SL9A1_RAT
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 03-AUG-2022, entry version 180.
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 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].
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 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 [3]
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 [4]
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 [5]
RP OLIGOMERIZATION, GLYCOSYLATION, UBIQUITINATION, AND MUTAGENESIS OF
RP 522-ILE--ILE-538.
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 [6]
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).
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 (PubMed:21543739). Interacts with CALM1 in a calcium-
CC dependent manner (By similarity). Interacts with TESC
CC (PubMed:18321853). Interacts (via residues 504-563; the juxtamembrane
CC region of the cytoplasmic C-terminal domain) 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). {ECO:0000250|UniProtKB:P19634,
CC ECO:0000269|PubMed:12576672, ECO:0000269|PubMed:18321853,
CC ECO:0000269|PubMed:21543739}.
CC -!- INTERACTION:
CC P26431; Q810D1: Chp2; NbExp=2; IntAct=EBI-77471, EBI-6146708;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein. Membrane; Multi-pass membrane protein. Cell membrane;
CC Multi-pass membrane protein. Note=Colocalizes with and CHP2 at the
CC plasma membrane (By similarity). Colocalizes with CHP1 at the reticulum
CC endoplasmic and plasma membrane. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Not tissue specific.
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 -!- 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: 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 GlyGen; P26431; 1 site.
DR iPTMnet; P26431; -.
DR PhosphoSitePlus; P26431; -.
DR PaxDb; P26431; -.
DR PRIDE; P26431; -.
DR Ensembl; ENSRNOT00000011049; ENSRNOP00000011049; ENSRNOG00000007982.
DR GeneID; 24782; -.
DR KEGG; rno:24782; -.
DR UCSC; RGD:3718; rat.
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; EFANYDH; -.
DR OrthoDB; 389547at2759; -.
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 tissues.
DR Genevisible; P26431; RN.
DR GO; GO:0016324; C:apical plasma membrane; ISO: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:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0014704; C:intercalated disc; IDA:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
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:0048306; F:calcium-dependent protein binding; ISS:UniProtKB.
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: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:cellular sodium ion homeostasis; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0070997; P:neuron death; 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:1903281; P:positive regulation of calcium:sodium antiporter activity; 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:0051930; P:regulation of sensory perception of pain; IMP:RGD.
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; IEA:Ensembl.
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_0000052351"
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..131
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 132..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 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 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 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 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 790
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 801
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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
