From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
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 .
[5]
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.
[6]
Interactions
Sodium–hydrogen antiporter 1 has been shown to
interact with
carbonic anhydrase II
[7] and
CHP .
[8]
[9]
[10] It is also the target of the experimental drug
rimeporide , which is being developed for the treatment of
Duchenne muscular dystrophy .
[11]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000090020 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000028854 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ 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 .
^ Cardone RA, Alfarouk KO, Elliott RL, Alqahtani SS, Ahmed SB, Aljarbou AN, et al. (July 2019).
"The Role of Sodium Hydrogen Exchanger 1 in Dysregulation of Proton Dynamics and Reprogramming of Cancer Metabolism as a Sequela" . International Journal of Molecular Sciences . 20 (15): 3694.
doi :
10.3390/ijms20153694 .
PMC
6696090 .
PMID
31357694 .
^ 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" . The Journal of Biological Chemistry . 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" . Biological & Pharmaceutical Bulletin . 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" . 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 .
^ 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 .
^ 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" . 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 .
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
By group
SLC1–10
(1): (2): (3): (4): (5): (6): (7): (8): (9): (10):
SLC11–20
(11): (12): (13): (14): (15): (16): (17): (18): (19): (20):
SLC21–30
(21): (22): (23): (24): (25): (26): (27): (28): (29): (30):
SLC31–40
(31): (32): (33): (34): (35): (36): (37): (38): (39): (40):
SLC41–48
(41): (42): (43): (44): (45): (46): (47): (48):