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Q9GZV3 (SC5A7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
High affinity choline transporter 1
Alternative name(s):
Hemicholinium-3-sensitive choline transporter
Short name=CHT
Solute carrier family 5 member 7
Gene names
Name:SLC5A7
Synonyms:CHT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length580 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Imports choline from the extracellular space to the neuron with high affinity. Choline uptake is the rate-limiting step in acetylcholine synthesis. Sodium ion- and chloride ion-dependent. Ref.1

Subunit structure

Homo-oligomerizes at cell surface. Ref.7

Subcellular location

Membrane; Multi-pass membrane protein Ref.1.

Tissue specificity

Expressed in putamen, spinal cord and medulla. Specific for cholinergic neurons.

Post-translational modification

Phosphorylated By similarity.

Involvement in disease

Neuronopathy, distal hereditary motor, 7A (HMN7A) [MIM:158580]: A neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMN7A is characterized by onset in the second decade of progressive distal muscle wasting and weakness affecting the upper and lower limbs and resulting in walking difficulties and hand grip. There is significant muscle atrophy of the hands and lower limbs. The disorder is associated with vocal cord paresis due to involvement of the tenth cranial nerve.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Miscellaneous

Specifically inhibited by nanomolar concentrations of hemicholinium 3.

Sequence similarities

Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family. [View classification]

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 580580High affinity choline transporter 1
PRO_0000105391

Regions

Topological domain1 – 66Extracellular Potential
Transmembrane7 – 2721Helical; Potential
Topological domain28 – 4821Cytoplasmic Potential
Transmembrane49 – 6921Helical; Potential
Topological domain70 – 8112Extracellular Potential
Transmembrane82 – 10221Helical; Potential
Topological domain103 – 12523Cytoplasmic Potential
Transmembrane126 – 14621Helical; Potential
Topological domain147 – 16418Extracellular Potential
Transmembrane165 – 18521Helical; Potential
Topological domain186 – 1916Cytoplasmic Potential
Transmembrane192 – 21221Helical; Potential
Topological domain213 – 23725Extracellular Potential
Transmembrane238 – 25821Helical; Potential
Topological domain259 – 27416Cytoplasmic Potential
Transmembrane275 – 29521Helical; Potential
Topological domain296 – 31722Extracellular Potential
Transmembrane318 – 33821Helical; Potential
Topological domain339 – 37638Cytoplasmic Potential
Transmembrane377 – 39721Helical; Potential
Topological domain398 – 4069Extracellular Potential
Transmembrane407 – 42721Helical; Potential
Topological domain428 – 4358Cytoplasmic Potential
Transmembrane436 – 45621Helical; Potential
Topological domain457 – 48125Extracellular Potential
Transmembrane482 – 50221Helical; Potential
Topological domain503 – 58078Cytoplasmic Potential

Amino acid modifications

Glycosylation3011N-linked (GlcNAc...) Potential

Natural variations

Natural variant891I → V 40% reduction in choline uptake rate; found in 0.06 of Ashkenazi Jews. Ref.8
Corresponds to variant rs1013940 [ dbSNP | Ensembl ].
VAR_020524

Experimental info

Mutagenesis891I → A: Only 20% of wild-type choline uptake activity. Ref.7
Mutagenesis4511E → Q: Only 5% of wild-type choline uptake activity. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Q9GZV3 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 66CB35496CB6E2D6

FASTA58063,204
        10         20         30         40         50         60 
MAFHVEGLIA IIVFYLLILL VGIWAAWRTK NSGSAEERSE AIIVGGRDIG LLVGGFTMTA 

        70         80         90        100        110        120 
TWVGGGYING TAEAVYVPGY GLAWAQAPIG YSLSLILGGL FFAKPMRSKG YVTMLDPFQQ 

       130        140        150        160        170        180 
IYGKRMGGLL FIPALMGEMF WAAAIFSALG ATISVIIDVD MHISVIISAL IATLYTLVGG 

       190        200        210        220        230        240 
LYSVAYTDVV QLFCIFVGLW ISVPFALSHP AVADIGFTAV HAKYQKPWLG TVDSSEVYSW 

       250        260        270        280        290        300 
LDSFLLLMLG GIPWQAYFQR VLSSSSATYA QVLSFLAAFG CLVMAIPAIL IGAIGASTDW 

       310        320        330        340        350        360 
NQTAYGLPDP KTTEEADMIL PIVLQYLCPV YISFFGLGAV SAAVMSSADS SILSASSMFA 

       370        380        390        400        410        420 
RNIYQLSFRQ NASDKEIVWV MRITVFVFGA SATAMALLTK TVYGLWYLSS DLVYIVIFPQ 

       430        440        450        460        470        480 
LLCVLFVKGT NTYGAVAGYV SGLFLRITGG EPYLYLQPLI FYPGYYPDDN GIYNQKFPFK 

       490        500        510        520        530        540 
TLAMVTSFLT NICISYLAKY LFESGTLPPK LDVFDAVVAR HSEENMDKTI LVKNENIKLD 

       550        560        570        580 
ELALVKPRQS MTLSSTFTNK EAFLDVDSSP EGSGTEDNLQ 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of a human, hemicholinium-3-sensitive choline transporter."
Apparsundaram S., Ferguson S.M., George A.L. Jr., Blakely R.D.
Biochem. Biophys. Res. Commun. 276:862-867(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
Tissue: Spinal cord.
[2]"Functional characterization of the human high-affinity choline transporter."
Okuda T., Haga T.
FEBS Lett. 484:92-97(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Spinal cord.
[3]"Molecular cloning of the human and murine high affinity choline transporters and characterization of the human gene structure."
Wieland A., Bonisch H., Bruess M.
Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Hypothalamus.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"Defective presynaptic choline transport underlies hereditary motor neuropathy."
Barwick K.E., Wright J., Al-Turki S., McEntagart M.M., Nair A., Chioza B., Al-Memar A., Modarres H., Reilly M.M., Dick K.J., Ruggiero A.M., Blakely R.D., Hurles M.E., Crosby A.H.
Am. J. Hum. Genet. 91:1103-1107(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN HMN7A.
[7]"Transmembrane topology and oligomeric structure of the high-affinity choline transporter."
Okuda T., Osawa C., Yamada H., Hayashi K., Nishikawa S., Ushio T., Kubo Y., Satou M., Ogawa H., Haga T.
J. Biol. Chem. 287:42826-42834(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY, SUBUNIT, MUTAGENESIS OF ILE-89 AND GLU-451.
[8]"Single nucleotide polymorphism of the human high affinity choline transporter alters transport rate."
Okuda T., Okamura M., Kaitsuka C., Haga T., Gurwitz D.
J. Biol. Chem. 277:45315-45322(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VAL-89.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF276871 mRNA. Translation: AAG25940.1.
AB043997 mRNA. Translation: BAB18161.1.
AJ401466 mRNA. Translation: CAC03717.1.
AJ308378 expand/collapse EMBL AC list , AJ308379, AJ308380, AJ308381, AJ308382, AJ308383, AJ308384 Genomic DNA. Translation: CAC88115.1.
AC009963 Genomic DNA. Translation: AAY14927.1.
BC111525 mRNA. Translation: AAI11526.1.
CCDSCCDS2074.1.
PIRJC7502.
RefSeqNP_068587.1. NM_021815.2.
UniGeneHs.287758.

3D structure databases

ProteinModelPortalQ9GZV3.
SMRQ9GZV3. Positions 81-443.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121915. 3 interactions.
STRING9606.ENSP00000264047.

Chemistry

BindingDBQ9GZV3.
ChEMBLCHEMBL4507.
DrugBankDB00122. Choline.
GuidetoPHARMACOLOGY914.

Protein family/group databases

TCDB2.A.21.8.2. the solute:sodium symporter (sss) family.

PTM databases

PhosphoSiteQ9GZV3.

Polymorphism databases

DMDM56404957.

Proteomic databases

PaxDbQ9GZV3.
PRIDEQ9GZV3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264047; ENSP00000264047; ENSG00000115665.
ENST00000409059; ENSP00000387346; ENSG00000115665.
GeneID60482.
KEGGhsa:60482.
UCSCuc002tdv.3. human.

Organism-specific databases

CTD60482.
GeneCardsGC02P108602.
HGNCHGNC:14025. SLC5A7.
HPAHPA046105.
MIM158580. phenotype.
608761. gene.
neXtProtNX_Q9GZV3.
Orphanet139589. Distal hereditary motor neuropathy type 7.
PharmGKBPA37838.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0591.
HOGENOMHOG000016386.
HOVERGENHBG054160.
InParanoidQ9GZV3.
KOK14387.
OMAHAKYQKP.
OrthoDBEOG7P8P7C.
PhylomeDBQ9GZV3.
TreeFamTF314588.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.
REACT_20679. Amine compound SLC transporters.

Gene expression databases

ArrayExpressQ9GZV3.
BgeeQ9GZV3.
CleanExHS_SLC5A7.
GenevestigatorQ9GZV3.

Family and domain databases

InterProIPR001734. Na/solute_symporter.
[Graphical view]
PANTHERPTHR11819. PTHR11819. 1 hit.
PfamPF00474. SSF. 1 hit.
[Graphical view]
PROSITEPS50283. NA_SOLUT_SYMP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCholine_transporter.
GenomeRNAi60482.
NextBio65355.
PROQ9GZV3.
SOURCESearch...

Entry information

Entry nameSC5A7_HUMAN
AccessionPrimary (citable) accession number: Q9GZV3
Secondary accession number(s): Q53TF2
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM