P48029 (SC6A8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium- and chloride-dependent creatine transporter 1
Short name=CT1
Short name=Creatine transporter 1

Alternative name(s):
Solute carrier family 6 member 8

Gene names

Name:

SLC6A8

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	635 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for the uptake of creatine in muscles and brain.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Predominantly expressed in skeletal muscle and kidney. Also found in brain, heart, colon, testis and prostate. Ref.1 Ref.2
Involvement in disease	Defects in SLC6A8 are the cause of X-linked creatine deficiency syndrome (XL-CDS) [MIM:300352]. XL-CDS causes developmental delay, hypotonia, mental retardation, seizures, short stature and midface hypoplasia. Ref.8 Ref.9 Ref.10 Ref.11
Sequence similarities	Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A8 subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Sodium transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	creatine metabolic process Traceable author statement. Source: Reactome muscle contraction Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Inferred from electronic annotation. Source: InterPro
Molecular function	creatine:sodium symporter activity Traceable author statement. Source: ProtInc neurotransmitter:sodium symporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 635	635	Sodium- and chloride-dependent creatine transporter 1		PRO_0000214774
Regions
	Topological domain	1 – 60	60	Cytoplasmic Potential
	Transmembrane	61 – 81	21	Helical; Potential
	Topological domain	82 – 87	6	Extracellular Potential
	Transmembrane	88 – 108	21	Helical; Potential
	Topological domain	109 – 138	30	Cytoplasmic Potential
	Transmembrane	139 – 159	21	Helical; Potential
	Topological domain	160 – 230	71	Extracellular Potential
	Transmembrane	231 – 251	21	Helical; Potential
	Topological domain	252 – 269	18	Cytoplasmic Potential
	Transmembrane	270 – 290	21	Helical; Potential
	Topological domain	291 – 304	14	Extracellular Potential
	Transmembrane	305 – 325	21	Helical; Potential
	Topological domain	326 – 341	16	Cytoplasmic Potential
	Transmembrane	342 – 362	21	Helical; Potential
	Topological domain	363 – 394	32	Extracellular Potential
	Transmembrane	395 – 415	21	Helical; Potential
	Topological domain	416 – 444	29	Cytoplasmic Potential
	Transmembrane	445 – 465	21	Helical; Potential
	Topological domain	466 – 479	14	Extracellular Potential
	Transmembrane	480 – 500	21	Helical; Potential
	Topological domain	501 – 520	20	Cytoplasmic Potential
	Transmembrane	521 – 541	21	Helical; Potential
	Topological domain	542 – 560	19	Extracellular Potential
	Transmembrane	561 – 581	21	Helical; Potential
	Topological domain	582 – 635	54	Cytoplasmic Potential
Amino acid modifications
	Modified residue	620	1	Phosphothreonine Ref.7
	Glycosylation	192	1	N-linked (GlcNAc...) Potential
	Glycosylation	197	1	N-linked (GlcNAc...) Potential
	Glycosylation	548	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	87	1	G → R in XL-CDS. Ref.10		VAR_020525
	Natural variant	132	1	G → V in XL-CDS. Ref.11		VAR_063707
	Natural variant	164	1	T → S. Corresponds to variant rs642454 [ dbSNP | Ensembl ].		VAR_034483
	Natural variant	337	1	C → W in XL-CDS. Ref.10		VAR_063708
	Natural variant	381	1	G → R in XL-CDS. Ref.8		VAR_020526
	Natural variant	390	1	P → L in XL-CDS. Ref.10		VAR_020527
	Natural variant	408	1	Missing in XL-CDS.		VAR_020528
	Natural variant	491	1	C → W in XL-CDS. Ref.11		VAR_063709
	Natural variant	554	1	P → L in XL-CDS. Ref.10		VAR_020529
	Natural variant	560	1	M → V. Ref.10		VAR_063710
Experimental info
	Sequence conflict	24 – 25	2	AP → VS in AAB32284. Ref.2
	Sequence conflict	32	1	A → S in AAB32284. Ref.2
	Sequence conflict	38	1	V → A in AAB32284. Ref.2
	Sequence conflict	42 – 45	4	TPGG → APSS in AAB32284. Ref.2
	Sequence conflict	193	1	A → D in AAB32284. Ref.2
	Sequence conflict	223	1	G → T in AAB32284. Ref.2
	Sequence conflict	285	1	A → P in AAC41688. Ref.1
	Sequence conflict	368	1	A → T in AAB32284. Ref.2
	Sequence conflict	434	1	P → R in AAH81558. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P48029 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 9FAFE100B2A5B845	FASTA	635	70,523
	10 20 30 40 50 60 MAKKSAENGI YSVSGDEKKG PLIAPGPDGA PAKGDGPVGL GTPGGRLAVP PRETWTRQMD 70 80 90 100 110 120 FIMSCVGFAV GLGNVWRFPY LCYKNGGGVF LIPYVLIALV GGIPIFFLEI SLGQFMKAGS 130 140 150 160 170 180 INVWNICPLF KGLGYASMVI VFYCNTYYIM VLAWGFYYLV KSFTTTLPWA TCGHTWNTPD 190 200 210 220 230 240 CVEIFRHEDC ANASLANLTC DQLADRRSPV IEFWENKVLR LSGGLEVPGA LNWEVTLCLL 250 260 270 280 290 300 ACWVLVYFCV WKGVKSTGKI VYFTATFPYV VLVVLLVRGV LLPGALDGII YYLKPDWSKL 310 320 330 340 350 360 GSPQVWIDAG TQIFFSYAIG LGALTALGSY NRFNNNCYKD AIILALINSG TSFFAGFVVF 370 380 390 400 410 420 SILGFMAAEQ GVHISKVAES GPGLAFIAYP RAVTLMPVAP LWAALFFFML LLLGLDSQFV 430 440 450 460 470 480 GVEGFITGLL DLLPASYYFR FQREISVALC CALCFVIDLS MVTDGGMYVF QLFDYYSASG 490 500 510 520 530 540 TTLLWQAFWE CVVVAWVYGA DRFMDDIACM IGYRPCPWMK WCWSFFTPLV CMGIFIFNVV 550 560 570 580 590 600 YYEPLVYNNT YVYPWWGEAM GWAFALSSML CVPLHLLGCL LRAKGTMAER WQHLTQPIWG 610 620 630 LHHLEYRAQD ADVRGLTTLT PVSESSKVVV VESVM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, pharmacological characterization, and genomic localization of the human creatine transporter." Nash S.R., Giros B., Kingsmore S.F., Rochelle J.M., Suter S.T., Gregor P., Seldin M.F., Caron M.G. Recept. Channels 2:165-174(1994) [PubMed: 7953292] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Kidney.
[2]	"The cloning and expression of a human creatine transporter." Sora I., Richman J., Santoro G., Wei H., Wang Y., Vanderah T., Horvath R., Nguyen M., Waite S., Roeske W.R. Biochem. Biophys. Res. Commun. 204:419-427(1994) [PubMed: 7945388] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Brain.
[3]	"The genomic organization of a human creatine transporter (CRTR) gene located in Xq28." Sandoval N., Bauer D., Brenner V., Coy J.F., Drescher B., Kioschis P., Korn B., Nyakatura G., Poustka A., Reichwald K., Rosenthal A., Platzer M. Genomics 35:383-385(1996) [PubMed: 8661155] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Genomic organization of the human creatine transporter and CDM genes." Eichler E.E., Lu F., Shen Y., Muzny D.M., Gibbs R.A., Nelson D.L. Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye and Testis.
[7]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-620, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28." Hahn K.A., Salomons G.S., Tackels-Horne D., Wood T.C., Taylor H.A., Schroer R.J., Lubs H.A., Jakobs C., Olson R.L., Holden K.R., Stevenson R.E., Schwartz C.E. Am. J. Hum. Genet. 70:1349-1356(2002) [PubMed: 11898126] [Abstract] Cited for: VARIANT XL-CDS ARG-381.
[9]	"X-linked creatine deficiency syndrome: a novel mutation in creatine transporter gene SLC6A8." Bizzi A., Bugiani M., Salomons G.S., Hunneman D.H., Moroni I., Estienne M., Danesi U., Jakobs C., Uziel G. Ann. Neurol. 52:227-231(2002) [PubMed: 12210795] [Abstract] Cited for: VARIANT XL-CDS PHE-408 DEL.
[10]	"High prevalence of SLC6A8 deficiency in X-linked mental retardation." Rosenberg E.H., Almeida L.S., Kleefstra T., deGrauw R.S., Yntema H.G., Bahi N., Moraine C., Ropers H.-H., Fryns J.-P., deGrauw T.J., Jakobs C., Salomons G.S. Am. J. Hum. Genet. 75:97-105(2004) [PubMed: 15154114] [Abstract] Cited for: VARIANTS XL-CDS ARG-87; TRP-337; LEU-390 AND LEU-554, VARIANT VAL-560.
[11]	"High frequency of creatine deficiency syndromes in patients with unexplained mental retardation." Lion-Francois L., Cheillan D., Pitelet G., Acquaviva-Bourdain C., Bussy G., Cotton F., Guibaud L., Gerard D., Rivier C., Vianey-Saban C., Jakobs C., Salomons G.S., des Portes V. Neurology 67:1713-1714(2006) [PubMed: 17101918] [Abstract] Cited for: VARIANTS XL-CDS VAL-132 AND TRP-491.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	L31409 mRNA. Translation: AAC41688.1. S74039 mRNA. Translation: AAB32284.1. U52111 Genomic DNA. No translation available. Z66539 Genomic DNA. Translation: CAA91442.1. U36341 Genomic DNA. Translation: AAA79507.1. BC012355 mRNA. Translation: AAH12355.1. BC081558 mRNA. Translation: AAH81558.1.
IPI	IPI00007582.
PIR	G02095. JC2386.
RefSeq	NP_001136277.1. NM_001142805.1. NP_001136278.1. NM_001142806.1. NP_005620.1. NM_005629.3.
UniGene	Hs.540696.
3D structure databases
ProteinModelPortal	P48029.
ModBase	Search...
Protein-protein interaction databases
STRING	P48029.
PTM databases
PhosphoSite	P48029.
Polymorphism databases
DMDM	1352529.
Proteomic databases
PRIDE	P48029.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000253122; ENSP00000253122; ENSG00000130821.
GeneID	6535.
KEGG	hsa:6535.
UCSC	uc004fib.2. human.
Organism-specific databases
CTD	6535.
GeneCards	GC0XP152953.
H-InvDB	HIX0017134.
HGNC	HGNC:11055. SLC6A8.
HPA	HPA008802.
MIM	300036. gene. 300352. phenotype.
neXtProt	NX_P48029.
Orphanet	52503. X-linked creatine transporter deficiency.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06111.
HOVERGEN	HBG071421.
OMA	PPRETWT.
OrthoDB	EOG4M3984.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P48029.
Bgee	P48029.
CleanEx	HS_SLC6A8.
Genevestigator	P48029.
GermOnline	ENSG00000130821. Homo sapiens.
Family and domain databases
InterPro	IPR000175. Na/ntran_symport. IPR002984. Na/ntran_symport_creatine. [Graphical view]
KO	K05041.
PANTHER	PTHR11616. Na/ntran_symport. 1 hit.
Pfam	PF00209. SNF. 1 hit. [Graphical view]
PRINTS	PR01199. CRTTRANSPORT. PR00176. NANEUSMPORT.
PROSITE	PS00610. NA_NEUROTRAN_SYMP_1. 1 hit. PS00754. NA_NEUROTRAN_SYMP_2. 1 hit. PS50267. NA_NEUROTRAN_SYMP_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00148. Creatine.
NextBio	25427.
SOURCE	Search...

Entry information

Entry name

SC6A8_HUMAN

Accession

Primary (citable) accession number: P48029
Secondary accession number(s): Q66I36

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	January 25, 2012
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.