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InterPro-Version: 108.0
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{
"metadata": {
"accession": "IPR001970",
"entry_id": null,
"type": "family",
"go_terms": [
{
"identifier": "GO:0015385",
"name": "sodium:proton antiporter activity",
"category": {
"code": "F",
"name": "molecular_function"
}
},
{
"identifier": "GO:0006814",
"name": "sodium ion transport",
"category": {
"code": "P",
"name": "biological_process"
}
},
{
"identifier": "GO:0006885",
"name": "regulation of pH",
"category": {
"code": "P",
"name": "biological_process"
}
},
{
"identifier": "GO:0016020",
"name": "membrane",
"category": {
"code": "C",
"name": "cellular_component"
}
}
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"source_database": "interpro",
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"prints": {
"PR01085": "NAHEXCHNGR1"
}
},
"integrated": null,
"hierarchy": {
"accession": "IPR018422",
"name": "Cation/H+ exchanger, CPA1 family",
"type": "Family",
"children": [
{
"accession": "IPR004705",
"name": "Cation/H+ exchanger, CPA1 family, bacteria",
"type": "Family",
"children": []
},
{
"accession": "IPR004709",
"name": "Na+/H+ exchanger",
"type": "Family",
"children": [
{
"accession": "IPR001953",
"name": "Sodium/hydrogen exchanger 2/4",
"type": "Family",
"children": []
},
{
"accession": "IPR001970",
"name": "Sodium/hydrogen exchanger 1-like",
"type": "Family",
"children": []
},
{
"accession": "IPR002090",
"name": "Sodium/hydrogen exchanger 6/7/9",
"type": "Family",
"children": []
}
]
},
{
"accession": "IPR018410",
"name": "Na+/H+ exchanger, isoforms 3/5",
"type": "Family",
"children": []
}
]
},
"name": {
"name": "Sodium/hydrogen exchanger 1-like",
"short": "NHE-1-like"
},
"description": [
{
"text": "<p>Sodium proton exchangers (NHEs) constitute a large family of integral membrane protein transporters that are responsible for the counter-transport of protons and sodium ions across lipid bilayers [[cite:PUB00044828], [cite:PUB00044829]]. These proteins are found in organisms across all domains of life. In archaea, bacteria, yeast and plants, these exchangers provide increased salt tolerance by removing sodium in exchanger for extracellular protons. In mammals they participate in the regulation of cell pH, volume, and intracellular sodium concentration, as well as for the reabsorption of NaCl across renal, intestinal, and other epithelia [[cite:PUB00044830], [cite:PUB00044831], [cite:PUB00044832], [cite:PUB00044833]]. Human NHE is also involved in heart disease, cell growth and in cell differentiation [[cite:PUB00044834]]. The removal of intracellular protons in exchange for extracellular sodium effectively eliminates excess acid from actively metabolising cells. In mammalian cells, NHE activity is found in both the plasma membrane and inner mitochondrial membrane. To date, nine mammalian isoforms have been identified (designated NHE1-NHE9) [[cite:PUB00002996], [cite:PUB00003039]]. These exchangers are highly-regulated (glyco)phosphoproteins, which, based on their primary structure, appear to contain 10-12 membrane-spanning regions (M) at the N terminus and a large cytoplasmic region at the C terminus. The transmembrane regions M3-M12 share identity with other members of the family. The M6 and M7 regions are highly conserved. Thus, this is thought to be the region that is involved in the transport of sodium and hydrogen ions. The cytoplasmic region has little similarity throughout the family. There is some evidence that the exchangers may exist in the cell membrane as homodimers, but little is currently known about the mechanism of their antiport [[cite:PUB00001715]].</p>",
"llm": false,
"checked": false,
"updated": false
},
{
"text": "<p>Sodium/hydrogen exchanger 1 (NHE-1) is found in virtually all tissues and cells in mammals and is involved in numerous physiological processes, including regulation of intracellular pH, cellular volume, cytoskeletal organisation, heart disease and cancer [[cite:PUB00044826], [cite:PUB00044827], [cite:PUB00044835]]. In epithelial cells, NHE-1 is largely restricted to the basolateral membrane, which specific subcellular localisation is thought to be important to the functioning of these epithelia. This protein comprises two domains: an N-terminal membrane domain that functions to transport ions, and a C-terminal cytoplasmic regulatory domain that regulates the activity and mediates cytoskeletal interactions.</p>\n\n<p>NHE-1 plays a role in survival and migration and invasion of several cancers [[cite:PUB00100483], [cite:PUB00100485]]. It was shown to be activated at physiological levels of NO [[cite:PUB00100484]].</p>",
"llm": false,
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"PUB00002996": {
"PMID": 9278382,
"ISBN": null,
"volume": "272",
"issue": "36",
"year": 1997,
"title": "Na+/H+ exchangers of mammalian cells.",
"URL": null,
"raw_pages": "22373-6",
"medline_journal": "J Biol Chem",
"ISO_journal": "J. Biol. Chem.",
"authors": [
"Orlowski J",
"Grinstein S."
],
"DOI_URL": "http://dx.doi.org/10.1074/jbc.272.36.22373"
},
"PUB00003039": {
"PMID": 9507001,
"ISBN": null,
"volume": "273",
"issue": "12",
"year": 1998,
"title": "Identification of a mitochondrial Na+/H+ exchanger.",
"URL": null,
"raw_pages": "6951-9",
"medline_journal": "J Biol Chem",
"ISO_journal": "J. Biol. Chem.",
"authors": [
"Numata M",
"Petrecca K",
"Lake N",
"Orlowski J."
],
"DOI_URL": "http://dx.doi.org/10.1074/jbc.273.12.6951"
},
"PUB00001715": {
"PMID": 9537504,
"ISBN": null,
"volume": "424",
"issue": "1-2",
"year": 1998,
"title": "Comparative molecular analysis of Na+/H+ exchangers: a unified model for Na+/H+ antiport?",
"URL": null,
"raw_pages": "1-5",
"medline_journal": "FEBS Lett",
"ISO_journal": "FEBS Lett.",
"authors": [
"Dibrov P",
"Fliegel L."
],
"DOI_URL": "http://dx.doi.org/10.1016/S0014-5793(98)00119-7"
},
"PUB00044832": {
"PMID": 16513813,
"ISBN": null,
"volume": "57",
"issue": "5",
"year": 2006,
"title": "Alkali cation exchangers: roles in cellular homeostasis and stress tolerance.",
"URL": null,
"raw_pages": "1181-99",
"medline_journal": "J Exp Bot",
"ISO_journal": "J. Exp. Bot.",
"authors": [
"Pardo JM",
"Cubero B",
"Leidi EO",
"Quintero FJ."
],
"DOI_URL": "http://dx.doi.org/10.1093/jxb/erj114"
},
"PUB00044833": {
"PMID": 11187762,
"ISBN": null,
"volume": "72",
"issue": "11",
"year": 2000,
"title": "[Structure function and regulation of the mammalian Na+/H+ exchangers]",
"URL": null,
"raw_pages": "1329-34",
"medline_journal": "Seikagaku",
"ISO_journal": "Seikagaku",
"authors": [
"Wakabayashi S."
],
"DOI_URL": null
},
"PUB00044834": {
"PMID": 17218973,
"ISBN": null,
"volume": "84",
"issue": "11",
"year": 2006,
"title": "Physiological role and regulation of the Na+/H+ exchanger.",
"URL": null,
"raw_pages": "1081-95",
"medline_journal": "Can J Physiol Pharmacol",
"ISO_journal": "Can. J. Physiol. Pharmacol.",
"authors": [
"Malo ME",
"Fliegel L."
],
"DOI_URL": "http://dx.doi.org/10.1139/Y06-065"
},
"PUB00044826": {
"PMID": 17209804,
"ISBN": null,
"volume": "401",
"issue": "3",
"year": 2007,
"title": "Structural and functional analysis of the Na+/H+ exchanger.",
"URL": null,
"raw_pages": "623-33",
"medline_journal": "Biochem J",
"ISO_journal": "Biochem. J.",
"authors": [
"Slepkov ER",
"Rainey JK",
"Sykes BD",
"Fliegel L."
],
"DOI_URL": "http://dx.doi.org/10.1042/BJ20061062"
},
"PUB00044827": {
"PMID": 19001864,
"ISBN": null,
"volume": "2",
"issue": "5",
"year": 2008,
"title": "Structure and function of the human Na(+)/H(+) exchanger isoform 1.",
"URL": null,
"raw_pages": null,
"medline_journal": "Channels (Austin)",
"ISO_journal": null,
"authors": [
"Kemp G",
"Young H",
"Fliegel L."
],
"DOI_URL": null
},
"PUB00044835": {
"PMID": 11807182,
"ISBN": null,
"volume": "42",
"issue": null,
"year": 2002,
"title": "The changing face of the Na+/H+ exchanger, NHE1: structure, regulation, and cellular actions.",
"URL": null,
"raw_pages": "527-52",
"medline_journal": "Annu Rev Pharmacol Toxicol",
"ISO_journal": "Annu. Rev. Pharmacol. Toxicol.",
"authors": [
"Putney LK",
"Denker SP",
"Barber DL."
],
"DOI_URL": "http://dx.doi.org/10.1146/annurev.pharmtox.42.092001.143801"
},
"PUB00044828": {
"PMID": 12027219,
"ISBN": null,
"volume": "15 Suppl 5",
"issue": null,
"year": 2002,
"title": "The Na+/H+ exchanger gene family.",
"URL": null,
"raw_pages": "S3-21",
"medline_journal": "J Nephrol",
"ISO_journal": "J. Nephrol.",
"authors": [
"Burckhardt G",
"Di Sole F",
"Helmle-Kolb C."
],
"DOI_URL": null
},
"PUB00044829": {
"PMID": 12502567,
"ISBN": null,
"volume": "976",
"issue": null,
"year": 2002,
"title": "Multiple modes of regulation of Na+/H+ exchangers.",
"URL": null,
"raw_pages": "248-58",
"medline_journal": "Ann N Y Acad Sci",
"ISO_journal": "Ann. N. Y. Acad. Sci.",
"authors": [
"Hayashi H",
"Szaszi K",
"Grinstein S."
],
"DOI_URL": null
},
"PUB00044830": {
"PMID": 16734752,
"ISBN": null,
"volume": "187",
"issue": "1-2",
"year": 2006,
"title": "Na+/H+ exchangers and the regulation of volume.",
"URL": null,
"raw_pages": "159-67",
"medline_journal": "Acta Physiol (Oxf)",
"ISO_journal": null,
"authors": [
"Alexander RT",
"Grinstein S."
],
"DOI_URL": null
},
"PUB00044831": {
"PMID": 17071327,
"ISBN": null,
"volume": "26",
"issue": "5",
"year": 2006,
"title": "Na+/H+ exchangers in renal regulation of acid-base balance.",
"URL": null,
"raw_pages": "334-44",
"medline_journal": "Semin Nephrol",
"ISO_journal": "Semin. Nephrol.",
"authors": [
"Bobulescu IA",
"Moe OW."
],
"DOI_URL": "http://dx.doi.org/10.1016/j.semnephrol.2006.07.001"
},
"PUB00100484": {
"PMID": 31742355,
"ISBN": null,
"volume": "116",
"issue": "12",
"year": 2020,
"title": "Nitric oxide modulates cardiomyocyte pH control through a biphasic effect on sodium/hydrogen exchanger-1.",
"URL": null,
"raw_pages": "1958-1971",
"medline_journal": "Cardiovasc Res",
"ISO_journal": "Cardiovasc Res",
"authors": [
"Richards MA",
"Simon JN",
"Ma R",
"Loonat AA",
"Crabtree MJ",
"Paterson DJ",
"Fahlman RP",
"Casadei B",
"Fliegel L",
"Swietach P."
],
"DOI_URL": null
},
"PUB00100485": {
"PMID": 24717311,
"ISBN": null,
"volume": "35",
"issue": "9",
"year": 2014,
"title": "Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H⁺ extrusion, cell migration and survival.",
"URL": null,
"raw_pages": "2014-24",
"medline_journal": "Carcinogenesis",
"ISO_journal": "Carcinogenesis",
"authors": [
"Cong D",
"Zhu W",
"Shi Y",
"Pointer KB",
"Clark PA",
"Shen H",
"Kuo JS",
"Hu S",
"Sun D."
],
"DOI_URL": null
},
"PUB00100483": {
"PMID": 15535843,
"ISBN": null,
"volume": "6",
"issue": "6",
"year": 2004,
"title": "The Na+-H+ exchanger-1 induces cytoskeletal changes involving reciprocal RhoA and Rac1 signaling, resulting in motility and invasion in MDA-MB-435 cells.",
"URL": null,
"raw_pages": "R616-28",
"medline_journal": "Breast Cancer Res",
"ISO_journal": "Breast Cancer Res",
"authors": [
"Paradiso A",
"Cardone RA",
"Bellizzi A",
"Bagorda A",
"Guerra L",
"Tommasino M",
"Casavola V",
"Reshkin SJ."
],
"DOI_URL": null
}
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"name": "Structure of Calcineurin in complex with NHE1 peptide"
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}
