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Protein

Sodium- and chloride-dependent creatine transporter 1

Gene

SLC6A8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Required for the uptake of creatine in muscles and brain.

GO - Molecular functioni

GO - Biological processi

  • creatine metabolic process Source: Reactome
  • creatine transmembrane transport Source: UniProtKB
  • muscle contraction Source: ProtInc

Keywordsi

Biological processIon transport, Sodium transport, Symport, Transport
LigandSodium

Enzyme and pathway databases

ReactomeiR-HSA-71288 Creatine metabolism

Protein family/group databases

TCDBi2.A.22.3.11 the neurotransmitter:sodium symporter (nss) family

Names & Taxonomyi

Protein namesi
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 namesi
Name:SLC6A8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000130821.15
HGNCiHGNC:11055 SLC6A8
MIMi300036 gene
neXtProtiNX_P48029

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 60CytoplasmicSequence analysisAdd BLAST60
Transmembranei61 – 81HelicalSequence analysisAdd BLAST21
Topological domaini82 – 87ExtracellularSequence analysis6
Transmembranei88 – 108HelicalSequence analysisAdd BLAST21
Topological domaini109 – 138CytoplasmicSequence analysisAdd BLAST30
Transmembranei139 – 159HelicalSequence analysisAdd BLAST21
Topological domaini160 – 230ExtracellularSequence analysisAdd BLAST71
Transmembranei231 – 251HelicalSequence analysisAdd BLAST21
Topological domaini252 – 269CytoplasmicSequence analysisAdd BLAST18
Transmembranei270 – 290HelicalSequence analysisAdd BLAST21
Topological domaini291 – 304ExtracellularSequence analysisAdd BLAST14
Transmembranei305 – 325HelicalSequence analysisAdd BLAST21
Topological domaini326 – 341CytoplasmicSequence analysisAdd BLAST16
Transmembranei342 – 362HelicalSequence analysisAdd BLAST21
Topological domaini363 – 394ExtracellularSequence analysisAdd BLAST32
Transmembranei395 – 415HelicalSequence analysisAdd BLAST21
Topological domaini416 – 444CytoplasmicSequence analysisAdd BLAST29
Transmembranei445 – 465HelicalSequence analysisAdd BLAST21
Topological domaini466 – 479ExtracellularSequence analysisAdd BLAST14
Transmembranei480 – 500HelicalSequence analysisAdd BLAST21
Topological domaini501 – 520CytoplasmicSequence analysisAdd BLAST20
Transmembranei521 – 541HelicalSequence analysisAdd BLAST21
Topological domaini542 – 560ExtracellularSequence analysisAdd BLAST19
Transmembranei561 – 581HelicalSequence analysisAdd BLAST21
Topological domaini582 – 635CytoplasmicSequence analysisAdd BLAST54

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Cerebral creatine deficiency syndrome 1 (CCDS1)9 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn X-linked disorder of creatine transport characterized by mental retardation, severe speech delay, behavioral abnormalities, and seizures. Carrier females may show mild neuropsychologic impairment.
See also OMIM:300352
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07179180Y → H in CCDS1. 1 Publication1
Natural variantiVAR_02052587G → R in CCDS1; decreased creatine transporter activity. 2 PublicationsCorresponds to variant dbSNP:rs122453115EnsemblClinVar.1
Natural variantiVAR_075564107Missing in CCDS1; decreased creatine transporter activity. 1 Publication1
Natural variantiVAR_063707132G → V in CCDS1. 1 PublicationCorresponds to variant dbSNP:rs122453117EnsemblClinVar.1
Natural variantiVAR_070563336Missing in CCDS1; decreased creatine transporter activity. 3 Publications1
Natural variantiVAR_063708337C → W in CCDS1; decreased creatine transporter activity. 2 PublicationsCorresponds to variant dbSNP:rs122453116EnsemblClinVar.1
Natural variantiVAR_075565347Missing in CCDS1; decreased creatine transporter activity. 1 Publication1
Natural variantiVAR_020526381G → R in CCDS1. 1 PublicationCorresponds to variant dbSNP:rs122453114EnsemblClinVar.1
Natural variantiVAR_071792383G → C in CCDS1. 1 Publication1
Natural variantiVAR_020527390P → L in CCDS1; decreased creatine transporter activity. 2 Publications1
Natural variantiVAR_075566391R → W in CCDS1; decreased creatine transporter activity. 1 Publication1
Natural variantiVAR_020528408Missing in CCDS1. 1 Publication1
Natural variantiVAR_071793448A → D in CCDS1. 1 Publication1
Natural variantiVAR_063709491C → W in CCDS1. 1 PublicationCorresponds to variant dbSNP:rs122453118EnsemblClinVar.1
Natural variantiVAR_071794539V → I in CCDS1. 1 PublicationCorresponds to variant dbSNP:rs782354054Ensembl.1
Natural variantiVAR_074268552V → L in CCDS1; unknown pathological significance; 35.0% of wild type creatine transporter activity. 1 PublicationCorresponds to variant dbSNP:rs372567920Ensembl.1
Natural variantiVAR_020529554P → L in CCDS1; decreased creatine transporter activity. 2 PublicationsCorresponds to variant dbSNP:rs397515559EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi6535
GeneReviewsiSLC6A8
MalaCardsiSLC6A8
MIMi300352 phenotype
OpenTargetsiENSG00000130821
Orphaneti52503 X-linked creatine transporter deficiency
PharmGKBiPA35915

Chemistry databases

DrugBankiDB00148 Creatine

Polymorphism and mutation databases

BioMutaiSLC6A8
DMDMi1352529

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002147741 – 635Sodium- and chloride-dependent creatine transporter 1Add BLAST635

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei42PhosphothreonineCombined sources1
Glycosylationi192N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi197N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi548N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei617PhosphothreonineCombined sources1
Modified residuei620PhosphothreonineCombined sources1
Modified residuei623PhosphoserineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP48029
PaxDbiP48029
PeptideAtlasiP48029
PRIDEiP48029
ProteomicsDBi55833
55834 [P48029-2]
55835 [P48029-3]

PTM databases

iPTMnetiP48029
PhosphoSitePlusiP48029
SwissPalmiP48029

Expressioni

Tissue specificityi

Predominantly expressed in skeletal muscle and kidney. Also found in brain, heart, colon, testis and prostate.2 Publications

Gene expression databases

BgeeiENSG00000130821
CleanExiHS_SLC6A8
ExpressionAtlasiP48029 baseline and differential
GenevisibleiP48029 HS

Interactioni

Protein-protein interaction databases

BioGridi112426, 11 interactors
IntActiP48029, 5 interactors
STRINGi9606.ENSP00000253122

Structurei

3D structure databases

ProteinModelPortaliP48029
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3659 Eukaryota
COG0733 LUCA
GeneTreeiENSGT00760000118857
HOGENOMiHOG000203877
HOVERGENiHBG071421
InParanoidiP48029
KOiK05039
OMAiVPPRETW
OrthoDBiEOG091G08PX
PhylomeDBiP48029
TreeFamiTF343812

Family and domain databases

InterProiView protein in InterPro
IPR000175 Na/ntran_symport
IPR002984 Na/ntran_symport_creatine
IPR037272 SNS_sf
PANTHERiPTHR11616 PTHR11616, 1 hit
PfamiView protein in Pfam
PF00209 SNF, 1 hit
PRINTSiPR01199 CRTTRANSPORT
PR00176 NANEUSMPORT
SUPFAMiSSF161070 SSF161070, 2 hits
PROSITEiView protein in PROSITE
PS00610 NA_NEUROTRAN_SYMP_1, 1 hit
PS00754 NA_NEUROTRAN_SYMP_2, 1 hit
PS50267 NA_NEUROTRAN_SYMP_3, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P48029-1) [UniParc]FASTAAdd to basket
Also known as: CRT1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAKKSAENGI YSVSGDEKKG PLIAPGPDGA PAKGDGPVGL GTPGGRLAVP
60 70 80 90 100
PRETWTRQMD FIMSCVGFAV GLGNVWRFPY LCYKNGGGVF LIPYVLIALV
110 120 130 140 150
GGIPIFFLEI SLGQFMKAGS INVWNICPLF KGLGYASMVI VFYCNTYYIM
160 170 180 190 200
VLAWGFYYLV KSFTTTLPWA TCGHTWNTPD CVEIFRHEDC ANASLANLTC
210 220 230 240 250
DQLADRRSPV IEFWENKVLR LSGGLEVPGA LNWEVTLCLL ACWVLVYFCV
260 270 280 290 300
WKGVKSTGKI VYFTATFPYV VLVVLLVRGV LLPGALDGII YYLKPDWSKL
310 320 330 340 350
GSPQVWIDAG TQIFFSYAIG LGALTALGSY NRFNNNCYKD AIILALINSG
360 370 380 390 400
TSFFAGFVVF SILGFMAAEQ GVHISKVAES GPGLAFIAYP RAVTLMPVAP
410 420 430 440 450
LWAALFFFML LLLGLDSQFV GVEGFITGLL DLLPASYYFR FQREISVALC
460 470 480 490 500
CALCFVIDLS MVTDGGMYVF QLFDYYSASG TTLLWQAFWE CVVVAWVYGA
510 520 530 540 550
DRFMDDIACM IGYRPCPWMK WCWSFFTPLV CMGIFIFNVV YYEPLVYNNT
560 570 580 590 600
YVYPWWGEAM GWAFALSSML CVPLHLLGCL LRAKGTMAER WQHLTQPIWG
610 620 630
LHHLEYRAQD ADVRGLTTLT PVSESSKVVV VESVM
Length:635
Mass (Da):70,523
Last modified:February 1, 1996 - v1
Checksum:i9FAFE100B2A5B845
GO
Isoform 2 (identifier: P48029-2) [UniParc]FASTAAdd to basket
Also known as: CRT2, SLC6A8B

The sequence of this isoform differs from the canonical sequence as follows:
     1-259: MAKKSAENGI...VWKGVKSTGK → MLPTLQIQGP...TASAEQPGPQ
     417-417: S → SQVCMGLWDREPGGGRREGCRQGKGWRRCGDRPELPWP
     464-464: D → DVSGVGGLPVTSGGRLPSSLTGLCPQ
     498-498: Y → YGRSWLRAGLGDGGGEGRSPAWPSRLTSPQ

Show »
Length:732
Mass (Da):80,137
Checksum:i1BC824884EC299A8
GO
Isoform 3 (identifier: P48029-3) [UniParc]FASTAAdd to basket
Also known as: SLC6A8C

The sequence of this isoform differs from the canonical sequence as follows:
     1-365: Missing.

Show »
Length:270
Mass (Da):30,580
Checksum:i398EA89851EAE536
GO
Isoform 4 (identifier: P48029-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-115: Missing.

Note: No experimental confirmation available.
Show »
Length:520
Mass (Da):58,453
Checksum:i83FF6FA9A9A8C1A3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24 – 25AP → VS in AAB32284 (PubMed:7945388).Curated2
Sequence conflicti32A → S in AAB32284 (PubMed:7945388).Curated1
Sequence conflicti38V → A in AAB32284 (PubMed:7945388).Curated1
Sequence conflicti42 – 45TPGG → APSS in AAB32284 (PubMed:7945388).Curated4
Sequence conflicti136A → G in BAG58415 (PubMed:14702039).Curated1
Sequence conflicti193A → D in AAB32284 (PubMed:7945388).Curated1
Sequence conflicti223G → T in AAB32284 (PubMed:7945388).Curated1
Sequence conflicti285A → P in AAC41688 (PubMed:7953292).Curated1
Sequence conflicti368A → T in AAB32284 (PubMed:7945388).Curated1
Sequence conflicti434P → R in AAH81558 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0755624K → R Polymorphism; no effect on creatine transporter activity. 1 Publication1
Natural variantiVAR_07556326G → R Polymorphism; no effect on creatine transporter activity. 1 Publication1
Natural variantiVAR_07179180Y → H in CCDS1. 1 Publication1
Natural variantiVAR_02052587G → R in CCDS1; decreased creatine transporter activity. 2 PublicationsCorresponds to variant dbSNP:rs122453115EnsemblClinVar.1
Natural variantiVAR_075564107Missing in CCDS1; decreased creatine transporter activity. 1 Publication1
Natural variantiVAR_063707132G → V in CCDS1. 1 PublicationCorresponds to variant dbSNP:rs122453117EnsemblClinVar.1
Natural variantiVAR_034483164T → S. Corresponds to variant dbSNP:rs642454Ensembl.1
Natural variantiVAR_074262186R → H Polymorphism; 82.0% of wild type creatine transporter activity. 1 PublicationCorresponds to variant dbSNP:rs372601430EnsemblClinVar.1
Natural variantiVAR_074263270V → M Polymorphism; no effect on creatine transporter activity. 1 PublicationCorresponds to variant dbSNP:rs146985734Ensembl.1
Natural variantiVAR_074264294K → Q Polymorphism; no effect on creatine transporter activity. 1 PublicationCorresponds to variant dbSNP:rs376937460Ensembl.1
Natural variantiVAR_074265314F → L Polymorphism; 65.0% of wild type creatine transporter activity. 1 PublicationCorresponds to variant dbSNP:rs144678921Ensembl.1
Natural variantiVAR_074266318A → T Polymorphism; 78.0% of wild type creatine transporter activity. 1 PublicationCorresponds to variant dbSNP:rs373953317Ensembl.1
Natural variantiVAR_070563336Missing in CCDS1; decreased creatine transporter activity. 3 Publications1
Natural variantiVAR_063708337C → W in CCDS1; decreased creatine transporter activity. 2 PublicationsCorresponds to variant dbSNP:rs122453116EnsemblClinVar.1
Natural variantiVAR_075565347Missing in CCDS1; decreased creatine transporter activity. 1 Publication1
Natural variantiVAR_020526381G → R in CCDS1. 1 PublicationCorresponds to variant dbSNP:rs122453114EnsemblClinVar.1
Natural variantiVAR_071792383G → C in CCDS1. 1 Publication1
Natural variantiVAR_020527390P → L in CCDS1; decreased creatine transporter activity. 2 Publications1
Natural variantiVAR_075566391R → W in CCDS1; decreased creatine transporter activity. 1 Publication1
Natural variantiVAR_020528408Missing in CCDS1. 1 Publication1
Natural variantiVAR_071793448A → D in CCDS1. 1 Publication1
Natural variantiVAR_063709491C → W in CCDS1. 1 PublicationCorresponds to variant dbSNP:rs122453118EnsemblClinVar.1
Natural variantiVAR_071794539V → I in CCDS1. 1 PublicationCorresponds to variant dbSNP:rs782354054Ensembl.1
Natural variantiVAR_074267550T → S2 PublicationsCorresponds to variant dbSNP:rs199635059EnsemblClinVar.1
Natural variantiVAR_074268552V → L in CCDS1; unknown pathological significance; 35.0% of wild type creatine transporter activity. 1 PublicationCorresponds to variant dbSNP:rs372567920Ensembl.1
Natural variantiVAR_020529554P → L in CCDS1; decreased creatine transporter activity. 2 PublicationsCorresponds to variant dbSNP:rs397515559EnsemblClinVar.1
Natural variantiVAR_063710560M → V Polymorphism; no effect on creatine transporter activity. 2 PublicationsCorresponds to variant dbSNP:rs145438966EnsemblClinVar.1
Natural variantiVAR_074269564F → L Polymorphism; no effect on creatine transporter activity. 1 PublicationCorresponds to variant dbSNP:rs201044530EnsemblClinVar.1
Natural variantiVAR_074270611A → T Polymorphism; no effect on creatine transporter activity. 1 PublicationCorresponds to variant dbSNP:rs146949376EnsemblClinVar.1
Natural variantiVAR_074271624E → K Polymorphism; no effect on creatine transporter activity. 1 PublicationCorresponds to variant dbSNP:rs368555229Ensembl.1
Natural variantiVAR_075567629V → I Polymorphism; no effect on creatine transporter activity. 1 PublicationCorresponds to variant dbSNP:rs781899045Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0439161 – 365Missing in isoform 3. 1 PublicationAdd BLAST365
Alternative sequenceiVSP_0439171 – 259MAKKS…KSTGK → MLPTLQIQGPAAFAPGDRGP GRHCPFPVPITPTGALLPVS DSCDSLVDLVWPSVTYLALG TQSRVWPHPLGAPGQAGESP EQRRQCLELWDMASSLGDKV PRAACGKRGQTVWQLHLACL CLAQFHSPPAQPPPLSRRGG GPDPDPISRSLPGPPTPALP THSYSSHSPRAPRLLSPLRR APRGSPAPHRHASLQTNEAP RELPHCTWPGLPGRSLAPSF LWREPWLGGQWGPLNIPARK GDRRRWEWGCEGGGATASAE QPGPQ in isoform 2. 1 PublicationAdd BLAST259
Alternative sequenceiVSP_0463161 – 115Missing in isoform 4. 1 PublicationAdd BLAST115
Alternative sequenceiVSP_043918417S → SQVCMGLWDREPGGGRREGC RQGKGWRRCGDRPELPWP in isoform 2. 1 Publication1
Alternative sequenceiVSP_043919464D → DVSGVGGLPVTSGGRLPSSL TGLCPQ in isoform 2. 1 Publication1
Alternative sequenceiVSP_043920498Y → YGRSWLRAGLGDGGGEGRSP AWPSRLTSPQ in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L31409 mRNA Translation: AAC41688.1
S74039 mRNA Translation: AAB32284.1
U17986 mRNA Translation: AAA86990.1
EU280316 mRNA Translation: ABZ82022.1
AK295495 mRNA Translation: BAG58415.1
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
CCDSiCCDS14726.1 [P48029-1]
CCDS48190.1 [P48029-4]
PIRiG02095
JC2386
RefSeqiNP_001136277.1, NM_001142805.1
NP_001136278.1, NM_001142806.1 [P48029-4]
NP_005620.1, NM_005629.3 [P48029-1]
UniGeneiHs.540696

Genome annotation databases

EnsembliENST00000253122; ENSP00000253122; ENSG00000130821 [P48029-1]
ENST00000430077; ENSP00000403041; ENSG00000130821 [P48029-4]
GeneIDi6535
KEGGihsa:6535
UCSCiuc011myx.2 human [P48029-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSC6A8_HUMAN
AccessioniPrimary (citable) accession number: P48029
Secondary accession number(s): B2KY47
, B4DIA3, E9PFC0, Q13032, Q66I36
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: June 20, 2018
This is version 172 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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