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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
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