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Protein

Sodium/hydrogen exchanger 3

Gene

Slc9a3

Organism
Rattus norvegicus (Rat)
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. Plays an important role in signal transduction.By similarity

GO - Molecular functioni

  • PDZ domain binding Source: UniProtKB
  • sodium:proton antiporter activity Source: RGD

GO - Biological processi

  • circadian rhythm Source: RGD
  • receptor-mediated endocytosis Source: RGD
  • regulation of pH Source: RGD
  • regulation of sodium ion transport Source: RGD
  • response to glucocorticoid Source: RGD
  • sodium ion transport Source: RGD
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Protein family/group databases

TCDBi2.A.36.1.2. 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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3720. Slc9a3.

Subcellular locationi

  • Apical cell membrane 1 Publication; Multi-pass membrane protein

  • Note: In intestinal epithelial cells, localizes to the ileal brush border. Phosphorylation at Ser-661 by SGK1 is associated with increased abundance at the cell membrane. Angiotensin-2 enhances apical expression (By similarity).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1111CytoplasmicSequence analysisAdd
BLAST
Intramembranei12 – 2514Name=A/M1Sequence analysisAdd
BLAST
Topological domaini26 – 5126CytoplasmicSequence analysisAdd
BLAST
Intramembranei52 – 7019Name=B/M2Sequence analysisAdd
BLAST
Topological domaini71 – 766CytoplasmicSequence analysis
Transmembranei77 – 9620Helical; Name=C/M3Sequence analysisAdd
BLAST
Topological domaini97 – 10913ExtracellularSequence analysisAdd
BLAST
Transmembranei110 – 13021Helical; Name=D/M4Sequence analysisAdd
BLAST
Topological domaini131 – 1366CytoplasmicSequence analysis
Transmembranei137 – 15721Helical; Name=E/M5Sequence analysisAdd
BLAST
Topological domaini158 – 17720ExtracellularSequence analysisAdd
BLAST
Transmembranei178 – 19922Helical; Name=F/M5ASequence analysisAdd
BLAST
Topological domaini200 – 2078CytoplasmicSequence analysis
Transmembranei208 – 22922Helical; Name=G/M5BSequence analysisAdd
BLAST
Topological domaini230 – 24920ExtracellularSequence analysisAdd
BLAST
Transmembranei250 – 27122Helical; Name=H/M6Sequence analysisAdd
BLAST
Topological domaini272 – 28716CytoplasmicSequence analysisAdd
BLAST
Transmembranei288 – 30619Helical; Name=I/M7Sequence analysisAdd
BLAST
Topological domaini307 – 33731ExtracellularSequence analysisAdd
BLAST
Transmembranei338 – 35922Helical; Name=J/M8Sequence analysisAdd
BLAST
Topological domaini360 – 3667CytoplasmicSequence analysis
Transmembranei367 – 38721Helical; Name=K/M9Sequence analysisAdd
BLAST
Topological domaini388 – 40215ExtracellularSequence analysisAdd
BLAST
Intramembranei403 – 42321Name=LSequence analysisAdd
BLAST
Topological domaini424 – 4329ExtracellularSequence analysis
Transmembranei433 – 45321Helical; Name=M/M10Sequence analysisAdd
BLAST
Topological domaini454 – 831378CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB
  • brush border Source: RGD
  • brush border membrane Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry

GuidetoPHARMACOLOGYi950.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 831831Sodium/hydrogen exchanger 3PRO_0000052358Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi323 – 3231N-linked (GlcNAc...)Sequence analysis
Modified residuei552 – 5521PhosphoserineCombined sources1 Publication
Modified residuei560 – 5601PhosphoserineCombined sources
Modified residuei590 – 5901PhosphoserineBy similarity
Modified residuei605 – 6051Phosphoserine1 Publication
Modified residuei661 – 6611Phosphoserine; by SGK1By similarity
Modified residuei807 – 8071PhosphoserineCombined sources
Modified residuei810 – 8101PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated by PKA, which inhibits activity. Phosphorylation at Ser-661 by SGK1 is associated with increased abundance at the cell membrane (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP26433.
PRIDEiP26433.

PTM databases

iPTMnetiP26433.
PhosphoSiteiP26433.

Expressioni

Tissue specificityi

Most abundant in colon and small intestine, followed by kidney and stomach. In kidney, expressed in proximal tubules and outer medulla (at protein level) (PubMed:20584908).1 Publication

Interactioni

Subunit structurei

Binds SLC9A3R1 and SLC9A3R2. Interacts with PDZD3 and interactions decrease in response to elevated calcium ion levels. Interacts with PDZK1 (via C-terminal PDZ domain) (By similarity). Interacts with CHP1, CHP2 and SHANK2 (PubMed:12576672, PubMed:16293618). Interacts with AHCYL1; the interaction is required for SLC9A3 activity (PubMed:20584908).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Chp2Q810D13EBI-961694,EBI-6146708
Shank2Q9QX742EBI-961694,EBI-397902

GO - Molecular functioni

Protein-protein interaction databases

BioGridi246908. 1 interaction.
IntActiP26433. 5 interactions.
MINTiMINT-152540.
STRINGi10116.ENSRNOP00000020711.

Structurei

3D structure databases

ProteinModelPortaliP26433.
SMRiP26433. Positions 107-132, 201-226.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni588 – 66578Interaction with PDZD3By similarityAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1966. Eukaryota.
COG0025. LUCA.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiP26433.
KOiK12040.
PhylomeDBiP26433.

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.

Sequencei

Sequence statusi: Complete.

P26433-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWHPALGPGW KPLLALAVAV TSLRGVRGIE EEPNSGGSFQ IVTFKWHHVQ
60 70 80 90 100
DPYIIALWIL VASLAKIVFH LSHKVTSVVP ESALLIVLGL VLGGIVWAAD
110 120 130 140 150
HIASFTLTPT LFFFYLLPPI VLDAGYFMPN RLFFGNLGTI LLYAVIGTIW
160 170 180 190 200
NAATTGLSLY GVFLSGLMGE LKIGLLDFLL FGSLIAAVDP VAVLAVFEEV
210 220 230 240 250
HVNEVLFIIV FGESLLNDAV TVVLYNVFES FVTLGGDAVT GVDCVKGIVS
260 270 280 290 300
FFVVSLGGTL VGVIFAFLLS LVTRFTKHVR IIEPGFVFVI SYLSYLTSEM
310 320 330 340 350
LSLSAILAIT FCGICCQKYV KANISEQSAT TVRYTMKMLA SGAETIIFMF
360 370 380 390 400
LGISAVDPVI WTWNTAFVLL TLVFISVYRA IGVVLQTWIL NRYRMVQLET
410 420 430 440 450
IDQVVMSYGG LRGAVAYALV VLLDEKKVKE KNLFVSTTLI VVFFTVIFQG
460 470 480 490 500
LTIKPLVQWL KVKRSEQREP KLNEKLHGRA FDHILSAIED ISGQIGHNYL
510 520 530 540 550
RDKWSNFDRK FLSKVLMRRS AQKSRDRILN VFHELNLKDA ISYVAEGERR
560 570 580 590 600
GSLAFIRSPS TDNMVNVDFS TPRPSTVEAS VSYFLRENVS AVCLDMQSLE
610 620 630 640 650
QRRRSIRDTE DMVTHHTLQQ YLYKPRQEYK HLYSRHELTP NEDEKQDKEI
660 670 680 690 700
FHRTMRKRLE SFKSAKLGIN QNKKAAKLYK RERAQKRRNS SIPNGKLPME
710 720 730 740 750
NLAHNFTIKE KDLELSEPEE ATNYEEISGG IEFLASVTKD VASDSGAGID
760 770 780 790 800
NPVFSPDEDL DPSILSRVPP WLSPGETVVP SQRARVQIPN SPSNFRRLTP
810 820 830
FRLSNKSVDS FLQADGPEEQ LQPASPESTH M
Length:831
Mass (Da):93,105
Last modified:August 1, 1992 - v1
Checksum:i77A4BF10DFF99E3F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M85300 mRNA. Translation: AAA41702.1.
PIRiB40204.
RefSeqiNP_036786.1. NM_012654.1.
UniGeneiRn.9706.

Genome annotation databases

GeneIDi24784.
KEGGirno:24784.
UCSCiRGD:3720. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M85300 mRNA. Translation: AAA41702.1.
PIRiB40204.
RefSeqiNP_036786.1. NM_012654.1.
UniGeneiRn.9706.

3D structure databases

ProteinModelPortaliP26433.
SMRiP26433. Positions 107-132, 201-226.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246908. 1 interaction.
IntActiP26433. 5 interactions.
MINTiMINT-152540.
STRINGi10116.ENSRNOP00000020711.

Chemistry

GuidetoPHARMACOLOGYi950.

Protein family/group databases

TCDBi2.A.36.1.2. the monovalent cation:proton antiporter-1 (cpa1) family.

PTM databases

iPTMnetiP26433.
PhosphoSiteiP26433.

Proteomic databases

PaxDbiP26433.
PRIDEiP26433.

Protocols and materials databases

DNASUi24784.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24784.
KEGGirno:24784.
UCSCiRGD:3720. rat.

Organism-specific databases

CTDi6550.
RGDi3720. Slc9a3.

Phylogenomic databases

eggNOGiKOG1966. Eukaryota.
COG0025. LUCA.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiP26433.
KOiK12040.
PhylomeDBiP26433.

Miscellaneous databases

PROiP26433.

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_RAT
AccessioniPrimary (citable) accession number: P26433
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: September 7, 2016
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

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. 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.