SLC9A3
entrez
6550
canonical
uniprot
P48764
canonical
ensembl
ENSG00000066230
resolver
ensp
ENSP00000264938
resolver
ensp
ENSP00000422983
resolver
genesymbol
SLC9A3
resolver
genesymbol_syn
NHE3
resolver
hgnc
HGNC:11073
resolver
uniprot
B7ZKR2
resolver
uniprot
E9PF67
resolver
uniprot
Q3MIW3
resolver
uniprot_entry
SL9A3_HUMAN
resolver
uniprot_sec
B7ZKR2
resolver
uniprot_sec
E9PF67
resolver
uniprot_sec
Q3MIW3
resolver
activity_regulation
ACTIVITY REGULATION: Seems to switch between active and inactive modes in response to various stimuli (PubMed:35613257). Activated directly or indirectly by membrane phosphatidylinositol (PIs) (PubMed:35613257). Regulated by a variety of auxiliary proteins, which facilitate the maturation, cell surface expression and function of the transporter (PubMed:18829453, PubMed:25851603, PubMed:35613257). Inhibited specifically by the drug tenapanor (PubMed:24622516). {ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:24622516, ECO:0000269|PubMed:25851603, ECO:0000269|PubMed:35613257}.
uniprot
proteins
amino_acid_sequence
MWGLGARGPDRGLLLALALGGLARAGGVEVEPGGAHGESGGFQVVTFEWAHVQDPYVIALWILVASLAKIGFHLSHKVTSVVPESALLIVLGLVLGGIVWAADHIASFTLTPTVFFFYLLPPIVLDAGYFMPNRLFFGNLGTILLYAVVGTVWNAATTGLSLYGVFLSGLMGDLQIGLLDFLLFGSLMAAVDPVAVLAVFEEVHVNEVLFIIVFGESLLNDAVTVVLYNVFESFVALGGDNVTGVDCVKGIVSFFVVSLGGTLVGVVFAFLLSLVTRFTKHVRIIEPGFVFIISYLSYLTSEMLSLSAILAITFCGICCQKYVKANISEQSATTVRYTMKMLASSAETIIFMFLGISAVNPFIWTWNTAFVLLTLVFISVYRAIGVVLQTWLLNRYRMVQLEPIDQVVLSYGGLRGAVAFALVVLLDGDKVKEKNLFVSTTIIVVFFTVIFQGLTIKPLVQWLKVKRSEHREPRLNEKLHGRAFDHILSAIEDISGQIGHNYLRDKWSHFDRKFLSRVLMRRSAQKSRDRILNVFHELNLKDAISYVAEGERRGSLAFIRSPSTDNVVNVDFTPRSSTVEASVSYLLRENVSAVCLDMQSLEQRRRSIRDAEDMVTHHTLQQYLYKPRQEYKHLYSRHELTPTEDEKQDREIFHRTMRKRLESFKSTKLGLNQNKKAAKLYKRERAQKRRNSSIPNGKLPMESPAQNFTIKEKDLELSDTEEPPNYDEEMSGGIEFLASVTKDTASDSPAGIDNPVFSPDEALDRSLLARLPPWLSPGETVVPSQRARTQIPYSPGTFCRLMPFRLSSKSVDSFLQADGPEERPPAALPESTHM
uniprot
proteins
disease_involvement
DISEASE: Diarrhea 8, secretory sodium, congenital (DIAR8) [MIM:616868]: A disease characterized by watery secretory diarrhea with prenatal onset, prominent abdominal distension after birth due to dilated fluid-filled loops of intestine, elevated fecal sodium concentrations and low urinary sodium concentrations. {ECO:0000269|PubMed:26358773, ECO:0000269|PubMed:31276831}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Plasma membrane Na(+)/H(+) antiporter (PubMed:18829453, PubMed:26358773, PubMed:35613257). Exchanges intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry, playing a key role in salt and fluid absorption and pH homeostasis (By similarity). Major apical Na(+)/H(+) exchanger in kidney and intestine playing an important role in renal and intestine Na(+) absorption and blood pressure regulation (PubMed:24622516, PubMed:26358773). {ECO:0000250|UniProtKB:G3X939, ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:24622516, ECO:0000269|PubMed:26358773, ECO:0000269|PubMed:35613257}.
uniprot
proteins
mass_dalton
92855
uniprot
proteins
mutagenesis
MUTAGEN 397; /note="R->A,D: Abolishes sodium:proton antiporter activity. Does not affect cell membrane expression or localization to recycling endosomes."; /evidence="ECO:0000269|PubMed:35613257"; MUTAGEN 500; /note="H->A,D: Increases sodium:proton antiporter activity."; /evidence="ECO:0000269|PubMed:35613257"; MUTAGEN 635; /note="Y->A: Decreases cell membrane expression. Increases sodium:proton antiporter activity."; /evidence="ECO:0000269|PubMed:35613257"; MUTAGEN 637; /note="R->A: Increases sodium:proton antiporter activity; when associated with A-638."; /evidence="ECO:0000269|PubMed:35613257"; MUTAGEN 638; /note="H->A: Increases sodium:proton antiporter activity; when associated with A-638."; /evidence="ECO:0000269|PubMed:35613257
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by PKA, which inhibits activity. Phosphorylation at Ser-663 by SGK1 is associated with increased abundance at the cell membrane. Phosphorylation at Ser-718 by CSNK2A1 regulates SLC9A3 activity through the formation of multiple signaling complexes (By similarity). {ECO:0000250|UniProtKB:P26432, ECO:0000250|UniProtKB:P26433}.
uniprot
proteins
protein_family
Monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18829453
uniprot
proteins
pubmed
19088451
uniprot
proteins
pubmed
20584908
uniprot
proteins
pubmed
24622516
uniprot
proteins
pubmed
25851603
uniprot
proteins
pubmed
26358773
uniprot
proteins
pubmed
31276831
uniprot
proteins
pubmed
35613257
uniprot
proteins
pubmed
7631746
uniprot
proteins
sequence_length
834
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000269|PubMed:19088451, ECO:0000269|PubMed:26358773}; Multi-pass membrane protein {ECO:0000269|PubMed:35613257}. Cell membrane {ECO:0000269|PubMed:25851603, ECO:0000269|PubMed:35613257}; Multi-pass membrane protein {ECO:0000269|PubMed:35613257}. Recycling endosome membrane {ECO:0000269|PubMed:35613257}; Multi-pass membrane protein {ECO:0000269|PubMed:35613257}. Early endosome membrane {ECO:0000269|PubMed:25851603}; Multi-pass membrane protein {ECO:0000269|PubMed:35613257}. 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). {ECO:0000250|UniProtKB:Q28362}.
uniprot
proteins
transmembrane_region
TRANSMEM 52..74; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 83..102; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 112..129; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 133..168; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 182..203; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 206..237; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 245..279; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 282..304; /note="Helical; Name=8"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 307..323; /note="Helical; Name=9"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 331..359; /note="Helical; Name=10"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 368..389; /note="Helical; Name=11"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 403..426; /note="Helical; Name=12"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U"; TRANSMEM 434..467; /note="Helical; Name=13"; /evidence="ECO:0000269|PubMed:35613257, ECO:0000312|PDB:7X2U
uniprot
proteins