Sodium–hydrogen antiporter 1

Solute carrier family 9 (sodium/hydrogen exchanger), member 1
PDB rendering based on 2bec.
Available structures PDB 1Y4E, 2BEC, 2E30, 2HTG, 2KBV, 2L0E
Identifiers
Symbols	SLC9A1; APNH; FLJ42224; NHE1
External IDs	OMIM: 107310 MGI: 102462 HomoloGene: 20660 GeneCards: SLC9A1 Gene
Gene Ontology Molecular function • protein binding • transcription factor binding • antiporter activity • solute:hydrogen antiporter activity • sodium:hydrogen antiporter activity Cellular component • membrane fraction • plasma membrane • integral to membrane • basolateral plasma membrane • membrane raft Biological process • response to acid • ion transport • cation transport • sodium ion transport • regulation of pH • intracellular protein kinase cascade • response to acidity • response to organic cyclic compound • cell growth • cell differentiation • response to drug • positive regulation of anti-apoptosis • transmembrane transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6548	20544
Ensembl	ENSG00000090020	ENSMUSG00000028854
UniProt	P19634	Q3TN68
RefSeq (mRNA)	NM_003047.3	NM_016981.2
RefSeq (protein)	NP_003038.2	NP_058677.1
Location (UCSC)	Chr 1: 27.43 – 27.49 Mb	Chr 4: 132.93 – 132.98 Mb
PubMed search	[1]	[2]

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.

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.

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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2408441. 
• 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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=452875. 
• Dudley CR, Giuffra LA, Tippett P, et al. (1991). "The Na+/H+ antiporter: a "melt" polymorphism allows regional mapping to the short arm of chromosome 1.". Hum. Genet. 86 (1): 79–83. 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, et al. (1994). "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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=38044. 
• Shrode LD, Gan BS, D'Souza SJ, et al. (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, et al. (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, et al. (2001). "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, Abe Ji , 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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99926. 
• 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.