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FLASH GENE
Symbol SLC9A1 contributors: mct/ - updated : 01-02-2013
HGNC name solute carrier family 9 (sodium/hydrogen exchanger), member 1
HGNC id 11071
Corresponding disease
SCAR19 spinocerebellar ataxia, autosomal recessive 19
Location 1p36.11      Physical location : 27.425.300 - 27.481.451
Synonym name
  • solute carrier family 9 (sodium/hydrogen exchanger), isoform 1 (antiporter, Na+/H+, amiloride sensitive)
  • antiporter (exchanger),Na+/H+
  • Na+/H+ antiporter, amiloride-sensitive
  • Na-Li countertransporter
  • Na(+)/H(+) exchanger isoform 1
    • Synonym symbol(s) APNH, APNH1, ASA, NHE1, FLJ42224, NHE-1, NHE
    DNA
    TYPE functioning gene
    STRUCTURE 56.15 kb     12 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 4587 100 815 - 2007 17662110
    addressed to the plasma membrane (PMID: 17339404)
    - - - 65 - in all cell types of the endocrine pancreas and in the adrenal medulla 2007 17339404
    addressed to the membrane of secretory granules
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     mouthtongue  highly
    Endocrineparathyroid   highly
     thyroid   highly
    Urinarykidney    
    Visualeyeuveachoroid  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoblast Homo sapiens
    cell lineage
    cell lines squamous cell carcinoma
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a large 500 AAs N-terminal membrane domain that mediates transport and consists of 12 transmembrane segments and several membrane-associated segments
  • TM IX composed of residues 339-363 is critical with pore-lining residues and a kink at the functionally important residue Ser351
  • a large acidic cytoplasmic C-terminal domain, intracellular regulatory domain, with a C-terminal intracellular tail intrinsically disordered, and SLC9A1 normal function depends on a protein recognition element within this region that may be linked to SLC9A1 trafficking via an acidic ER export motif
  • extracellular regions believed to contribute to cation coordination, transport and sensitivity to inhibitors (extracellular loop 2, EL2, is critical to its function)
    • HOMOLOGY
    interspecies homolog to murine Npe1
    Homologene
    FAMILY
  • monovalent cation: proton antiporter 1 (CPA1) transporter family
    • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text basolateral membrane
    basic FUNCTION
  • regulates intracellular pH by removing one intracellular H+ in exchange for one extracellular Na+
  • involved in intracellular pH regulation and cell volume
  • involved in regulating ion transport in several organs
  • blood-brain barrier Na/H exchanger, potentially stimulated during ischemia to participate in cerebral edema formation
  • membrane protein that regulates intracellular pH (pHi) by removing one intracellular H(+) in exchange for one extracellular Na(+)
  • with AKT1, has functions, including cell growth and survival, that might be regulated by increased H(+) efflux
  • highly regulated membrane protein that is required for pH homoeostasis in cardiomyocytes
  • responsible for regulating intracellular pH, cell volume, cell migration, and proliferation
  • contributes to the increased DNA synthesis and cell cycle progression of transformed cells by increasing intracellular pH
  • plays pivotal roles in cellular pH and volume homeostasis, and its dysfunction is implicated in several clinically important diseases
  • in mineralizing osteoblasts, slightly basic basal pHi is maintained, and external acid load is dissipated, by high-capacity Na(+) /H(+) exchange via SLC9A1 and SLC9A6
  • role for SLC9A1 in the long-term regulation of renal tubule function, suggesting that the regulatory interaction whereby SLC9A1 enhances the activity of SLC9A3 in the medullary thick ascending limb and plays a role in the chronic regulation of HCO(3)(-) absorption
  • normally quiescent Na(+)/H(+) exchanger-1 (SLC9A1) defends against proximal tubular epithelial cell (PTC)apoptosis, and is regulated by PI(4,5)P(2) binding
  • regulates intracellular pH by removing a single intracellular H(+) in exchange for one extracellular Na(+)
  • plays an important role in Ca(2+) signaling and cell proliferation in human central nervous system (CNS) pericytes
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • NEDD4 and ARRB1 as key regulators of SLC9A1 ubiquitylation, endocytosis, and function
  • binding of CHP stabilizes SLC9A1 and increases its plasma membrane localization by masking a SLC9A1 disposal signal
  • interaction between CHP2 and SLC9A1 (NHE1), two membrane proteins, is essential for protecting cells from serum deprivation-induced death
  • BRAF bound to the cytosolic regulatory tail of SLC9A1 (can directly bind to the C-terminal 182 AAs of SLC9A1 protein)
  • EPB41 binds directly to the SLC9A1cd (cytoplasmic domain of SLC9Q1) through the interaction of an EED motif in the EPB41 FERM (4.1/ezrin/radixin/moesin) domain
  • site-specific interactions of HSPA13 with SLC4A4 and SLC9A1 and subsequent modulation of membrane transporter expression
  • mitochondrial Na(+) influx via SLC8B1 is antagonized by Na(+) efflux, which is mediated by the mitochondrial SLC9A1
    • cell & other
    REGULATION
    repressed by mild oxidative stress (represses promoter activity and expression via an early oxidation phase blocked by reducing agents, and a late phase requiring an iron-dependent increase in caspases 3 and 6 activities)
    Other EPB41 regulates SLC9A1 activity through a direct protein-protein interaction that can be modulated by intracellular pH and Na(+) and Ca(2+) concentrations
    ASSOCIATED DISORDERS
    corresponding disease(s) SCAR19
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in slow-wawe epilepsy
    constitutional       gain of function
    is sufficient to initiate cardiac hypertrophy and heart failure mainly through activation of CaMKII-histone deacetylase pathway
    tumoral       gain of function
    promote metastasis in human mammary epithelial cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS