ID:SL9A1_HUMAN DESCRIPTION: RecName: Full=Sodium/hydrogen exchanger 1; AltName: Full=APNH; AltName: Full=Na(+)/H(+) antiporter, amiloride-sensitive; AltName: Full=Na(+)/H(+) exchanger 1; Short=NHE-1; AltName: Full=Solute carrier family 9 member 1; 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. BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Fully active at acidic pHs, the antiporter is virtually turned off at neutral pH; SUBUNIT: Oligomer (By similarity). 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. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Cell membrane; Multi-pass membrane protein. Note=Colocalizes with CHP1 at the reticulum endoplasmic (By similarity). Colocalizes with CHP1 and CHP2 at the plasma membrane. TISSUE SPECIFICITY: Kidney and intestine. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. PTM: O-glycosylated. PTM: Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1 (By similarity). MISCELLANEOUS: Inhibited by amiloride and 5-amino-substituted derivatives and activated in a cooperative fashion by intracellular H(+). In quiescent cells upon growth factor stimulation, the apparent affinity for internal H(+) is increased, resulting in a persistent rise in cytoplasmic pH. SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. 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. CAUTION: Although PubMed:12809501 report that TESC-binding results in a decrease in activity, studies with rat SLC9A1 show that TESC- binding results in the maturation and accumulation of SLC9A1 at the cell surface. CAUTION: Although PubMed:12809501 report that CHP1 and TESC bind to SLC9A1 at different sites, studies with rat SLC9A1 show that they bind at the same C-terminal site.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P19634
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005515 protein binding GO:0005516 calmodulin binding GO:0005546 phosphatidylinositol-4,5-bisphosphate binding GO:0015297 antiporter activity GO:0015299 solute:proton antiporter activity GO:0015385 sodium:proton antiporter activity GO:0015386 potassium:proton antiporter activity GO:0030346 protein phosphatase 2B binding GO:0030674 protein binding, bridging GO:0032947 protein complex scaffold GO:0048306 calcium-dependent protein binding GO:0086040 sodium:proton antiporter activity involved in regulation of cardiac muscle cell membrane potential
Biological Process: GO:0002026 regulation of the force of heart contraction GO:0006811 ion transport GO:0006812 cation transport GO:0006814 sodium ion transport GO:0006883 cellular sodium ion homeostasis GO:0006885 regulation of pH GO:0010447 response to acidic pH GO:0010613 positive regulation of cardiac muscle hypertrophy GO:0010882 regulation of cardiac muscle contraction by calcium ion signaling GO:0014070 response to organic cyclic compound GO:0016477 cell migration GO:0030011 maintenance of cell polarity GO:0030154 cell differentiation GO:0030214 hyaluronan catabolic process GO:0030307 positive regulation of cell growth GO:0032869 cellular response to insulin stimulus GO:0035794 positive regulation of mitochondrial membrane permeability GO:0035994 response to muscle stretch GO:0036376 sodium ion export from cell GO:0043065 positive regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0045760 positive regulation of action potential GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0051259 protein oligomerization GO:0051453 regulation of intracellular pH GO:0051492 regulation of stress fiber assembly GO:0051893 regulation of focal adhesion assembly GO:0051930 regulation of sensory perception of pain GO:0055007 cardiac muscle cell differentiation GO:0055085 transmembrane transport GO:0070417 cellular response to cold GO:0070886 positive regulation of calcineurin-NFAT signaling cascade GO:0070997 neuron death GO:0071236 cellular response to antibiotic GO:0071257 cellular response to electrical stimulus GO:0071260 cellular response to mechanical stimulus GO:0071407 cellular response to organic cyclic compound GO:0071456 cellular response to hypoxia GO:0071468 cellular response to acidic pH GO:0071805 potassium ion transmembrane transport GO:0071872 cellular response to epinephrine stimulus GO:0086003 cardiac muscle cell contraction GO:0086036 regulation of cardiac muscle cell membrane potential GO:0086092 regulation of the force of heart contraction by cardiac conduction GO:0098719 sodium ion import across plasma membrane GO:0098735 positive regulation of the force of heart contraction GO:1902533 positive regulation of intracellular signal transduction GO:1902600 hydrogen ion transmembrane transport GO:1903281 positive regulation of calcium:sodium antiporter activity
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
