Q28036 · SL9A1_BOVIN

  • Protein
    Sodium/hydrogen exchanger 1
  • Gene
    SLC9A1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at transcript level
  • Annotation score
    5/5

Function

function

Electroneutral Na+ /H+ antiporter that extrudes Na+ in exchange for external protons driven by the inward sodium ion chemical gradient, protecting cells from acidification that occurs from metabolism (By similarity).
Exchanges intracellular H+ ions for extracellular Na+ in 1:1 stoichiometry (By similarity).
Plays a key role in maintening intracellular pH neutral and cell volume, and thus is important for cell growth, proliferation, migration and survival. In addition, can transport lithium Li+ and functions also as a Na+/Li+ antiporter. SLC9A1 also functions in membrane anchoring and organization of scaffolding complexes that coordinate signaling inputs (By similarity).

Miscellaneous

Predicted models used for more than 20 years predicted 10-12 transmembrane segments. More recently, the structure of SLC9A1 has been solved and reveals that SLC9A1 possesses 13 transmembrane regions.

Caution

The interacting region with TESC is conflicting: In human, it has been reported that SLC9A1 interacts with TESC via the juxtamembrane region of the cytoplasmic C-terminal domain, including residues 503-545. However, another publication has reported interaction with TESC via residues 633-817, the region of the cytoplasmic C-terminus more distal to the membrane.

Catalytic activity

Activity regulation

Activated at acidic pHs. Inhibited by amiloride and 5-amino-substituted derivatives. Inhibited by cariporide and eniporide. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) bind and differentially regulate SLC9A1 activity.

Features

Showing features for site.

TypeIDPosition(s)Description
Site161Channel pore-lining

GO annotations

AspectTerm
Cellular Componentbasolateral plasma membrane
Cellular Componentcytoplasm
Cellular Componentplasma membrane
Molecular Functioncalcium-dependent protein binding
Molecular Functioncalmodulin binding
Molecular Functionpotassium:proton antiporter activity
Molecular Functionsodium:proton antiporter activity
Biological Processcellular response to acidic pH
Biological Processpotassium ion transmembrane transport
Biological Processprotein complex oligomerization
Biological Processregulation of intracellular pH
Biological Processregulation of pH
Biological Processresponse to acidic pH
Biological Processsodium ion export across plasma membrane
Biological Processsodium ion import across plasma membrane

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Sodium/hydrogen exchanger 1
  • Alternative names
    • Na(+)/H(+) exchanger 1 (NHE-1)
    • Solute carrier family 9 member 1

Gene names

    • Name
      SLC9A1
    • Synonyms
      NHE1

Organism names

  • Taxonomic identifier
  • Strain
    • Hereford
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos

Accessions

  • Primary accession
    Q28036
  • Secondary accessions
    • F1MHK2

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Basolateral cell membrane
; Multi-pass membrane protein

Features

Showing features for topological domain, transmembrane.

Type
IDPosition(s)Description
Topological domain1-98Extracellular
Transmembrane99-121Helical; Name=1
Topological domain122-130Cytoplasmic
Transmembrane131-148Helical; Name=2
Topological domain149-158Extracellular
Transmembrane159-176Helical; Name=3
Topological domain177-186Cytoplasmic
Transmembrane187-215Helical; Name=4
Topological domain216-222Extracellular
Transmembrane223-249Helical; Name=5
Topological domain250-252Cytoplasmic
Transmembrane253-283Helical; Name=6
Topological domain284-287Extracellular
Transmembrane288-322Helical; Name=7
Topological domain323-328Cytoplasmic
Transmembrane329-341Helical; Name=8
Topological domain342-350Extracellular
Transmembrane351-371Helical; Name=9
Topological domain372-373Cytoplasmic
Transmembrane374-404Helical; Name=10
Topological domain405-410Extracellular
Transmembrane411-438Helical; Name=11
Topological domain439-444Cytoplasmic
Transmembrane445-469Helical; Name=12
Topological domain470-475Extracellular
Transmembrane476-505Helical; Name=13
Topological domain506-818Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for chain, glycosylation, modified residue.

Type
IDPosition(s)Description
ChainPRO_00000523451-818Sodium/hydrogen exchanger 1
Glycosylation75N-linked (GlcNAc...) asparagine
Modified residue599Phosphoserine
Modified residue602Phosphoserine
Modified residue603Phosphothreonine
Modified residue605Phosphoserine
Modified residue648Phosphoserine
Modified residue693Phosphoserine
Modified residue697Phosphoserine
Modified residue703Phosphoserine
Modified residue723Phosphoserine
Modified residue726Phosphoserine
Modified residue729Phosphoserine
Modified residue782Phosphothreonine
Modified residue788Phosphoserine
Modified residue790Phosphoserine
Modified residue799Phosphoserine

Post-translational modification

Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1.
O-glycosylated.
Palmitoylated; may play a major role in SLC9A1 regulation.
Phosphorylation at Thr-782 increases SLC9A1 activity. Specifically dephosphorylated at Thr-782 by PPP3CA that negatively regulates SLC9A1 activity. Phosphorylation at Ser-648 by AKT1 reduces SLC9A1 binding to CALM1.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Homodimer; dimerization is crucial for its function (By similarity).
Oligomer (By similarity).
Interacts with CALM in a calcium-dependent manner (By similarity).
Interacts with TESC (By similarity).
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 (By similarity).
Interacts with CHP2; the interaction occurs in a calcium-dependent manner (By similarity).
Interacts with EZR; regulates the cytoskeletal interactions of SLC9A1 and promotes stress fiber formation (By similarity).

Protein-protein interaction databases

Structure

3D structure databases

Family & Domains

Features

Showing features for region, compositional bias.

Type
IDPosition(s)Description
Region44-76Disordered
Region503-545Interaction with TESC
Region509-516PI(4,5)P2-binding region
Region515-545Interaction with CHP2
Region540-545Confers pH-dependent PI(4,5)P2 binding
Region552-560PI(4,5)P2-binding region
Region633-818Interaction with CALM1
Region633-818Interaction with TESC
Region684-687Interaction with PPP3CA
Region715-720Interaction with PPP3CA
Region741-818Disordered
Compositional bias770-797Polar residues

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    818
  • Mass (Da)
    90,976
  • Last updated
    2023-09-13 v2
  • Checksum
    63831EE3F0FF0262
MLLWPGASGLPPPRIFPSLLVVVALVGLLPVLRSYGLQISPTASTIRGSEPPRERSIGDVTTAPPELAPESRPVNHSFAEHSPKARKAFPVLGIDYQHVRIPFEIALWILLACLMKIGFHVIPTISSIVPESCLLIVVGLLVGGLIKGVGETPPILQSEVFFLFLLPPIILDAGYFLPLRQFTENLGTILIFAVVGTLWNAFFLGGLMYAVCLVGGEQINNIGLLENLLFGSIISAVDPVAVLAVFEEIHINELLHILVFGESLLNDAVTVVLYHLFEEFANYDRVGIVDIILGFLSFFVVSLGGVFVGVVYGVIAAFTSRFTSHIRVIEPLFVFLYSYMAYLSAELFHLSGIMALIASGVVMRPYVEANISHKSHTTIKYFLKMWSSVSETLIFIFLGVSTVAGSHHWNWTFVISTLLFCLIARVLGVLGLTWFINKFRIVKLTPKDQFIIAYGGLRGAIAFSLGYLLDKKHFPMCDLFLTAIITVIFFTVFVQGMTIRPLVDLLAVKKKQETKRSINEEIHTQFLDHLLTGIEDICGHYGHHHWKDKLNRFNKKYVKKCLIAGERSKEPQLIAFYHKMEMKQAIELVESGGMGKIPSAVSTVSMQNIHPKSLPAERILPALSKDKEEEIRKILRNNLQKTRQRLRSYNRHTLVADPYEEAWNQMLLRRQKARQLEQKISNYLTVPAHKLDSPTMSRARIGSDPLAYEPKADLPVITIDPASPQSPESVDLVNEELKGKVLGLSRDPGRLAEEEEDDKDPDGGLTMRTKEPSSPGTDDVFTPAPSDSPSSQRIQRCLSDPGPHPEPGEGEPFIPKGQ

Features

Showing features for sequence conflict, compositional bias.

Type
IDPosition(s)Description
Sequence conflict759-764in Ref. 1; AAA91483
Compositional bias770-797Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
NKLS02000002
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
U49432
EMBL· GenBank· DDBJ
AAA91483.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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