ENST00000253122.10; ENSP00000253122.5; NM_005629.4; NP_005620.1.
DR UCSC; uc011myx.2; human. [P48029-1]
DR CTD; 6535; -.
DR DisGeNET; 6535; -.
DR GeneCards; SLC6A8; -.
DR GeneReviews; SLC6A8; -.
DR HGNC; HGNC:11055; SLC6A8.
DR HPA; ENSG00000130821; Low tissue specificity.
DR MalaCards; SLC6A8; -.
DR MIM; 300036; gene.
DR MIM; 300352; phenotype.
DR neXtProt; NX_P48029; -.
DR OpenTargets; ENSG00000130821; -.
DR Orphanet; 52503; X-linked creatine transporter deficiency.
DR PharmGKB; PA35915; -.
DR VEuPathDB; HostDB:ENSG00000130821; -.
DR eggNOG; KOG3660; Eukaryota.
DR GeneTree; ENSGT00940000155869; -.
DR HOGENOM; CLU_006855_9_5_1; -.
DR InParanoid; P48029; -.
DR OMA; CVEIFRQ; -.
DR PhylomeDB; P48029; -.
DR TreeFam; TF343812; -.
DR PathwayCommons; P48029; -.
DR Reactome; R-HSA-71288; Creatine metabolism.
DR SignaLink; P48029; -.
DR SIGNOR; P48029; -.
DR BioGRID-ORCS; 6535; 33 hits in 703 CRISPR screens.
DR ChiTaRS; SLC6A8; human.
DR GeneWiki; SLC6A8; -.
DR GenomeRNAi; 6535; -.
DR Pharos; P48029; Tbio.
DR PRO; PR:P48029; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P48029; protein.
DR Bgee; ENSG00000130821; Expressed in inferior olivary complex and 198 other tissues.
DR ExpressionAtlas; P48029; baseline and differential.
DR Genevisible; P48029; HS.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005308; F:creatine transmembrane transporter activity; NAS:UniProtKB.
DR GO; GO:0005309; F:creatine:sodium symporter activity; TAS:Reactome.
DR GO; GO:0006600; P:creatine metabolic process; TAS:Reactome.
DR GO; GO:0015881; P:creatine transmembrane transport; IMP:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0006836; P:neurotransmitter transport; IEA:InterPro.
DR GO; GO:0071705; P:nitrogen compound transport; IDA:ARUK-UCL.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR002984; Na/ntran_symport_creatine.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR01199; CRTTRANSPORT.
DR PRINTS; PR00176; NANEUSMPORT.
DR SUPFAM; SSF161070; SSF161070; 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.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Glycoprotein;
KW Intellectual disability; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Sodium; Sodium transport; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..635
FT /note="Sodium- and chloride-dependent creatine transporter
FT 1"
FT /id="PRO_0000214774"
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..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 42
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 617
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 620
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VBW1"
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 1..365
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18515020"
FT /id="VSP_043916"
FT VAR_SEQ 1..259
FT /note="MAKKSAENGIYSVSGDEKKGPLIAPGPDGAPAKGDGPVGLGTPGGRLAVPPR
FT ETWTRQMDFIMSCVGFAVGLGNVWRFPYLCYKNGGGVFLIPYVLIALVGGIPIFFLEIS
FT LGQFMKAGSINVWNICPLFKGLGYASMVIVFYCNTYYIMVLAWGFYYLVKSFTTTLPWA
FT TCGHTWNTPDCVEIFRHEDCANASLANLTCDQLADRRSPVIEFWENKVLRLSGGLEVPG
FT ALNWEVTLCLLACWVLVYFCVWKGVKSTGK -> MLPTLQIQGPAAFAPGDRGPGRHCP
FT FPVPITPTGALLPVSDSCDSLVDLVWPSVTYLALGTQSRVWPHPLGAPGQAGESPEQRR
FT QCLELWDMASSLGDKVPRAACGKRGQTVWQLHLACLCLAQFHSPPAQPPPLSRRGGGPD
FT PDPISRSLPGPPTPALPTHSYSSHSPRAPRLLSPLRRAPRGSPAPHRHASLQTNEAPRE
FT LPHCTWPGLPGRSLAPSFLWREPWLGGQWGPLNIPARKGDRRRWEWGCEGGGATASAEQ
FT PGPQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7622069"
FT /id="VSP_043917"
FT VAR_SEQ 1..115
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046316"
FT VAR_SEQ 417
FT /note="S -> SQVCMGLWDREPGGGRREGCRQGKGWRRCGDRPELPWP (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:7622069"
FT /id="VSP_043918"
FT VAR_SEQ 464
FT /note="D -> DVSGVGGLPVTSGGRLPSSLTGLCPQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7622069"
FT /id="VSP_043919"
FT VAR_SEQ 498
FT /note="Y -> YGRSWLRAGLGDGGGEGRSPAWPSRLTSPQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7622069"
FT /id="VSP_043920"
FT VARIANT 4
FT /note="K -> R (no effect on creatine transporter activity;
FT dbSNP:rs1190261367)"
FT /evidence="ECO:0000269|PubMed:17465020"
FT /id="VAR_075562"
FT VARIANT 26
FT /note="G -> R (no effect on creatine transporter activity;
FT dbSNP:rs1233444890)"
FT /evidence="ECO:0000269|PubMed:17465020"
FT /id="VAR_075563"
FT VARIANT 80
FT /note="Y -> H (in CCDS1)"
FT /evidence="ECO:0000269|PubMed:23660394"
FT /id="VAR_071791"
FT VARIANT 87
FT /note="G -> R (in CCDS1; decreased creatine transporter
FT activity; dbSNP:rs122453115)"
FT /evidence="ECO:0000269|PubMed:15154114,
FT ECO:0000269|PubMed:17465020"
FT /id="VAR_020525"
FT VARIANT 107
FT /note="Missing (in CCDS1; decreased creatine transporter
FT activity)"
FT /evidence="ECO:0000269|PubMed:17465020"
FT /id="VAR_075564"
FT VARIANT 132
FT /note="G -> V (in CCDS1; dbSNP:rs122453117)"
FT /evidence="ECO:0000269|PubMed:17101918"
FT /id="VAR_063707"
FT VARIANT 164
FT /note="T -> S (in dbSNP:rs642454)"
FT /id="VAR_034483"
FT VARIANT 186
FT /note="R -> H (82.0% of wild type creatine transporter
FT activity; dbSNP:rs372601430)"
FT /evidence="ECO:0000269|PubMed:25861866"
FT /id="VAR_074262"
FT VARIANT 270
FT /note="V -> M (no effect on creatine transporter activity;
FT dbSNP:rs146985734)"
FT /evidence="ECO:0000269|PubMed:25861866"
FT /id="VAR_074263"
FT VARIANT 294
FT /note="K -> Q (no effect on creatine transporter activity;
FT dbSNP:rs376937460)"
FT /evidence="ECO:0000269|PubMed:25861866"
FT /id="VAR_074264"
FT VARIANT 314
FT /note="F -> L (65.0% of wild type creatine transporter
FT activity; dbSNP:rs144678921)"
FT /evidence="ECO:0000269|PubMed:25861866"
FT /id="VAR_074265"
FT VARIANT 318
FT /note="A -> T (78.0% of wild type creatine transporter
FT activity; dbSNP:rs373953317)"
FT /evidence="ECO:0000269|PubMed:25861866"
FT /id="VAR_074266"
FT VARIANT 336
FT /note="Missing (in CCDS1; decreased creatine transporter
FT activity; dbSNP:rs782433037)"
FT /evidence="ECO:0000269|PubMed:17465020,
FT ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:24123876"
FT /id="VAR_070563"
FT VARIANT 337
FT /note="C -> W (in CCDS1; decreased creatine transporter
FT activity; dbSNP:rs122453116)"
FT /evidence="ECO:0000269|PubMed:15154114,
FT ECO:0000269|PubMed:17465020"
FT /id="VAR_063708"
FT VARIANT 347
FT /note="Missing (in CCDS1; decreased creatine transporter
FT activity)"
FT /evidence="ECO:0000269|PubMed:17465020"
FT /id="VAR_075565"
FT VARIANT 381
FT /note="G -> R (in CCDS1; dbSNP:rs122453114)"
FT /evidence="ECO:0000269|PubMed:11898126"
FT /id="VAR_020526"
FT VARIANT 383
FT /note="G -> C (in CCDS1)"
FT /evidence="ECO:0000269|PubMed:23660394"
FT /id="VAR_071792"
FT VARIANT 390
FT /note="P -> L (in CCDS1; decreased creatine transporter
FT activity)"
FT /evidence="ECO:0000269|PubMed:15154114,
FT ECO:0000269|PubMed:17465020"
FT /id="VAR_020527"
FT VARIANT 391
FT /note="R -> W (in CCDS1; decreased creatine transporter
FT activity; dbSNP:rs1557045267)"
FT /evidence="ECO:0000269|PubMed:17465020"
FT /id="VAR_075566"
FT VARIANT 408
FT /note="Missing (in CCDS1; dbSNP:rs80338740)"
FT /evidence="ECO:0000269|PubMed:12210795"
FT /id="VAR_020528"
FT VARIANT 448
FT /note="A -> D (in CCDS1)"
FT /evidence="ECO:0000269|PubMed:23660394"
FT /id="VAR_071793"
FT VARIANT 491
FT /note="C -> W (in CCDS1; dbSNP:rs122453118)"
FT /evidence="ECO:0000269|PubMed:17101918"
FT /id="VAR_063709"
FT VARIANT 539
FT /note="V -> I (in CCDS1; dbSNP:rs782354054)"
FT /evidence="ECO:0000269|PubMed:23660394"
FT /id="VAR_071794"
FT VARIANT 550
FT /note="T -> S (in dbSNP:rs199635059)"
FT /evidence="ECO:0000269|PubMed:23092983,
FT ECO:0000269|PubMed:25861866"
FT /id="VAR_074267"
FT VARIANT 552
FT /note="V -> L (in CCDS1; unknown pathological significance;
FT 35.0% of wild type creatine transporter activity;
FT dbSNP:rs372567920)"
FT /evidence="ECO:0000269|PubMed:25861866"
FT /id="VAR_074268"
FT VARIANT 554
FT /note="P -> L (in CCDS1; decreased creatine transporter
FT activity; dbSNP:rs397515559)"
FT /evidence="ECO:0000269|PubMed:15154114,
FT ECO:0000269|PubMed:17465020"
FT /id="VAR_020529"
FT VARIANT 560
FT /note="M -> V (no effect on creatine transporter activity;
FT dbSNP:rs145438966)"
FT /evidence="ECO:0000269|PubMed:15154114,
FT ECO:0000269|PubMed:17465020"
FT /id="VAR_063710"
FT VARIANT 564
FT /note="F -> L (no effect on creatine transporter activity;
FT dbSNP:rs201044530)"
FT /evidence="ECO:0000269|PubMed:25861866"
FT /id="VAR_074269"
FT VARIANT 611
FT /note="A -> T (no effect on creatine transporter activity;
FT dbSNP:rs146949376)"
FT /evidence="ECO:0000269|PubMed:25861866"
FT /id="VAR_074270"
FT VARIANT 624
FT /note="E -> K (no effect on creatine transporter activity;
FT dbSNP:rs368555229)"
FT /evidence="ECO:0000269|PubMed:25861866"
FT /id="VAR_074271"
FT VARIANT 629
FT /note="V -> I (no effect on creatine transporter activity;
FT dbSNP:rs781899045)"
FT /evidence="ECO:0000269|PubMed:17465020"
FT /id="VAR_075567"
FT CONFLICT 24..25
FT /note="AP -> VS (in Ref. 2; AAB32284)"
FT /evidence="ECO:0000305"
FT CONFLICT 32
FT /note="A -> S (in Ref. 2; AAB32284)"
FT /evidence="ECO:0000305"
FT CONFLICT 38
FT /note="V -> A (in Ref. 2; AAB32284)"
FT /evidence="ECO:0000305"
FT CONFLICT 42..45
FT /note="TPGG -> APSS (in Ref. 2; AAB32284)"
FT /evidence="ECO:0000305"
FT CONFLICT 136
FT /note="A -> G (in Ref. 7; BAG58415)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="A -> D (in Ref. 2; AAB32284)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="G -> T (in Ref. 2; AAB32284)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="A -> P (in Ref. 1; AAC41688)"
FT /evidence="ECO:0000305"
FT CONFLICT 368
FT /note="A -> T (in Ref. 2; AAB32284)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="P -> R (in Ref. 9; AAH81558)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 635 AA; 70523 MW; 9FAFE100B2A5B845 CRC64;
MAKKSAENGI YSVSGDEKKG PLIAPGPDGA PAKGDGPVGL GTPGGRLAVP PRETWTRQMD
FIMSCVGFAV GLGNVWRFPY LCYKNGGGVF LIPYVLIALV GGIPIFFLEI SLGQFMKAGS
INVWNICPLF KGLGYASMVI VFYCNTYYIM VLAWGFYYLV KSFTTTLPWA TCGHTWNTPD
CVEIFRHEDC ANASLANLTC DQLADRRSPV IEFWENKVLR LSGGLEVPGA LNWEVTLCLL
ACWVLVYFCV WKGVKSTGKI VYFTATFPYV VLVVLLVRGV LLPGALDGII YYLKPDWSKL
GSPQVWIDAG TQIFFSYAIG LGALTALGSY NRFNNNCYKD AIILALINSG TSFFAGFVVF
SILGFMAAEQ GVHISKVAES GPGLAFIAYP RAVTLMPVAP LWAALFFFML LLLGLDSQFV
GVEGFITGLL DLLPASYYFR FQREISVALC CALCFVIDLS MVTDGGMYVF QLFDYYSASG
TTLLWQAFWE CVVVAWVYGA DRFMDDIACM IGYRPCPWMK WCWSFFTPLV CMGIFIFNVV
YYEPLVYNNT YVYPWWGEAM GWAFALSSML CVPLHLLGCL LRAKGTMAER WQHLTQPIWG
LHHLEYRAQD ADVRGLTTLT PVSESSKVVV VESVM
