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

 SL9A1_RAT               Reviewed;         820 AA.
P26431;
01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 2.
22-NOV-2017, entry version 155.
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;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=Sprague-Dawley; TISSUE=Heart;
PubMed=1577762;
Orlowski J., Kandasamy R.A., Shull G.E.;
"Molecular cloning of putative members of the Na/H exchanger gene
family. cDNA cloning, deduced amino acid sequence, and mRNA tissue
expression of the rat Na/H exchanger NHE-1 and two structurally
related proteins.";
J. Biol. Chem. 267:9331-9339(1992).
[2]
GLYCOSYLATION.
PubMed=9688597;
Shrode L.D., Gan B.S., D'Souza S.J., Orlowski J., Grinstein S.;
"Topological analysis of NHE1, the ubiquitous Na+/H+ exchanger using
chymotryptic cleavage.";
Am. J. Physiol. 275:C431-C439(1998).
[3]
INTERACTION WITH CHP1 AND CHP2.
PubMed=12576672; DOI=10.1248/bpb.26.148;
Inoue H., Nakamura Y., Nagita M., Takai T., Masuda M., Nakamura N.,
Kanazawa H.;
"Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-
binding protein, is expressed in intestinal epithelium.";
Biol. Pharm. Bull. 26:148-155(2003).
[4]
INTERACTION WITH TESC, AND MUTAGENESIS OF 530-PHE--LEU-535.
PubMed=18321853; DOI=10.1074/jbc.M800267200;
Zaun H.C., Shrier A., Orlowski J.;
"Calcineurin B homologous protein 3 promotes the biosynthetic
maturation, cell surface stability, and optimal transport of the
Na+/H+ exchanger NHE1 isoform.";
J. Biol. Chem. 283:12456-12467(2008).
[5]
OLIGOMERIZATION, GLYCOSYLATION, UBIQUITINATION, AND MUTAGENESIS OF
522-ILE--ILE-538.
PubMed=21543739; DOI=10.1152/ajpcell.00404.2010;
Matsushita M., Tanaka H., Mitsui K., Kanazawa H.;
"Dual functional significance of calcineurin homologous protein 1
binding to Na(+)/H(+) exchanger isoform 1.";
Am. J. Physiol. 301:C280-C288(2011).
[6]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-603; SER-609; SER-697;
SER-701; SER-707; SER-727; SER-730; SER-733; SER-790 AND SER-801, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22673903; DOI=10.1038/ncomms1871;
Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
Lundby C., Olsen J.V.;
"Quantitative maps of protein phosphorylation sites across 14
different rat organs and tissues.";
Nat. Commun. 3:876-876(2012).
-!- 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: 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). Oligomer. Interacts with
CHP1, CHP2 and TESC. {ECO:0000250, ECO:0000269|PubMed:12576672,
ECO:0000269|PubMed:18321853}.
-!- INTERACTION:
Q810D1:Chp2; NbExp=2; IntAct=EBI-77471, EBI-6146708;
-!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
membrane protein. Membrane; Multi-pass membrane protein. Cell
membrane; Multi-pass membrane protein. Note=Colocalizes with and
CHP2 at the plasma membrane (By similarity). Colocalizes with CHP1
at the reticulum endoplasmic and plasma membrane. {ECO:0000250}.
-!- TISSUE SPECIFICITY: Not tissue specific.
-!- PTM: N-glycosylated and O-glycosylated in the N-terminal region.
{ECO:0000269|PubMed:21543739, ECO:0000269|PubMed:9688597}.
-!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
Ubiquitination is reduced by CHP1. {ECO:0000269|PubMed:21543739}.
-!- 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}.
-!- CAUTION: Although PubMed:18321853 show that TESC-binding results
in the maturation and accumulation of SLC9A1 at the cell surface,
previous studies with human SLC9A1 report that TESC-binding
results in a decrease in activity. {ECO:0000305}.
-!- CAUTION: Although PubMed:18321853 show that they CHP1 and TESC
bind at the same C-terminal site, previous studies with human
SLC9A1 report that they bind to different sites. {ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; M85299; AAA98479.1; -; mRNA.
PIR; A40204; A40204.
RefSeq; NP_036784.1; NM_012652.1.
UniGene; Rn.5025; -.
ProteinModelPortal; P26431; -.
SMR; P26431; -.
BioGrid; 246906; 1.
IntAct; P26431; 3.
STRING; 10116.ENSRNOP00000011049; -.
BindingDB; P26431; -.
ChEMBL; CHEMBL2577; -.
GuidetoPHARMACOLOGY; 948; -.
TCDB; 2.A.36.1.1; the monovalent cation:proton antiporter-1 (cpa1) family.
iPTMnet; P26431; -.
PhosphoSitePlus; P26431; -.
PaxDb; P26431; -.
PRIDE; P26431; -.
Ensembl; ENSRNOT00000011049; ENSRNOP00000011049; ENSRNOG00000007982.
GeneID; 24782; -.
KEGG; rno:24782; -.
UCSC; RGD:3718; rat.
CTD; 6548; -.
RGD; 3718; Slc9a1.
eggNOG; KOG1966; Eukaryota.
eggNOG; COG0025; LUCA.
GeneTree; ENSGT00760000119074; -.
HOGENOM; HOG000247044; -.
HOVERGEN; HBG052615; -.
InParanoid; P26431; -.
KO; K05742; -.
OMA; YDRVGIV; -.
OrthoDB; EOG091G02Q0; -.
PhylomeDB; P26431; -.
TreeFam; TF317212; -.
Reactome; R-RNO-2160916; Hyaluronan uptake and degradation.
Reactome; R-RNO-425986; Sodium/Proton exchangers.
PRO; PR:P26431; -.
Proteomes; UP000002494; Chromosome 5.
Bgee; ENSRNOG00000007982; -.
Genevisible; P26431; RN.
GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
GO; GO:0090533; C:cation-transporting ATPase complex; ISO:RGD.
GO; GO:0009986; C:cell surface; IDA:RGD.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
GO; GO:0070062; C:extracellular exosome; ISO:RGD.
GO; GO:0005925; C:focal adhesion; ISO:RGD.
GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
GO; GO:0014704; C:intercalated disc; IDA:RGD.
GO; GO:0016020; C:membrane; ISO:RGD.
GO; GO:0045121; C:membrane raft; IDA:RGD.
GO; GO:0005739; C:mitochondrion; IDA:RGD.
GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO; GO:0042383; C:sarcolemma; IDA:RGD.
GO; GO:0030315; C:T-tubule; IDA:RGD.
GO; GO:0048306; F:calcium-dependent protein binding; ISS:UniProtKB.
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:RGD.
GO; GO:0015385; F:sodium:proton antiporter activity; IDA:UniProtKB.
GO; GO:0086003; P:cardiac muscle cell contraction; IEP:RGD.
GO; GO:0055007; P:cardiac muscle cell differentiation; ISO:RGD.
GO; GO:0030154; P:cell differentiation; IEP:RGD.
GO; GO:0016049; P:cell growth; IEP:RGD.
GO; GO:0071468; P:cellular response to acidic pH; ISS:UniProtKB.
GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
GO; GO:0071257; P:cellular response to electrical stimulus; IEP:RGD.
GO; GO:0071872; P:cellular response to epinephrine stimulus; ISO:RGD.
GO; GO:0071456; P:cellular response to hypoxia; IDA:RGD.
GO; GO:0032869; P:cellular response to insulin stimulus; IDA:RGD.
GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
GO; GO:0006883; P:cellular sodium ion homeostasis; ISO:RGD.
GO; GO:1902600; P:hydrogen ion transmembrane transport; ISO:RGD.
GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
GO; GO:0070997; P:neuron death; IMP:RGD.
GO; GO:0045760; P:positive regulation of action potential; IMP:RGD.
GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; ISO:RGD.
GO; GO:1903281; P:positive regulation of calcium:sodium antiporter activity; ISO:RGD.
GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:RGD.
GO; GO:0030307; P:positive regulation of cell growth; IMP:RGD.
GO; GO:1902533; P:positive regulation of intracellular signal transduction; IMP:RGD.
GO; GO:0035794; P:positive regulation of mitochondrial membrane permeability; IMP:RGD.
GO; GO:0098735; P:positive regulation of the force of heart contraction; ISO:RGD.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISO:RGD.
GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; ISO:RGD.
GO; GO:0051453; P:regulation of intracellular pH; IMP:RGD.
GO; GO:0006885; P:regulation of pH; ISS:UniProtKB.
GO; GO:0051930; P:regulation of sensory perception of pain; IMP:RGD.
GO; GO:0002026; P:regulation of the force of heart contraction; IMP:RGD.
GO; GO:0086092; P:regulation of the force of heart contraction by cardiac conduction; ISO:RGD.
GO; GO:0010447; P:response to acidic pH; IDA:UniProtKB.
GO; GO:0042493; P:response to drug; IEP:RGD.
GO; GO:0035994; P:response to muscle stretch; ISO:RGD.
GO; GO:0014070; P:response to organic cyclic compound; IDA:RGD.
GO; GO:0071436; P:sodium ion export; ISS:UniProtKB.
GO; GO:0098719; P:sodium ion import across plasma membrane; ISO:RGD.
GO; GO:0006814; P:sodium ion transport; ISO:RGD.
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_0000052351.
TOPO_DOM 1 12 Cytoplasmic. {ECO:0000255}.
TRANSMEM 13 33 Helical; Name=M1. {ECO:0000255}.
TOPO_DOM 34 105 Extracellular. {ECO:0000255}.
TRANSMEM 106 131 Helical; Name=M2. {ECO:0000255}.
TOPO_DOM 132 133 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:22673903}.
MOD_RES 606 606 Phosphoserine.
{ECO:0000250|UniProtKB:P19634}.
MOD_RES 607 607 Phosphothreonine.
{ECO:0000250|UniProtKB:Q61165}.
MOD_RES 609 609 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 697 697 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 701 701 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 707 707 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 727 727 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 730 730 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 733 733 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 755 755 Phosphothreonine.
{ECO:0000250|UniProtKB:Q61165}.
MOD_RES 790 790 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 801 801 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
CARBOHYD 374 374 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
MUTAGEN 522 538 INEEIHTQFLDHLLTGI->QNEEQHTQQLDHQQTGQ:
Abolishes interaction with TESC and
markedly reduces transporter activity.
Does not alter its cell membrane
localization.
{ECO:0000269|PubMed:21543739}.
MUTAGEN 530 535 FLDHLL->AADHAA: Abolishes interaction
with TESC and markedly reduces
transporter activity. Does not alter its
cell membrane localization.
{ECO:0000269|PubMed:18321853}.
MUTAGEN 530 535 FLDHLL->QQDHQQ: Abolishes interaction
with TESC and markedly reduces
transporter activity. Does not alter its
cell membrane localization.
{ECO:0000269|PubMed:18321853}.
MUTAGEN 530 535 FLDHLL->RRDHRR: Abolishes interaction
with TESC and markedly reduces
transporter activity. Does not alter its
cell membrane localization.
{ECO:0000269|PubMed:18321853}.
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


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