Sodium–hydrogen antiporter 1

Solute carrier family 9, subfamily A (NHE1, cation proton antiporter 1), member 1
PDB rendering based on 2bec.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1Y4E​, 2BEC​, 2E30​, 2HTG​, 2KBV​, 2L0E​, 2MDF​, 2YGG​
Identifiers
Symbols	SLC9A1 ; APNH; LIKNS; NHE-1; NHE1; PPP1R143
External IDs	OMIM: 107310 MGI: 102462 HomoloGene: 20660 ChEMBL: 2781 GeneCards: SLC9A1 Gene
Gene ontology Molecular function • protein binding • calmodulin binding • phosphatidylinositol-4,5-bisphosphate binding • solute:proton antiporter activity • sodium:proton antiporter activity • protein phosphatase 2B binding • protein binding, bridging • protein complex scaffold • calcium-dependent protein binding • sodium:proton antiporter activity involved in regulation of cardiac muscle cell membrane potential Cellular component • nucleoplasm • cytoplasm • mitochondrion • endoplasmic reticulum • endoplasmic reticulum membrane • plasma membrane • integral component of plasma membrane • focal adhesion • cell surface • intercalated disc • integral component of membrane • basolateral plasma membrane • apical plasma membrane • lamellipodium • T-tubule • membrane raft • perinuclear region of cytoplasm • extracellular exosome • cation-transporting ATPase complex Biological process • carbohydrate metabolic process • ion transport • cellular sodium ion homeostasis • regulation of pH • response to acidic pH • positive regulation of cardiac muscle hypertrophy • regulation of cardiac muscle contraction by calcium ion signaling • cell growth • cell migration • maintenance of cell polarity • glycosaminoglycan metabolic process • hyaluronan metabolic process • hyaluronan catabolic process • positive regulation of cell growth • cellular response to insulin stimulus • positive regulation of mitochondrial membrane permeability • response to muscle stretch • response to drug • positive regulation of apoptotic process • negative regulation of apoptotic process • small molecule metabolic process • positive regulation of action potential • positive regulation of transcription from RNA polymerase II promoter • protein oligomerization • regulation of intracellular pH • regulation of stress fiber assembly • positive regulation of NFAT protein import into nucleus • regulation of focal adhesion assembly • regulation of sensory perception of pain • cardiac muscle cell differentiation • transmembrane transport • positive regulation of calcineurin-NFAT signaling cascade • neuron death • cellular response to antibiotic • cellular response to electrical stimulus • cellular response to mechanical stimulus • sodium ion export • cellular response to hypoxia • cellular response to acidic pH • cellular response to epinephrine stimulus • cardiac muscle cell contraction • regulation of cardiac muscle cell membrane potential • regulation of the force of heart contraction by cardiac conduction • sodium ion import across plasma membrane • positive regulation of the force of heart contraction • hydrogen ion transmembrane transport • positive regulation of calcium:sodium antiporter activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6548	20544
Ensembl	ENSG00000090020	ENSMUSG00000028854
UniProt	P19634	Q61165
RefSeq (mRNA)	NM_003047	NM_016981
RefSeq (protein)	NP_003038	NP_058677
Location (UCSC)	Chr 1: 27.1 – 27.17 Mb	Chr 4: 133.37 – 133.42 Mb
PubMed search

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.^[1]

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.^[2]

Interactions

Sodium–hydrogen antiporter 1 has been shown to interact with carbonic anhydrase II^[3] and CHP.^[4][5][6] It is also the target of the experimental drug rimeporide, which is being developed for the treatment of Duchenne muscular dystrophy.^[7]

References

1. Fliegel L, Dyck JR, Wang H, Fong C, Haworth RS (August 1993). "Cloning and analysis of the human myocardial Na+/H+ exchanger". Mol. Cell. Biochem. 125 (2): 137–43. doi:10.1007/BF00936442. PMID 8283968.
2. Mattei MG, Sardet C, Franchi A, Pouysségur J (1988). "The human amiloride-sensitive Na+/H+ antiporter: localization to chromosome 1 by in situ hybridization". Cytogenet. Cell Genet. 48 (1): 6–8. doi:10.1159/000132575. PMID 2846238.
3. Li X, Alvarez B, Casey JR, Reithmeier RA, Fliegel L (September 2002). "Carbonic anhydrase II binds to and enhances activity of the Na+/H+ exchanger". J. Biol. Chem. 277 (39): 36085–91. doi:10.1074/jbc.M111952200. PMID 12138085.
4. Inoue H, Nakamura Y, Nagita M, Takai T, Masuda M, Nakamura N, Kanazawa H (February 2003). "Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium". Biol. Pharm. Bull. 26 (2): 148–55. doi:10.1248/bpb.26.148. PMID 12576672.
5. Lin X, Barber DL (October 1996). "A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange". Proc. Natl. Acad. Sci. U.S.A. 93 (22): 12631–6. doi:10.1073/pnas.93.22.12631. PMC 38044. PMID 8901634.
6. Pang T, Su X, Wakabayashi S, Shigekawa M (May 2001). "Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers". J. Biol. Chem. 276 (20): 17367–72. doi:10.1074/jbc.M100296200. PMID 11350981.
7. Spreitzer, Helmut (26 May 2015). "Rimeporide". Österreichische Apothekerzeitung (in German) 69 (11): 12.

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". Am. J. Respir. Crit. Care Med. 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". Am. J. Physiol. Lung Cell Mol. Physiol. 289 (5): L867–74. doi:10.1152/ajplung.00455.2004. PMID 15964895.
• Cingolani HE, Ennis IL (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 (2007). "Beyond ion translocation: structural functions of the sodium-hydrogen exchanger isoform-1". Curr. Opin. Nephrol. Hypertens. 16 (4): 365–72. doi:10.1097/MNH.0b013e3281bd888d. PMID 17565280.
• Tse CM, Ma AI, Yang VW, Watson AJ, Levine S, Montrose MH, Potter J, Sardet C, Pouyssegur J, Donowitz M (1991). "Molecular cloning and expression of a cDNA encoding the rabbit ileal villus cell basolateral membrane Na+/H+ exchanger". EMBO J. 10 (8): 1957–67. PMC 452875. PMID 1712287.
• Dudley CR, Giuffra LA, Tippett P, Kidd KK, Reeders ST (1990). "The Na+/H+ antiporter: a "melt" polymorphism allows regional mapping to the short arm of chromosome 1". Hum. Genet. 86 (1): 79–83. doi:10.1007/bf00205179. PMID 1979310.
• Sardet C, Counillon L, Franchi A, Pouysségur J (1990). "Growth factors induce phosphorylation of the Na+/H+ antiporter, glycoprotein of 110 kD". Science 247 (4943): 723–6. doi:10.1126/science.2154036. PMID 2154036.
• Sardet C, Franchi A, Pouysségur J (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.
• Mattei MG, Sardet C, Franchi A, Pouysségur J (1988). "The human amiloride-sensitive Na+/H+ antiporter: localization to chromosome 1 by in situ hybridization". Cytogenet. Cell Genet. 48 (1): 6–8. doi:10.1159/000132575. PMID 2846238.
• Counillon L, Pouysségur J, Reithmeier RA (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 (1993). "Cloning and analysis of the human myocardial Na+/H+ exchanger". Mol. Cell. Biochem. 125 (2): 137–43. doi:10.1007/BF00936442. PMID 8283968.
• Lin X, Barber DL (1996). "A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange". Proc. Natl. Acad. Sci. U.S.A. 93 (22): 12631–6. doi:10.1073/pnas.93.22.12631. PMC 38044. PMID 8901634.
• Shrode LD, Gan BS, D'Souza SJ, Orlowski J, Grinstein S (1998). "Topological analysis of NHE1, the ubiquitous Na+/H+ exchanger using chymotryptic cleavage". Am. J. Physiol. 275 (2 Pt 1): C431–9. PMID 9688597.
• Wakabayashi S, Pang T, Su X, Shigekawa M (2000). "A novel topology model of the human Na(+)/H(+) exchanger isoform 1". J. Biol. Chem. 275 (11): 7942–9. doi:10.1074/jbc.275.11.7942. PMID 10713111.
• Garden OA, Musk P, Worthington-White DA, Dewey MJ, Rich IN (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 Genet. Cytogenet. 120 (1): 37–43. doi:10.1016/S0165-4608(99)00246-0. PMID 10913675.
• Denker SP, Huang DC, Orlowski J, Furthmayr H, Barber DL (2000). "Direct binding of the Na--H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H(+) translocation". Mol. Cell 6 (6): 1425–36. doi:10.1016/S1097-2765(00)00139-8. PMID 11163215.
• Lehoux S, Florian JA, Berk BC (2001). "14-3-3 Binding to Na+/H+ exchanger isoform-1 is associated with serum-dependent activation of Na+/H+ exchange". J. Biol. Chem. 276 (19): 15794–800. doi:10.1074/jbc.M100410200. PMID 11279064.
• Pang T, Su X, Wakabayashi S, Shigekawa M (2001). "Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers". J. Biol. Chem. 276 (20): 17367–72. doi:10.1074/jbc.M100296200. PMID 11350981.
• Yan W, Nehrke K, Choi J, Barber DL (2001). "The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor". J. Biol. Chem. 276 (33): 31349–56. doi:10.1074/jbc.M102679200. PMID 11369779.
• Khaled AR, Moor AN, Li A, Kim K, Ferris DK, Muegge K, Fisher RJ, Fliegel L, Durum SK (2001). "Trophic factor withdrawal: p38 mitogen-activated protein kinase activates NHE1, which induces intracellular alkalinization". Mol. Cell. Biol. 21 (22): 7545–57. doi:10.1128/MCB.21.22.7545-7557.2001. PMC 99926. PMID 11604491.
• Mailänder J, Müller-Esterl W, Dedio J (2001). "Human homolog of mouse tescalcin associates with Na(+)/H(+) exchanger type-1". FEBS Lett. 507 (3): 331–5. doi:10.1016/S0014-5793(01)02986-6. PMID 11696366.
• Shen MR, Wilkins RJ, Chou CY, Ellory JC (2002). "Anion exchanger isoform 2 operates in parallel with Na(+)/H(+) exchanger isoform 1 during regulatory volume decrease of human cervical cancer cells". FEBS Lett. 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, Clegg RW, Gratton E, Holleran WM, Elias PM, Mauro TM (2002). "NHE1 regulates the stratum corneum permeability barrier homeostasis. Microenvironment acidification assessed with fluorescence lifetime imaging". J. Biol. Chem. 277 (49): 47399–406. doi:10.1074/jbc.M204759200. PMID 12221084.