Sodium/hydrogen exchanger 1

Details

Name
Sodium/hydrogen exchanger 1
Synonyms
  • APNH
  • APNH1
  • Na(+)/H(+) antiporter, amiloride-sensitive
  • Na(+)/H(+) exchanger 1
  • NHE-1
  • NHE1
  • Solute carrier family 9 member 1
Gene Name
SLC9A1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0022271|Sodium/hydrogen exchanger 1
MVLRSGICGLSPHRIFPSLLVVVALVGLLPVLRSHGLQLSPTASTIRSSEPPRERSIGDV
TTAPPEVTPESRPVNHSVTDHGMKPRKAFPVLGIDYTHVRTPFEISLWILLACLMKIGFH
VIPTISSIVPESCLLIVVGLLVGGLIKGVGETPPFLQSDVFFLFLLPPIILDAGYFLPLR
QFTENLGTILIFAVVGTLWNAFFLGGLMYAVCLVGGEQINNIGLLDNLLFGSIISAVDPV
AVLAVFEEIHINELLHILVFGESLLNDAVTVVLYHLFEEFANYEHVGIVDIFLGFLSFFV
VALGGVLVGVVYGVIAAFTSRFTSHIRVIEPLFVFLYSYMAYLSAELFHLSGIMALIASG
VVMRPYVEANISHKSHTTIKYFLKMWSSVSETLIFIFLGVSTVAGSHHWNWTFVISTLLF
CLIARVLGVLGLTWFINKFRIVKLTPKDQFIIAYGGLRGAIAFSLGYLLDKKHFPMCDLF
LTAIITVIFFTVFVQGMTIRPLVDLLAVKKKQETKRSINEEIHTQFLDHLLTGIEDICGH
YGHHHWKDKLNRFNKKYVKKCLIAGERSKEPQLIAFYHKMEMKQAIELVESGGMGKIPSA
VSTVSMQNIHPKSLPSERILPALSKDKEEEIRKILRNNLQKTRQRLRSYNRHTLVADPYE
EAWNQMLLRRQKARQLEQKINNYLTVPAHKLDSPTMSRARIGSDPLAYEPKEDLPVITID
PASPQSPESVDLVNEELKGKVLGLSRDPAKVAEEDEDDDGGIMMRSKETSSPGTDDVFTP
APSDSPSSQRIQRCLSDPGPHPEPGEGEPFFPKGQ
Number of residues
815
Molecular Weight
90762.13
Theoretical pI
7.22
GO Classification
Functions
calcium-dependent protein binding / phosphatidylinositol-4,5-bisphosphate binding / protein binding, bridging / protein complex scaffold / protein phosphatase 2B binding / sodium / solute
Processes
carbohydrate metabolic process / cardiac muscle cell contraction / cardiac muscle cell differentiation / cell growth / cell migration / cellular response to acidic pH / cellular response to antibiotic / cellular response to electrical stimulus / cellular response to epinephrine stimulus / cellular response to hypoxia / cellular response to insulin stimulus / cellular response to mechanical stimulus / cellular sodium ion homeostasis / glycosaminoglycan metabolic process / hyaluronan catabolic process / hyaluronan metabolic process / hydrogen ion transmembrane transport / ion transport / maintenance of cell polarity / negative regulation of apoptotic process / neuron death / positive regulation of action potential / positive regulation of apoptotic process / positive regulation of calcineurin-NFAT signaling cascade / positive regulation of calcium / positive regulation of cardiac muscle hypertrophy / positive regulation of cell growth / positive regulation of mitochondrial membrane permeability / positive regulation of NFAT protein import into nucleus / positive regulation of the force of heart contraction / positive regulation of transcription from RNA polymerase II promoter / protein oligomerization / regulation of cardiac muscle cell membrane potential / regulation of cardiac muscle contraction by calcium ion signaling / regulation of focal adhesion assembly / regulation of intracellular pH / regulation of pH / regulation of sensory perception of pain / regulation of stress fiber assembly / regulation of the force of heart contraction by cardiac conduction / response to acidic pH / response to drug / response to muscle stretch / small molecule metabolic process / sodium ion export / sodium ion import across plasma membrane / transmembrane transport
Components
apical plasma membrane / basolateral plasma membrane / cation-transporting ATPase complex / cell surface / cytoplasm / endoplasmic reticulum / endoplasmic reticulum membrane / extracellular exosome / focal adhesion / integral component of membrane / integral component of plasma membrane / intercalated disc / lamellipodium / membrane raft / mitochondrion / nucleoplasm / perinuclear region of cytoplasm / plasma membrane / T-tubule
General Function
Solute:proton antiporter activity
Specific Function
Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction.
Pfam Domain Function
Transmembrane Regions
13-33 106-127 130-149 155-174 192-211 228-247 257-276 295-315 339-358 411-430 449-470 480-499
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0022272|Sodium/hydrogen exchanger 1 (SLC9A1)
ATGGTTCTGCGGTCTGGCATCTGTGGCCTCTCTCCACATCGGATCTTCCCTTCCTTACTC
GTGGTGGTTGCTTTGGTGGGGCTGCTGCCTGTTCTCAGGAGCCATGGCCTCCAGCTCAGC
CCAACTGCCAGCACCATTCGAAGCTCAGAGCCACCACGAGAACGCTCGATTGGGGATGTC
ACCACCGCTCCACCGGAGGTCACCCCAGAGAGCCGCCCTGTTAATCATTCCGTCACTGAT
CATGGCATGAAGCCGCGCAAGGCCTTTCCAGTCCTGGGCATCGACTACACACACGTGCGC
ACCCCCTTCGAGATCTCCCTCTGGATCCTTCTGGCCTGCCTCATGAAGATAGGTTTCCAT
GTGATCCCCACTATCTCAAGCATCGTCCCGGAGAGCTGCCTGCTGATCGTGGTGGGGCTG
CTGGTGGGGGGCCTGATCAAGGGTGTAGGCGAGACACCCCCCTTCCTGCAGTCCGACGTC
TTCTTCCTCTTCCTGCTGCCGCCCATCATCCTGGATGCGGGCTACTTCCTGCCACTGCGG
CAGTTCACAGAAAACCTGGGCACCATCCTGATCTTTGCCGTGGTGGGCACGCTGTGGAAC
GCCTTCTTCCTGGGCGGCCTCATGTACGCCGTGTGCCTGGTGGGCGGTGAGCAGATCAAC
AACATCGGCCTCCTGGACAACCTGCTCTTCGGCAGCATCATCTCGGCCGTGGACCCCGTG
GCGGTTCTGGCTGTCTTTGAGGAAATTCACATCAATGAGCTGCTGCACATCCTTGTTTTT
GGGGAGTCCTTGCTCAATGACGCCGTCACTGTGGTCCTGTATCACCTCTTTGAGGAGTTT
GCCAACTACGAACACGTGGGCATCGTGGACATCTTCCTCGGCTTCCTGAGCTTCTTCGTG
GTGGCCCTGGGCGGGGTGCTTGTGGGCGTGGTCTACGGGGTCATCGCAGCCTTCACCTCC
CGATTTACCTCCCACATCCGGGTCATCGAGCCGCTCTTCGTCTTCCTCTACAGCTACATG
GCCTACTTGTCAGCCGAGCTCTTCCACCTGTCAGGCATCATGGCGCTCATAGCCTCAGGA
GTGGTGATGCGCCCCTATGTGGAGGCCAACATCTCCCACAAGTCCCACACCACCATCAAA
TACTTCCTGAAGATGTGGAGCAGCGTCAGCGAGACCCTCATCTTCATCTTCCTCGGCGTC
TCCACGGTGGCCGGCTCCCACCACTGGAACTGGACCTTCGTCATCAGCACCCTGCTCTTC
TGCCTCATCGCCCGCGTGCTGGGGGTGCTGGGCCTGACCTGGTTCATCAACAAGTTCCGT
ATCGTGAAGCTGACCCCCAAGGACCAGTTCATCATCGCCTATGGGGGCCTGCGAGGGGCC
ATCGCCTTCTCTCTGGGCTACCTCCTGGACAAGAAGCACTTCCCCATGTGTGACCTGTTC
CTCACTGCCATCATCACTGTCATCTTCTTCACCGTCTTTGTGCAGGGCATGACCATTCGG
CCCCTGGTAGACCTGTTGGCTGTGAAGAAAAAGCAAGAGACGAAGCGCTCCATCAACGAA
GAGATCCACACACAGTTCCTGGACCACCTTCTGACAGGCATCGAAGACATCTGTGGCCAC
TACGGTCACCACCACTGGAAGGACAAGCTCAACCGGTTTAATAAGAAATATGTGAAGAAG
TGTCTGATAGCTGGCGAGCGCTCCAAGGAGCCCCAGCTCATTGCCTTCTACCACAAGATG
GAGATGAAGCAGGCCATCGAGCTGGTGGAGAGCGGGGGCATGGGCAAGATCCCCTCTGCC
GTCTCCACCGTCTCCATGCAGAACATCCACCCCAAGTCCCTGCCTTCCGAGCGCATCCTG
CCAGCACTGTCCAAGGACAAGGAGGAGGAGATCCGCAAAATCCTGAGGAACAACTTGCAG
AAGACCAGGCAGCGGCTGCGGTCCTACAACAGACACACGCTGGTGGCAGACCCCTACGAG
GAAGCCTGGAACCAGATGCTGCTCCGGAGGCAGAAGGCCCGGCAGCTGGAGCAGAAGATC
AACAACTACCTGACGGTGCCAGCCCACAAGCTGGACTCACCCACCATGTCTCGGGCCCGC
ATCGGCTCAGACCCACTGGCCTATGAGCCGAAGGAGGACCTGCCTGTCATCACCATCGAC
CCGGCTTCCCCGCAGTCACCCGAGTCTGTGGACCTGGTGAATGAAGAGCTGAAGGGCAAA
GTCTTAGGGTTGAGCCGGGATCCTGCAAAGGTGGCTGAGGAGGACGAGGACGACGATGGG
GGCATCATGATGCGGAGCAAGGAGACTTCGTCCCCAGGAACCGACGATGTCTTCACCCCC
GCGCCCAGTGACAGCCCCAGCTCCCAGAGGATACAGCGCTGCCTCAGTGACCCAGGCCCA
CACCCTGAGCCTGGGGAGGGAGAACCGTTCTTCCCCAAGGGGCAGTAA
Chromosome Location
1
Locus
1p36.1-p35
External Identifiers
ResourceLink
UniProtKB IDP19634
UniProtKB Entry NameSL9A1_HUMAN
GenBank Protein ID178753
GenBank Gene IDM81768
GenAtlas IDSLC9A1
HGNC IDHGNC:11071
General References
  1. Sardet C, Franchi A, Pouyssegur J: Molecular cloning, primary structure, and expression of the human growth factor-activatable Na+/H+ antiporter. Cell. 1989 Jan 27;56(2):271-80. [Article]
  2. Sardet C, Counillon L, Franchi A, Pouyssegur J: Growth factors induce phosphorylation of the Na+/H+ antiporter, glycoprotein of 110 kD. Science. 1990 Feb 9;247(4943):723-6. [Article]
  3. Tse CM, Ma AI, Yang VW, Watson AJ, Levine S, Montrose MH, Potter J, Sardet C, Pouyssegur J, Donowitz M: Molecular cloning and expression of a cDNA encoding the rabbit ileal villus cell basolateral membrane Na+/H+ exchanger. EMBO J. 1991 Aug;10(8):1957-67. [Article]
  4. Fliegel L, Dyck JR, Wang H, Fong C, Haworth RS: Cloning and analysis of the human myocardial Na+/H+ exchanger. Mol Cell Biochem. 1993 Aug 25;125(2):137-43. [Article]
  5. Garden OA, Musk P, Worthington-White DA, Dewey MJ, Rich IN: 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. 2000 Jul 1;120(1):37-43. [Article]
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  8. Counillon L, Pouyssegur J, Reithmeier RA: The Na+/H+ exchanger NHE-1 possesses N- and O-linked glycosylation restricted to the first N-terminal extracellular domain. Biochemistry. 1994 Aug 30;33(34):10463-9. [Article]
  9. Goss G, Orlowski J, Grinstein S: Coimmunoprecipitation of a 24-kDa protein with NHE1, the ubiquitous isoform of the Na+/H+ exchanger. Am J Physiol. 1996 May;270(5 Pt 1):C1493-502. [Article]
  10. Lin X, Barber DL: A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12631-6. [Article]
  11. Shrode LD, Gan BS, D'Souza SJ, Orlowski J, Grinstein S: Topological analysis of NHE1, the ubiquitous Na+/H+ exchanger using chymotryptic cleavage. Am J Physiol. 1998 Aug;275(2 Pt 1):C431-9. [Article]
  12. Wakabayashi S, Pang T, Su X, Shigekawa M: A novel topology model of the human Na(+)/H(+) exchanger isoform 1. J Biol Chem. 2000 Mar 17;275(11):7942-9. [Article]
  13. Mailander J, Muller-Esterl W, Dedio J: Human homolog of mouse tescalcin associates with Na(+)/H(+) exchanger type-1. FEBS Lett. 2001 Nov 2;507(3):331-5. [Article]
  14. Pang T, Su X, Wakabayashi S, Shigekawa M: Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers. J Biol Chem. 2001 May 18;276(20):17367-72. Epub 2001 Feb 28. [Article]
  15. Pang T, Wakabayashi S, Shigekawa M: Expression of calcineurin B homologous protein 2 protects serum deprivation-induced cell death by serum-independent activation of Na+/H+ exchanger. J Biol Chem. 2002 Nov 15;277(46):43771-7. Epub 2002 Sep 10. [Article]
  16. Li X, Liu Y, Kay CM, Muller-Esterl W, Fliegel L: The Na+/H+ exchanger cytoplasmic tail: structure, function, and interactions with tescalcin. Biochemistry. 2003 Jun 24;42(24):7448-56. [Article]
  17. Pang T, Hisamitsu T, Mori H, Shigekawa M, Wakabayashi S: Role of calcineurin B homologous protein in pH regulation by the Na+/H+ exchanger 1: tightly bound Ca2+ ions as important structural elements. Biochemistry. 2004 Mar 30;43(12):3628-36. [Article]
  18. Slepkov ER, Chow S, Lemieux MJ, Fliegel L: Proline residues in transmembrane segment IV are critical for activity, expression and targeting of the Na+/H+ exchanger isoform 1. Biochem J. 2004 Apr 1;379(Pt 1):31-8. [Article]
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  20. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [Article]
  21. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
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  23. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  24. Li QH, Wang LH, Lin YN, Chang GQ, Li HW, Jin WN, Hu RH, Pang TX: Nuclear accumulation of calcineurin B homologous protein 2 (CHP2) results in enhanced proliferation of tumor cells. Genes Cells. 2011 Apr;16(4):416-26. doi: 10.1111/j.1365-2443.2011.01497.x. Epub 2011 Mar 11. [Article]
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  27. Guissart C, Li X, Leheup B, Drouot N, Montaut-Verient B, Raffo E, Jonveaux P, Roux AF, Claustres M, Fliegel L, Koenig M: Mutation of SLC9A1, encoding the major Na(+)/H(+) exchanger, causes ataxia-deafness Lichtenstein-Knorr syndrome. Hum Mol Genet. 2015 Jan 15;24(2):463-70. doi: 10.1093/hmg/ddu461. Epub 2014 Sep 8. [Article]
  28. Slepkov ER, Rainey JK, Li X, Liu Y, Cheng FJ, Lindhout DA, Sykes BD, Fliegel L: Structural and functional characterization of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger. J Biol Chem. 2005 May 6;280(18):17863-72. Epub 2005 Jan 26. [Article]
  29. Ben Ammar Y, Takeda S, Sugawara M, Miyano M, Mori H, Wakabayashi S: Crystallization and preliminary crystallographic analysis of the human calcineurin homologous protein CHP2 bound to the cytoplasmic region of the Na+/H+ exchanger NHE1. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Oct 1;61(Pt 10):956-8. Epub 2005 Sep 30. [Article]
  30. Ammar YB, Takeda S, Hisamitsu T, Mori H, Wakabayashi S: Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation. EMBO J. 2006 Jun 7;25(11):2315-25. Epub 2006 May 18. [Article]
  31. Mishima M, Wakabayashi S, Kojima C: Solution structure of the cytoplasmic region of Na+/H+ exchanger 1 complexed with essential cofactor calcineurin B homologous protein 1. J Biol Chem. 2007 Jan 26;282(4):2741-51. Epub 2006 Oct 18. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00594AmilorideapprovedunknowninhibitorDetails
DB02624Homoserine LactoneexperimentalunknownDetails
DB06468CariporideinvestigationalunknownDetails
DB01043Memantineapproved, investigationalunknownDetails