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P48764 (SL9A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium/hydrogen exchanger 3
Alternative name(s):
Na(+)/H(+) exchanger 3
Short name=NHE-3
Solute carrier family 9 member 3
Gene names
Name:SLC9A3
Synonyms:NHE3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length834 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Plays an important role in signal transduction.

Subunit structure

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. Ref.4

Subcellular location

Apical cell 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. Ref.4

Post-translational modification

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

Sequence similarities

Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. [View classification]

Caution

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

Ontologies

Keywords
   Biological processAntiport
Ion transport
Sodium transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandSodium
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_procession transport

Traceable author statement. Source: Reactome

regulation of pH

Inferred from electronic annotation. Source: Ensembl

sodium ion transmembrane transport

Inferred from sequence or structural similarity. Source: GOC

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

brush border

Inferred from sequence or structural similarity. Source: UniProtKB

brush border membrane

Inferred from sequence or structural similarity. Source: UniProtKB

cell surface

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionPDZ domain binding

Inferred from sequence or structural similarity. Source: UniProtKB

sodium:hydrogen antiporter activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MAST2Q6P0Q82EBI-7816923,EBI-493777

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P48764-1)

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.
Isoform 2 (identifier: P48764-2)

The sequence of this isoform differs from the canonical sequence as follows:
     452-460: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 834834Sodium/hydrogen exchanger 3
PRO_0000052356

Regions

Topological domain1 – 1212Cytoplasmic Potential
Intramembrane13 – 2412Name=A/M1; Potential
Topological domain25 – 5430Cytoplasmic Potential
Intramembrane55 – 7319Name=B/M2; Potential
Topological domain74 – 796Cytoplasmic Potential
Transmembrane80 – 9920Helical; Name=C/M3; Potential
Topological domain100 – 11213Extracellular Potential
Transmembrane113 – 13321Helical; Name=D/M4; Potential
Topological domain134 – 1396Cytoplasmic Potential
Transmembrane140 – 16021Helical; Name=E/M5; Potential
Topological domain161 – 18020Extracellular Potential
Transmembrane181 – 20222Helical; Name=F/M5A; Potential
Topological domain203 – 2108Cytoplasmic Potential
Transmembrane211 – 23222Helical; Name=G/M5B; Potential
Topological domain233 – 25220Extracellular Potential
Transmembrane253 – 27422Helical; Name=H/M6; Potential
Topological domain275 – 29016Cytoplasmic Potential
Transmembrane291 – 30919Helical; Name=I/M7; Potential
Topological domain310 – 34031Extracellular Potential
Transmembrane341 – 36222Helical; Name=J/M8; Potential
Topological domain363 – 3697Cytoplasmic Potential
Transmembrane370 – 39021Helical; Name=K/M9; Potential
Topological domain391 – 40515Extracellular Potential
Intramembrane406 – 42621Name=L; Potential
Topological domain427 – 4359Extracellular Potential
Transmembrane436 – 45621Helical; Name=M/M10; Potential
Topological domain457 – 834378Cytoplasmic Potential
Region590 – 66778Interaction with PDZD3 By similarity

Amino acid modifications

Modified residue5551Phosphoserine By similarity
Modified residue6071Phosphoserine By similarity
Modified residue6631Phosphoserine; by SGK1
Glycosylation2411N-linked (GlcNAc...) Potential
Glycosylation3261N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence452 – 4609Missing in isoform 2.
VSP_053989
Natural variant7991C → R. Ref.1 Ref.3
Corresponds to variant rs2247114 [ dbSNP | Ensembl ].
VAR_060593

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 24, 2009. Version 2.
Checksum: 3E7CE3267F6E86F7

FASTA83492,855
        10         20         30         40         50         60 
MWGLGARGPD RGLLLALALG GLARAGGVEV EPGGAHGESG GFQVVTFEWA HVQDPYVIAL 

        70         80         90        100        110        120 
WILVASLAKI GFHLSHKVTS VVPESALLIV LGLVLGGIVW AADHIASFTL TPTVFFFYLL 

       130        140        150        160        170        180 
PPIVLDAGYF MPNRLFFGNL GTILLYAVVG TVWNAATTGL SLYGVFLSGL MGDLQIGLLD 

       190        200        210        220        230        240 
FLLFGSLMAA VDPVAVLAVF EEVHVNEVLF IIVFGESLLN DAVTVVLYNV FESFVALGGD 

       250        260        270        280        290        300 
NVTGVDCVKG IVSFFVVSLG GTLVGVVFAF LLSLVTRFTK HVRIIEPGFV FIISYLSYLT 

       310        320        330        340        350        360 
SEMLSLSAIL AITFCGICCQ KYVKANISEQ SATTVRYTMK MLASSAETII FMFLGISAVN 

       370        380        390        400        410        420 
PFIWTWNTAF VLLTLVFISV YRAIGVVLQT WLLNRYRMVQ LEPIDQVVLS YGGLRGAVAF 

       430        440        450        460        470        480 
ALVVLLDGDK VKEKNLFVST TIIVVFFTVI FQGLTIKPLV QWLKVKRSEH REPRLNEKLH 

       490        500        510        520        530        540 
GRAFDHILSA IEDISGQIGH NYLRDKWSHF DRKFLSRVLM RRSAQKSRDR ILNVFHELNL 

       550        560        570        580        590        600 
KDAISYVAEG ERRGSLAFIR SPSTDNVVNV DFTPRSSTVE ASVSYLLREN VSAVCLDMQS 

       610        620        630        640        650        660 
LEQRRRSIRD AEDMVTHHTL QQYLYKPRQE YKHLYSRHEL TPTEDEKQDR EIFHRTMRKR 

       670        680        690        700        710        720 
LESFKSTKLG LNQNKKAAKL YKRERAQKRR NSSIPNGKLP MESPAQNFTI KEKDLELSDT 

       730        740        750        760        770        780 
EEPPNYDEEM SGGIEFLASV TKDTASDSPA GIDNPVFSPD EALDRSLLAR LPPWLSPGET 

       790        800        810        820        830 
VVPSQRARTQ IPYSPGTFCR LMPFRLSSKS VDSFLQADGP EERPPAALPE STHM 

« Hide

Isoform 2 [UniParc].

Checksum: AEFBDB9089FC18C9
Show »

FASTA82591,904

References

« Hide 'large scale' references
[1]"Cloning, tissue distribution, and functional analysis of the human Na+/N+ exchanger isoform, NHE3."
Brant S.R., Yun C.H., Donowitz M., Tse C.-M.
Am. J. Physiol. 269:C198-C206(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-799.
Tissue: Kidney cortex.
[2]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ARG-799.
Tissue: Colon.
[4]"Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism."
Zachos N.C., Hodson C., Kovbasnjuk O., Li X., Thelin W.R., Cha B., Milgram S., Donowitz M.
Cell. Physiol. Biochem. 22:693-704(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PDZD3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRB40205.
RefSeqNP_001271280.1. NM_001284351.1.
NP_004165.2. NM_004174.2.
UniGeneHs.658120.

3D structure databases

ProteinModelPortalP48764.
SMRP48764. Positions 204-229, 294-321, 460-502, 608-666.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112440. 7 interactions.
IntActP48764. 1 interaction.
MINTMINT-1787470.
STRING9606.ENSP00000264938.

Chemistry

ChEMBLCHEMBL3273.

Protein family/group databases

TCDB2.A.36.1.15. the monovalent cation:proton antiporter-1 (cpa1) family.

PTM databases

PhosphoSiteP48764.

Polymorphism databases

DMDM269849652.

Proteomic databases

PaxDbP48764.
PRIDEP48764.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264938; ENSP00000264938; ENSG00000066230.
ENST00000514375; ENSP00000422983; ENSG00000066230.
GeneID6550.
KEGGhsa:6550.
UCSCuc003jbe.2. human.

Organism-specific databases

CTD6550.
GeneCardsGC05M000473.
H-InvDBHIX0004707.
HIX0032039.
HGNCHGNC:11073. SLC9A3.
HPAHPA036493.
HPA036669.
MIM182307. gene.
neXtProtNX_P48764.
PharmGKBPA316.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0025.
HOGENOMHOG000247044.
HOVERGENHBG052615.
InParanoidP48764.
KOK12040.
OMARDKWSNF.
OrthoDBEOG7KQ20Z.
PhylomeDBP48764.
TreeFamTF317212.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP48764.
BgeeP48764.
CleanExHS_SLC9A3.
GenevestigatorP48764.

Family and domain databases

InterProIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR018410. Na/H_exchanger_3/5.
IPR004709. NaH_exchanger.
[Graphical view]
PANTHERPTHR10110. PTHR10110. 1 hit.
PfamPF00999. Na_H_Exchanger. 1 hit.
[Graphical view]
PRINTSPR01084. NAHEXCHNGR.
PR01087. NAHEXCHNGR3.
TIGRFAMsTIGR00840. b_cpa1. 1 hit.
ProtoNetSearch...

Other

GeneWikiSodium%E2%80%93hydrogen_antiporter_3.
GenomeRNAi6550.
NextBio25493.
PROP48764.
SOURCESearch...

Entry information

Entry nameSL9A3_HUMAN
AccessionPrimary (citable) accession number: P48764
Secondary accession number(s): B7ZKR2, E9PF67, Q3MIW3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: November 24, 2009
Last modified: April 16, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM