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P26431 (SL9A1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium/hydrogen exchanger 1
Alternative name(s):
Na(+)/H(+) exchanger 1
Short name=NHE-1
Solute carrier family 9 member 1
Gene names
Name:Slc9a1
Synonyms:Nhe1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length820 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Interacts with calmodulin and TESC. Interacts (via the juxtamembrane region of the cytoplasmic C-terminus 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. Ref.3 Ref.4 Ref.5

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein. Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. Note: Colocalizes with and CHP2 at the plasma membrane By similarity. Colocalizes with CHP1 at the reticulum endoplasmic and plasma membrane.

Tissue specificity

Not tissue specific.

Post-translational modification

N-glycosylated and O-glycosylated in the N-terminal region. Ref.2 Ref.5

Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1. Ref.5

Sequence similarities

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

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.

Although Ref.4 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.

Although Ref.4 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.

Ontologies

Keywords
   Biological processAntiport
Ion transport
Sodium transport
Transport
   Cellular componentCell membrane
Endoplasmic reticulum
Membrane
   DomainTransmembrane
Transmembrane helix
   LigandCalmodulin-binding
Sodium
   PTMGlycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac muscle cell contraction

Inferred from expression pattern PubMed 20868366. Source: RGD

cardiac muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

cell differentiation

Inferred from expression pattern PubMed 16495213. Source: RGD

cell growth

Inferred from expression pattern PubMed 15452191. Source: RGD

cellular response to acidity

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to antibiotic

Inferred from expression pattern PubMed 20868366. Source: RGD

cellular response to electrical stimulus

Inferred from expression pattern PubMed 20868366. Source: RGD

cellular response to hypoxia

Inferred from direct assay PubMed 20868366. Source: RGD

cellular response to insulin stimulus

Inferred from direct assay PubMed 20868366. Source: RGD

cellular response to organic cyclic compound

Inferred from expression pattern PubMed 20868366. Source: RGD

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 17552965. Source: RGD

neuron death

Inferred from mutant phenotype PubMed 19328212. Source: RGD

positive regulation of action potential

Inferred from mutant phenotype PubMed 18319243. Source: RGD

positive regulation of cell growth

Inferred from mutant phenotype PubMed 19687166. Source: RGD

positive regulation of intracellular signal transduction

Inferred from mutant phenotype PubMed 14600156. Source: RGD

positive regulation of mitochondrial membrane permeability

Inferred from mutant phenotype PubMed 21297023. Source: RGD

regulation of intracellular pH

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of pH

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of sensory perception of pain

Inferred from mutant phenotype PubMed 21763398. Source: RGD

regulation of the force of heart contraction

Inferred from mutant phenotype PubMed 21659487. Source: RGD

response to acid

Inferred from sequence or structural similarity. Source: UniProtKB

response to acidity

Inferred from direct assay Ref.4. Source: UniProtKB

response to drug

Inferred from expression pattern PubMed 15452191. Source: RGD

response to organic cyclic compound

Inferred from direct assay PubMed 17308111. Source: RGD

sodium ion export

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentT-tubule

Inferred from direct assay PubMed 20868366. Source: RGD

basolateral plasma membrane

Inferred from direct assay PubMed 9438178. Source: RGD

cell surface

Inferred from direct assay PubMed 20868366. Source: RGD

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum

Inferred from direct assay Ref.5. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intercalated disc

Inferred from direct assay PubMed 20868366. Source: RGD

membrane raft

Inferred from direct assay PubMed 16002403. Source: RGD

mitochondrion

Inferred from direct assay PubMed 21297023. Source: RGD

perinuclear region of cytoplasm

Inferred from direct assay PubMed 20868366. Source: RGD

plasma membrane

Inferred from direct assay Ref.4Ref.5. Source: UniProtKB

sarcolemma

Inferred from direct assay PubMed 20868366. Source: RGD

   Molecular_functioncalcium-dependent protein binding

Inferred from sequence or structural similarity. Source: UniProtKB

sodium:hydrogen antiporter activity

Inferred from direct assay Ref.4. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Chp2Q810D12EBI-77471,EBI-6146708

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 820820Sodium/hydrogen exchanger 1
PRO_0000052351

Regions

Topological domain1 – 1212Cytoplasmic Potential
Transmembrane13 – 3321Helical; Name=M1; Potential
Topological domain34 – 10572Extracellular Potential
Transmembrane106 – 13126Helical; Name=M2; Potential
Topological domain132 – 1332Cytoplasmic Potential
Transmembrane134 – 15320Helical; Name=M3; Potential
Topological domain154 – 1585Extracellular Potential
Transmembrane159 – 17820Helical; Name=M4; Potential
Topological domain179 – 19517Cytoplasmic Potential
Transmembrane196 – 21520Helical; Name=M5; Potential
Topological domain216 – 23116Extracellular Potential
Transmembrane232 – 25120Helical; Name=M6; Potential
Topological domain252 – 2609Cytoplasmic Potential
Transmembrane261 – 28020Helical; Name=M7; Potential
Topological domain281 – 29818Extracellular Potential
Transmembrane299 – 31921Helical; Name=M8; Potential
Topological domain320 – 34223Cytoplasmic Potential
Transmembrane343 – 36220Helical; Name=M9; Potential
Topological domain363 – 38523Extracellular Potential
Intramembrane386 – 40621Name=H10; By similarity
Topological domain407 – 4148Extracellular Potential
Transmembrane415 – 43420Helical; Name=M10; Potential
Topological domain435 – 45218Cytoplasmic Potential
Transmembrane453 – 47422Helical; Name=M11; Potential
Topological domain475 – 4839Extracellular Potential
Transmembrane484 – 50320Helical; Name=M12; Potential
Topological domain504 – 820317Cytoplasmic Potential
Region520 – 54324Interaction with CHP2 By similarity

Sites

Site1651Channel pore-lining By similarity

Amino acid modifications

Modified residue6031Phosphoserine By similarity
Modified residue6091Phosphoserine By similarity
Modified residue6971Phosphoserine By similarity
Modified residue7011Phosphoserine By similarity
Modified residue7071Phosphoserine By similarity
Modified residue7271Phosphoserine By similarity
Modified residue7301Phosphoserine By similarity
Modified residue7331Phosphoserine By similarity
Modified residue7901Phosphoserine By similarity
Glycosylation3741N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis522 – 53817INEEI…LLTGI → QNEEQHTQQLDHQQTGQ: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. Ref.5
Mutagenesis530 – 5356FLDHLL → AADHAA: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. Ref.4
Mutagenesis530 – 5356FLDHLL → QQDHQQ: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. Ref.4
Mutagenesis530 – 5356FLDHLL → RRDHRR: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P26431 [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: 58398DE74A9642FB

FASTA82091,647
        10         20         30         40         50         60 
MMLRWSGIWG LYPPRIFPSL LVVVALVGLL PVLRSHGLQL NPTASTIRGS EPPRERSIGD 

        70         80         90        100        110        120 
VTTAPSEPLH HPDDRNLTNL YIEHGAKPVR KAFPVLDIDY LHVRTPFEIS LWILLACLMK 

       130        140        150        160        170        180 
IGFHVIPTIS SIVPESCLLI VVGLLVGGLI KGVGETPPFL QSDVFFLFLL PPIILDAGYF 

       190        200        210        220        230        240 
LPLRQFTENL GTILIFAVVG TLWNAFFLGG LLYAVCLVGG EQINNIGLLD TLLFGSIISA 

       250        260        270        280        290        300 
VDPVAVLAVF EEIHINELLH ILVFGESLLN DAVTVVLYHL FEEFASYEYV GISDIFLGFL 

       310        320        330        340        350        360 
SFFVVSLGGV FVGVVYGVIA AFTSRFTSHI RVIEPLFVFL YSYMAYLSAE LFHLSGIMAL 

       370        380        390        400        410        420 
IASGVVMRPY VEANISHKSH TTIKYFLKMW SSVSETLIFI FLGVSTVAGS HQWNWTFVIS 

       430        440        450        460        470        480 
TLLFCLIARV LGVLVLTWFI NKFRIVKLTP KDQFIIAYGG LRGAIAFSLG YLLDKKHFPM 

       490        500        510        520        530        540 
CDLFLTAIIT VIFFTVFVQG MTIRPLVDLL AVKKKQETKR SINEEIHTQF LDHLLTGIED 

       550        560        570        580        590        600 
ICGHYGHHHW KDKLNRFNKK YVKKCLIAGE RSKEPQLIAF YHKMEMKQAI ELVESGGMGK 

       610        620        630        640        650        660 
IPSAVSTVSM QNIHPKSAAS ERILPALSKD KEEEIRKILR SNLQKTRQRL RSYNRHTLVA 

       670        680        690        700        710        720 
DPYEEAWNQM LLRRQKARQL EQKITNYLTV PAHKLDSPTM SRARIGSDPL AYEPKADLPV 

       730        740        750        760        770        780 
ITIDPASPQS PESVDLVNEE LKGKVLGLKR GPRTTPEEEE EDEDGVIMIR SKEPSSPGTD 

       790        800        810        820 
DVFTPGPSDS PGSQRIQRCL SDPGPHPEPG EGEPFIPKGQ 

« Hide

References

[1]"Molecular cloning of putative members of the Na/H exchanger gene family. cDNA cloning, deduced amino acid sequence, and mRNA tissue expression of the rat Na/H exchanger NHE-1 and two structurally related proteins."
Orlowski J., Kandasamy R.A., Shull G.E.
J. Biol. Chem. 267:9331-9339(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Heart.
[2]"Topological analysis of NHE1, the ubiquitous Na+/H+ exchanger using chymotryptic cleavage."
Shrode L.D., Gan B.S., D'Souza S.J., Orlowski J., Grinstein S.
Am. J. Physiol. 275:C431-C439(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION.
[3]"Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium."
Inoue H., Nakamura Y., Nagita M., Takai T., Masuda M., Nakamura N., Kanazawa H.
Biol. Pharm. Bull. 26:148-155(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CHP1 AND CHP2.
[4]"Calcineurin B homologous protein 3 promotes the biosynthetic maturation, cell surface stability, and optimal transport of the Na+/H+ exchanger NHE1 isoform."
Zaun H.C., Shrier A., Orlowski J.
J. Biol. Chem. 283:12456-12467(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TESC, MUTAGENESIS OF 530-PHE--LEU-535.
[5]"Dual functional significance of calcineurin homologous protein 1 binding to Na(+)/H(+) exchanger isoform 1."
Matsushita M., Tanaka H., Mitsui K., Kanazawa H.
Am. J. Physiol. 301:C280-C288(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: OLIGOMERIZATION, GLYCOSYLATION, UBIQUITINATION, MUTAGENESIS OF 522-ILE--ILE-538.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M85299 mRNA. Translation: AAA98479.1.
PIRA40204.
RefSeqNP_036784.1. NM_012652.1.
UniGeneRn.5025.

3D structure databases

ProteinModelPortalP26431.
SMRP26431. Positions 159-184, 254-279, 342-369, 507-549.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP26431. 3 interactions.
STRING10116.ENSRNOP00000011049.

Chemistry

BindingDBP26431.
ChEMBLCHEMBL2577.

Protein family/group databases

TCDB2.A.36.1.1. the monovalent cation:proton antiporter-1 (cpa1) family.

PTM databases

PhosphoSiteP26431.

Proteomic databases

PaxDbP26431.
PRIDEP26431.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000011049; ENSRNOP00000011049; ENSRNOG00000007982.
GeneID24782.
KEGGrno:24782.
UCSCRGD:3718. rat.

Organism-specific databases

CTD6548.
RGD3718. Slc9a1.

Phylogenomic databases

eggNOGCOG0025.
GeneTreeENSGT00560000077158.
HOGENOMHOG000247044.
HOVERGENHBG052615.
InParanoidP26431.
KOK05742.
OMAYDRVGIV.
OrthoDBEOG7XWPN4.
PhylomeDBP26431.
TreeFamTF317212.

Gene expression databases

GenevestigatorP26431.

Family and domain databases

InterProIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR001970. Na/H_exchanger_1.
IPR004709. NaH_exchanger.
[Graphical view]
PANTHERPTHR10110. PTHR10110. 1 hit.
PfamPF00999. Na_H_Exchanger. 1 hit.
[Graphical view]
PRINTSPR01084. NAHEXCHNGR.
PR01085. NAHEXCHNGR1.
TIGRFAMsTIGR00840. b_cpa1. 1 hit.
ProtoNetSearch...

Other

NextBio604392.
PROP26431.

Entry information

Entry nameSL9A1_RAT
AccessionPrimary (citable) accession number: P26431
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families