UniProtKB - P48764 (SL9A3_HUMAN)
Sodium/hydrogen exchanger 3
SLC9A3
Functioni
Caution
GO - Molecular functioni
- PDZ domain binding Source: UniProtKB
- potassium:proton antiporter activity Source: GO_Central
- sodium:proton antiporter activity Source: UniProtKB
GO - Biological processi
- ion transport Source: Reactome
- potassium ion transmembrane transport Source: GO_Central
- regulation of intracellular pH Source: GO_Central
- sodium ion import across plasma membrane Source: UniProtKB
Keywordsi
Biological process | Antiport, Ion transport, Sodium transport, Transport |
Ligand | Sodium |
Enzyme and pathway databases
PathwayCommonsi | P48764 |
Reactomei | R-HSA-425986, Sodium/Proton exchangers |
SIGNORi | P48764 |
Protein family/group databases
TCDBi | 2.A.36.1.15, the monovalent cation:proton antiporter-1 (cpa1) family |
Names & Taxonomyi
Protein namesi | Recommended name: Sodium/hydrogen exchanger 3CuratedAlternative name(s): Na(+)/H(+) exchanger 31 Publication Short name: NHE-31 Publication Solute carrier family 9 member 3 |
Gene namesi | |
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:ENSG00000066230.10 |
HGNCi | HGNC:11073, SLC9A3 |
MIMi | 182307, gene |
neXtProti | NX_P48764 |
Subcellular locationi
Plasma membrane
- Apical cell membrane 2 Publications; Multi-pass membrane protein 1 Publication
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).By similarity
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Plasma Membrane
- apical plasma membrane Source: UniProtKB
- brush border membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- brush border Source: UniProtKB
- cell surface Source: UniProtKB
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 12 | CytoplasmicSequence analysisAdd BLAST | 12 | |
Intramembranei | 13 – 24 | Name=A/M1Sequence analysisAdd BLAST | 12 | |
Topological domaini | 25 – 54 | CytoplasmicSequence analysisAdd BLAST | 30 | |
Intramembranei | 55 – 73 | Name=B/M2Sequence analysisAdd BLAST | 19 | |
Topological domaini | 74 – 79 | CytoplasmicSequence analysis | 6 | |
Transmembranei | 80 – 99 | Helical; Name=C/M3Sequence analysisAdd BLAST | 20 | |
Topological domaini | 100 – 112 | ExtracellularSequence analysisAdd BLAST | 13 | |
Transmembranei | 113 – 133 | Helical; Name=D/M4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 134 – 139 | CytoplasmicSequence analysis | 6 | |
Transmembranei | 140 – 160 | Helical; Name=E/M5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 161 – 180 | ExtracellularSequence analysisAdd BLAST | 20 | |
Transmembranei | 181 – 202 | Helical; Name=F/M5ASequence analysisAdd BLAST | 22 | |
Topological domaini | 203 – 210 | CytoplasmicSequence analysis | 8 | |
Transmembranei | 211 – 232 | Helical; Name=G/M5BSequence analysisAdd BLAST | 22 | |
Topological domaini | 233 – 252 | ExtracellularSequence analysisAdd BLAST | 20 | |
Transmembranei | 253 – 274 | Helical; Name=H/M6Sequence analysisAdd BLAST | 22 | |
Topological domaini | 275 – 290 | CytoplasmicSequence analysisAdd BLAST | 16 | |
Transmembranei | 291 – 309 | Helical; Name=I/M7Sequence analysisAdd BLAST | 19 | |
Topological domaini | 310 – 340 | ExtracellularSequence analysisAdd BLAST | 31 | |
Transmembranei | 341 – 362 | Helical; Name=J/M8Sequence analysisAdd BLAST | 22 | |
Topological domaini | 363 – 369 | CytoplasmicSequence analysis | 7 | |
Transmembranei | 370 – 390 | Helical; Name=K/M9Sequence analysisAdd BLAST | 21 | |
Topological domaini | 391 – 405 | ExtracellularSequence analysisAdd BLAST | 15 | |
Intramembranei | 406 – 426 | Name=LSequence analysisAdd BLAST | 21 | |
Topological domaini | 427 – 435 | ExtracellularSequence analysis | 9 | |
Transmembranei | 436 – 456 | Helical; Name=M/M10Sequence analysisAdd BLAST | 21 | |
Topological domaini | 457 – 834 | CytoplasmicSequence analysisAdd BLAST | 378 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Involvement in diseasei
Diarrhea 8, secretory sodium, congenital (DIAR8)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_076419 | 127 | A → T in DIAR8; unknown pathological significance; does not affect cell membrane localization; reduces weakly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs1047334552Ensembl. | 1 | |
Natural variantiVAR_076420 | 269 | A → T in DIAR8; decreases cell membrane expression; reduces Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs869312807EnsemblClinVar. | 1 | |
Natural variantiVAR_076421 | 311 | A → V in DIAR8; decreases cell membrane expression; reduces strongly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs869312806EnsemblClinVar. | 1 | |
Natural variantiVAR_076422 | 382 | R → Q in DIAR8; decreases cell membrane localization; reduces strongly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs766076524EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 6550 |
MalaCardsi | SLC9A3 |
MIMi | 616868, phenotype |
OpenTargetsi | ENSG00000066230 |
Orphaneti | 103908, Congenital sodium diarrhea |
PharmGKBi | PA316 |
Miscellaneous databases
Pharosi | P48764, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3273 |
DrugBanki | DB11761, Tenapanor |
Polymorphism and mutation databases
BioMutai | SLC9A3 |
DMDMi | 269849652 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000052356 | 1 – 834 | Sodium/hydrogen exchanger 3Add BLAST | 834 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 241 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 326 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 555 | PhosphoserineBy similarity | 1 | |
Modified residuei | 563 | PhosphoserineBy similarity | 1 | |
Modified residuei | 592 | PhosphoserineBy similarity | 1 | |
Modified residuei | 607 | PhosphoserineBy similarity | 1 | |
Modified residuei | 663 | Phosphoserine; by SGK1By similarity | 1 | |
Modified residuei | 810 | PhosphoserineBy similarity | 1 | |
Modified residuei | 813 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
jPOSTi | P48764 |
MassIVEi | P48764 |
PaxDbi | P48764 |
PeptideAtlasi | P48764 |
PRIDEi | P48764 |
ProteomicsDBi | 20040 55946 [P48764-1] |
PTM databases
GlyGeni | P48764, 2 sites |
iPTMneti | P48764 |
PhosphoSitePlusi | P48764 |
Expressioni
Gene expression databases
Bgeei | ENSG00000066230, Expressed in cortex of kidney and 108 other tissues |
ExpressionAtlasi | P48764, baseline and differential |
Genevisiblei | P48764, HS |
Organism-specific databases
HPAi | ENSG00000066230, Tissue enhanced (gallbladder, intestine, kidney) |
Interactioni
Subunit structurei
Binds SLC9A3R1 and SLC9A3R2.
Interacts with CHP1, CHP2 and SHANK2.
Interacts with PDZK1 (via C-terminal PDZ domain) (By similarity).
Interacts with PDZD3 and interactions decrease in response to elevated calcium ion levels.
Interacts with AHCYL1; the interaction is required for SLC9A3 activity (PubMed:18829453, PubMed:20584908).
By similarity3 PublicationsBinary interactionsi
P48764
With | #Exp. | IntAct |
---|---|---|
MAST2 [Q6P0Q8] | 2 | EBI-7816923,EBI-493777 |
GO - Molecular functioni
- PDZ domain binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 112440, 9 interactors |
CORUMi | P48764 |
IntActi | P48764, 1 interactor |
MINTi | P48764 |
STRINGi | 9606.ENSP00000264938 |
Chemistry databases
BindingDBi | P48764 |
Miscellaneous databases
RNActi | P48764, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 590 – 667 | Interaction with PDZD3By similarityAdd BLAST | 78 |
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1966, Eukaryota |
GeneTreei | ENSGT00940000158616 |
HOGENOMi | CLU_005912_4_2_1 |
InParanoidi | P48764 |
OMAi | MVQLELI |
OrthoDBi | 389547at2759 |
PhylomeDBi | P48764 |
TreeFami | TF317212 |
Family and domain databases
InterProi | View protein in InterPro IPR006153, Cation/H_exchanger IPR018422, Cation/H_exchanger_CPA1 IPR018410, Na/H_exchanger_3/5 IPR004709, NaH_exchanger |
PANTHERi | PTHR10110, PTHR10110, 1 hit |
Pfami | View protein in Pfam PF00999, Na_H_Exchanger, 1 hit |
PRINTSi | PR01084, NAHEXCHNGR PR01087, NAHEXCHNGR3 |
TIGRFAMsi | TIGR00840, b_cpa1, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MWGLGARGPD RGLLLALALG GLARAGGVEV EPGGAHGESG GFQVVTFEWA
60 70 80 90 100
HVQDPYVIAL WILVASLAKI GFHLSHKVTS VVPESALLIV LGLVLGGIVW
110 120 130 140 150
AADHIASFTL TPTVFFFYLL PPIVLDAGYF MPNRLFFGNL GTILLYAVVG
160 170 180 190 200
TVWNAATTGL SLYGVFLSGL MGDLQIGLLD FLLFGSLMAA VDPVAVLAVF
210 220 230 240 250
EEVHVNEVLF IIVFGESLLN DAVTVVLYNV FESFVALGGD NVTGVDCVKG
260 270 280 290 300
IVSFFVVSLG GTLVGVVFAF LLSLVTRFTK HVRIIEPGFV FIISYLSYLT
310 320 330 340 350
SEMLSLSAIL AITFCGICCQ KYVKANISEQ SATTVRYTMK MLASSAETII
360 370 380 390 400
FMFLGISAVN PFIWTWNTAF VLLTLVFISV YRAIGVVLQT WLLNRYRMVQ
410 420 430 440 450
LEPIDQVVLS YGGLRGAVAF ALVVLLDGDK VKEKNLFVST TIIVVFFTVI
460 470 480 490 500
FQGLTIKPLV QWLKVKRSEH REPRLNEKLH GRAFDHILSA IEDISGQIGH
510 520 530 540 550
NYLRDKWSHF DRKFLSRVLM RRSAQKSRDR ILNVFHELNL KDAISYVAEG
560 570 580 590 600
ERRGSLAFIR SPSTDNVVNV DFTPRSSTVE ASVSYLLREN VSAVCLDMQS
610 620 630 640 650
LEQRRRSIRD AEDMVTHHTL QQYLYKPRQE YKHLYSRHEL TPTEDEKQDR
660 670 680 690 700
EIFHRTMRKR LESFKSTKLG LNQNKKAAKL YKRERAQKRR NSSIPNGKLP
710 720 730 740 750
MESPAQNFTI KEKDLELSDT EEPPNYDEEM SGGIEFLASV TKDTASDSPA
760 770 780 790 800
GIDNPVFSPD EALDRSLLAR LPPWLSPGET VVPSQRARTQ IPYSPGTFCR
810 820 830
LMPFRLSSKS VDSFLQADGP EERPPAALPE STHM
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A2R8Y780 | A0A2R8Y780_HUMAN | Sodium/hydrogen exchanger | SLC9A3 | 889 | Annotation score: | ||
A0A0G2JQZ3 | A0A0G2JQZ3_HUMAN | Sodium/hydrogen exchanger 3 | SLC9A3 | 70 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_076419 | 127 | A → T in DIAR8; unknown pathological significance; does not affect cell membrane localization; reduces weakly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs1047334552Ensembl. | 1 | |
Natural variantiVAR_076420 | 269 | A → T in DIAR8; decreases cell membrane expression; reduces Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs869312807EnsemblClinVar. | 1 | |
Natural variantiVAR_076421 | 311 | A → V in DIAR8; decreases cell membrane expression; reduces strongly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs869312806EnsemblClinVar. | 1 | |
Natural variantiVAR_076422 | 382 | R → Q in DIAR8; decreases cell membrane localization; reduces strongly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs766076524EnsemblClinVar. | 1 | |
Natural variantiVAR_060593 | 799 | C → R2 PublicationsCorresponds to variant dbSNP:rs2247114Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_053989 | 452 – 460 | Missing in isoform 2. 1 Publication | 9 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U28043 mRNA Translation: AAB48990.1 AC010442 Genomic DNA No translation available. AC106772 Genomic DNA No translation available. BC101669 mRNA Translation: AAI01670.1 BC101671 mRNA Translation: AAI01672.1 BC143328 mRNA Translation: AAI43329.1 |
CCDSi | CCDS3855.1 [P48764-1] CCDS64116.1 [P48764-2] |
PIRi | B40205 |
RefSeqi | NP_001271280.1, NM_001284351.2 [P48764-2] NP_004165.2, NM_004174.3 [P48764-1] |
Genome annotation databases
Ensembli | ENST00000264938; ENSP00000264938; ENSG00000066230 [P48764-1] ENST00000514375; ENSP00000422983; ENSG00000066230 [P48764-2] |
GeneIDi | 6550 |
KEGGi | hsa:6550 |
UCSCi | uc003jbe.3, human [P48764-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U28043 mRNA Translation: AAB48990.1 AC010442 Genomic DNA No translation available. AC106772 Genomic DNA No translation available. BC101669 mRNA Translation: AAI01670.1 BC101671 mRNA Translation: AAI01672.1 BC143328 mRNA Translation: AAI43329.1 |
CCDSi | CCDS3855.1 [P48764-1] CCDS64116.1 [P48764-2] |
PIRi | B40205 |
RefSeqi | NP_001271280.1, NM_001284351.2 [P48764-2] NP_004165.2, NM_004174.3 [P48764-1] |
3D structure databases
SMRi | P48764 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 112440, 9 interactors |
CORUMi | P48764 |
IntActi | P48764, 1 interactor |
MINTi | P48764 |
STRINGi | 9606.ENSP00000264938 |
Chemistry databases
BindingDBi | P48764 |
ChEMBLi | CHEMBL3273 |
DrugBanki | DB11761, Tenapanor |
Protein family/group databases
TCDBi | 2.A.36.1.15, the monovalent cation:proton antiporter-1 (cpa1) family |
PTM databases
GlyGeni | P48764, 2 sites |
iPTMneti | P48764 |
PhosphoSitePlusi | P48764 |
Polymorphism and mutation databases
BioMutai | SLC9A3 |
DMDMi | 269849652 |
Proteomic databases
jPOSTi | P48764 |
MassIVEi | P48764 |
PaxDbi | P48764 |
PeptideAtlasi | P48764 |
PRIDEi | P48764 |
ProteomicsDBi | 20040 55946 [P48764-1] |
Protocols and materials databases
Antibodypediai | 22241, 310 antibodies |
Genome annotation databases
Ensembli | ENST00000264938; ENSP00000264938; ENSG00000066230 [P48764-1] ENST00000514375; ENSP00000422983; ENSG00000066230 [P48764-2] |
GeneIDi | 6550 |
KEGGi | hsa:6550 |
UCSCi | uc003jbe.3, human [P48764-1] |
Organism-specific databases
CTDi | 6550 |
DisGeNETi | 6550 |
EuPathDBi | HostDB:ENSG00000066230.10 |
GeneCardsi | SLC9A3 |
HGNCi | HGNC:11073, SLC9A3 |
HPAi | ENSG00000066230, Tissue enhanced (gallbladder, intestine, kidney) |
MalaCardsi | SLC9A3 |
MIMi | 182307, gene 616868, phenotype |
neXtProti | NX_P48764 |
OpenTargetsi | ENSG00000066230 |
Orphaneti | 103908, Congenital sodium diarrhea |
PharmGKBi | PA316 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1966, Eukaryota |
GeneTreei | ENSGT00940000158616 |
HOGENOMi | CLU_005912_4_2_1 |
InParanoidi | P48764 |
OMAi | MVQLELI |
OrthoDBi | 389547at2759 |
PhylomeDBi | P48764 |
TreeFami | TF317212 |
Enzyme and pathway databases
PathwayCommonsi | P48764 |
Reactomei | R-HSA-425986, Sodium/Proton exchangers |
SIGNORi | P48764 |
Miscellaneous databases
BioGRID-ORCSi | 6550, 8 hits in 843 CRISPR screens |
GeneWikii | Sodium%E2%80%93hydrogen_antiporter_3 |
GenomeRNAii | 6550 |
Pharosi | P48764, Tchem |
PROi | PR:P48764 |
RNActi | P48764, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000066230, Expressed in cortex of kidney and 108 other tissues |
ExpressionAtlasi | P48764, baseline and differential |
Genevisiblei | P48764, HS |
Family and domain databases
InterProi | View protein in InterPro IPR006153, Cation/H_exchanger IPR018422, Cation/H_exchanger_CPA1 IPR018410, Na/H_exchanger_3/5 IPR004709, NaH_exchanger |
PANTHERi | PTHR10110, PTHR10110, 1 hit |
Pfami | View protein in Pfam PF00999, Na_H_Exchanger, 1 hit |
PRINTSi | PR01084, NAHEXCHNGR PR01087, NAHEXCHNGR3 |
TIGRFAMsi | TIGR00840, b_cpa1, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SL9A3_HUMAN | |
Accessioni | P48764Primary (citable) accession number: P48764 Secondary accession number(s): B7ZKR2, E9PF67, Q3MIW3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1996 |
Last sequence update: | November 24, 2009 | |
Last modified: | December 2, 2020 | |
This is version 172 of the entry and version 2 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 chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - 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 entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations