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Protein

Sodium/hydrogen exchanger 1

Gene

Slc9a1

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei165Channel pore-liningBy similarity1

GO - Molecular functioni

  • calcium-dependent protein binding Source: UniProtKB
  • sodium:proton antiporter activity Source: UniProtKB

GO - Biological processi

  • cardiac muscle cell contraction Source: RGD
  • cardiac muscle cell differentiation Source: Ensembl
  • cell differentiation Source: RGD
  • cell growth Source: RGD
  • cellular response to acidic pH Source: UniProtKB
  • cellular response to antibiotic Source: RGD
  • cellular response to electrical stimulus Source: RGD
  • cellular response to epinephrine stimulus Source: Ensembl
  • cellular response to hypoxia Source: RGD
  • cellular response to insulin stimulus Source: RGD
  • cellular response to organic cyclic compound Source: RGD
  • cellular sodium ion homeostasis Source: Ensembl
  • negative regulation of apoptotic process Source: RGD
  • neuron death Source: RGD
  • positive regulation of action potential Source: RGD
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of calcineurin-NFAT signaling cascade Source: Ensembl
  • positive regulation of calcium:sodium antiporter activity Source: Ensembl
  • positive regulation of cardiac muscle hypertrophy Source: Ensembl
  • positive regulation of cell growth Source: RGD
  • positive regulation of intracellular signal transduction Source: RGD
  • positive regulation of mitochondrial membrane permeability Source: RGD
  • positive regulation of NFAT protein import into nucleus Source: Ensembl
  • positive regulation of the force of heart contraction Source: Ensembl
  • positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • regulation of cardiac muscle contraction by calcium ion signaling Source: Ensembl
  • regulation of intracellular pH Source: UniProtKB
  • regulation of pH Source: UniProtKB
  • regulation of sensory perception of pain Source: RGD
  • regulation of the force of heart contraction Source: RGD
  • regulation of the force of heart contraction by cardiac conduction Source: Ensembl
  • response to acidic pH Source: UniProtKB
  • response to drug Source: RGD
  • response to muscle stretch Source: Ensembl
  • response to organic cyclic compound Source: RGD
  • sodium ion export Source: UniProtKB
  • sodium ion import across plasma membrane Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Calmodulin-binding, Sodium

Enzyme and pathway databases

ReactomeiR-RNO-2160916. Hyaluronan uptake and degradation.
R-RNO-425986. Sodium/Proton exchangers.

Protein family/group databases

TCDBi2.A.36.1.1. the monovalent cation:proton antiporter-1 (cpa1) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/hydrogen exchanger 1
Alternative name(s):
Na(+)/H(+) exchanger 1
Short name:
NHE-1
Solute carrier family 9 member 1
Gene namesi
Name:Slc9a1
Synonyms:Nhe1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi3718. Slc9a1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 12CytoplasmicSequence analysisAdd BLAST12
Transmembranei13 – 33Helical; Name=M1Sequence analysisAdd BLAST21
Topological domaini34 – 105ExtracellularSequence analysisAdd BLAST72
Transmembranei106 – 131Helical; Name=M2Sequence analysisAdd BLAST26
Topological domaini132 – 133CytoplasmicSequence analysis2
Transmembranei134 – 153Helical; Name=M3Sequence analysisAdd BLAST20
Topological domaini154 – 158ExtracellularSequence analysis5
Transmembranei159 – 178Helical; Name=M4Sequence analysisAdd BLAST20
Topological domaini179 – 195CytoplasmicSequence analysisAdd BLAST17
Transmembranei196 – 215Helical; Name=M5Sequence analysisAdd BLAST20
Topological domaini216 – 231ExtracellularSequence analysisAdd BLAST16
Transmembranei232 – 251Helical; Name=M6Sequence analysisAdd BLAST20
Topological domaini252 – 260CytoplasmicSequence analysis9
Transmembranei261 – 280Helical; Name=M7Sequence analysisAdd BLAST20
Topological domaini281 – 298ExtracellularSequence analysisAdd BLAST18
Transmembranei299 – 319Helical; Name=M8Sequence analysisAdd BLAST21
Topological domaini320 – 342CytoplasmicSequence analysisAdd BLAST23
Transmembranei343 – 362Helical; Name=M9Sequence analysisAdd BLAST20
Topological domaini363 – 385ExtracellularSequence analysisAdd BLAST23
Intramembranei386 – 406Name=H10By similarityAdd BLAST21
Topological domaini407 – 414ExtracellularSequence analysis8
Transmembranei415 – 434Helical; Name=M10Sequence analysisAdd BLAST20
Topological domaini435 – 452CytoplasmicSequence analysisAdd BLAST18
Transmembranei453 – 474Helical; Name=M11Sequence analysisAdd BLAST22
Topological domaini475 – 483ExtracellularSequence analysis9
Transmembranei484 – 503Helical; Name=M12Sequence analysisAdd BLAST20
Topological domaini504 – 820CytoplasmicSequence analysisAdd BLAST317

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • basolateral plasma membrane Source: RGD
  • cation-transporting ATPase complex Source: Ensembl
  • cell surface Source: RGD
  • cytoplasm Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • extracellular exosome Source: Ensembl
  • focal adhesion Source: Ensembl
  • integral component of plasma membrane Source: Ensembl
  • intercalated disc Source: RGD
  • membrane raft Source: RGD
  • mitochondrion Source: RGD
  • nucleoplasm Source: Ensembl
  • perinuclear region of cytoplasm Source: RGD
  • plasma membrane Source: UniProtKB
  • sarcolemma Source: RGD
  • T-tubule Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi522 – 538INEEI…LLTGI → QNEEQHTQQLDHQQTGQ: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. 1 PublicationAdd BLAST17
Mutagenesisi530 – 535FLDHLL → AADHAA: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. 1 Publication6
Mutagenesisi530 – 535FLDHLL → QQDHQQ: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. 1 Publication6
Mutagenesisi530 – 535FLDHLL → RRDHRR: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. 1 Publication6

Chemistry databases

ChEMBLiCHEMBL2577.
GuidetoPHARMACOLOGYi948.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000523511 – 820Sodium/hydrogen exchanger 1Add BLAST820

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi374N-linked (GlcNAc...)Sequence analysis1
Modified residuei603PhosphoserineCombined sources1
Modified residuei606PhosphoserineBy similarity1
Modified residuei607PhosphothreonineBy similarity1
Modified residuei609PhosphoserineCombined sources1
Modified residuei697PhosphoserineCombined sources1
Modified residuei701PhosphoserineCombined sources1
Modified residuei707PhosphoserineCombined sources1
Modified residuei727PhosphoserineCombined sources1
Modified residuei730PhosphoserineCombined sources1
Modified residuei733PhosphoserineCombined sources1
Modified residuei755PhosphothreonineBy similarity1
Modified residuei790PhosphoserineCombined sources1
Modified residuei801PhosphoserineCombined sources1

Post-translational modificationi

N-glycosylated and O-glycosylated in the N-terminal region.2 Publications
Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP26431.
PRIDEiP26431.

PTM databases

iPTMnetiP26431.
PhosphoSitePlusiP26431.

Expressioni

Tissue specificityi

Not tissue specific.

Gene expression databases

BgeeiENSRNOG00000007982.
GenevisibleiP26431. RN.

Interactioni

Subunit structurei

Interacts with calmodulin and TESC. Interacts (via the juxtamembrane region of the cytoplasmic C-terminal domain) with CHP1; the interaction occurs at the plasma membrane in a calcium-dependent manner. Interacts with CHP2; the interaction occurs in a calcium-dependent manner (By similarity). Oligomer. Interacts with CHP1, CHP2 and TESC.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Chp2Q810D12EBI-77471,EBI-6146708

GO - Molecular functioni

Protein-protein interaction databases

BioGridi246906. 1 interactor.
IntActiP26431. 3 interactors.
STRINGi10116.ENSRNOP00000011049.

Chemistry databases

BindingDBiP26431.

Structurei

3D structure databases

ProteinModelPortaliP26431.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni520 – 543Interaction with CHP2By similarityAdd BLAST24

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1966. Eukaryota.
COG0025. LUCA.
GeneTreeiENSGT00760000119074.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiP26431.
KOiK05742.
OMAiYDRVGIV.
OrthoDBiEOG091G02Q0.
PhylomeDBiP26431.
TreeFamiTF317212.

Family and domain databases

InterProiIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR001970. Na/H_exchanger_1.
IPR004709. NaH_exchanger.
IPR032103. NHE_CaM-bd.
[Graphical view]
PANTHERiPTHR10110. PTHR10110. 1 hit.
PTHR10110:SF59. PTHR10110:SF59. 1 hit.
PfamiPF00999. Na_H_Exchanger. 1 hit.
PF16644. NEXCaM_BD. 1 hit.
[Graphical view]
PRINTSiPR01084. NAHEXCHNGR.
PR01085. NAHEXCHNGR1.
TIGRFAMsiTIGR00840. b_cpa1. 1 hit.

Sequencei

Sequence statusi: Complete.

P26431-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMLRWSGIWG LYPPRIFPSL LVVVALVGLL PVLRSHGLQL NPTASTIRGS
60 70 80 90 100
EPPRERSIGD VTTAPSEPLH HPDDRNLTNL YIEHGAKPVR KAFPVLDIDY
110 120 130 140 150
LHVRTPFEIS LWILLACLMK IGFHVIPTIS SIVPESCLLI VVGLLVGGLI
160 170 180 190 200
KGVGETPPFL QSDVFFLFLL PPIILDAGYF LPLRQFTENL GTILIFAVVG
210 220 230 240 250
TLWNAFFLGG LLYAVCLVGG EQINNIGLLD TLLFGSIISA VDPVAVLAVF
260 270 280 290 300
EEIHINELLH ILVFGESLLN DAVTVVLYHL FEEFASYEYV GISDIFLGFL
310 320 330 340 350
SFFVVSLGGV FVGVVYGVIA AFTSRFTSHI RVIEPLFVFL YSYMAYLSAE
360 370 380 390 400
LFHLSGIMAL IASGVVMRPY VEANISHKSH TTIKYFLKMW SSVSETLIFI
410 420 430 440 450
FLGVSTVAGS HQWNWTFVIS TLLFCLIARV LGVLVLTWFI NKFRIVKLTP
460 470 480 490 500
KDQFIIAYGG LRGAIAFSLG YLLDKKHFPM CDLFLTAIIT VIFFTVFVQG
510 520 530 540 550
MTIRPLVDLL AVKKKQETKR SINEEIHTQF LDHLLTGIED ICGHYGHHHW
560 570 580 590 600
KDKLNRFNKK YVKKCLIAGE RSKEPQLIAF YHKMEMKQAI ELVESGGMGK
610 620 630 640 650
IPSAVSTVSM QNIHPKSAAS ERILPALSKD KEEEIRKILR SNLQKTRQRL
660 670 680 690 700
RSYNRHTLVA DPYEEAWNQM LLRRQKARQL EQKITNYLTV PAHKLDSPTM
710 720 730 740 750
SRARIGSDPL AYEPKADLPV ITIDPASPQS PESVDLVNEE LKGKVLGLKR
760 770 780 790 800
GPRTTPEEEE EDEDGVIMIR SKEPSSPGTD DVFTPGPSDS PGSQRIQRCL
810 820
SDPGPHPEPG EGEPFIPKGQ
Length:820
Mass (Da):91,647
Last modified:October 1, 1996 - v2
Checksum:i58398DE74A9642FB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M85299 mRNA. Translation: AAA98479.1.
PIRiA40204.
RefSeqiNP_036784.1. NM_012652.1.
UniGeneiRn.5025.

Genome annotation databases

EnsembliENSRNOT00000011049; ENSRNOP00000011049; ENSRNOG00000007982.
GeneIDi24782.
KEGGirno:24782.
UCSCiRGD:3718. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M85299 mRNA. Translation: AAA98479.1.
PIRiA40204.
RefSeqiNP_036784.1. NM_012652.1.
UniGeneiRn.5025.

3D structure databases

ProteinModelPortaliP26431.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246906. 1 interactor.
IntActiP26431. 3 interactors.
STRINGi10116.ENSRNOP00000011049.

Chemistry databases

BindingDBiP26431.
ChEMBLiCHEMBL2577.
GuidetoPHARMACOLOGYi948.

Protein family/group databases

TCDBi2.A.36.1.1. the monovalent cation:proton antiporter-1 (cpa1) family.

PTM databases

iPTMnetiP26431.
PhosphoSitePlusiP26431.

Proteomic databases

PaxDbiP26431.
PRIDEiP26431.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000011049; ENSRNOP00000011049; ENSRNOG00000007982.
GeneIDi24782.
KEGGirno:24782.
UCSCiRGD:3718. rat.

Organism-specific databases

CTDi6548.
RGDi3718. Slc9a1.

Phylogenomic databases

eggNOGiKOG1966. Eukaryota.
COG0025. LUCA.
GeneTreeiENSGT00760000119074.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiP26431.
KOiK05742.
OMAiYDRVGIV.
OrthoDBiEOG091G02Q0.
PhylomeDBiP26431.
TreeFamiTF317212.

Enzyme and pathway databases

ReactomeiR-RNO-2160916. Hyaluronan uptake and degradation.
R-RNO-425986. Sodium/Proton exchangers.

Miscellaneous databases

PROiP26431.

Gene expression databases

BgeeiENSRNOG00000007982.
GenevisibleiP26431. RN.

Family and domain databases

InterProiIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR001970. Na/H_exchanger_1.
IPR004709. NaH_exchanger.
IPR032103. NHE_CaM-bd.
[Graphical view]
PANTHERiPTHR10110. PTHR10110. 1 hit.
PTHR10110:SF59. PTHR10110:SF59. 1 hit.
PfamiPF00999. Na_H_Exchanger. 1 hit.
PF16644. NEXCaM_BD. 1 hit.
[Graphical view]
PRINTSiPR01084. NAHEXCHNGR.
PR01085. NAHEXCHNGR1.
TIGRFAMsiTIGR00840. b_cpa1. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiSL9A1_RAT
AccessioniPrimary (citable) accession number: P26431
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

The region between transmembrane regions M4 and M5 and between M6 and M7 (also termed intracellular loops IL2 and IL4, respectively) seem to be localized at least in part in the membrane. The hydrophobic region H10 is proposed to be located within the membrane.Curated
Although PubMed:18321853 show that TESC-binding results in the maturation and accumulation of SLC9A1 at the cell surface, previous studies with human SLC9A1 report that TESC-binding results in a decrease in activity.Curated
Although PubMed:18321853 show that they CHP1 and TESC bind at the same C-terminal site, previous studies with human SLC9A1 report that they bind to different sites.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.