SL9A1_MOUSE
ID SL9A1_MOUSE Reviewed; 820 AA.
AC Q61165;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Sodium/hydrogen exchanger 1;
DE AltName: Full=Na(+)/H(+) exchanger 1;
DE Short=NHE-1;
DE AltName: Full=Solute carrier family 9 member 1;
GN Name=Slc9a1; Synonyms=Nhe1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=11931388; DOI=10.1023/a:1017984311138;
RA Dewey M.J., Ennis T.M., Bowman L.H.;
RT "cDNA cloning and expression of the mouse Na/H antiporter (NHE-1) and a
RT potential splice variant.";
RL Mol. Biol. Rep. 28:111-117(2001).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-603; SER-609 AND SER-707, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-697 AND SER-707, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-697, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-603; SER-606; THR-607;
RP SER-609; SER-697; SER-701; SER-707; SER-727; SER-730; SER-733; THR-755;
RP SER-790 AND SER-792, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Involved in pH regulation to eliminate acids generated by
CC active metabolism or to counter adverse environmental conditions. Major
CC proton extruding system driven by the inward sodium ion chemical
CC gradient. Plays an important role in signal transduction.
CC -!- SUBUNIT: Oligomer (By similarity). Interacts with CALM1 in a calcium-
CC dependent manner (By similarity). Interacts with TESC (By similarity).
CC Interacts (via the juxtamembrane region of the cytoplasmic C-terminal
CC domain) with CHP1; the interaction occurs at the plasma membrane in a
CC calcium-dependent manner (By similarity). Interacts with CHP2; the
CC interaction occurs in a calcium-dependent manner (By similarity).
CC {ECO:0000250|UniProtKB:P19634, ECO:0000250|UniProtKB:P26431}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC Endoplasmic reticulum membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Cell membrane; Multi-pass membrane protein.
CC Note=Colocalizes with CHP1 and CHP2 at the reticulum endoplasmic and
CC plasma membrane. {ECO:0000250}.
CC -!- PTM: O-glycosylated. {ECO:0000250}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC Ubiquitination is reduced by CHP1 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1)
CC transporter (TC 2.A.36) family. {ECO:0000305}.
CC -!- CAUTION: The region between transmembrane regions M4 and M5 and between
CC M6 and M7 (also termed intracellular loops IL2 and IL4, respectively)
CC seem to be localized at least in part in the membrane. The hydrophobic
CC region H10 is proposed to be located within the membrane.
CC {ECO:0000305}.
CC -!- CAUTION: The interacting region with TESC is conflicting: In human, it
CC has been reported that SLC9A1 interacts with TESC via the juxtamembrane
CC region of the cytoplasmic C-terminal domain, including residues 507-
CC 549. However, another publication has reported interaction with TESC
CC via residues 637-820, the region of the cytoplasmic C-terminus more
CC distal to the membrane. {ECO:0000305}.
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DR EMBL; U51112; AAA92976.1; -; mRNA.
DR CCDS; CCDS38903.1; -.
DR RefSeq; NP_058677.1; NM_016981.2.
DR AlphaFoldDB; Q61165; -.
DR BMRB; Q61165; -.
DR SMR; Q61165; -.
DR BioGRID; 203321; 13.
DR IntAct; Q61165; 1.
DR STRING; 10090.ENSMUSP00000030669; -.
DR GlyConnect; 2723; 1 N-Linked glycan (1 site).
DR GlyGen; Q61165; 2 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q61165; -.
DR PhosphoSitePlus; Q61165; -.
DR SwissPalm; Q61165; -.
DR jPOST; Q61165; -.
DR MaxQB; Q61165; -.
DR PaxDb; Q61165; -.
DR PRIDE; Q61165; -.
DR ProteomicsDB; 261375; -.
DR Antibodypedia; 30723; 273 antibodies from 37 providers.
DR DNASU; 20544; -.
DR Ensembl; ENSMUST00000030669; ENSMUSP00000030669; ENSMUSG00000028854.
DR GeneID; 20544; -.
DR KEGG; mmu:20544; -.
DR UCSC; uc008vcs.1; mouse.
DR CTD; 6548; -.
DR MGI; MGI:102462; Slc9a1.
DR VEuPathDB; HostDB:ENSMUSG00000028854; -.
DR eggNOG; KOG1966; Eukaryota.
DR GeneTree; ENSGT00940000156338; -.
DR HOGENOM; CLU_005912_4_1_1; -.
DR InParanoid; Q61165; -.
DR OMA; EFANYDH; -.
DR OrthoDB; 389547at2759; -.
DR PhylomeDB; Q61165; -.
DR TreeFam; TF317212; -.
DR Reactome; R-MMU-2160916; Hyaluronan uptake and degradation.
DR Reactome; R-MMU-425986; Sodium/Proton exchangers.
DR BioGRID-ORCS; 20544; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Slc9a1; mouse.
DR PRO; PR:Q61165; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q61165; protein.
DR Bgee; ENSMUSG00000028854; Expressed in epithelium of stomach and 236 other tissues.
DR ExpressionAtlas; Q61165; baseline and differential.
DR Genevisible; Q61165; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0090533; C:cation-transporting ATPase complex; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0014704; C:intercalated disc; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR GO; GO:0030315; C:T-tubule; ISO:MGI.
DR GO; GO:1990351; C:transporter complex; IDA:MGI.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0015386; F:potassium:proton antiporter activity; IBA:GO_Central.
DR GO; GO:0030346; F:protein phosphatase 2B binding; ISO:MGI.
DR GO; GO:0015385; F:sodium:proton antiporter activity; IDA:MGI.
DR GO; GO:0086003; P:cardiac muscle cell contraction; IEA:Ensembl.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IMP:MGI.
DR GO; GO:0071468; P:cellular response to acidic pH; ISS:UniProtKB.
DR GO; GO:0071236; P:cellular response to antibiotic; IEA:Ensembl.
DR GO; GO:0070417; P:cellular response to cold; IEA:Ensembl.
DR GO; GO:0071257; P:cellular response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; ISO:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:MGI.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0070997; P:neuron death; ISO:MGI.
DR GO; GO:0045760; P:positive regulation of action potential; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; ISO:MGI.
DR GO; GO:1903281; P:positive regulation of calcium:sodium antiporter activity; ISO:MGI.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:MGI.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; ISO:MGI.
DR GO; GO:0035794; P:positive regulation of mitochondrial membrane permeability; ISO:MGI.
DR GO; GO:0098735; P:positive regulation of the force of heart contraction; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB.
DR GO; GO:1902600; P:proton transmembrane transport; ISO:MGI.
DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; ISO:MGI.
DR GO; GO:0051453; P:regulation of intracellular pH; ISO:MGI.
DR GO; GO:0006885; P:regulation of pH; IDA:MGI.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISO:MGI.
DR GO; GO:0086092; P:regulation of the force of heart contraction by cardiac conduction; ISO:MGI.
DR GO; GO:0010447; P:response to acidic pH; IMP:MGI.
DR GO; GO:0035994; P:response to muscle stretch; ISO:MGI.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR GO; GO:0036376; P:sodium ion export across plasma membrane; ISS:UniProtKB.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; ISO:MGI.
DR GO; GO:0006814; P:sodium ion transport; IDA:MGI.
DR GO; GO:0048863; P:stem cell differentiation; IMP:MGI.
DR InterPro; IPR006153; Cation/H_exchanger.
DR InterPro; IPR018422; Cation/H_exchanger_CPA1.
DR InterPro; IPR004709; NaH_exchanger.
DR InterPro; IPR001970; NHE-1-like.
DR InterPro; IPR032103; NHE_CaM-bd.
DR PANTHER; PTHR10110; PTHR10110; 1.
DR PANTHER; PTHR10110:SF59; PTHR10110:SF59; 1.
DR Pfam; PF00999; Na_H_Exchanger; 1.
DR Pfam; PF16644; NEXCaM_BD; 1.
DR PRINTS; PR01084; NAHEXCHNGR.
DR PRINTS; PR01085; NAHEXCHNGR1.
DR TIGRFAMs; TIGR00840; b_cpa1; 1.
PE 1: Evidence at protein level;
KW Antiport; Calmodulin-binding; Cell membrane; Endoplasmic reticulum;
KW Glycoprotein; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Sodium; Sodium transport; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation.
FT CHAIN 1..820
FT /note="Sodium/hydrogen exchanger 1"
FT /id="PRO_0000052348"
FT TOPO_DOM 1..12
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 13..33
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 34..105
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..126
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 127..133
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 134..153
FT /note="Helical; Name=M3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 154..158
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 159..178
FT /note="Helical; Name=M4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 179..195
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 196..215
FT /note="Helical; Name=M5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 216..231
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..251
FT /note="Helical; Name=M6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 252..260
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 261..280
FT /note="Helical; Name=M7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..298
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 299..319
FT /note="Helical; Name=M8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..342
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 343..362
FT /note="Helical; Name=M9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..385
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 386..406
FT /note="Name=H10"
FT /evidence="ECO:0000250"
FT TOPO_DOM 407..414
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 415..434
FT /note="Helical; Name=M10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..452
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 453..474
FT /note="Helical; Name=M11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 475..483
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 484..503
FT /note="Helical; Name=M12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 504..820
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 40..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 507..549
FT /note="Interaction with TESC"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT REGION 519..549
FT /note="Interaction with CHP2"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT REGION 637..820
FT /note="Interaction with CALM1"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT REGION 637..820
FT /note="Interaction with TESC"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT REGION 748..820
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 777..799
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 165
FT /note="Channel pore-lining"
FT /evidence="ECO:0000250"
FT MOD_RES 603
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 606
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 607
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 609
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 697
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 701
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 707
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 727
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 730
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 733
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 755
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 790
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 792
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 801
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26431"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ 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
