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Sodium/hydrogen exchanger 1 (Na( )/H( ) exchanger 1) (NHE-1) (Solute carrier family 9 member 1)

 SL9A1_MOUSE             Reviewed;         820 AA.
Q61165;
01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
01-NOV-1997, sequence version 1.
20-JUN-2018, entry version 159.
RecName: Full=Sodium/hydrogen exchanger 1;
AltName: Full=Na(+)/H(+) exchanger 1;
Short=NHE-1;
AltName: Full=Solute carrier family 9 member 1;
Name=Slc9a1; Synonyms=Nhe1;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=BALB/cJ;
PubMed=11931388; DOI=10.1023/A:1017984311138;
Dewey M.J., Ennis T.M., Bowman L.H.;
"cDNA cloning and expression of the mouse Na/H antiporter (NHE-1) and
a potential splice variant.";
Mol. Biol. Rep. 28:111-117(2001).
[2]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brain cortex;
PubMed=17114649; DOI=10.1074/mcp.M600046-MCP200;
Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D.,
Gerrits B., Panse C., Schlapbach R., Mansuy I.M.;
"Qualitative and quantitative analyses of protein phosphorylation in
naive and stimulated mouse synaptosomal preparations.";
Mol. Cell. Proteomics 6:283-293(2007).
[3]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-603; SER-609 AND
SER-707, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
TISSUE=Liver;
PubMed=17242355; DOI=10.1073/pnas.0609836104;
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
"Large-scale phosphorylation analysis of mouse liver.";
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
[4]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-697 AND SER-707, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
Thibault P.;
"The phagosomal proteome in interferon-gamma-activated macrophages.";
Immunity 30:143-154(2009).
[5]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-697, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Embryonic fibroblast;
PubMed=19131326; DOI=10.1074/mcp.M800451-MCP200;
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
"Large scale localization of protein phosphorylation by use of
electron capture dissociation mass spectrometry.";
Mol. Cell. Proteomics 8:904-912(2009).
[6]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-603; SER-606; THR-607;
SER-609; SER-697; SER-701; SER-707; SER-727; SER-730; SER-733;
THR-755; SER-790 AND SER-792, AND IDENTIFICATION BY MASS SPECTROMETRY
[LARGE SCALE ANALYSIS].
TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
Pancreas, Spleen, and Testis;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
-!- 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.
-!- SUBUNIT: Oligomer. Interacts with calmodulin and TESC. Interacts
(via the juxtamembrane region of the cytoplasmic C-terminal
domain) with CHP1; the interaction occurs at the plasma membrane
in a calcium-dependent manner. Interacts with CHP2; the
interaction occurs in a calcium-dependent manner (By similarity).
{ECO:0000250}.
-!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
Endoplasmic reticulum membrane {ECO:0000250}; Multi-pass membrane
protein {ECO:0000250}. Cell membrane; Multi-pass membrane protein.
Note=Colocalizes with CHP1 and CHP2 at the reticulum endoplasmic
and plasma membrane. {ECO:0000250}.
-!- PTM: O-glycosylated. {ECO:0000250}.
-!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
Ubiquitination is reduced by CHP1 (By similarity). {ECO:0000250}.
-!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1
(CPA1) transporter (TC 2.A.36) family. {ECO:0000305}.
-!- CAUTION: The region between transmembrane regions M4 and M5 and
between M6 and M7 (also termed intracellular loops IL2 and IL4,
respectively) seem to be localized at least in part in the
membrane. The hydrophobic region H10 is proposed to be located
within the membrane. {ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; U51112; AAA92976.1; -; mRNA.
CCDS; CCDS38903.1; -.
RefSeq; NP_058677.1; NM_016981.2.
UniGene; Mm.4312; -.
ProteinModelPortal; Q61165; -.
SMR; Q61165; -.
BioGrid; 203321; 1.
IntAct; Q61165; 1.
STRING; 10090.ENSMUSP00000030669; -.
iPTMnet; Q61165; -.
PhosphoSitePlus; Q61165; -.
SwissPalm; Q61165; -.
MaxQB; Q61165; -.
PaxDb; Q61165; -.
PRIDE; Q61165; -.
Ensembl; ENSMUST00000030669; ENSMUSP00000030669; ENSMUSG00000028854.
GeneID; 20544; -.
KEGG; mmu:20544; -.
UCSC; uc008vcs.1; mouse.
CTD; 6548; -.
MGI; MGI:102462; Slc9a1.
eggNOG; KOG1966; Eukaryota.
eggNOG; COG0025; LUCA.
GeneTree; ENSGT00760000119074; -.
HOGENOM; HOG000247044; -.
HOVERGEN; HBG052615; -.
InParanoid; Q61165; -.
KO; K05742; -.
OMA; YDRVGIV; -.
OrthoDB; EOG091G02Q0; -.
TreeFam; TF317212; -.
Reactome; R-MMU-2160916; Hyaluronan uptake and degradation.
Reactome; R-MMU-425986; Sodium/Proton exchangers.
PRO; PR:Q61165; -.
Proteomes; UP000000589; Chromosome 4.
Bgee; ENSMUSG00000028854; -.
ExpressionAtlas; Q61165; baseline and differential.
Genevisible; Q61165; MM.
GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
GO; GO:0090533; C:cation-transporting ATPase complex; ISO:MGI.
GO; GO:0009986; C:cell surface; ISO:MGI.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
GO; GO:0014704; C:intercalated disc; ISO:MGI.
GO; GO:0016020; C:membrane; IDA:MGI.
GO; GO:0045121; C:membrane raft; ISO:MGI.
GO; GO:0005739; C:mitochondrion; ISO:MGI.
GO; GO:0005654; C:nucleoplasm; ISO:MGI.
GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
GO; GO:0042383; C:sarcolemma; ISO:MGI.
GO; GO:0030315; C:T-tubule; ISO:MGI.
GO; GO:0048306; F:calcium-dependent protein binding; ISO:MGI.
GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
GO; GO:0015386; F:potassium:proton antiporter activity; IBA:GO_Central.
GO; GO:0030346; F:protein phosphatase 2B binding; ISO:MGI.
GO; GO:0015385; F:sodium:proton antiporter activity; IDA:MGI.
GO; GO:0086003; P:cardiac muscle cell contraction; IEA:Ensembl.
GO; GO:0055007; P:cardiac muscle cell differentiation; IMP:MGI.
GO; GO:0071468; P:cellular response to acidic pH; ISS:UniProtKB.
GO; GO:0071236; P:cellular response to antibiotic; IEA:Ensembl.
GO; GO:0070417; P:cellular response to cold; IEA:Ensembl.
GO; GO:0071257; P:cellular response to electrical stimulus; IEA:Ensembl.
GO; GO:0071872; P:cellular response to epinephrine stimulus; ISO:MGI.
GO; GO:0071456; P:cellular response to hypoxia; ISO:MGI.
GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI.
GO; GO:0006883; P:cellular sodium ion homeostasis; ISO:MGI.
GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
GO; GO:0070997; P:neuron death; ISO:MGI.
GO; GO:0045760; P:positive regulation of action potential; ISO:MGI.
GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; ISO:MGI.
GO; GO:1903281; P:positive regulation of calcium:sodium antiporter activity; ISO:MGI.
GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:MGI.
GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
GO; GO:1902533; P:positive regulation of intracellular signal transduction; ISO:MGI.
GO; GO:0035794; P:positive regulation of mitochondrial membrane permeability; ISO:MGI.
GO; GO:0098735; P:positive regulation of the force of heart contraction; ISO:MGI.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB.
GO; GO:1902600; P:proton transmembrane transport; ISO:MGI.
GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; ISO:MGI.
GO; GO:0051453; P:regulation of intracellular pH; ISO:MGI.
GO; GO:0006885; P:regulation of pH; IDA:MGI.
GO; GO:0051930; P:regulation of sensory perception of pain; ISO:MGI.
GO; GO:0002026; P:regulation of the force of heart contraction; ISO:MGI.
GO; GO:0086092; P:regulation of the force of heart contraction by cardiac conduction; ISO:MGI.
GO; GO:0010447; P:response to acidic pH; IMP:MGI.
GO; GO:0035994; P:response to muscle stretch; ISO:MGI.
GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
GO; GO:0036376; P:sodium ion export across plasma membrane; ISS:UniProtKB.
GO; GO:0098719; P:sodium ion import across plasma membrane; ISO:MGI.
GO; GO:0006814; P:sodium ion transport; IDA:MGI.
InterPro; IPR006153; Cation/H_exchanger.
InterPro; IPR018422; Cation/H_exchanger_CPA1.
InterPro; IPR001970; Na/H_exchanger_1.
InterPro; IPR004709; NaH_exchanger.
InterPro; IPR032103; NHE_CaM-bd.
PANTHER; PTHR10110; PTHR10110; 1.
PANTHER; PTHR10110:SF59; PTHR10110:SF59; 1.
Pfam; PF00999; Na_H_Exchanger; 1.
Pfam; PF16644; NEXCaM_BD; 1.
PRINTS; PR01084; NAHEXCHNGR.
PRINTS; PR01085; NAHEXCHNGR1.
TIGRFAMs; TIGR00840; b_cpa1; 1.
1: Evidence at protein level;
Antiport; Calmodulin-binding; Cell membrane; Complete proteome;
Endoplasmic reticulum; Glycoprotein; Ion transport; Membrane;
Phosphoprotein; Reference proteome; Sodium; Sodium transport;
Transmembrane; Transmembrane helix; Transport; Ubl conjugation.
CHAIN 1 820 Sodium/hydrogen exchanger 1.
/FTId=PRO_0000052348.
TOPO_DOM 1 12 Cytoplasmic. {ECO:0000255}.
TRANSMEM 13 33 Helical; Name=M1. {ECO:0000255}.
TOPO_DOM 34 105 Extracellular. {ECO:0000255}.
TRANSMEM 106 126 Helical; Name=M2. {ECO:0000255}.
TOPO_DOM 127 133 Cytoplasmic. {ECO:0000255}.
TRANSMEM 134 153 Helical; Name=M3. {ECO:0000255}.
TOPO_DOM 154 158 Extracellular. {ECO:0000255}.
TRANSMEM 159 178 Helical; Name=M4. {ECO:0000255}.
TOPO_DOM 179 195 Cytoplasmic. {ECO:0000255}.
TRANSMEM 196 215 Helical; Name=M5. {ECO:0000255}.
TOPO_DOM 216 231 Extracellular. {ECO:0000255}.
TRANSMEM 232 251 Helical; Name=M6. {ECO:0000255}.
TOPO_DOM 252 260 Cytoplasmic. {ECO:0000255}.
TRANSMEM 261 280 Helical; Name=M7. {ECO:0000255}.
TOPO_DOM 281 298 Extracellular. {ECO:0000255}.
TRANSMEM 299 319 Helical; Name=M8. {ECO:0000255}.
TOPO_DOM 320 342 Cytoplasmic. {ECO:0000255}.
TRANSMEM 343 362 Helical; Name=M9. {ECO:0000255}.
TOPO_DOM 363 385 Extracellular. {ECO:0000255}.
INTRAMEM 386 406 Name=H10. {ECO:0000250}.
TOPO_DOM 407 414 Extracellular. {ECO:0000255}.
TRANSMEM 415 434 Helical; Name=M10. {ECO:0000255}.
TOPO_DOM 435 452 Cytoplasmic. {ECO:0000255}.
TRANSMEM 453 474 Helical; Name=M11. {ECO:0000255}.
TOPO_DOM 475 483 Extracellular. {ECO:0000255}.
TRANSMEM 484 503 Helical; Name=M12. {ECO:0000255}.
TOPO_DOM 504 820 Cytoplasmic. {ECO:0000255}.
REGION 520 543 Interaction with CHP2. {ECO:0000250}.
SITE 165 165 Channel pore-lining. {ECO:0000250}.
MOD_RES 603 603 Phosphoserine.
{ECO:0000244|PubMed:17242355,
ECO:0000244|PubMed:21183079}.
MOD_RES 606 606 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 607 607 Phosphothreonine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 609 609 Phosphoserine.
{ECO:0000244|PubMed:17242355,
ECO:0000244|PubMed:21183079}.
MOD_RES 697 697 Phosphoserine.
{ECO:0000244|PubMed:19131326,
ECO:0000244|PubMed:19144319,
ECO:0000244|PubMed:21183079}.
MOD_RES 701 701 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 707 707 Phosphoserine.
{ECO:0000244|PubMed:17242355,
ECO:0000244|PubMed:19144319,
ECO:0000244|PubMed:21183079}.
MOD_RES 727 727 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 730 730 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 733 733 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 755 755 Phosphothreonine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 790 790 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 792 792 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 801 801 Phosphoserine.
{ECO:0000250|UniProtKB:P26431}.
CARBOHYD 374 374 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
SEQUENCE 820 AA; 91468 MW; 0589C4D08DD348BE CRC64;
MMLRWSGVWG FHPPRIFPSL LVVVALVGLL PVLRSHGLQH SPTASTIRGS EPPRERSIGD
VTTAPSEPLH RPDDHNLTNL IIEHGGKPSR KAFPVLDIDY PHVRTPFEIS LWILLACLMK
IGFHVIPTIS SIVPESCLLI VVGLLVGGLI KGVGETPPFL QSDVFFLFLL PPIILDAGYF
LPLRQFTENL GTILIFAVVG TLWNAFFLGG LLYAVCLVGG EQINNIGLLD TLLFGSIISA
VDPVAVLAVF EEIHINELLH ILVFGESLLN DAVTVVLYHL FEEFASYDSV GISDIFLGFL
SFFVVALGGV FVGVVYGVIA AFTSRFTSHI RVIEPLFVFL YSYMAYLSAE LFHLSGIMAL
IASGVVMRPY VEANISHKSH TTIKYFLKMW SSVSETLIFI FLGVSTVAGS HQWNWTFVIS
TLLFCLIARV LGVLVLTWFI NKFRIVKLTP KDQFIIAYGG LRGAIAFSLG YLLDKKHFPM
CDLFLTAIIT VIFFTVFVQG MTIRPLVDLL AVKKKQETKR SINEEIHTQF LDHLLTGIED
ICGHYGHHHW KDKLNRFNKK YVKKCLIAGE RSKEPQLIAF YHKMEMKQAI ELVESGGMGK
IPSAVSTVSM QNIHPKAVTS DRILPALSKD KEEEIRKILR SNLQKTRQRL RSYNRHTLVA
DPYEEAWNQM LLRRQKARQL EQKITNYLTV PAHKLDSPTL SRARIGSDPL AYEPKADLPV
ITIDPASPQS PESVDLVNEE LKGKVLGLNR GPRVTPEEEE EDEDGIIMIR SKEPSSPGTD
DVFTPGSSDS PSSQRIQRCL SDPGPHPEPG EGEPFIPKGQ


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