UniProtKB - Q9GZV3 (SC5A7_HUMAN)
Protein
High affinity choline transporter 1
Gene
SLC5A7
Organism
Homo sapiens (Human)
Status
Functioni
Transmembrane transporter that imports choline from the extracellular space into the neuron with high affinity. Choline uptake is the rate-limiting step in acetylcholine synthesis. Sodium ion- and chloride ion-dependent.2 Publications
Miscellaneous
Specifically inhibited by nanomolar concentrations of hemicholinium 3.
GO - Molecular functioni
- choline:sodium symporter activity Source: MGI
- choline binding Source: Ensembl
- choline transmembrane transporter activity Source: UniProtKB
GO - Biological processi
- acetylcholine biosynthetic process Source: UniProtKB
- choline transport Source: GO_Central
- neuromuscular synaptic transmission Source: GO_Central
- neurotransmitter secretion Source: Reactome
- synaptic transmission, cholinergic Source: GO_Central
- transmembrane transport Source: Reactome
Keywordsi
Biological process | Ion transport, Neurotransmitter biosynthesis, Sodium transport, Symport, Transport |
Ligand | Sodium |
Enzyme and pathway databases
PathwayCommonsi | Q9GZV3 |
Reactomei | R-HSA-264642, Acetylcholine Neurotransmitter Release Cycle R-HSA-425366, Transport of bile salts and organic acids, metal ions and amine compounds R-HSA-5619114, Defective SLC5A7 causes distal hereditary motor neuronopathy 7A (HMN7A) R-HSA-5658471, Defective SLC5A7 causes distal hereditary motor neuronopathy 7A (HMN7A) |
Protein family/group databases
TCDBi | 2.A.21.8.2, the solute:sodium symporter (sss) family |
Names & Taxonomyi
Protein namesi | Recommended name: High affinity choline transporter 1Alternative name(s): Hemicholinium-3-sensitive choline transporter Short name: CHT Solute carrier family 5 member 7 |
Gene namesi | Name:SLC5A7 Synonyms:CHT1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000115665.8 |
HGNCi | HGNC:14025, SLC5A7 |
MIMi | 608761, gene |
neXtProti | NX_Q9GZV3 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication
Other locations
- Membrane 1 Publication; Multi-pass membrane protein 1 Publication
- synapse 1 Publication
Note: Localized at the neuromuscular junction.1 Publication
Plasma Membrane
- plasma membrane Source: MGI
Other locations
- axon Source: GO_Central
- dendrite Source: GO_Central
- integral component of membrane Source: UniProtKB
- neuromuscular junction Source: UniProtKB
- perikaryon Source: GO_Central
- presynapse Source: GOC
- synapse Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 6 | ExtracellularSequence analysis | 6 | |
Transmembranei | 7 – 27 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 28 – 48 | CytoplasmicSequence analysisAdd BLAST | 21 | |
Transmembranei | 49 – 69 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 70 – 81 | ExtracellularSequence analysisAdd BLAST | 12 | |
Transmembranei | 82 – 102 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 103 – 125 | CytoplasmicSequence analysisAdd BLAST | 23 | |
Transmembranei | 126 – 146 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 147 – 164 | ExtracellularSequence analysisAdd BLAST | 18 | |
Transmembranei | 165 – 185 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 186 – 191 | CytoplasmicSequence analysis | 6 | |
Transmembranei | 192 – 212 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 213 – 237 | ExtracellularSequence analysisAdd BLAST | 25 | |
Transmembranei | 238 – 258 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 259 – 274 | CytoplasmicSequence analysisAdd BLAST | 16 | |
Transmembranei | 275 – 295 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 296 – 317 | ExtracellularSequence analysisAdd BLAST | 22 | |
Transmembranei | 318 – 338 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 339 – 376 | CytoplasmicSequence analysisAdd BLAST | 38 | |
Transmembranei | 377 – 397 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 398 – 406 | ExtracellularSequence analysis | 9 | |
Transmembranei | 407 – 427 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 428 – 435 | CytoplasmicSequence analysis | 8 | |
Transmembranei | 436 – 456 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 457 – 481 | ExtracellularSequence analysisAdd BLAST | 25 | |
Transmembranei | 482 – 502 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 503 – 580 | CytoplasmicSequence analysisAdd BLAST | 78 |
Keywords - Cellular componenti
Cell junction, Cell membrane, Membrane, SynapsePathology & Biotechi
Involvement in diseasei
Neuronopathy, distal hereditary motor, 7A (HMN7A)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMMyasthenic syndrome, congenital, 20, presynaptic (CMS20)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS20 is an autosomal recessive, pre-synaptic form characterized by severe hypotonia and episodic apnea soon after birth, generalized limb fatigability and weakness, delayed walking, ptosis, poor sucking and swallowing.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077854 | 48 | D → G in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs886039768EnsemblClinVar. | 1 | |
Natural variantiVAR_077855 | 65 | G → E in CMS20; loss of choline transmembrane transporter activity; no effect on localization at plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs886039765EnsemblClinVar. | 1 | |
Natural variantiVAR_077856 | 105 | P → S in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs886039766EnsemblClinVar. | 1 | |
Natural variantiVAR_077857 | 111 | Y → H in CMS20; no effect on localization at plasma membrane. 1 Publication | 1 | |
Natural variantiVAR_077858 | 175 | Y → C in CMS20; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1331713195Ensembl. | 1 | |
Natural variantiVAR_077859 | 291 | I → T in CMS20; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs375397889Ensembl. | 1 | |
Natural variantiVAR_077860 | 344 | V → L in CMS20; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_077861 | 361 | R → Q in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs147656110EnsemblClinVar. | 1 | |
Natural variantiVAR_077862 | 418 | F → V in CMS20; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_077863 | 446 | R → G in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 89 | I → A: Only 20% of wild-type choline uptake activity. 1 Publication | 1 | |
Mutagenesisi | 451 | E → Q: Only 5% of wild-type choline uptake activity. 1 Publication | 1 |
Keywords - Diseasei
Congenital myasthenic syndrome, Disease mutation, Neurodegeneration, NeuropathyOrganism-specific databases
DisGeNETi | 60482 |
GeneReviewsi | SLC5A7 |
MalaCardsi | SLC5A7 |
MIMi | 158580, phenotype 617143, phenotype |
OpenTargetsi | ENSG00000115665 |
Orphaneti | 139589, Distal hereditary motor neuropathy type 7 98914, Presynaptic congenital myasthenic syndromes |
PharmGKBi | PA37838 |
Miscellaneous databases
Pharosi | Q9GZV3, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4507 |
DrugBanki | DB00122, Choline DB14006, Choline salicylate |
DrugCentrali | Q9GZV3 |
GuidetoPHARMACOLOGYi | 914 |
Polymorphism and mutation databases
BioMutai | SLC5A7 |
DMDMi | 56404957 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000105391 | 1 – 580 | High affinity choline transporter 1Add BLAST | 580 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 301 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Phosphorylated.By similarity
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | Q9GZV3 |
PeptideAtlasi | Q9GZV3 |
PRIDEi | Q9GZV3 |
ProteomicsDBi | 80155 |
PTM databases
GlyGeni | Q9GZV3, 1 site |
iPTMneti | Q9GZV3 |
PhosphoSitePlusi | Q9GZV3 |
Expressioni
Tissue specificityi
Expressed in putamen, spinal cord and medulla. Specific for cholinergic neurons.
Gene expression databases
Bgeei | ENSG00000115665, Expressed in muscle layer of sigmoid colon and 78 other tissues |
Genevisiblei | Q9GZV3, HS |
Organism-specific databases
HPAi | ENSG00000115665, Tissue enriched (brain) |
Interactioni
Subunit structurei
Protein-protein interaction databases
BioGRIDi | 121915, 4 interactors |
STRINGi | 9606.ENSP00000264047 |
Chemistry databases
BindingDBi | Q9GZV3 |
Miscellaneous databases
RNActi | Q9GZV3, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 502 – 580 | Mediates interaction with SEC14L1By similarityAdd BLAST | 79 |
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3761, Eukaryota |
GeneTreei | ENSGT00690000101915 |
HOGENOMi | CLU_018808_10_0_1 |
InParanoidi | Q9GZV3 |
OMAi | HSKEIMD |
OrthoDBi | 799628at2759 |
PhylomeDBi | Q9GZV3 |
TreeFami | TF314588 |
Family and domain databases
Gene3Di | 1.20.1730.10, 1 hit |
InterProi | View protein in InterPro IPR038377, Na/Glc_symporter_sf IPR001734, Na/solute_symporter |
Pfami | View protein in Pfam PF00474, SSF, 1 hit |
PROSITEi | View protein in PROSITE PS50283, NA_SOLUT_SYMP_3, 1 hit |
i Sequence
Sequence statusi: Complete.
Q9GZV3-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAFHVEGLIA IIVFYLLILL VGIWAAWRTK NSGSAEERSE AIIVGGRDIG
60 70 80 90 100
LLVGGFTMTA TWVGGGYING TAEAVYVPGY GLAWAQAPIG YSLSLILGGL
110 120 130 140 150
FFAKPMRSKG YVTMLDPFQQ IYGKRMGGLL FIPALMGEMF WAAAIFSALG
160 170 180 190 200
ATISVIIDVD MHISVIISAL IATLYTLVGG LYSVAYTDVV QLFCIFVGLW
210 220 230 240 250
ISVPFALSHP AVADIGFTAV HAKYQKPWLG TVDSSEVYSW LDSFLLLMLG
260 270 280 290 300
GIPWQAYFQR VLSSSSATYA QVLSFLAAFG CLVMAIPAIL IGAIGASTDW
310 320 330 340 350
NQTAYGLPDP KTTEEADMIL PIVLQYLCPV YISFFGLGAV SAAVMSSADS
360 370 380 390 400
SILSASSMFA RNIYQLSFRQ NASDKEIVWV MRITVFVFGA SATAMALLTK
410 420 430 440 450
TVYGLWYLSS DLVYIVIFPQ LLCVLFVKGT NTYGAVAGYV SGLFLRITGG
460 470 480 490 500
EPYLYLQPLI FYPGYYPDDN GIYNQKFPFK TLAMVTSFLT NICISYLAKY
510 520 530 540 550
LFESGTLPPK LDVFDAVVAR HSEENMDKTI LVKNENIKLD ELALVKPRQS
560 570 580
MTLSSTFTNK EAFLDVDSSP EGSGTEDNLQ
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077854 | 48 | D → G in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs886039768EnsemblClinVar. | 1 | |
Natural variantiVAR_077855 | 65 | G → E in CMS20; loss of choline transmembrane transporter activity; no effect on localization at plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs886039765EnsemblClinVar. | 1 | |
Natural variantiVAR_020524 | 89 | I → V 40% reduction in choline uptake rate; found in 0.06 of Ashkenazi Jews. 1 PublicationCorresponds to variant dbSNP:rs1013940EnsemblClinVar. | 1 | |
Natural variantiVAR_077856 | 105 | P → S in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs886039766EnsemblClinVar. | 1 | |
Natural variantiVAR_077857 | 111 | Y → H in CMS20; no effect on localization at plasma membrane. 1 Publication | 1 | |
Natural variantiVAR_077858 | 175 | Y → C in CMS20; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1331713195Ensembl. | 1 | |
Natural variantiVAR_077859 | 291 | I → T in CMS20; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs375397889Ensembl. | 1 | |
Natural variantiVAR_077860 | 344 | V → L in CMS20; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_077861 | 361 | R → Q in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs147656110EnsemblClinVar. | 1 | |
Natural variantiVAR_077862 | 418 | F → V in CMS20; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_077863 | 446 | R → G in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF276871 mRNA Translation: AAG25940.1 AB043997 mRNA Translation: BAB18161.1 AJ401466 mRNA Translation: CAC03717.1 AJ308378 , AJ308379, AJ308380, AJ308381, AJ308382, AJ308383, AJ308384 Genomic DNA Translation: CAC88115.1 AC009963 Genomic DNA Translation: AAY14927.1 BC111525 mRNA Translation: AAI11526.1 |
CCDSi | CCDS2074.1 |
PIRi | JC7502 |
RefSeqi | NP_001291934.1, NM_001305005.2 NP_068587.1, NM_021815.4 |
Genome annotation databases
Ensembli | ENST00000264047; ENSP00000264047; ENSG00000115665 ENST00000409059; ENSP00000387346; ENSG00000115665 |
GeneIDi | 60482 |
KEGGi | hsa:60482 |
UCSCi | uc002tdv.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF276871 mRNA Translation: AAG25940.1 AB043997 mRNA Translation: BAB18161.1 AJ401466 mRNA Translation: CAC03717.1 AJ308378 , AJ308379, AJ308380, AJ308381, AJ308382, AJ308383, AJ308384 Genomic DNA Translation: CAC88115.1 AC009963 Genomic DNA Translation: AAY14927.1 BC111525 mRNA Translation: AAI11526.1 |
CCDSi | CCDS2074.1 |
PIRi | JC7502 |
RefSeqi | NP_001291934.1, NM_001305005.2 NP_068587.1, NM_021815.4 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 121915, 4 interactors |
STRINGi | 9606.ENSP00000264047 |
Chemistry databases
BindingDBi | Q9GZV3 |
ChEMBLi | CHEMBL4507 |
DrugBanki | DB00122, Choline DB14006, Choline salicylate |
DrugCentrali | Q9GZV3 |
GuidetoPHARMACOLOGYi | 914 |
Protein family/group databases
TCDBi | 2.A.21.8.2, the solute:sodium symporter (sss) family |
PTM databases
GlyGeni | Q9GZV3, 1 site |
iPTMneti | Q9GZV3 |
PhosphoSitePlusi | Q9GZV3 |
Polymorphism and mutation databases
BioMutai | SLC5A7 |
DMDMi | 56404957 |
Proteomic databases
PaxDbi | Q9GZV3 |
PeptideAtlasi | Q9GZV3 |
PRIDEi | Q9GZV3 |
ProteomicsDBi | 80155 |
Protocols and materials databases
Antibodypediai | 33052, 83 antibodies |
Genome annotation databases
Ensembli | ENST00000264047; ENSP00000264047; ENSG00000115665 ENST00000409059; ENSP00000387346; ENSG00000115665 |
GeneIDi | 60482 |
KEGGi | hsa:60482 |
UCSCi | uc002tdv.4, human |
Organism-specific databases
CTDi | 60482 |
DisGeNETi | 60482 |
EuPathDBi | HostDB:ENSG00000115665.8 |
GeneCardsi | SLC5A7 |
GeneReviewsi | SLC5A7 |
HGNCi | HGNC:14025, SLC5A7 |
HPAi | ENSG00000115665, Tissue enriched (brain) |
MalaCardsi | SLC5A7 |
MIMi | 158580, phenotype 608761, gene 617143, phenotype |
neXtProti | NX_Q9GZV3 |
OpenTargetsi | ENSG00000115665 |
Orphaneti | 139589, Distal hereditary motor neuropathy type 7 98914, Presynaptic congenital myasthenic syndromes |
PharmGKBi | PA37838 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3761, Eukaryota |
GeneTreei | ENSGT00690000101915 |
HOGENOMi | CLU_018808_10_0_1 |
InParanoidi | Q9GZV3 |
OMAi | HSKEIMD |
OrthoDBi | 799628at2759 |
PhylomeDBi | Q9GZV3 |
TreeFami | TF314588 |
Enzyme and pathway databases
PathwayCommonsi | Q9GZV3 |
Reactomei | R-HSA-264642, Acetylcholine Neurotransmitter Release Cycle R-HSA-425366, Transport of bile salts and organic acids, metal ions and amine compounds R-HSA-5619114, Defective SLC5A7 causes distal hereditary motor neuronopathy 7A (HMN7A) R-HSA-5658471, Defective SLC5A7 causes distal hereditary motor neuronopathy 7A (HMN7A) |
Miscellaneous databases
BioGRID-ORCSi | 60482, 5 hits in 840 CRISPR screens |
GeneWikii | Choline_transporter |
GenomeRNAii | 60482 |
Pharosi | Q9GZV3, Tchem |
PROi | PR:Q9GZV3 |
RNActi | Q9GZV3, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000115665, Expressed in muscle layer of sigmoid colon and 78 other tissues |
Genevisiblei | Q9GZV3, HS |
Family and domain databases
Gene3Di | 1.20.1730.10, 1 hit |
InterProi | View protein in InterPro IPR038377, Na/Glc_symporter_sf IPR001734, Na/solute_symporter |
Pfami | View protein in Pfam PF00474, SSF, 1 hit |
PROSITEi | View protein in PROSITE PS50283, NA_SOLUT_SYMP_3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SC5A7_HUMAN | |
Accessioni | Q9GZV3Primary (citable) accession number: Q9GZV3 Secondary accession number(s): Q53TF2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 7, 2004 |
Last sequence update: | March 1, 2001 | |
Last modified: | December 2, 2020 | |
This is version 152 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations