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

RefSeq (mRNA)

RefSeq (protein)

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.^[1]

1 Function
2 Interactions
3 References
4 Further reading

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]

References

^ 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.
^ 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.
^ 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.
^ 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.
^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=38044.
^ 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.

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.

PDB gallery

2bec: Crystal structure of CHP2 in complex with its binding region in NHE1 and insights into the mechanism of pH regulation

2e30: Solution structure of the cytoplasmic region of Na+/H+ exchanger 1 complexed with essential cofactor calcineurin B homologous protein 1

Membrane proteins, carrier proteins: membrane transport proteins solute carrier (TC 2A)

By group

SLC1–10

(1) high affinity glutamate and neutral amino-acid transporter (SLC1A1, 2, 3, 4, 5, 6, 7)

(2) facilitative GLUT transporter (SLC2A1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)

(3) heavy subunits of heterodimeric amino-acid transporters (SLC3A1, 2)

(4) bicarbonate transporter (SLC4A1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

(5) sodium glucose cotransporter (SLC5A1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)

(6) sodium- and chloride- dependent sodium:neurotransmitter symporters (SLC6A1, SLC6A2, SLC6A3, SLC6A4, SLC6A5, SLC6A6, SLC6A7, SLC6A8, SLC6A9, SLC6A10, SLC6A11, SLC6A12, SLC6A13, SLC6A14, SLC6A15, SLC6A16, SLC6A17, SLC6A18, SLC6A19, SLC6A20)

(7) cationic amino-acid transporter/glycoprotein-associated (SLC7A1, SLC7A2, SLC7A3, SLC7A4) glycoprotein-associated/light or catalytic subunits of heterodimeric amino-acid transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A9, SLC7A10, SLC7A11, SLC7A13, SLC7A14)

(8) Na+/Ca2+ exchanger (SLC8A1, SLC8A2, SLC8A3)

(9) Na+/H+ exchanger (SLC9A1, SLC9A2, SLC9A3, SLC9A4, SLC9A5, SLC9A6, SLC9A7, SLC9A8, SLC9A9, SLC9A10, SLC9A11)

(10) sodium bile salt cotransport (SLC10A1, SLC10A2, SLC10A3, SLC10A4, SLC10A5, SLC10A6, SLC10A7); 10A1 · 10A2 · 10A3 · 10A7

SLC11–20

(11) proton coupled metal ion transporter (SLC11A1, SLC11A2) 11A3

(12) electroneutral cation-Cl cotransporter (SLC12A1, SLC12A1, SLC12A2, SLC12A3, SLC12A4, SLC12A5, SLC12A6, SLC12A7, SLC12A8, SLC12A9)

(13) human Na+-sulfate/carboxylate cotransporter (SLC13A1, SLC13A2, SLC13A3, SLC13A4, SLC13A5)

(14) urea transporter (SLC14A1, SLC14A2)

(15) proton oligopeptide cotransporter (SLC15A1, SLC15A2, SLC15A3, SLC15A4)

(16) monocarboxylate transporter (SLC16A1, SLC16A2, SLC16A3, SLC16A4, SLC16A5, SLC16A6, SLC16A7, SLC16A8, SLC16A9, SLC16A10, SLC16A11, SLC16A12, SLC16A13, SLC16A14)

(17) vesicular glutamate transporter (SLC17A1, SLC17A2, SLC17A3, SLC17A4, SLC17A5, SLC17A6, SLC17A7, SLC17A8, SLC17A9)

(18) vesicular amine transporter (SLC18A1, SLC18A2, SLC18A3)

(19) folate/thiamine transporter (SLC19A1, SLC19A2, SLC19A3)

(20) type III Na+-phosphate cotransporter (SLC20A1, SLC20A2)

SLC21–30

(21) organic anion transporting (SLCO1A2, SLCO1B1, SLCO1B3, SLCO1B4, SLCO1C1) (SLCO2A1, SLCO2B1) (SLCO3A1) (SLCO4A1, SLCO4C1) (SLCO5A1) (SLCO6A1)

(22) organic cation/anion/zwitterion transporter (SLC22A1, SLC22A2, SLC22A3, SLC22A4, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLC22A9, SLC22A10, SLC22A11, SLC22A12, SLC22A13, SLC22A14, SLC22A15, SLC22A16, SLC22A17, SLC22A18, SLC22A19, SLC22A20)

(23) Na+-dependent ascorbic acid transporter (SLC23A1, SLC23A2, SLC23A3, SLC23A4)

(24) Na+/(Ca2+-K+) exchanger (SLC24A1, SLC24A2, SLC24A3, SLC24A4, SLC24A5, SLC24A6)

(25) mitochondrial carrier (SLC25A1, SLC25A2, SLC25A3, SLC25A4, SLC25A5, SLC25A6, SLC25A7, SLC25A8, SLC25A9, SLC25A10, SLC25A11, SLC25A12, SLC25A13, SLC25A14, SLC25A15, SLC25A16, SLC25A17, SLC25A18, SLC25A19, SLC25A20, SLC25A21, SLC25A22, SLC25A23, SLC25A24, SLC25A25, SLC25A26, SLC25A27, SLC25A28, SLC25A29, SLC25A30, SLC25A31, SLC25A32, SLC25A33, SLC25A34, SLC25A35, SLC25A36, SLC25A37, SLC25A38, SLC25A39, SLC25A40, SLC25A41, SLC25A42, SLC25A43, SLC25A44, SLC25A45, SLC25A46)

(26) multifunctional anion exchanger (SLC26A1, SLC26A2, SLC26A3, SLC26A4, SLC26A5, SLC26A6, SLC26A7, SLC26A8, SLC26A9, SLC26A10, SLC26A11)

(27) fatty acid transport proteins (SLC27A1, SLC27A2, SLC27A3, SLC27A4, SLC27A5, SLC27A6)

(28) Na+-coupled nucleoside transport (SLC28A1, SLC28A2, SLC28A3

(29) facilitative nucleoside transporter (SLC29A1, SLC29A2, SLC29A3, SLC29A4)

(30) zinc efflux (SLC30A1, SLC30A2, SLC30A3, SLC30A4, SLC30A5, SLC30A6, SLC30A7, SLC30A8, SLC30A9, SLC30A10)

SLC31–40

(31) copper transporter (SLC31A1)

(32) vesicular inhibitory amino-acid transporter (SLC32A1)

(33) Acetyl-CoA transporter (SLC33A1)

(34) type II Na+-phosphate cotransporter (SLC34A1, SLC34A2, SLC34A3)

(35) nucleoside-sugar transporter (SLC35A1, SLC35A2, SLC35A3, SLC35A4, SLC35A5) (SLC35B1, SLC35B2, SLC35B3, SLC35B4) (SLC35C1, SLC35C2) (SLC35D1, SLC35D2, SLC35D3) (SLC35E1, SLC35E2, SLC35E3, SLC35E4)

(36) proton-coupled amino-acid transporter (SLC36A1, SLC36A2, SLC36A3, SLC36A4)36A2 ·

(37) sugar-phosphate/phosphate exchanger (SLC37A1, SLC37A2, SLC37A3, SLC37A4)

(38) System A & N, sodium-coupled neutral amino-acid transporter (SLC38A1, SLC38A2, SLC38A3, SLC38A4, SLC38A5, SLC38A6, SLC38A10)

(39) metal ion transporter (SLC39A1, SLC39A2, SLC39A3, SLC39A4, SLC39A5, SLC39A6, SLC39A7, SLC39A8, SLC39A9, SLC39A10, SLC39A11, SLC39A12, SLC39A13, SLC39A14)

(40) basolateral iron transporter (SLC40A1)

SLC41–48

(41) MgtE-like magnesium transporter (SLC41A1, SLC41A2, SLC41A3)

(42) Ammonia transporter (RhAG, RhBG, RhCG)

(43) Na+-independent, system-L like amino-acid transporter (SLC43A1, SLC43A2, SLC43A3)

(44) Choline-like transporter (SLC44A1, SLC44A2, SLC44A3, SLC44A4, SLC44A5)

(45) Putative sugar transporter (SLC45A1, SLC45A2, SLC54A3, SLC45A4)

(46) Folate transporter (SLC46A1, SLC46A2)

(47) multidrug and toxin extrusion (SLC47A1, SLC47A2)

(48) Heme transporter

SLCO1–4

O1A2 · O1B1 · O1B3 · O2B1 · O431 · O4A1

Ion pumps

Symporter, Cotransporter	Na+/K+/2Cl- - Na/Pi3 - Na+/Cl- - Na/glucose - Na+/I- - Cl-/K+ (4, 5)

Antiporter (exchanger)	Na+/H+ - Na+/Ca2+ (Na+/(Ca2+-K+)) - Cl-/HCO3- (Band 3) - Cl-formate exchanger - Cl-oxalate exchanger

see also solute carrier disorders
B memb: cead, trns (1A, 1C, 1F, 2A, 3A1, 3A2-3, 3D), othr

Sodium–hydrogen antiporter 1

Contents

Function

Interactions

References

Further reading