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Protein

Sodium/hydrogen exchanger 3

Gene

SLC9A3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient (PubMed:26358773). Plays an important role in signal transduction.1 Publication

Caution

The number, localization and denomination of hydrophobic domains in the Na+/H+ exchangers vary among authors.Curated

GO - Molecular functioni

  • PDZ domain binding Source: UniProtKB
  • potassium:proton antiporter activity Source: GO_Central
  • sodium:proton antiporter activity Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processAntiport, Ion transport, Sodium transport, Transport
LigandSodium

Enzyme and pathway databases

ReactomeiR-HSA-425986 Sodium/Proton exchangers
SIGNORiP48764

Protein family/group databases

TCDBi2.A.36.1.15 the monovalent cation:proton antiporter-1 (cpa1) family

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/hydrogen exchanger 3Curated
Alternative name(s):
Na(+)/H(+) exchanger 31 Publication
Short name:
NHE-31 Publication
Solute carrier family 9 member 3
Gene namesi
Name:SLC9A3Imported
Synonyms:NHE31 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000066230.10
HGNCiHGNC:11073 SLC9A3
MIMi182307 gene
neXtProtiNX_P48764

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 12CytoplasmicSequence analysisAdd BLAST12
Intramembranei13 – 24Name=A/M1Sequence analysisAdd BLAST12
Topological domaini25 – 54CytoplasmicSequence analysisAdd BLAST30
Intramembranei55 – 73Name=B/M2Sequence analysisAdd BLAST19
Topological domaini74 – 79CytoplasmicSequence analysis6
Transmembranei80 – 99Helical; Name=C/M3Sequence analysisAdd BLAST20
Topological domaini100 – 112ExtracellularSequence analysisAdd BLAST13
Transmembranei113 – 133Helical; Name=D/M4Sequence analysisAdd BLAST21
Topological domaini134 – 139CytoplasmicSequence analysis6
Transmembranei140 – 160Helical; Name=E/M5Sequence analysisAdd BLAST21
Topological domaini161 – 180ExtracellularSequence analysisAdd BLAST20
Transmembranei181 – 202Helical; Name=F/M5ASequence analysisAdd BLAST22
Topological domaini203 – 210CytoplasmicSequence analysis8
Transmembranei211 – 232Helical; Name=G/M5BSequence analysisAdd BLAST22
Topological domaini233 – 252ExtracellularSequence analysisAdd BLAST20
Transmembranei253 – 274Helical; Name=H/M6Sequence analysisAdd BLAST22
Topological domaini275 – 290CytoplasmicSequence analysisAdd BLAST16
Transmembranei291 – 309Helical; Name=I/M7Sequence analysisAdd BLAST19
Topological domaini310 – 340ExtracellularSequence analysisAdd BLAST31
Transmembranei341 – 362Helical; Name=J/M8Sequence analysisAdd BLAST22
Topological domaini363 – 369CytoplasmicSequence analysis7
Transmembranei370 – 390Helical; Name=K/M9Sequence analysisAdd BLAST21
Topological domaini391 – 405ExtracellularSequence analysisAdd BLAST15
Intramembranei406 – 426Name=LSequence analysisAdd BLAST21
Topological domaini427 – 435ExtracellularSequence analysis9
Transmembranei436 – 456Helical; Name=M/M10Sequence analysisAdd BLAST21
Topological domaini457 – 834CytoplasmicSequence analysisAdd BLAST378

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Diarrhea 8, secretory sodium, congenital (DIAR8)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:616868
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076419127A → 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_076420269A → T in DIAR8; decreases cell membrane expression; reduces Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs869312807EnsemblClinVar.1
Natural variantiVAR_076421311A → V in DIAR8; decreases cell membrane expression; reduces strongly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs869312806EnsemblClinVar.1
Natural variantiVAR_076422382R → Q in DIAR8; decreases cell membrane localization; reduces strongly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs766076524EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6550
MalaCardsiSLC9A3
MIMi616868 phenotype
OpenTargetsiENSG00000066230
Orphaneti103908 Congenital sodium diarrhea
PharmGKBiPA316

Chemistry databases

ChEMBLiCHEMBL3273

Polymorphism and mutation databases

BioMutaiSLC9A3
DMDMi269849652

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000523561 – 834Sodium/hydrogen exchanger 3Add BLAST834

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi241N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi326N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei555PhosphoserineBy similarity1
Modified residuei563PhosphoserineBy similarity1
Modified residuei592PhosphoserineBy similarity1
Modified residuei607PhosphoserineBy similarity1
Modified residuei663Phosphoserine; by SGK1By similarity1
Modified residuei810PhosphoserineBy similarity1
Modified residuei813PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated by PKA, which inhibits activity. Phosphorylation at Ser-663 by SGK1 is associated with increased abundance at the cell membrane.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP48764
PeptideAtlasiP48764
PRIDEiP48764
ProteomicsDBi55946

PTM databases

iPTMnetiP48764
PhosphoSitePlusiP48764

Expressioni

Gene expression databases

BgeeiENSG00000066230 Expressed in 84 organ(s), highest expression level in cortex of kidney
CleanExiHS_SLC9A3
GenevisibleiP48764 HS

Organism-specific databases

HPAiHPA036493
HPA036669

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 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAST2Q6P0Q82EBI-7816923,EBI-493777

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112440, 9 interactors
CORUMiP48764
IntActiP48764, 1 interactor
MINTiP48764
STRINGi9606.ENSP00000264938

Chemistry databases

BindingDBiP48764

Structurei

3D structure databases

ProteinModelPortaliP48764
SMRiP48764
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni590 – 667Interaction with PDZD3By similarityAdd BLAST78

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1966 Eukaryota
COG0025 LUCA
GeneTreeiENSGT00760000119074
HOGENOMiHOG000247044
HOVERGENiHBG052615
InParanoidiP48764
KOiK12040
OMAiSKILMRR
OrthoDBiEOG091G02Q0
PhylomeDBiP48764
TreeFamiTF317212

Family and domain databases

InterProiView protein in InterPro
IPR006153 Cation/H_exchanger
IPR018422 Cation/H_exchanger_CPA1
IPR018410 Na/H_exchanger_3/5
IPR004709 NaH_exchanger
PANTHERiPTHR10110 PTHR10110, 1 hit
PfamiView protein in Pfam
PF00999 Na_H_Exchanger, 1 hit
PRINTSiPR01084 NAHEXCHNGR
PR01087 NAHEXCHNGR3
TIGRFAMsiTIGR00840 b_cpa1, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P48764-1) [UniParc]FASTAAdd to basket

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.

« Hide
        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
Length:834
Mass (Da):92,855
Last modified:November 24, 2009 - v2
Checksum:i3E7CE3267F6E86F7
GO
Isoform 2 (identifier: P48764-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     452-460: Missing.

Note: No experimental confirmation available.
Show »
Length:825
Mass (Da):91,904
Checksum:iAEFBDB9089FC18C9
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8Y780A0A2R8Y780_HUMAN
Sodium/hydrogen exchanger
SLC9A3
889Annotation score:
A0A0G2JQZ3A0A0G2JQZ3_HUMAN
Sodium/hydrogen exchanger 3
SLC9A3
70Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076419127A → 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_076420269A → T in DIAR8; decreases cell membrane expression; reduces Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs869312807EnsemblClinVar.1
Natural variantiVAR_076421311A → V in DIAR8; decreases cell membrane expression; reduces strongly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs869312806EnsemblClinVar.1
Natural variantiVAR_076422382R → Q in DIAR8; decreases cell membrane localization; reduces strongly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant dbSNP:rs766076524EnsemblClinVar.1
Natural variantiVAR_060593799C → R2 PublicationsCorresponds to variant dbSNP:rs2247114Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_053989452 – 460Missing in isoform 2. 1 Publication9

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
CCDSiCCDS3855.1 [P48764-1]
CCDS64116.1 [P48764-2]
PIRiB40205
RefSeqiNP_001271280.1, NM_001284351.2 [P48764-2]
NP_004165.2, NM_004174.3 [P48764-1]
UniGeneiHs.658120

Genome annotation databases

EnsembliENST00000264938; ENSP00000264938; ENSG00000066230 [P48764-1]
ENST00000514375; ENSP00000422983; ENSG00000066230 [P48764-2]
GeneIDi6550
KEGGihsa:6550
UCSCiuc003jbe.3 human [P48764-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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
CCDSiCCDS3855.1 [P48764-1]
CCDS64116.1 [P48764-2]
PIRiB40205
RefSeqiNP_001271280.1, NM_001284351.2 [P48764-2]
NP_004165.2, NM_004174.3 [P48764-1]
UniGeneiHs.658120

3D structure databases

ProteinModelPortaliP48764
SMRiP48764
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112440, 9 interactors
CORUMiP48764
IntActiP48764, 1 interactor
MINTiP48764
STRINGi9606.ENSP00000264938

Chemistry databases

BindingDBiP48764
ChEMBLiCHEMBL3273

Protein family/group databases

TCDBi2.A.36.1.15 the monovalent cation:proton antiporter-1 (cpa1) family

PTM databases

iPTMnetiP48764
PhosphoSitePlusiP48764

Polymorphism and mutation databases

BioMutaiSLC9A3
DMDMi269849652

Proteomic databases

PaxDbiP48764
PeptideAtlasiP48764
PRIDEiP48764
ProteomicsDBi55946

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264938; ENSP00000264938; ENSG00000066230 [P48764-1]
ENST00000514375; ENSP00000422983; ENSG00000066230 [P48764-2]
GeneIDi6550
KEGGihsa:6550
UCSCiuc003jbe.3 human [P48764-1]

Organism-specific databases

CTDi6550
DisGeNETi6550
EuPathDBiHostDB:ENSG00000066230.10
GeneCardsiSLC9A3
H-InvDBiHIX0004707
HIX0032039
HGNCiHGNC:11073 SLC9A3
HPAiHPA036493
HPA036669
MalaCardsiSLC9A3
MIMi182307 gene
616868 phenotype
neXtProtiNX_P48764
OpenTargetsiENSG00000066230
Orphaneti103908 Congenital sodium diarrhea
PharmGKBiPA316
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1966 Eukaryota
COG0025 LUCA
GeneTreeiENSGT00760000119074
HOGENOMiHOG000247044
HOVERGENiHBG052615
InParanoidiP48764
KOiK12040
OMAiSKILMRR
OrthoDBiEOG091G02Q0
PhylomeDBiP48764
TreeFamiTF317212

Enzyme and pathway databases

ReactomeiR-HSA-425986 Sodium/Proton exchangers
SIGNORiP48764

Miscellaneous databases

ChiTaRSiSLC9A3 human
GeneWikiiSodium%E2%80%93hydrogen_antiporter_3
GenomeRNAii6550
PROiPR:P48764
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000066230 Expressed in 84 organ(s), highest expression level in cortex of kidney
CleanExiHS_SLC9A3
GenevisibleiP48764 HS

Family and domain databases

InterProiView protein in InterPro
IPR006153 Cation/H_exchanger
IPR018422 Cation/H_exchanger_CPA1
IPR018410 Na/H_exchanger_3/5
IPR004709 NaH_exchanger
PANTHERiPTHR10110 PTHR10110, 1 hit
PfamiView protein in Pfam
PF00999 Na_H_Exchanger, 1 hit
PRINTSiPR01084 NAHEXCHNGR
PR01087 NAHEXCHNGR3
TIGRFAMsiTIGR00840 b_cpa1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSL9A3_HUMAN
AccessioniPrimary (citable) accession number: P48764
Secondary accession number(s): B7ZKR2, E9PF67, Q3MIW3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: November 24, 2009
Last modified: November 7, 2018
This is version 158 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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