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 27-MAR-2024, entry version 204. 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), TISSUE SPECIFICITY, FUNCTION, RP TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. 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), TISSUE SPECIFICITY, FUNCTION, RP TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. 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 1), FUNCTION, TRANSPORTER ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ALA-285. RC TISSUE=Heart; RX PubMed=9882430; DOI=10.1006/abbi.1998.0959; RA Dai W., Vinnakota S., Qian X., Kunze D.L., Sarkar H.K.; RT "Molecular characterization of the human CRT-1 creatine transporter RT expressed in Xenopus oocytes."; RL Arch. Biochem. Biophys. 361:75-84(1999). RN [6] 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 [7] 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 [8] 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 [9] 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 [10] 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 [11] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=12433955; DOI=10.1113/jphysiol.2002.026377; RA Peral M.J., Garcia-Delgado M., Calonge M.L., Duran J.M., De La Horra M.C., RA Wallimann T., Speer O., Ilundain A.; RT "Human, rat and chicken small intestinal Na+ - Cl- -creatine transporter: RT functional, molecular characterization and localization."; RL J. Physiol. (Lond.) 545:133-144(2002). RN [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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, CHARACTERIZATION OF VARIANTS RP ARG-4; ARG-26; VAL-560 AND ILE-629, FUNCTION, AND TRANSPORTER ACTIVITY. 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 [20] 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 [21] 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 [22] RP VARIANTS CCDS1 GLY-41 DEL; ARG-181; ASN-336 DEL AND GLY-499 DEL, RP CHARACTERIZATION OF VARIANTS CCDS1 GLY-41 DEL; ARG-181; ASN-336 DEL AND RP GLY-499 DEL, FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=22644605; DOI=10.1007/s10545-012-9495-9; RA Valayannopoulos V., Bakouh N., Mazzuca M., Nonnenmacher L., Hubert L., RA Makaci F.L., Chabli A., Salomons G.S., Mellot-Draznieks C., Brule E., RA de Lonlay P., Toulhoat H., Munnich A., Planelles G., de Keyzer Y.; RT "Functional and electrophysiological characterization of four non- RT truncating mutations responsible for creatine transporter (SLC6A8) RT deficiency syndrome."; RL J. Inherit. Metab. Dis. 36:103-112(2013). RN [23] 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 [24] 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 [25] 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, CHARACTERIZATION OF VARIANTS HIS-186; MET-270; GLN-294; LEU-314; RP THR-318; LEU-564; THR-611 AND LYS-624, FUNCTION, AND TRANSPORTER ACTIVITY. 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: Creatine:sodium symporter which mediates the uptake of CC creatine (PubMed:7953292, PubMed:7945388, PubMed:9882430, CC PubMed:17465020, PubMed:22644605, PubMed:25861866). Plays an important CC role in supplying creatine to the brain via the blood-brain barrier (By CC similarity). {ECO:0000250|UniProtKB:Q8VBW1, CC ECO:0000269|PubMed:17465020, ECO:0000269|PubMed:22644605, CC ECO:0000269|PubMed:25861866, ECO:0000269|PubMed:7945388, CC ECO:0000269|PubMed:7953292, ECO:0000269|PubMed:9882430}. 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:17465020, ECO:0000269|PubMed:22644605, CC ECO:0000269|PubMed:25861866, ECO:0000269|PubMed:7945388, CC ECO:0000269|PubMed:7953292, ECO:0000269|PubMed:9882430}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=77 mM for creatine {ECO:0000269|PubMed:7953292}; CC KM=14.9 uM for creatine {ECO:0000269|PubMed:7945388}; CC KM=20 uM for creatine {ECO:0000269|PubMed:9882430}; CC KM=59 mM for sodium {ECO:0000269|PubMed:9882430}; CC KM=5 mM for chloride {ECO:0000269|PubMed:9882430}; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22644605}; CC Multi-pass membrane protein {ECO:0000255}. Apical cell membrane CC {ECO:0000269|PubMed:12433955}; Multi-pass membrane protein CC {ECO:0000255}. 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 -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q8VBW1}. 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:22644605, CC ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23660394, CC ECO:0000269|PubMed:24123876, ECO:0000269|PubMed:25861866}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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; 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; 116. DR IntAct; P48029; 19. DR MINT; P48029; -. DR STRING; 9606.ENSP00000253122; -. DR ChEMBL; CHEMBL5209634; -. DR DrugBank; DB00148; Creatine. DR DrugBank; DB13191; Phosphocreatine. DR TCDB; 2.A.22.3.11; the neurotransmitter:sodium symporter (nss) family. DR GlyCosmos; P48029; 4 sites, 1 glycan. 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; 9606-ENSP00000253122; -. DR PeptideAtlas; P48029; -. DR ProteomicsDB; 20071; -. DR ProteomicsDB; 55833; -. [P48029-1] DR ProteomicsDB; 55834; -. [P48029-2] DR ProteomicsDB; 55835; -. [P48029-3] DR Pumba; P48029; -. DR Antibodypedia; 1476; 232 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 AGR; HGNC:11055; -. 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 OrthoDB; 3084493at2759; -. 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; 38 hits in 786 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 200 other cell types or tissues. DR ExpressionAtlas; P48029; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IMP:UniProtKB. DR GO; GO:0005308; F:creatine transmembrane transporter activity; NAS:UniProtKB. 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: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 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; P48029; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; 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 41 FT /note="Missing (in CCDS1; uncertain significance; loss of FT creatine transporter activity; no effect on cell membrane FT localization)" FT /evidence="ECO:0000269|PubMed:22644605" FT /id="VAR_086684" 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 181 FT /note="C -> R (in CCDS1; uncertain significance; loss of FT creatine transporter activity; no effect on cell membrane FT localization)" FT /evidence="ECO:0000269|PubMed:22644605" FT /id="VAR_086685" 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; no effect on cell membrane localization; FT dbSNP:rs782433037)" FT /evidence="ECO:0000269|PubMed:17465020, FT ECO:0000269|PubMed:22644605, ECO:0000269|PubMed:23033978, FT 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 499 FT /note="Missing (in CCDS1; uncertain significance; loss of FT creatine transporter activity; no effect on cell membrane FT localization)" FT /evidence="ECO:0000269|PubMed:22644605" FT /id="VAR_086686" 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; uncertain significance; 35.0% of FT 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 MUTAGEN 285 FT /note="A->P: No effect on creatine transporter activity." FT /evidence="ECO:0000269|PubMed:9882430" 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. 8; 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. 10; 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 //