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Protein

Sodium/hydrogen exchanger 3

Gene

SLC9A3

Organism
Oryctolagus cuniculus (Rabbit)
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: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

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
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

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

  • Note: In intestinal epithelial cells, localizes to the ileal brush border (By similarity). Phosphorylation at Ser-663 by SGK1 is associated with increased abundance at the cell membrane. Angiotensin-2 enhances apical expression (By similarity).By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 11CytoplasmicSequence analysisAdd BLAST11
Transmembranei12 – 27Helical; Name=M1Sequence analysisAdd BLAST16
Topological domaini28 – 59ExtracellularSequence analysisAdd BLAST32
Transmembranei60 – 79Helical; Name=M2Sequence analysisAdd BLAST20
Topological domaini80 – 81CytoplasmicSequence analysis2
Transmembranei82 – 101Helical; Name=M3Sequence analysisAdd BLAST20
Topological domaini102 – 110ExtracellularSequence analysis9
Transmembranei111 – 130Helical; Name=M4Sequence analysisAdd BLAST20
Topological domaini131 – 134CytoplasmicSequence analysis4
Transmembranei135 – 154Helical; Name=M5Sequence analysisAdd BLAST20
Topological domaini155 – 180ExtracellularSequence analysisAdd BLAST26
Transmembranei181 – 200Helical; Name=M5ASequence analysisAdd BLAST20
Topological domaini201 – 209CytoplasmicSequence analysis9
Transmembranei210 – 229Helical; Name=M5BSequence analysisAdd BLAST20
Topological domaini230 – 249ExtracellularSequence analysisAdd BLAST20
Transmembranei250 – 269Helical; Name=M6Sequence analysisAdd BLAST20
Topological domaini270 – 298CytoplasmicSequence analysisAdd BLAST29
Transmembranei299 – 319Helical; Name=M7Sequence analysisAdd BLAST21
Topological domaini320 – 339ExtracellularSequence analysisAdd BLAST20
Transmembranei340 – 359Helical; Name=M8Sequence analysisAdd BLAST20
Topological domaini360 – 366CytoplasmicSequence analysis7
Transmembranei367 – 385Helical; Name=M9Sequence analysisAdd BLAST19
Topological domaini386 – 435ExtracellularSequence analysisAdd BLAST50
Transmembranei436 – 455Helical; Name=M10Sequence analysisAdd BLAST20
Topological domaini456 – 832CytoplasmicSequence analysisAdd BLAST377

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2096985.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000523571 – 832Sodium/hydrogen exchanger 3Add BLAST832

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi325N-linked (GlcNAc...)Sequence analysis1
Modified residuei554PhosphoserineBy similarity1
Modified residuei562PhosphoserineBy similarity1
Modified residuei592PhosphoserineBy similarity1
Modified residuei607PhosphoserineBy similarity1
Modified residuei663Phosphoserine; by SGK11 Publication1
Modified residuei813PhosphoserineBy similarity1
Modified residuei816PhosphoserineBy similarity1

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 similarity1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

PTM databases

iPTMnetiP26432.

Expressioni

Tissue specificityi

Intestinal and kidney specific. Most abundant in kidney cortex, followed equally by ileum and ascending colon, then kidney medulla and jejunum. Is absent from duodenum and descending colon.

Interactioni

Subunit structurei

Interacts with CHP1, CHP2 and SHANK2 (By similarity). Interacts with PDZD3 and interactions decrease in response to elevated calcium ion levels. Binds SLC9A3R1 and SLC9A3R2. Interacts with PDZK1 (via C-terminal PDZ domain). Interacts with AHCYL1; the interaction is required for SLC9A3 activity (PubMed:18829453).By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000024686.

Structurei

3D structure databases

ProteinModelPortaliP26432.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni590 – 667Interaction with PDZD31 PublicationAdd BLAST78
Regioni591 – 696Interaction with AHCYL11 PublicationAdd BLAST106

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1966. Eukaryota.
COG0025. LUCA.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiP26432.
KOiK12040.

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.

P26432-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGRGGCGPC WGLLLALVLA LGALPWTQGA EQEHHDEIQG FQIVTFKWHH
60 70 80 90 100
VQDPYIIALW VLVASLAKIV FHLSHKVTSV VPESALLIVL GLVLGGIVLA
110 120 130 140 150
ADHIASFTLT PTVFFFYLLP PIVLDAGYFM PNRLFFSNLG SILLYAVVGT
160 170 180 190 200
VWNAATTGLS LYGVFLSGIM GELKIGLLDF LLFGSLIAAV DPVAVLAVFE
210 220 230 240 250
EVHVNEVLFI IVFGESLLND AVTVVLYNVF QSFVTLGGDK VTGVDCVKGI
260 270 280 290 300
VSFFVVSLGG TLVGVVFAFL LSLVTRFTKH VRVIEPGFVF IISYLSYLTS
310 320 330 340 350
EMLSLSSILA ITFCGICCQK YVKANISEQS ATTVRYTMKM LASGAETIIF
360 370 380 390 400
MFLGISAVDP LIWTWNTAFV LLTLLFVSVF RAIGVVLQTW LLNRYRMVQL
410 420 430 440 450
ELIDQVVMSY GGLRGAVAFA LVALLDGNKV KEKNLFVSTT IIVVFFTVIF
460 470 480 490 500
QGLTIKPLVQ WLKVKRSEHR EPKLNEKLHG RAFDHILSAI EDISGQIGHN
510 520 530 540 550
YLRDKWANFD RRFLSKLLMR QSAQKSRDRI LNVFHELNLK DAISYVTEGE
560 570 580 590 600
RRGSLAFIRS PSTDNMVNVD FSTPRPSTVE ASVSYLLRES ASAVCLDMQS
610 620 630 640 650
LEQRRRSVRD AEDVITHHTL QQYLYKPRQE YKHLYSRHVL SPSEDEKQDK
660 670 680 690 700
EIFHRTMRKR LESFKSAKLG LGQSKKATKH KRERERAQKR RNSSVPNGKL
710 720 730 740 750
PLDSPAYGLT LKERELELSD PEEAPDYYEA EKMSGGIEFL ASVTKDTTSD
760 770 780 790 800
SPAGIDNPVF SPDEDLAPSL LARVPPWLSP GEAVVPSQRA RVQIPYSPGN
810 820 830
FRRLAPFRLS NKSVDSFLLA EDGAEHPEST HM
Length:832
Mass (Da):92,749
Last modified:August 1, 1992 - v1
Checksum:i8C8BB7C296CF8740
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti144L → P.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M87007 mRNA. Translation: AAA31420.1.
PIRiA40205.
RefSeqiNP_001076166.1. NM_001082697.1.
UniGeneiOcu.1936.

Genome annotation databases

GeneIDi100009430.
KEGGiocu:100009430.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M87007 mRNA. Translation: AAA31420.1.
PIRiA40205.
RefSeqiNP_001076166.1. NM_001082697.1.
UniGeneiOcu.1936.

3D structure databases

ProteinModelPortaliP26432.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000024686.

Chemistry databases

ChEMBLiCHEMBL2096985.

PTM databases

iPTMnetiP26432.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100009430.
KEGGiocu:100009430.

Organism-specific databases

CTDi6550.

Phylogenomic databases

eggNOGiKOG1966. Eukaryota.
COG0025. LUCA.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiP26432.
KOiK12040.

Miscellaneous databases

PROiP26432.

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_RABIT
AccessioniPrimary (citable) accession number: P26432
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: October 5, 2016
This is version 121 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.