P53794 · SC5A3_HUMAN
- ProteinSodium/myo-inositol cotransporter
- GeneSLC5A3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids718 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Electrogenic Na+-coupled sugar symporter that actively transports myo-inositol and its stereoisomer scyllo-inositol across the plasma membrane, with a Na+ to sugar coupling ratio of 2:1 (By similarity).
Maintains myo-inositol concentration gradient that defines cell volume and fluid balance during osmotic stress, in particular in the fetoplacental unit and central nervous system (By similarity).
Forms coregulatory complexes with voltage-gated K+ ion channels, allosterically altering ion selectivity, voltage dependence and gating kinetics of the channel. In turn, K+ efflux through the channel forms a local electrical gradient that modulates electrogenic Na+-coupled myo-inositol influx through the transporter (PubMed:24595108, PubMed:28793216).
Associates with KCNQ1-KCNE2 channel in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (By similarity) (PubMed:24595108).
Associates with KCNQ2-KCNQ3 channel altering ion selectivity, increasing Na+ and Cs+ permeation relative to K+ permeation (PubMed:28793216).
Provides myo-inositol precursor for biosynthesis of phosphoinositides such as PI(4,5)P2, thus indirectly affecting the activity of phosphoinositide-dependent ion channels and Ca2+ signaling upon osmotic stress (PubMed:27217553).
Maintains myo-inositol concentration gradient that defines cell volume and fluid balance during osmotic stress, in particular in the fetoplacental unit and central nervous system (By similarity).
Forms coregulatory complexes with voltage-gated K+ ion channels, allosterically altering ion selectivity, voltage dependence and gating kinetics of the channel. In turn, K+ efflux through the channel forms a local electrical gradient that modulates electrogenic Na+-coupled myo-inositol influx through the transporter (PubMed:24595108, PubMed:28793216).
Associates with KCNQ1-KCNE2 channel in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (By similarity) (PubMed:24595108).
Associates with KCNQ2-KCNQ3 channel altering ion selectivity, increasing Na+ and Cs+ permeation relative to K+ permeation (PubMed:28793216).
Provides myo-inositol precursor for biosynthesis of phosphoinositides such as PI(4,5)P2, thus indirectly affecting the activity of phosphoinositide-dependent ion channels and Ca2+ signaling upon osmotic stress (PubMed:27217553).
Catalytic activity
- myo-inositol(out) + 2 Na+(out) = myo-inositol(in) + 2 Na+(in)myo-inositol (out)CHEBI:17268
+ 2 Na+ (out)CHEBI:29101= myo-inositol (in)CHEBI:17268+ 2 Na+ (in)CHEBI:29101 - 2 Na+(out) + scyllo-inositol(out) = 2 Na+(in) + scyllo-inositol(in)
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 24 | Implicated in sodium coupling | ||||
Sequence: G | ||||||
Site | 285 | Implicated in sodium coupling | ||||
Sequence: R |
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSodium/myo-inositol cotransporter
- Short namesNa(+)/myo-inositol cotransporter
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP53794
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Apical cell membrane ; Multi-pass membrane protein
Basolateral cell membrane ; Multi-pass membrane protein
Note: Colocalizes with KCNQ1 at the apical membrane of choroid plexus epithelium.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-9 | Extracellular | ||||
Sequence: MRAVLDTAD | ||||||
Transmembrane | 10-29 | Helical | ||||
Sequence: IAIVALYFILVMCIGFFAMW | ||||||
Topological domain | 30-38 | Cytoplasmic | ||||
Sequence: KSNRSTVSG | ||||||
Transmembrane | 39-57 | Helical | ||||
Sequence: YFLAGRSMTWVAIGASLFV | ||||||
Topological domain | 58-86 | Extracellular | ||||
Sequence: SNIGSEHFIGLAGSGAASGFAVGAWEFNA | ||||||
Transmembrane | 87-110 | Helical | ||||
Sequence: LLLLQLLGWVFIPIYIRSGVYTMP | ||||||
Topological domain | 111-123 | Cytoplasmic | ||||
Sequence: EYLSKRFGGHRIQ | ||||||
Transmembrane | 124-144 | Helical | ||||
Sequence: VYFAALSLILYIFTKLSVDLY | ||||||
Topological domain | 145-157 | Extracellular | ||||
Sequence: SGALFIQESLGWN | ||||||
Transmembrane | 158-183 | Helical | ||||
Sequence: LYVSVILLIGMTALLTVTGGLVAVIY | ||||||
Topological domain | 184-186 | Cytoplasmic | ||||
Sequence: TDT | ||||||
Transmembrane | 187-205 | Helical | ||||
Sequence: LQALLMIIGALTLMIISIM | ||||||
Topological domain | 206-303 | Extracellular | ||||
Sequence: EIGGFEEVKRRYMLASPDVTSILLTYNLSNTNSCNVSPKKEALKMLRNPTDEDVPWPGFILGQTPASVWYWCADQVIVQRVLAAKNIAHAKGSTLMAG | ||||||
Transmembrane | 304-324 | Helical | ||||
Sequence: FLKLLPMFIIVVPGMISRILF | ||||||
Topological domain | 325-353 | Cytoplasmic | ||||
Sequence: TDDIACINPEHCMLVCGSRAGCSNIAYPR | ||||||
Transmembrane | 354-376 | Helical | ||||
Sequence: LVMKLVPVGLRGLMMAVMIAALM | ||||||
Topological domain | 377-406 | Extracellular | ||||
Sequence: SDLDSIFNSASTIFTLDVYKLIRKSASSRE | ||||||
Transmembrane | 407-430 | Helical | ||||
Sequence: LMIVGRIFVAFMVVISIAWVPIIV | ||||||
Topological domain | 431-443 | Cytoplasmic | ||||
Sequence: EMQGGQMYLYIQE | ||||||
Transmembrane | 444-462 | Helical | ||||
Sequence: VADYLTPPVAALFLLAIFW | ||||||
Topological domain | 463-510 | Extracellular | ||||
Sequence: KRCNEQGAFYGGMAGFVLGAVRLILAFAYRAPECDQPDNRPGFIKDIH | ||||||
Transmembrane | 511-532 | Helical | ||||
Sequence: YMYVATGLFWVTGLITVIVSLL | ||||||
Topological domain | 533-695 | Cytoplasmic | ||||
Sequence: TPPPTKEQIRTTTFWSKKNLVVKENCSPKEEPYKMQEKSILRCSENNETINHIIPNGKSEDSIKGLQPEDVNLLVTCREEGNPVASLGHSEAETPVDAYSNGQAALMGEKERKKETDDGGRYWKFIDWFCGFKSKSLSKRSLRDLMEEEAVCLQMLEETRQVK | ||||||
Transmembrane | 696-716 | Helical | ||||
Sequence: VILNIGLFAVCSLGIFMFVYF | ||||||
Topological domain | 717-718 | Extracellular | ||||
Sequence: SL |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_061875 | 50 | in dbSNP:rs8129891 | |||
Sequence: A → T | ||||||
Natural variant | VAR_061876 | 566 | in dbSNP:rs4817617 | |||
Sequence: K → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 598 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), glycosylation, modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000105381 | 1-718 | UniProt | Sodium/myo-inositol cotransporter | |||
Sequence: MRAVLDTADIAIVALYFILVMCIGFFAMWKSNRSTVSGYFLAGRSMTWVAIGASLFVSNIGSEHFIGLAGSGAASGFAVGAWEFNALLLLQLLGWVFIPIYIRSGVYTMPEYLSKRFGGHRIQVYFAALSLILYIFTKLSVDLYSGALFIQESLGWNLYVSVILLIGMTALLTVTGGLVAVIYTDTLQALLMIIGALTLMIISIMEIGGFEEVKRRYMLASPDVTSILLTYNLSNTNSCNVSPKKEALKMLRNPTDEDVPWPGFILGQTPASVWYWCADQVIVQRVLAAKNIAHAKGSTLMAGFLKLLPMFIIVVPGMISRILFTDDIACINPEHCMLVCGSRAGCSNIAYPRLVMKLVPVGLRGLMMAVMIAALMSDLDSIFNSASTIFTLDVYKLIRKSASSRELMIVGRIFVAFMVVISIAWVPIIVEMQGGQMYLYIQEVADYLTPPVAALFLLAIFWKRCNEQGAFYGGMAGFVLGAVRLILAFAYRAPECDQPDNRPGFIKDIHYMYVATGLFWVTGLITVIVSLLTPPPTKEQIRTTTFWSKKNLVVKENCSPKEEPYKMQEKSILRCSENNETINHIIPNGKSEDSIKGLQPEDVNLLVTCREEGNPVASLGHSEAETPVDAYSNGQAALMGEKERKKETDDGGRYWKFIDWFCGFKSKSLSKRSLRDLMEEEAVCLQMLEETRQVKVILNIGLFAVCSLGIFMFVYFSL | |||||||
Modified residue (large scale data) | 37 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Glycosylation | 232 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue (large scale data) | 591 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 594 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 594 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 632 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 632 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Structure
Sequence
- Sequence statusComplete
- Length718
- Mass (Da)79,664
- Last updated2024-01-24 v4
- ChecksumE83EFF81DBF567BB
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 31 | in Ref. 1; AAC41747 | ||||
Sequence: S → C |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L38500 EMBL· GenBank· DDBJ | AAC41747.2 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF027153 EMBL· GenBank· DDBJ | AAC39548.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AP001719 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |