Q9JKZ2 · SC5A3_MOUSE
- 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 (PubMed:12582158, PubMed:24595108).
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 (By similarity) (PubMed:24595108).
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 (PubMed:24595108).
Associates with KCNQ2-KCNQ3 channel altering ion selectivity, increasing Na+ and Cs+ permeation relative to K+ permeation (By similarity).
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 (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 (PubMed:12582158, PubMed:24595108).
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 (By similarity) (PubMed:24595108).
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 (PubMed:24595108).
Associates with KCNQ2-KCNQ3 channel altering ion selectivity, increasing Na+ and Cs+ permeation relative to K+ permeation (By similarity).
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 (By similarity).
(Microbial infection) Functions as a retroviral receptor for M813 murine leukemia virus (MuLV) entry.
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
Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | basolateral plasma membrane | |
Cellular Component | perinuclear region of cytoplasm | |
Cellular Component | plasma membrane | |
Cellular Component | voltage-gated potassium channel complex | |
Molecular Function | glucose:sodium symporter activity | |
Molecular Function | myo-inositol:sodium symporter activity | |
Molecular Function | potassium channel regulator activity | |
Molecular Function | transmembrane transporter binding | |
Biological Process | inositol metabolic process | |
Biological Process | myo-inositol transport | |
Biological Process | peripheral nervous system development | |
Biological Process | positive regulation of catalytic activity | |
Biological Process | positive regulation of protein localization to membrane | |
Biological Process | positive regulation of reactive oxygen species biosynthetic process | |
Biological Process | regulation of respiratory gaseous exchange |
Keywords
- Biological process
- Ligand
Enzyme and pathway 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 > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9JKZ2
- 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: MRAVLEAAD | ||||||
Transmembrane | 10-29 | Helical | ||||
Sequence: IAVVALYFILVMCIGFFAMW | ||||||
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: VYFAALSLLLYIFTKLSVDLY | ||||||
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: LQALLMIIGALTLMVISMV | ||||||
Topological domain | 206-303 | Extracellular | ||||
Sequence: KIGGFEEVKRRYMLASPDVASILLKYNLSNTNACMVHPKANALKMLRDPTDEDVPWPGFILGQTPASVWYWCADQVIVQRVLAAKNIAHAKGSTLMAG | ||||||
Transmembrane | 304-324 | Helical | ||||
Sequence: FLKLLPMFIIVVPGMISRIVF | ||||||
Topological domain | 325-353 | Cytoplasmic | ||||
Sequence: ADEIACINPEHCMQVCGSRAGCSNIAYPR | ||||||
Transmembrane | 354-376 | Helical | ||||
Sequence: LVMTLVPVGLRGLMMAVMIAALM | ||||||
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: KRCNEQGAFYGGMAGFVLGAVRLILAFTYRAPECDQPDNRPGFIKDIH | ||||||
Transmembrane | 511-532 | Helical | ||||
Sequence: YMYVATALFWITGLITVIVSLL | ||||||
Topological domain | 533-695 | Cytoplasmic | ||||
Sequence: TPPPTKDQIRTTTFWSKKTLVTKESCSQKDEPYKMQEKSILQCSENSEVISHTIPNGKSEDSIKGLQPEDVNLLVTCREEGNPVASMGHSEAETPVDAYSNGQAALMGEREREKETENRSRYWKFIDWFCGFKSKSLSKRSLRDLMDEEAVCLQMLEETPQVK | ||||||
Transmembrane | 696-716 | Helical | ||||
Sequence: VILNIGLFAVCSLGIFMFVYF | ||||||
Topological domain | 717-718 | Extracellular | ||||
Sequence: SL |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mutant embryos show brain myo-inositol deficiency and central apnea and die soon after birth due to hypoventilation.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 32 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000105382 | 1-718 | Sodium/myo-inositol cotransporter | |||
Sequence: MRAVLEAADIAVVALYFILVMCIGFFAMWKSNRSTVSGYFLAGRSMTWVAIGASLFVSNIGSEHFIGLAGSGAASGFAVGAWEFNALLLLQLLGWVFIPIYIRSGVYTMPEYLSKRFGGHRIQVYFAALSLLLYIFTKLSVDLYSGALFIQESLGWNLYVSVILLIGMTALLTVTGGLVAVIYTDTLQALLMIIGALTLMVISMVKIGGFEEVKRRYMLASPDVASILLKYNLSNTNACMVHPKANALKMLRDPTDEDVPWPGFILGQTPASVWYWCADQVIVQRVLAAKNIAHAKGSTLMAGFLKLLPMFIIVVPGMISRIVFADEIACINPEHCMQVCGSRAGCSNIAYPRLVMTLVPVGLRGLMMAVMIAALMSDLDSIFNSASTIFTLDVYKLIRKSASSRELMIVGRIFVAFMVVISIAWVPIIVEMQGGQMYLYIQEVADYLTPPVAALFLLAIFWKRCNEQGAFYGGMAGFVLGAVRLILAFTYRAPECDQPDNRPGFIKDIHYMYVATALFWITGLITVIVSLLTPPPTKDQIRTTTFWSKKTLVTKESCSQKDEPYKMQEKSILQCSENSEVISHTIPNGKSEDSIKGLQPEDVNLLVTCREEGNPVASMGHSEAETPVDAYSNGQAALMGEREREKETENRSRYWKFIDWFCGFKSKSLSKRSLRDLMDEEAVCLQMLEETPQVKVILNIGLFAVCSLGIFMFVYFSL | ||||||
Glycosylation | 232 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 594 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 632 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in kidney, placenta, and brain and at a lesser extent in thymus, lung, bladder, and testes (PubMed:12582158).
Expressed in the choroid plexus epithelium (at protein level) (PubMed:24595108).
Expressed in the choroid plexus epithelium (at protein level) (PubMed:24595108).
Developmental stage
Expressed in placenta at 14.5 dpc.
Gene expression databases
Interaction
Structure
Sequence
- Sequence statusComplete
- Length718
- Mass (Da)79,583
- Last updated2011-07-27 v2
- ChecksumD0371D6ECF08503B
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 653 | in Ref. 1; AAF43668 | ||||
Sequence: R → Q |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF220915 EMBL· GenBank· DDBJ | AAF43668.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH466602 EMBL· GenBank· DDBJ | EDL03793.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC140982 EMBL· GenBank· DDBJ | AAI40983.1 EMBL· GenBank· DDBJ | mRNA | ||
BC140983 EMBL· GenBank· DDBJ | AAI40984.1 EMBL· GenBank· DDBJ | mRNA |