M5A7P9 · SL9A3_TRISC
- ProteinSodium/hydrogen exchanger 3
- Geneslc9a3
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids832 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plasma membrane Na+/H+ antiporter. Exchanges intracellular H+ ions for extracellular Na+ in 1:1 stoichiometry, playing a key role in salt and fluid absorption and pH homeostasis. Major apical Na+/H+ exchanger in kidney and intestine playing an important role in renal and intestine Na+ absorption and blood pressure regulation.
Catalytic activity
- H+(out) + Na+(in) = H+(in) + Na+(out)
Activity regulation
Seems to switch between active and inactive modes in response to various stimuli (By similarity).
Activated directly or indirectly by membrane phosphatidylinositol (PIs) (By similarity).
Regulated by a variety of auxiliary proteins, which facilitate the maturation, cell surface expression and function of the transporter. Inhibited specifically by the drug tenapanor (By similarity).
Activated directly or indirectly by membrane phosphatidylinositol (PIs) (By similarity).
Regulated by a variety of auxiliary proteins, which facilitate the maturation, cell surface expression and function of the transporter. Inhibited specifically by the drug tenapanor (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 153 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 156 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 157 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 512 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 513 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 515 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) (UniProtKB | ChEBI) | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | brush border membrane | |
Cellular Component | early endosome membrane | |
Cellular Component | plasma membrane | |
Cellular Component | recycling endosome membrane | |
Molecular Function | identical protein binding | |
Molecular Function | phosphatidylinositol binding | |
Molecular Function | potassium:proton antiporter activity | |
Molecular Function | sodium:proton antiporter activity | |
Biological Process | regulation of intracellular pH | |
Biological Process | sodium ion import across plasma membrane |
Keywords
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameSodium/hydrogen exchanger 3
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Chondrichthyes > Elasmobranchii > Galeomorphii > Galeoidea > Carcharhiniformes > Triakidae > Triakis
Accessions
- Primary accessionM5A7P9
- Secondary accessions
Subcellular Location
UniProt Annotation
GO Annotation
Apical cell membrane ; Multi-pass membrane protein
Cell membrane ; Multi-pass membrane protein
Recycling endosome membrane ; Multi-pass membrane protein
Early endosome membrane ; Multi-pass membrane protein
Note: In intestinal epithelial cells, localizes to the ileal brush border. Phosphorylation at Ser-663 by SGK1 is associated with increased abundance at the cell membrane. Angiotensin-2 enhances apical expression (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 30-66 | Extracellular | ||||
Sequence: SEAETDPDSHTEHGDSHGGSREGNDTGFQIVTFRWEH | ||||||
Transmembrane | 67-89 | Helical; Name=1 | ||||
Sequence: VQTPYVIALWILVASLGKIVFHL | ||||||
Topological domain | 90-97 | Cytoplasmic | ||||
Sequence: SEKVTSVV | ||||||
Transmembrane | 98-117 | Helical; Name=2 | ||||
Sequence: PESALLIVLGLILGGIVWAA | ||||||
Topological domain | 118-126 | Extracellular | ||||
Sequence: DHSASFTLT | ||||||
Transmembrane | 127-144 | Helical; Name=3 | ||||
Sequence: PTVFFFYLLPPIVLDAGY | ||||||
Topological domain | 145-147 | Cytoplasmic | ||||
Sequence: FMP | ||||||
Transmembrane | 148-183 | Helical; Name=4 | ||||
Sequence: NRHFFGNLGTILTYAVIGTVWNAATTGLSLYGVFLL | ||||||
Topological domain | 184-196 | Extracellular | ||||
Sequence: GLMGDLKAGLLEF | ||||||
Transmembrane | 197-218 | Helical; Name=5 | ||||
Sequence: LLFGSLIAAVDPVAVLAVFEEV | ||||||
Topological domain | 219-220 | Cytoplasmic | ||||
Sequence: HV | ||||||
Transmembrane | 221-252 | Helical; Name=6 | ||||
Sequence: NEVLFIIVFGESLLNDAVTVVLYNVFNSFVEV | ||||||
Topological domain | 253-259 | Extracellular | ||||
Sequence: GAGNVQG | ||||||
Transmembrane | 260-294 | Helical; Name=7 | ||||
Sequence: LDYFKGIVSFFVVSLGGTAVGIIFAFILSLVTRFT | ||||||
Topological domain | 295-296 | Cytoplasmic | ||||
Sequence: KH | ||||||
Transmembrane | 297-319 | Helical; Name=8 | ||||
Sequence: VRVIEPGFVFVISYLSYLTADML | ||||||
Topological domain | 320-321 | Extracellular | ||||
Sequence: SL | ||||||
Transmembrane | 322-338 | Helical; Name=9 | ||||
Sequence: SAILAITFCGICCQKYV | ||||||
Topological domain | 339-345 | Cytoplasmic | ||||
Sequence: KANLCEQ | ||||||
Transmembrane | 346-374 | Helical; Name=10 | ||||
Sequence: SITTVRYAMKMLASGAETIIFMFLGISAV | ||||||
Topological domain | 375-382 | Extracellular | ||||
Sequence: NPTIWTWN | ||||||
Transmembrane | 383-404 | Helical; Name=11 | ||||
Sequence: TAFILLTLVFISVYRVIGVVIQ | ||||||
Topological domain | 405-417 | Cytoplasmic | ||||
Sequence: TWILNHYRVVQLE | ||||||
Transmembrane | 418-441 | Helical; Name=12 | ||||
Sequence: IIDQVVMSYGGLRGAVAFALVVLL | ||||||
Topological domain | 442-448 | Extracellular | ||||
Sequence: DSNYVGE | ||||||
Transmembrane | 449-482 | Helical; Name=13 | ||||
Sequence: RRLFVSTTIIVVYFTVIFQGLTIKPLVKWLKVKR | ||||||
Topological domain | 483-832 | Cytoplasmic | ||||
Sequence: SQHKEPLLNEKLHGRAFDHILSAIEDISGQIGHNYLRDKWTNFDRKYLSKIMMRKSAQISRDKILSVFRELNLKDAISYVSEGERKGSLAFIRSSSDVNVDFTGPRHSVVDSSVSAVLRESTSEVCLDMHAVENRAKSPKDREEIVTHHMLQQHLYKPRKRYRLNYSRHKLARSEGEKQDKEIFQRTMKKRLENFKPTKLGTNYTTKFRNMKKERAAKKKHSDAVPNGRLATHSVSFHVNKDSEVEDPADGGISFLITPASNDADETGTGIDNPSFSNEEDQSIYQMIPPWISNEETVIPSQRARLQIPRSPTNFRRLTPLQLSNRSIDAFLLADISDEHPLSFLPESSM |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-29 | |||||
Sequence: MGRNRSGCVARCVSLTALVLLLCCPVVRS | ||||||
Chain | PRO_0000423519 | 30-832 | Sodium/hydrogen exchanger 3 | |||
Sequence: SEAETDPDSHTEHGDSHGGSREGNDTGFQIVTFRWEHVQTPYVIALWILVASLGKIVFHLSEKVTSVVPESALLIVLGLILGGIVWAADHSASFTLTPTVFFFYLLPPIVLDAGYFMPNRHFFGNLGTILTYAVIGTVWNAATTGLSLYGVFLLGLMGDLKAGLLEFLLFGSLIAAVDPVAVLAVFEEVHVNEVLFIIVFGESLLNDAVTVVLYNVFNSFVEVGAGNVQGLDYFKGIVSFFVVSLGGTAVGIIFAFILSLVTRFTKHVRVIEPGFVFVISYLSYLTADMLSLSAILAITFCGICCQKYVKANLCEQSITTVRYAMKMLASGAETIIFMFLGISAVNPTIWTWNTAFILLTLVFISVYRVIGVVIQTWILNHYRVVQLEIIDQVVMSYGGLRGAVAFALVVLLDSNYVGERRLFVSTTIIVVYFTVIFQGLTIKPLVKWLKVKRSQHKEPLLNEKLHGRAFDHILSAIEDISGQIGHNYLRDKWTNFDRKYLSKIMMRKSAQISRDKILSVFRELNLKDAISYVSEGERKGSLAFIRSSSDVNVDFTGPRHSVVDSSVSAVLRESTSEVCLDMHAVENRAKSPKDREEIVTHHMLQQHLYKPRKRYRLNYSRHKLARSEGEKQDKEIFQRTMKKRLENFKPTKLGTNYTTKFRNMKKERAAKKKHSDAVPNGRLATHSVSFHVNKDSEVEDPADGGISFLITPASNDADETGTGIDNPSFSNEEDQSIYQMIPPWISNEETVIPSQRARLQIPRSPTNFRRLTPLQLSNRSIDAFLLADISDEHPLSFLPESSM |
Keywords
- PTM
Expression
Tissue specificity
Detected in early distal renal tubules in the kidney bundle zone, in proximal and late distal tubules in the kidney sinus zone, in absorptive epithelial cells of the intestine and in rectal epithelium (at protein level). Isoform 1 is expressed strongly in the gills, at intermediate levels in the kidney, spleen, rectum, spiral intestine and skin, and weakly in the brain, blood and rectal gland. Isoform 2 is expressed strongly in the kidney, rectum and spiral intestine, and weakly in muscles and the rectal gland.
Induction
High salinity induces expression of isoform 2 in the kidney; conversely, low salinity induces expression in the intestine.
Interaction
Subunit
Homodimer.
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 31-51 | Disordered | ||||
Sequence: EAETDPDSHTEHGDSHGGSRE | ||||||
Compositional bias | 32-49 | Basic and acidic residues | ||||
Sequence: AETDPDSHTEHGDSHGGS | ||||||
Region | 740-760 | Disordered | ||||
Sequence: TPASNDADETGTGIDNPSFSN | ||||||
Compositional bias | 742-760 | Polar residues | ||||
Sequence: ASNDADETGTGIDNPSFSN |
Domain
The C-terminal intracellular domain is subject to extensive post-translational modifications and binding partner interactions which regulate transporter activity, scaffolding functions, downstream events and localization.
Sequence similarities
Keywords
- Domain
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative promoter usage.
M5A7P9-1
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.
- Name1
- Synonymsg
- Length832
- Mass (Da)92,913
- Last updated2013-05-29 v1
- Checksum6ACB728455A4759C
M5A7P9-2
- Name2
- Synonymsk/i
- Differences from canonical
- 1-83: MGRNRSGCVARCVSLTALVLLLCCPVVRSSEAETDPDSHTEHGDSHGGSREGNDTGFQIVTFRWEHVQTPYVIALWILVASLG → MGKERSQCAGSRCLWSLALLAAGCSAAGTFSRSEPSAESQSSPQNSSNPGYQIVYFDWEYVEKPYVVAGWILVAGLA
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_047941 | 1-83 | in isoform 2 | |||
Sequence: MGRNRSGCVARCVSLTALVLLLCCPVVRSSEAETDPDSHTEHGDSHGGSREGNDTGFQIVTFRWEHVQTPYVIALWILVASLG → MGKERSQCAGSRCLWSLALLAAGCSAAGTFSRSEPSAESQSSPQNSSNPGYQIVYFDWEYVEKPYVVAGWILVAGLA | ||||||
Compositional bias | 32-49 | Basic and acidic residues | ||||
Sequence: AETDPDSHTEHGDSHGGS | ||||||
Compositional bias | 742-760 | Polar residues | ||||
Sequence: ASNDADETGTGIDNPSFSN |
Keywords
- Coding sequence diversity