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Protein

Sodium/hydrogen exchanger 3

Gene

SLC9A3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000066230-MONOMER.
ReactomeiR-HSA-425986. Sodium/Proton exchangers.

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

HGNCiHGNC:11073. SLC9A3.

Subcellular locationi

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

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB
  • brush border Source: UniProtKB
  • brush border membrane Source: UniProtKB
  • cell surface Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: UniProtKB
Complete GO annotation...

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 Publication1
Natural variantiVAR_076420269A → T in DIAR8; decreases cell membrane expression; reduces Na(+)/H(+) exchange activity. 1 Publication1
Natural variantiVAR_076421311A → V in DIAR8; decreases cell membrane expression; reduces strongly Na(+)/H(+) exchange activity. 1 Publication1
Natural variantiVAR_076422382R → Q in DIAR8; decreases cell membrane localization; reduces strongly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant rs766076524dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6550.
MIMi616868. phenotype.
OpenTargetsiENSG00000066230.
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...)Sequence analysis1
Glycosylationi326N-linked (GlcNAc...)Sequence 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.

PTM databases

iPTMnetiP48764.
PhosphoSitePlusiP48764.

Expressioni

Gene expression databases

BgeeiENSG00000066230.
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.
IntActiP48764. 1 interactor.
MINTiMINT-1787470.
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.
OMAiYTMKMLA.
OrthoDBiEOG091G02Q0.
PhylomeDBiP48764.
TreeFamiTF317212.

Family and domain databases

InterProiIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR018410. Na/H_exchanger_3/5.
IPR004709. NaH_exchanger.
[Graphical view]
PANTHERiPTHR10110. PTHR10110. 2 hits.
PfamiPF00999. Na_H_Exchanger. 1 hit.
[Graphical view]
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

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

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 Publication1
Natural variantiVAR_076420269A → T in DIAR8; decreases cell membrane expression; reduces Na(+)/H(+) exchange activity. 1 Publication1
Natural variantiVAR_076421311A → V in DIAR8; decreases cell membrane expression; reduces strongly Na(+)/H(+) exchange activity. 1 Publication1
Natural variantiVAR_076422382R → Q in DIAR8; decreases cell membrane localization; reduces strongly Na(+)/H(+) exchange activity. 1 PublicationCorresponds to variant rs766076524dbSNPEnsembl.1
Natural variantiVAR_060593799C → R.2 PublicationsCorresponds to variant rs2247114dbSNPEnsembl.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

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.
IntActiP48764. 1 interactor.
MINTiMINT-1787470.
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.

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.
GeneCardsiSLC9A3.
H-InvDBHIX0004707.
HIX0032039.
HGNCiHGNC:11073. SLC9A3.
HPAiHPA036493.
HPA036669.
MIMi182307. gene.
616868. phenotype.
neXtProtiNX_P48764.
OpenTargetsiENSG00000066230.
PharmGKBiPA316.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000066230-MONOMER.
ReactomeiR-HSA-425986. Sodium/Proton exchangers.

Miscellaneous databases

GeneWikiiSodium%E2%80%93hydrogen_antiporter_3.
GenomeRNAii6550.
PROiP48764.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000066230.
CleanExiHS_SLC9A3.
GenevisibleiP48764. HS.

Family and domain databases

InterProiIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR018410. Na/H_exchanger_3/5.
IPR004709. NaH_exchanger.
[Graphical view]
PANTHERiPTHR10110. PTHR10110. 2 hits.
PfamiPF00999. Na_H_Exchanger. 1 hit.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: November 24, 2009
Last modified: November 2, 2016
This is version 146 of the entry and version 2 of the sequence. [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

Caution

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.