ID   SL9A1_RAT               Reviewed;         820 AA.
AC   P26431;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   27-MAR-2024, entry version 189.
DE   RecName: Full=Sodium/hydrogen exchanger 1;
DE   AltName: Full=Na(+)/H(+) exchanger 1 {ECO:0000303|PubMed:1577762};
DE            Short=NHE-1 {ECO:0000303|PubMed:1577762};
DE   AltName: Full=Solute carrier family 9 member 1;
GN   Name=Slc9a1; Synonyms=Nhe1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   STRAIN=Sprague-Dawley; TISSUE=Heart;
RX   PubMed=1577762; DOI=10.1016/s0021-9258(19)50428-8;
RA   Orlowski J., Kandasamy R.A., Shull G.E.;
RT   "Molecular cloning of putative members of the Na/H exchanger gene family.
RT   cDNA cloning, deduced amino acid sequence, and mRNA tissue expression of
RT   the rat Na/H exchanger NHE-1 and two structurally related proteins.";
RL   J. Biol. Chem. 267:9331-9339(1992).
RN   [2]
RP   FUNCTION, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=6334130; DOI=10.1085/jgp.84.4.585;
RA   Grinstein S., Goetz J.D., Rothstein A.;
RT   "22Na+ fluxes in thymic lymphocytes. II. Amiloride-sensitive Na+/H+
RT   exchange pathway; reversibility of transport and asymmetry of the modifier
RT   site.";
RL   J. Gen. Physiol. 84:585-600(1984).
RN   [3]
RP   GLYCOSYLATION.
RX   PubMed=9688597; DOI=10.1152/ajpcell.1998.275.2.c431;
RA   Shrode L.D., Gan B.S., D'Souza S.J., Orlowski J., Grinstein S.;
RT   "Topological analysis of NHE1, the ubiquitous Na+/H+ exchanger using
RT   chymotryptic cleavage.";
RL   Am. J. Physiol. 275:C431-C439(1998).
RN   [4]
RP   FUNCTION, TRANSPORTER ACTIVITY, PI(4,5)P2-BINDING, AND ACTIVITY REGULATION.
RX   PubMed=10893269; DOI=10.1083/jcb.150.1.213;
RA   Aharonovitz O., Zaun H.C., Balla T., York J.D., Orlowski J., Grinstein S.;
RT   "Intracellular pH regulation by Na(+)/H(+) exchange requires
RT   phosphatidylinositol 4,5-bisphosphate.";
RL   J. Cell Biol. 150:213-224(2000).
RN   [5]
RP   FUNCTION, TRANSPORTER ACTIVITY, MUTAGENESIS OF GLU-266, AND INTERACTION
RP   WITH EZR.
RX   PubMed=11163215; DOI=10.1016/s1097-2765(00)00139-8;
RA   Denker S.P., Huang D.C., Orlowski J., Furthmayr H., Barber D.L.;
RT   "Direct binding of the Na--H exchanger NHE1 to ERM proteins regulates the
RT   cortical cytoskeleton and cell shape independently of H(+) translocation.";
RL   Mol. Cell 6:1425-1436(2000).
RN   [6]
RP   INTERACTION WITH CHP1 AND CHP2.
RX   PubMed=12576672; DOI=10.1248/bpb.26.148;
RA   Inoue H., Nakamura Y., Nagita M., Takai T., Masuda M., Nakamura N.,
RA   Kanazawa H.;
RT   "Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding
RT   protein, is expressed in intestinal epithelium.";
RL   Biol. Pharm. Bull. 26:148-155(2003).
RN   [7]
RP   INTERACTION WITH TESC, AND MUTAGENESIS OF 530-PHE--LEU-535.
RX   PubMed=18321853; DOI=10.1074/jbc.m800267200;
RA   Zaun H.C., Shrier A., Orlowski J.;
RT   "Calcineurin B homologous protein 3 promotes the biosynthetic maturation,
RT   cell surface stability, and optimal transport of the Na+/H+ exchanger NHE1
RT   isoform.";
RL   J. Biol. Chem. 283:12456-12467(2008).
RN   [8]
RP   OLIGOMERIZATION, GLYCOSYLATION, UBIQUITINATION, MUTAGENESIS OF
RP   522-ILE--ILE-538, AND SUBCELLULAR LOCATION.
RX   PubMed=21543739; DOI=10.1152/ajpcell.00404.2010;
RA   Matsushita M., Tanaka H., Mitsui K., Kanazawa H.;
RT   "Dual functional significance of calcineurin homologous protein 1 binding
RT   to Na(+)/H(+) exchanger isoform 1.";
RL   Am. J. Physiol. 301:C280-C288(2011).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-603; SER-609; SER-697;
RP   SER-701; SER-707; SER-727; SER-730; SER-733; SER-790 AND SER-801, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [10]
RP   PALMITOYLATION, AND FUNCTION.
RX   PubMed=34774621; DOI=10.1016/j.lfs.2021.120142;
RA   Hovde M.J., Bolland D.E., Armand A., Pitsch E., Bakker C., Kooiker A.J.,
RA   Provost J.J., Vaughan R.A., Wallert M.A., Foster J.D.;
RT   "Sodium hydrogen exchanger (NHE1) palmitoylation and potential functional
RT   regulation.";
RL   Life Sci. 288:120142-120142(2022).
CC   -!- FUNCTION: Electroneutral Na(+) /H(+) antiporter that extrudes Na(+) in
CC       exchange for external protons driven by the inward sodium ion chemical
CC       gradient, protecting cells from acidification that occurs from
CC       metabolism (Probable) (PubMed:10893269, PubMed:11163215). Exchanges
CC       intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry
CC       (PubMed:6334130). Plays a key role in maintening intracellular pH
CC       neutral and cell volume, and thus is important for cell growth,
CC       proliferation, migration and survival (PubMed:34774621). In addition,
CC       can transport lithium Li(+) and functions also as a Na(+)/Li(+)
CC       antiporter. SLC9A1 also functions in membrane anchoring and
CC       organization of scaffolding complexes that coordinate signaling inputs
CC       (By similarity). {ECO:0000250|UniProtKB:P19634,
CC       ECO:0000269|PubMed:10893269, ECO:0000269|PubMed:11163215,
CC       ECO:0000269|PubMed:34774621, ECO:0000269|PubMed:6334130,
CC       ECO:0000305|PubMed:6334130}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+)(out) + Na(+)(in) = H(+)(in) + Na(+)(out);
CC         Xref=Rhea:RHEA:29419, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:10893269, ECO:0000269|PubMed:11163215,
CC         ECO:0000305|PubMed:6334130};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+)(in) + Li(+)(out) = H(+)(out) + Li(+)(in);
CC         Xref=Rhea:RHEA:72407, ChEBI:CHEBI:15378, ChEBI:CHEBI:49713;
CC         Evidence={ECO:0000250|UniProtKB:P19634};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Li(+)(in) + Na(+)(out) = Li(+)(out) + Na(+)(in);
CC         Xref=Rhea:RHEA:72415, ChEBI:CHEBI:29101, ChEBI:CHEBI:49713;
CC         Evidence={ECO:0000250|UniProtKB:P19634};
CC   -!- ACTIVITY REGULATION: Activated at acidic pHs. Inhibited by cariporide
CC       and eniporide (By similarity). Inhibited by amiloride and 5-amino-
CC       substituted derivatives. Phosphatidylinositol 4,5-bisphosphate
CC       (PI(4,5)P2) bind and activates SLC9A1 transporter activity (Probable).
CC       {ECO:0000250|UniProtKB:P19634, ECO:0000305|PubMed:10893269}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Fully active at acidic pHs, the antiporter is virtually turned off at
CC         neutral pH. {ECO:0000305|PubMed:6334130};
CC   -!- SUBUNIT: Homodimer; dimerization is crucial for its function (By
CC       similarity). Oligomer (PubMed:21543739). Interacts with CALM1 in a
CC       calcium-dependent manner (By similarity). Interacts with TESC
CC       (PubMed:18321853). Interacts (via residues 504-563) with CHP1
CC       (PubMed:12576672). The interaction with CHP1 occurs at the plasma
CC       membrane in a calcium-dependent manner (By similarity). Interacts with
CC       CHP2 (PubMed:12576672). The interaction with CHP2 occurs in a calcium-
CC       dependent manner (By similarity). Interacts with EZR; regulates the
CC       cytoskeletal interactions of SLC9A1 and promotes stress fiber formation
CC       (PubMed:11163215). {ECO:0000250|UniProtKB:P19634,
CC       ECO:0000269|PubMed:11163215, ECO:0000269|PubMed:12576672,
CC       ECO:0000269|PubMed:18321853, ECO:0000269|PubMed:21543739}.
CC   -!- INTERACTION:
CC       P26431; Q810D1: Chp2; NbExp=2; IntAct=EBI-77471, EBI-6146708;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21543739};
CC       Multi-pass membrane protein {ECO:0000250|UniProtKB:P19634}. Basolateral
CC       cell membrane {ECO:0000250|UniProtKB:P48762}; Multi-pass membrane
CC       protein {ECO:0000250|UniProtKB:P19634}. Note=Localized basolaterally in
CC       every epithelial cell, except in the choroid plexus where SLC9A1 is
CC       expressed luminally. {ECO:0000250|UniProtKB:P19634}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:1577762}.
CC   -!- PTM: N-glycosylated and O-glycosylated in the N-terminal region.
CC       {ECO:0000269|PubMed:21543739, ECO:0000269|PubMed:9688597}.
CC   -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC       Ubiquitination is reduced by CHP1. {ECO:0000269|PubMed:21543739}.
CC   -!- PTM: Palmitoylated; may play a major role in SLC9A1 regulation.
CC       {ECO:0000269|PubMed:34774621}.
CC   -!- PTM: Phosphorylation at Thr-784 increases SLC9A1 activity; specifically
CC       dephosphorylated by PPP3CA. Specifically dephosphorylated at Thr-784 by
CC       PPP3CA that negatively regulates SLC9A1 activity. Phosphorylation at
CC       Ser-652 by AKT1 reduces SLC9A1 binding to CALM1.
CC       {ECO:0000250|UniProtKB:P19634}.
CC   -!- MISCELLANEOUS: Predicted models used for more than 20 years predicted
CC       10-12 transmembrane segments. Recently, the stucture of SLC9A1 has been
CC       solved and reveals that SLC9A1 posseses 13 transmembranes.
CC       {ECO:0000250|UniProtKB:P19634}.
CC   -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1)
CC       transporter (TC 2.A.36) family. {ECO:0000305}.
CC   -!- CAUTION: Although PubMed:18321853 show that TESC-binding results in the
CC       maturation and accumulation of SLC9A1 at the cell surface, previous
CC       studies with human SLC9A1 report that TESC-binding results in a
CC       decrease in activity. {ECO:0000305}.
CC   -!- CAUTION: The interacting region with TESC is conflicting: It has been
CC       reported that SLC9A1 interacts with TESC via the juxtamembrane region
CC       of the cytoplasmic C-terminal domain, including residues 505-571
CC       (PubMed:18321853). However, studies with human SLC9A1 report the
CC       interaction with TESC via residues 503-545 or via residues 633-815.
CC       {ECO:0000269|PubMed:18321853, ECO:0000305}.
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DR   EMBL; M85299; AAA98479.1; -; mRNA.
DR   PIR; A40204; A40204.
DR   RefSeq; NP_036784.1; NM_012652.1.
DR   AlphaFoldDB; P26431; -.
DR   BMRB; P26431; -.
DR   SMR; P26431; -.
DR   BioGRID; 246906; 1.
DR   IntAct; P26431; 3.
DR   STRING; 10116.ENSRNOP00000011049; -.
DR   BindingDB; P26431; -.
DR   ChEMBL; CHEMBL2577; -.
DR   DrugCentral; P26431; -.
DR   GuidetoPHARMACOLOGY; 948; -.
DR   TCDB; 2.A.36.1.1; the monovalent cation:proton antiporter-1 (cpa1) family.
DR   GlyCosmos; P26431; 1 site, No reported glycans.
DR   GlyGen; P26431; 1 site.
DR   iPTMnet; P26431; -.
DR   PhosphoSitePlus; P26431; -.
DR   SwissPalm; P26431; -.
DR   PaxDb; 10116-ENSRNOP00000011049; -.
DR   Ensembl; ENSRNOT00000011049.5; ENSRNOP00000011049.2; ENSRNOG00000007982.5.
DR   Ensembl; ENSRNOT00055042337; ENSRNOP00055034569; ENSRNOG00055024603.
DR   Ensembl; ENSRNOT00060051581; ENSRNOP00060042898; ENSRNOG00060029701.
DR   Ensembl; ENSRNOT00065050094; ENSRNOP00065041160; ENSRNOG00065028991.
DR   GeneID; 24782; -.
DR   KEGG; rno:24782; -.
DR   UCSC; RGD:3718; rat.
DR   AGR; RGD:3718; -.
DR   CTD; 6548; -.
DR   RGD; 3718; Slc9a1.
DR   eggNOG; KOG1966; Eukaryota.
DR   GeneTree; ENSGT00940000156338; -.
DR   HOGENOM; CLU_005912_4_1_1; -.
DR   InParanoid; P26431; -.
DR   OMA; MMRTKEP; -.
DR   OrthoDB; 1065060at2759; -.
DR   PhylomeDB; P26431; -.
DR   TreeFam; TF317212; -.
DR   Reactome; R-RNO-2160916; Hyaluronan uptake and degradation.
DR   Reactome; R-RNO-425986; Sodium/Proton exchangers.
DR   PRO; PR:P26431; -.
DR   Proteomes; UP000002494; Chromosome 5.
DR   Bgee; ENSRNOG00000007982; Expressed in stomach and 20 other cell types or tissues.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR   GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR   GO; GO:0090533; C:cation-transporting ATPase complex; ISO:RGD.
DR   GO; GO:0009986; C:cell surface; IDA:RGD.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0014704; C:intercalated disc; IDA:RGD.
DR   GO; GO:0016020; C:membrane; ISO:RGD.
DR   GO; GO:0045121; C:membrane raft; ISO:RGD.
DR   GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR   GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR   GO; GO:0030315; C:T-tubule; IDA:RGD.
DR   GO; GO:1990351; C:transporter complex; ISO:RGD.
DR   GO; GO:0048306; F:calcium-dependent protein binding; ISS:UniProtKB.
DR   GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0043167; F:ion binding; ISO:RGD.
DR   GO; GO:0005543; F:phospholipid binding; ISO:RGD.
DR   GO; GO:0015386; F:potassium:proton antiporter activity; IBA:GO_Central.
DR   GO; GO:0030346; F:protein phosphatase 2B binding; ISO:RGD.
DR   GO; GO:0015385; F:sodium:proton antiporter activity; IDA:UniProtKB.
DR   GO; GO:0086003; P:cardiac muscle cell contraction; IEP:RGD.
DR   GO; GO:0055007; P:cardiac muscle cell differentiation; ISO:RGD.
DR   GO; GO:0030154; P:cell differentiation; IEP:RGD.
DR   GO; GO:0071468; P:cellular response to acidic pH; ISS:UniProtKB.
DR   GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
DR   GO; GO:0070417; P:cellular response to cold; IEP:RGD.
DR   GO; GO:0071257; P:cellular response to electrical stimulus; IEP:RGD.
DR   GO; GO:0071872; P:cellular response to epinephrine stimulus; ISO:RGD.
DR   GO; GO:0071456; P:cellular response to hypoxia; IDA:RGD.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; IDA:RGD.
DR   GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0006883; P:intracellular sodium ion homeostasis; ISO:RGD.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR   GO; GO:0045760; P:positive regulation of action potential; IMP:RGD.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR   GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; ISO:RGD.
DR   GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:RGD.
DR   GO; GO:0030307; P:positive regulation of cell growth; IMP:RGD.
DR   GO; GO:1902533; P:positive regulation of intracellular signal transduction; IMP:RGD.
DR   GO; GO:0035794; P:positive regulation of mitochondrial membrane permeability; IMP:RGD.
DR   GO; GO:0098735; P:positive regulation of the force of heart contraction; ISO:RGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:1902600; P:proton transmembrane transport; ISO:RGD.
DR   GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; ISO:RGD.
DR   GO; GO:0051453; P:regulation of intracellular pH; IMP:RGD.
DR   GO; GO:0006885; P:regulation of pH; ISS:UniProtKB.
DR   GO; GO:0002026; P:regulation of the force of heart contraction; IMP:RGD.
DR   GO; GO:0086092; P:regulation of the force of heart contraction by cardiac conduction; ISO:RGD.
DR   GO; GO:0010447; P:response to acidic pH; IDA:UniProtKB.
DR   GO; GO:0035994; P:response to muscle stretch; ISO:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IDA:RGD.
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:RGD.
DR   GO; GO:0006814; P:sodium ion transport; ISO:RGD.
DR   GO; GO:0048863; P:stem cell differentiation; ISO:RGD.
DR   Gene3D; 6.10.140.1330; -; 1.
DR   Gene3D; 6.10.250.1040; -; 1.
DR   Gene3D; 6.10.250.2020; -; 1.
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   NCBIfam; TIGR00840; b_cpa1; 1.
DR   PANTHER; PTHR10110; SODIUM/HYDROGEN EXCHANGER; 1.
DR   PANTHER; PTHR10110:SF59; SODIUM_HYDROGEN EXCHANGER 1; 1.
DR   Pfam; PF00999; Na_H_Exchanger; 1.
DR   Pfam; PF16644; NEXCaM_BD; 1.
DR   PRINTS; PR01084; NAHEXCHNGR.
DR   PRINTS; PR01085; NAHEXCHNGR1.
DR   Genevisible; P26431; RN.
PE   1: Evidence at protein level;
KW   Antiport; Calmodulin-binding; Cell membrane; Glycoprotein; Ion transport;
KW   Lipoprotein; Membrane; Palmitate; 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_0000052351"
FT   TOPO_DOM        1..102
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        103..125
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        126..134
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        135..152
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        153..162
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        163..180
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        181..190
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        191..219
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        220..226
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        227..253
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        254..256
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        257..287
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        288..291
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        292..326
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        327..332
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        333..345
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        346..354
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        355..375
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        376..377
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        378..408
FT                   /note="Helical; Name=10"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        409..414
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        415..442
FT                   /note="Helical; Name=11"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        443..448
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        449..473
FT                   /note="Helical; Name=12"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        474..479
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        480..509
FT                   /note="Helical; Name=13"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   TOPO_DOM        510..820
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   REGION          44..71
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          505..571
FT                   /note="Interaction with TESC"
FT                   /evidence="ECO:0000269|PubMed:18321853"
FT   REGION          513..520
FT                   /note="PI(4,5)P2-binding region"
FT                   /evidence="ECO:0000269|PubMed:10893269"
FT   REGION          519..549
FT                   /note="Interaction with CHP2"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   REGION          544..549
FT                   /note="Confers pH-dependent PI(4,5)P2 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   REGION          556..564
FT                   /note="PI(4,5)P2-binding region"
FT                   /evidence="ECO:0000269|PubMed:10893269"
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          688..691
FT                   /note="Interaction with PPP3CA"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   REGION          719..724
FT                   /note="Interaction with PPP3CA"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   REGION          747..820
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        777..797
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:22673903"
FT   MOD_RES         606
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   MOD_RES         607
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q61165"
FT   MOD_RES         609
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         652
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   MOD_RES         697
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         701
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         707
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         727
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         730
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         733
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         755
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q61165"
FT   MOD_RES         784
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P19634"
FT   MOD_RES         790
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         801
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MUTAGEN         266
FT                   /note="E->I: Abolishes sodium:proton antiporter activity."
FT                   /evidence="ECO:0000269|PubMed:11163215"
FT   MUTAGEN         522..538
FT                   /note="INEEIHTQFLDHLLTGI->QNEEQHTQQLDHQQTGQ: Abolishes
FT                   interaction with TESC and markedly reduces transporter
FT                   activity. Does not alter its cell membrane localization."
FT                   /evidence="ECO:0000269|PubMed:21543739"
FT   MUTAGEN         530..535
FT                   /note="FLDHLL->AADHAA: Abolishes interaction with TESC and
FT                   markedly reduces transporter activity. Does not alter its
FT                   cell membrane localization."
FT                   /evidence="ECO:0000269|PubMed:18321853"
FT   MUTAGEN         530..535
FT                   /note="FLDHLL->QQDHQQ: Abolishes interaction with TESC and
FT                   markedly reduces transporter activity. Does not alter its
FT                   cell membrane localization."
FT                   /evidence="ECO:0000269|PubMed:18321853"
FT   MUTAGEN         530..535
FT                   /note="FLDHLL->RRDHRR: Abolishes interaction with TESC and
FT                   markedly reduces transporter activity. Does not alter its
FT                   cell membrane localization."
FT                   /evidence="ECO:0000269|PubMed:18321853"
SQ   SEQUENCE   820 AA;  91647 MW;  58398DE74A9642FB CRC64;
     MMLRWSGIWG LYPPRIFPSL LVVVALVGLL PVLRSHGLQL NPTASTIRGS EPPRERSIGD
     VTTAPSEPLH HPDDRNLTNL YIEHGAKPVR KAFPVLDIDY LHVRTPFEIS LWILLACLMK
     IGFHVIPTIS SIVPESCLLI VVGLLVGGLI KGVGETPPFL QSDVFFLFLL PPIILDAGYF
     LPLRQFTENL GTILIFAVVG TLWNAFFLGG LLYAVCLVGG EQINNIGLLD TLLFGSIISA
     VDPVAVLAVF EEIHINELLH ILVFGESLLN DAVTVVLYHL FEEFASYEYV GISDIFLGFL
     SFFVVSLGGV 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 QNIHPKSAAS ERILPALSKD KEEEIRKILR SNLQKTRQRL RSYNRHTLVA
     DPYEEAWNQM LLRRQKARQL EQKITNYLTV PAHKLDSPTM SRARIGSDPL AYEPKADLPV
     ITIDPASPQS PESVDLVNEE LKGKVLGLKR GPRTTPEEEE EDEDGVIMIR SKEPSSPGTD
     DVFTPGPSDS PGSQRIQRCL SDPGPHPEPG EGEPFIPKGQ
//