Sodium–hydrogen antiporter 1

The sodium-hydrogen antiporter 1 (NHE-1) also known as sodium/hydrogen exchanger 1 or SLC9A1 (SoLute Carrier family 9A1) is an isoform of sodium–hydrogen antiporter that in humans is encoded by the SLC9A1 gene.

SLC9A1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1Y4E, 2BEC, 2E30, 2KBV, 2L0E, 2MDF, 2YGG
Identifiers
Aliases	SLC9A1, APNH, NHE-1, NHE1, PPP1R143, LIKNS, Sodium–hydrogen antiporter 1, solute carrier family 9 member A1
External IDs	OMIM: 107310; MGI: 102462; HomoloGene: 20660; GeneCards: SLC9A1; OMA:SLC9A1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1p36.11 Start 27,098,809 bp End 27,166,981 bp
Gene location (Mouse) Chr. Chromosome 4 (mouse) Band 4 D2.3|4 66.25 cM Start 133,097,017 bp End 133,151,013 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parotid gland mucosa of transverse colon oocyte placenta body of stomach stromal cell of endometrium pylorus putamen mucosa of urinary bladder nasal epithelium Top expressed in epithelium of stomach zygote ankle joint pyloric antrum secondary oocyte mucous cell of stomach gastrula granulocyte decidua lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein-macromolecule adaptor activity calcium-dependent protein binding phosphatidylinositol-4,5-bisphosphate binding antiporter activity solute:proton antiporter activity sodium:proton antiporter activity involved in regulation of cardiac muscle cell membrane potential calmodulin binding protein binding molecular adaptor activity protein phosphatase 2B binding sodium:proton antiporter activity potassium:proton antiporter activity Cellular component cytoplasm membrane focal adhesion T-tubule mitochondrion perinuclear region of cytoplasm cation-transporting ATPase complex cell surface apical plasma membrane endoplasmic reticulum membrane raft extracellular exosome lamellipodium integral component of membrane intercalated disc plasma membrane nucleoplasm endoplasmic reticulum membrane integral component of plasma membrane basolateral plasma membrane sarcolemma Biological process regulation of cardiac muscle contraction by calcium ion signaling regulation of sensory perception of pain positive regulation of the force of heart contraction positive regulation of cardiac muscle hypertrophy cellular response to epinephrine stimulus positive regulation of action potential cellular response to mechanical stimulus maintenance of cell polarity cellular response to hypoxia positive regulation of mitochondrial membrane permeability response to muscle stretch proton transmembrane transport cellular sodium ion homeostasis cardiac muscle cell differentiation ion transport positive regulation of cell growth cellular response to insulin stimulus regulation of focal adhesion assembly regulation of cardiac muscle cell membrane potential response to acidic pH cell differentiation regulation of the force of heart contraction cellular response to organic cyclic compound cellular response to acidic pH cation transport negative regulation of apoptotic process regulation of the force of heart contraction by cardiac conduction regulation of pH cardiac muscle cell contraction neuron death hyaluronan catabolic process response to organic cyclic compound sodium ion transport regulation of intracellular pH positive regulation of intracellular signal transduction regulation of stress fiber assembly positive regulation of calcineurin-NFAT signaling cascade protein complex oligomerization sodium ion import across plasma membrane positive regulation of apoptotic process cellular response to antibiotic positive regulation of calcium:sodium antiporter activity cell migration positive regulation of transcription by RNA polymerase II cellular response to electrical stimulus potassium ion transmembrane transport transmembrane transport transport cellular response to cold sodium ion export across plasma membrane anion transmembrane transport sodium ion transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6548 20544 Ensembl ENSG00000090020 ENSMUSG00000028854 UniProt P19634 Q61165 RefSeq (mRNA) NM_003047 NM_016981 NM_001358455 RefSeq (protein) NP_003038 NP_058677 NP_001345384 Location (UCSC) Chr 1: 27.1 – 27.17 Mb Chr 4: 133.1 – 133.15 Mb PubMed search
Wikidata
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Function

The Na⁺/H⁺ antiporter (SLC9A1) is a ubiquitous membrane-bound enzyme involved in volume- and pH-regulation of vertebrate cells. It is inhibited by the non-specific diuretic drug amiloride and activated by a variety of signals including growth factors, mitogens, neurotransmitters, tumor promoters, and others.

Interactions

Sodium–hydrogen antiporter 1 has been shown to interact with carbonic anhydrase II and CHP. It is also the target of the experimental drug rimeporide, which is being developed for the treatment of Duchenne muscular dystrophy.

Further reading

• Yu L, Quinn DA, Garg HG, Hales CA (June 2008). "Deficiency of the NHE1 gene prevents hypoxia-induced pulmonary hypertension and vascular remodeling". American Journal of Respiratory and Critical Care Medicine. 177 (11): 1276–84. doi:10.1164/rccm.200710-1522OC. PMC 2408441. PMID 18310478.
• Rios EJ, Fallon M, Wang J, Shimoda LA (November 2005). "Chronic hypoxia elevates intracellular pH and activates Na+/H+ exchange in pulmonary arterial smooth muscle cells". American Journal of Physiology. Lung Cellular and Molecular Physiology. 289 (5): L867–74. doi:10.1152/ajplung.00455.2004. PMID 15964895. S2CID 16399637.
• Cingolani HE, Ennis IL (March 2007). "Sodium-hydrogen exchanger, cardiac overload, and myocardial hypertrophy". Circulation. 115 (9): 1090–100. doi:10.1161/CIRCULATIONAHA.106.626929. PMID 17339567.
• Meima ME, Mackley JR, Barber DL (July 2007). "Beyond ion translocation: structural functions of the sodium-hydrogen exchanger isoform-1". Current Opinion in Nephrology and Hypertension. 16 (4): 365–72. doi:10.1097/MNH.0b013e3281bd888d. PMID 17565280. S2CID 25616109.
• Tse CM, Ma AI, Yang VW, Watson AJ, Levine S, Montrose MH, et al. (August 1991). "Molecular cloning and expression of a cDNA encoding the rabbit ileal villus cell basolateral membrane Na+/H+ exchanger". The EMBO Journal. 10 (8): 1957–67. doi:10.1002/j.1460-2075.1991.tb07725.x. PMC 452875. PMID 1712287.
• Dudley CR, Giuffra LA, Tippett P, Kidd KK, Reeders ST (November 1990). "The Na+/H+ antiporter: a "melt" polymorphism allows regional mapping to the short arm of chromosome 1". Human Genetics. 86 (1): 79–83. doi:10.1007/bf00205179. PMID 1979310. S2CID 20107780.
• Sardet C, Counillon L, Franchi A, Pouysségur J (February 1990). "Growth factors induce phosphorylation of the Na+/H+ antiporter, glycoprotein of 110 kD". Science. 247 (4943): 723–6. Bibcode:1990Sci...247..723S. doi:10.1126/science.2154036. PMID 2154036.
• Sardet C, Franchi A, Pouysségur J (January 1989). "Molecular cloning, primary structure, and expression of the human growth factor-activatable Na+/H+ antiporter". Cell. 56 (2): 271–80. doi:10.1016/0092-8674(89)90901-X. PMID 2536298. S2CID 2782563.
• Mattei MG, Sardet C, Franchi A, Pouysségur J (1988). "The human amiloride-sensitive Na+/H+ antiporter: localization to chromosome 1 by in situ hybridization". Cytogenetics and Cell Genetics. 48 (1): 6–8. doi:10.1159/000132575. PMID 2846238.
• Counillon L, Pouysségur J, Reithmeier RA (August 1994). "The Na+/H+ exchanger NHE-1 possesses N- and O-linked glycosylation restricted to the first N-terminal extracellular domain". Biochemistry. 33 (34): 10463–9. doi:10.1021/bi00200a030. PMID 8068684.
• Fliegel L, Dyck JR, Wang H, Fong C, Haworth RS (August 1993). "Cloning and analysis of the human myocardial Na+/H+ exchanger". Molecular and Cellular Biochemistry. 125 (2): 137–43. doi:10.1007/BF00936442. PMID 8283968. S2CID 24360200.
• Lin X, Barber DL (October 1996). "A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange". Proceedings of the National Academy of Sciences of the United States of America. 93 (22): 12631–6. Bibcode:1996PNAS...9312631L. doi:10.1073/pnas.93.22.12631. PMC 38044. PMID 8901634.
• Shrode LD, Gan BS, D'Souza SJ, Orlowski J, Grinstein S (August 1998). "Topological analysis of NHE1, the ubiquitous Na+/H+ exchanger using chymotryptic cleavage". The American Journal of Physiology. 275 (2): C431-9. doi:10.1152/ajpcell.1998.275.2.C431. PMID 9688597.
• Wakabayashi S, Pang T, Su X, Shigekawa M (March 2000). "A novel topology model of the human Na(+)/H(+) exchanger isoform 1". The Journal of Biological Chemistry. 275 (11): 7942–9. doi:10.1074/jbc.275.11.7942. PMID 10713111.
• Garden OA, Musk P, Worthington-White DA, Dewey MJ, Rich IN (July 2000). "Silent polymorphisms within the coding region of human sodium/hydrogen exchanger isoform-1 cDNA in peripheral blood mononuclear cells of leukemia patients: A comparison with healthy controls". Cancer Genetics and Cytogenetics. 120 (1): 37–43. doi:10.1016/S0165-4608(99)00246-0. PMID 10913675.
• Denker SP, Huang DC, Orlowski J, Furthmayr H, Barber DL (December 2000). "Direct binding of the Na--H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H(+) translocation". Molecular Cell. 6 (6): 1425–36. doi:10.1016/S1097-2765(00)00139-8. PMID 11163215.
• Lehoux S, Florian JA, Berk BC (May 2001). "14-3-3 Binding to Na+/H+ exchanger isoform-1 is associated with serum-dependent activation of Na+/H+ exchange". The Journal of Biological Chemistry. 276 (19): 15794–800. doi:10.1074/jbc.M100410200. PMID 11279064.
• Pang T, Su X, Wakabayashi S, Shigekawa M (May 2001). "Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers". The Journal of Biological Chemistry. 276 (20): 17367–72. doi:10.1074/jbc.M100296200. PMID 11350981.
• Yan W, Nehrke K, Choi J, Barber DL (August 2001). "The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor". The Journal of Biological Chemistry. 276 (33): 31349–56. doi:10.1074/jbc.M102679200. PMID 11369779.
• Khaled AR, Moor AN, Li A, Kim K, Ferris DK, Muegge K, et al. (November 2001). "Trophic factor withdrawal: p38 mitogen-activated protein kinase activates NHE1, which induces intracellular alkalinization". Molecular and Cellular Biology. 21 (22): 7545–57. doi:10.1128/MCB.21.22.7545-7557.2001. PMC 99926. PMID 11604491.
• Mailänder J, Müller-Esterl W, Dedio J (November 2001). "Human homolog of mouse tescalcin associates with Na(+)/H(+) exchanger type-1". FEBS Letters. 507 (3): 331–5. doi:10.1016/S0014-5793(01)02986-6. PMID 11696366. S2CID 23406238.
• Shen MR, Wilkins RJ, Chou CY, Ellory JC (February 2002). "Anion exchanger isoform 2 operates in parallel with Na(+)/H(+) exchanger isoform 1 during regulatory volume decrease of human cervical cancer cells". FEBS Letters. 512 (1–3): 52–8. doi:10.1016/S0014-5793(01)03317-8. PMID 11852051.
• Behne MJ, Meyer JW, Hanson KM, Barry NP, Murata S, Crumrine D, et al. (December 2002). "NHE1 regulates the stratum corneum permeability barrier homeostasis. Microenvironment acidification assessed with fluorescence lifetime imaging". The Journal of Biological Chemistry. 277 (49): 47399–406. doi:10.1074/jbc.M204759200. PMID 12221084.