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P48764

- SL9A3_HUMAN

UniProt

P48764 - SL9A3_HUMAN

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Protein

Sodium/hydrogen exchanger 3

Gene
SLC9A3, NHE3
Organism
Homo sapiens (Human)
Status
Reviewed - 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. Plays an important role in signal transduction.

GO - Molecular functioni

  1. PDZ domain binding Source: UniProtKB
  2. protein binding Source: UniProtKB
  3. sodium:proton antiporter activity Source: UniProtKB

GO - Biological processi

  1. ion transport Source: Reactome
  2. regulation of pH Source: Ensembl
  3. sodium ion transmembrane transport Source: GOC
  4. transmembrane transport Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

ReactomeiREACT_19314. 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 3
Alternative name(s):
Na(+)/H(+) exchanger 3
Short name:
NHE-3
Solute carrier family 9 member 3
Gene namesi
Name:SLC9A3
Synonyms:NHE3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:11073. SLC9A3.

Subcellular locationi

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.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1212Cytoplasmic Reviewed predictionAdd
BLAST
Intramembranei13 – 2412Name=A/M1; Reviewed predictionAdd
BLAST
Topological domaini25 – 5430Cytoplasmic Reviewed predictionAdd
BLAST
Intramembranei55 – 7319Name=B/M2; Reviewed predictionAdd
BLAST
Topological domaini74 – 796Cytoplasmic Reviewed prediction
Transmembranei80 – 9920Helical; Name=C/M3; Reviewed predictionAdd
BLAST
Topological domaini100 – 11213Extracellular Reviewed predictionAdd
BLAST
Transmembranei113 – 13321Helical; Name=D/M4; Reviewed predictionAdd
BLAST
Topological domaini134 – 1396Cytoplasmic Reviewed prediction
Transmembranei140 – 16021Helical; Name=E/M5; Reviewed predictionAdd
BLAST
Topological domaini161 – 18020Extracellular Reviewed predictionAdd
BLAST
Transmembranei181 – 20222Helical; Name=F/M5A; Reviewed predictionAdd
BLAST
Topological domaini203 – 2108Cytoplasmic Reviewed prediction
Transmembranei211 – 23222Helical; Name=G/M5B; Reviewed predictionAdd
BLAST
Topological domaini233 – 25220Extracellular Reviewed predictionAdd
BLAST
Transmembranei253 – 27422Helical; Name=H/M6; Reviewed predictionAdd
BLAST
Topological domaini275 – 29016Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei291 – 30919Helical; Name=I/M7; Reviewed predictionAdd
BLAST
Topological domaini310 – 34031Extracellular Reviewed predictionAdd
BLAST
Transmembranei341 – 36222Helical; Name=J/M8; Reviewed predictionAdd
BLAST
Topological domaini363 – 3697Cytoplasmic Reviewed prediction
Transmembranei370 – 39021Helical; Name=K/M9; Reviewed predictionAdd
BLAST
Topological domaini391 – 40515Extracellular Reviewed predictionAdd
BLAST
Intramembranei406 – 42621Name=L; Reviewed predictionAdd
BLAST
Topological domaini427 – 4359Extracellular Reviewed prediction
Transmembranei436 – 45621Helical; Name=M/M10; Reviewed predictionAdd
BLAST
Topological domaini457 – 834378Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. apical plasma membrane Source: UniProtKB-SubCell
  2. brush border Source: UniProtKB
  3. brush border membrane Source: UniProtKB
  4. cell surface Source: UniProtKB
  5. extracellular vesicular exosome Source: UniProt
  6. integral component of membrane Source: UniProtKB-KW
  7. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA316.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 834834Sodium/hydrogen exchanger 3PRO_0000052356Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi241 – 2411N-linked (GlcNAc...) Reviewed prediction
Glycosylationi326 – 3261N-linked (GlcNAc...) Reviewed prediction
Modified residuei555 – 5551Phosphoserine By similarity
Modified residuei607 – 6071Phosphoserine By similarity
Modified residuei663 – 6631Phosphoserine; by SGK1 By similarity

Post-translational modificationi

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.

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP48764.
PRIDEiP48764.

PTM databases

PhosphoSiteiP48764.

Expressioni

Gene expression databases

ArrayExpressiP48764.
BgeeiP48764.
CleanExiHS_SLC9A3.
GenevestigatoriP48764.

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.1 Publication

Binary interactionsi

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

Protein-protein interaction databases

BioGridi112440. 7 interactions.
IntActiP48764. 1 interaction.
MINTiMINT-1787470.
STRINGi9606.ENSP00000264938.

Structurei

3D structure databases

ProteinModelPortaliP48764.
SMRiP48764. Positions 204-229, 294-321, 460-502, 608-666.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni590 – 66778Interaction with PDZD3 By similarityAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0025.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiP48764.
KOiK12040.
OMAiRDKWSNF.
OrthoDBiEOG7KQ20Z.
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. 1 hit.
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. Align

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

MWGLGARGPD RGLLLALALG GLARAGGVEV EPGGAHGESG GFQVVTFEWA    50
HVQDPYVIAL WILVASLAKI GFHLSHKVTS VVPESALLIV LGLVLGGIVW 100
AADHIASFTL TPTVFFFYLL PPIVLDAGYF MPNRLFFGNL GTILLYAVVG 150
TVWNAATTGL SLYGVFLSGL MGDLQIGLLD FLLFGSLMAA VDPVAVLAVF 200
EEVHVNEVLF IIVFGESLLN DAVTVVLYNV FESFVALGGD NVTGVDCVKG 250
IVSFFVVSLG GTLVGVVFAF LLSLVTRFTK HVRIIEPGFV FIISYLSYLT 300
SEMLSLSAIL AITFCGICCQ KYVKANISEQ SATTVRYTMK MLASSAETII 350
FMFLGISAVN PFIWTWNTAF VLLTLVFISV YRAIGVVLQT WLLNRYRMVQ 400
LEPIDQVVLS YGGLRGAVAF ALVVLLDGDK VKEKNLFVST TIIVVFFTVI 450
FQGLTIKPLV QWLKVKRSEH REPRLNEKLH GRAFDHILSA IEDISGQIGH 500
NYLRDKWSHF DRKFLSRVLM RRSAQKSRDR ILNVFHELNL KDAISYVAEG 550
ERRGSLAFIR SPSTDNVVNV DFTPRSSTVE ASVSYLLREN VSAVCLDMQS 600
LEQRRRSIRD AEDMVTHHTL QQYLYKPRQE YKHLYSRHEL TPTEDEKQDR 650
EIFHRTMRKR LESFKSTKLG LNQNKKAAKL YKRERAQKRR NSSIPNGKLP 700
MESPAQNFTI KEKDLELSDT EEPPNYDEEM SGGIEFLASV TKDTASDSPA 750
GIDNPVFSPD EALDRSLLAR LPPWLSPGET VVPSQRARTQ IPYSPGTFCR 800
LMPFRLSSKS VDSFLQADGP EERPPAALPE STHM 834
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti799 – 7991C → R.2 Publications
Corresponds to variant rs2247114 [ dbSNP | Ensembl ].
VAR_060593

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei452 – 4609Missing in isoform 2. VSP_053989

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_001284351.1. [P48764-2]
NP_004165.2. NM_004174.2. [P48764-1]
UniGeneiHs.658120.

Genome annotation databases

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

Polymorphism databases

DMDMi269849652.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_001284351.1. [P48764-2 ]
NP_004165.2. NM_004174.2. [P48764-1 ]
UniGenei Hs.658120.

3D structure databases

ProteinModelPortali P48764.
SMRi P48764. Positions 204-229, 294-321, 460-502, 608-666.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112440. 7 interactions.
IntActi P48764. 1 interaction.
MINTi MINT-1787470.
STRINGi 9606.ENSP00000264938.

Chemistry

ChEMBLi CHEMBL3273.

Protein family/group databases

TCDBi 2.A.36.1.15. the monovalent cation:proton antiporter-1 (cpa1) family.

PTM databases

PhosphoSitei P48764.

Polymorphism databases

DMDMi 269849652.

Proteomic databases

PaxDbi P48764.
PRIDEi P48764.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000264938 ; ENSP00000264938 ; ENSG00000066230 .
ENST00000514375 ; ENSP00000422983 ; ENSG00000066230 .
GeneIDi 6550.
KEGGi hsa:6550.
UCSCi uc003jbe.2. human. [P48764-1 ]

Organism-specific databases

CTDi 6550.
GeneCardsi GC05M000473.
H-InvDB HIX0004707.
HIX0032039.
HGNCi HGNC:11073. SLC9A3.
HPAi HPA036493.
HPA036669.
MIMi 182307. gene.
neXtProti NX_P48764.
PharmGKBi PA316.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0025.
HOGENOMi HOG000247044.
HOVERGENi HBG052615.
InParanoidi P48764.
KOi K12040.
OMAi RDKWSNF.
OrthoDBi EOG7KQ20Z.
PhylomeDBi P48764.
TreeFami TF317212.

Enzyme and pathway databases

Reactomei REACT_19314. Sodium/Proton exchangers.

Miscellaneous databases

GeneWikii Sodium%E2%80%93hydrogen_antiporter_3.
GenomeRNAii 6550.
NextBioi 25493.
PROi P48764.
SOURCEi Search...

Gene expression databases

ArrayExpressi P48764.
Bgeei P48764.
CleanExi HS_SLC9A3.
Genevestigatori P48764.

Family and domain databases

InterProi IPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR018410. Na/H_exchanger_3/5.
IPR004709. NaH_exchanger.
[Graphical view ]
PANTHERi PTHR10110. PTHR10110. 1 hit.
Pfami PF00999. Na_H_Exchanger. 1 hit.
[Graphical view ]
PRINTSi PR01084. NAHEXCHNGR.
PR01087. NAHEXCHNGR3.
TIGRFAMsi TIGR00840. b_cpa1. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

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: September 3, 2014
This is version 126 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

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

External Data

Dasty 3

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