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UniProtKB - P26431 (SL9A1_RAT)

UniProt

P26431 - SL9A1_RAT

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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)LengthDescriptionGraphical viewFeature identifierActions
Sitei165 – 1651Channel pore-liningBy similarity

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus
Proteomesi
  • UP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi3718. Slc9a1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1212CytoplasmicSequence analysisAdd
BLAST
Transmembranei13 – 3321Helical; Name=M1Sequence analysisAdd
BLAST
Topological domaini34 – 10572ExtracellularSequence analysisAdd
BLAST
Transmembranei106 – 13126Helical; Name=M2Sequence analysisAdd
BLAST
Topological domaini132 – 1332CytoplasmicSequence analysis
Transmembranei134 – 15320Helical; Name=M3Sequence analysisAdd
BLAST
Topological domaini154 – 1585ExtracellularSequence analysis
Transmembranei159 – 17820Helical; Name=M4Sequence analysisAdd
BLAST
Topological domaini179 – 19517CytoplasmicSequence analysisAdd
BLAST
Transmembranei196 – 21520Helical; Name=M5Sequence analysisAdd
BLAST
Topological domaini216 – 23116ExtracellularSequence analysisAdd
BLAST
Transmembranei232 – 25120Helical; Name=M6Sequence analysisAdd
BLAST
Topological domaini252 – 2609CytoplasmicSequence analysis
Transmembranei261 – 28020Helical; Name=M7Sequence analysisAdd
BLAST
Topological domaini281 – 29818ExtracellularSequence analysisAdd
BLAST
Transmembranei299 – 31921Helical; Name=M8Sequence analysisAdd
BLAST
Topological domaini320 – 34223CytoplasmicSequence analysisAdd
BLAST
Transmembranei343 – 36220Helical; Name=M9Sequence analysisAdd
BLAST
Topological domaini363 – 38523ExtracellularSequence analysisAdd
BLAST
Intramembranei386 – 40621Name=H10By similarityAdd
BLAST
Topological domaini407 – 4148ExtracellularSequence analysis
Transmembranei415 – 43420Helical; Name=M10Sequence analysisAdd
BLAST
Topological domaini435 – 45218CytoplasmicSequence analysisAdd
BLAST
Transmembranei453 – 47422Helical; Name=M11Sequence analysisAdd
BLAST
Topological domaini475 – 4839ExtracellularSequence analysis
Transmembranei484 – 50320Helical; Name=M12Sequence analysisAdd
BLAST
Topological domaini504 – 820317CytoplasmicSequence analysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi522 – 53817INEEI…LLTGI → QNEEQHTQQLDHQQTGQ: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. 1 PublicationAdd
BLAST
Mutagenesisi530 – 5356FLDHLL → AADHAA: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. 1 Publication
Mutagenesisi530 – 5356FLDHLL → QQDHQQ: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. 1 Publication
Mutagenesisi530 – 5356FLDHLL → RRDHRR: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. 1 Publication

Chemistry

ChEMBLiCHEMBL2577.
GuidetoPHARMACOLOGYi948.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 820820Sodium/hydrogen exchanger 1PRO_0000052351Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi374 – 3741N-linked (GlcNAc...)Sequence analysis
Modified residuei603 – 6031PhosphoserineCombined sources
Modified residuei606 – 6061PhosphoserineBy similarity
Modified residuei607 – 6071PhosphothreonineBy similarity
Modified residuei609 – 6091PhosphoserineCombined sources
Modified residuei697 – 6971PhosphoserineCombined sources
Modified residuei701 – 7011PhosphoserineCombined sources
Modified residuei707 – 7071PhosphoserineCombined sources
Modified residuei727 – 7271PhosphoserineCombined sources
Modified residuei730 – 7301PhosphoserineCombined sources
Modified residuei733 – 7331PhosphoserineCombined sources
Modified residuei755 – 7551PhosphothreonineBy similarity
Modified residuei790 – 7901PhosphoserineCombined sources
Modified residuei801 – 8011PhosphoserineCombined sources

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.
PhosphoSiteiP26431.

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 interaction.
IntActiP26431. 3 interactions.
STRINGi10116.ENSRNOP00000011049.

Chemistry

BindingDBiP26431.

Structurei

3D structure databases

ProteinModelPortaliP26431.
SMRiP26431. Positions 159-184, 254-279, 342-369, 507-549.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni520 – 54324Interaction with CHP2By similarityAdd
BLAST

Sequence similaritiesi

Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. [View classification]Curated

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.
SMRiP26431. Positions 159-184, 254-279, 342-369, 507-549.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246906. 1 interaction.
IntActiP26431. 3 interactions.
STRINGi10116.ENSRNOP00000011049.

Chemistry

BindingDBiP26431.
ChEMBLiCHEMBL2577.
GuidetoPHARMACOLOGYi948.

Protein family/group databases

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

PTM databases

iPTMnetiP26431.
PhosphoSiteiP26431.

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: September 7, 2016
This is version 147 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.