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P48764

- SL9A3_HUMAN

UniProt

P48764 - SL9A3_HUMAN

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Protein

Sodium/hydrogen exchanger 3

Gene

SLC9A3

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. 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 1 Publication; 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.

GO - Cellular componenti

  1. apical plasma membrane Source: Ensembl
  2. brush border Source: UniProtKB
  3. brush border membrane Source: UniProtKB
  4. cell surface Source: UniProtKB
  5. extracellular vesicular exosome Source: UniProtKB
  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...)Sequence Analysis
Glycosylationi326 – 3261N-linked (GlcNAc...)Sequence Analysis
Modified residuei555 – 5551PhosphoserineBy similarity
Modified residuei607 – 6071PhosphoserineBy similarity
Modified residuei663 – 6631Phosphoserine; by SGK1By similarity

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.
PRIDEiP48764.

PTM databases

PhosphoSiteiP48764.

Expressioni

Gene expression databases

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.By similarity1 Publication

Binary interactionsi

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

Protein-protein interaction databases

BioGridi112440. 11 interactions.
IntActiP48764. 1 interaction.
MINTiMINT-1787470.
STRINGi9606.ENSP00000264938.

Structurei

3D structure databases

ProteinModelPortaliP48764.
SMRiP48764. Positions 180-228.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1212CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini25 – 5430CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini74 – 796CytoplasmicSequence Analysis
Topological domaini100 – 11213ExtracellularSequence AnalysisAdd
BLAST
Topological domaini134 – 1396CytoplasmicSequence Analysis
Topological domaini161 – 18020ExtracellularSequence AnalysisAdd
BLAST
Topological domaini203 – 2108CytoplasmicSequence Analysis
Topological domaini233 – 25220ExtracellularSequence AnalysisAdd
BLAST
Topological domaini275 – 29016CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini310 – 34031ExtracellularSequence AnalysisAdd
BLAST
Topological domaini363 – 3697CytoplasmicSequence Analysis
Topological domaini391 – 40515ExtracellularSequence AnalysisAdd
BLAST
Topological domaini427 – 4359ExtracellularSequence Analysis
Topological domaini457 – 834378CytoplasmicSequence AnalysisAdd
BLAST

Intramembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Intramembranei13 – 2412Name=A/M1Sequence AnalysisAdd
BLAST
Intramembranei55 – 7319Name=B/M2Sequence AnalysisAdd
BLAST
Intramembranei406 – 42621Name=LSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei80 – 9920Helical; Name=C/M3Sequence AnalysisAdd
BLAST
Transmembranei113 – 13321Helical; Name=D/M4Sequence AnalysisAdd
BLAST
Transmembranei140 – 16021Helical; Name=E/M5Sequence AnalysisAdd
BLAST
Transmembranei181 – 20222Helical; Name=F/M5ASequence AnalysisAdd
BLAST
Transmembranei211 – 23222Helical; Name=G/M5BSequence AnalysisAdd
BLAST
Transmembranei253 – 27422Helical; Name=H/M6Sequence AnalysisAdd
BLAST
Transmembranei291 – 30919Helical; Name=I/M7Sequence AnalysisAdd
BLAST
Transmembranei341 – 36222Helical; Name=J/M8Sequence AnalysisAdd
BLAST
Transmembranei370 – 39021Helical; Name=K/M9Sequence AnalysisAdd
BLAST
Transmembranei436 – 45621Helical; Name=M/M10Sequence AnalysisAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni590 – 66778Interaction with PDZD3By similarityAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0025.
GeneTreeiENSGT00760000119074.
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

        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)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. 1 PublicationVSP_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. [P48764-1]
ENST00000514375; ENSP00000422983; ENSG00000066230. [P48764-2]
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 180-228.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112440. 11 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 . [P48764-1 ]
ENST00000514375 ; ENSP00000422983 ; ENSG00000066230 . [P48764-2 ]
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.
GeneTreei ENSGT00760000119074.
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

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: October 29, 2014
This is version 128 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