SL9A1_RABIT
ID SL9A1_RABIT Reviewed; 816 AA.
AC P23791;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 153.
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Ileal villus;
RX PubMed=1712287; DOI=10.1002/j.1460-2075.1991.tb07725.x;
RA Tse C.-M., Ma A.I., Yang V.W., Watson A.J.M., Levine S., Montrose M.H.,
RA Potter J., Sardet C., Pouyssegur J., Donowitz M.;
RT "Molecular cloning and expression of a cDNA encoding the rabbit ileal
RT villus cell basolateral membrane Na+/H+ exchanger.";
RL EMBO J. 10:1957-1967(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=1661611; DOI=10.1016/0167-4781(91)90221-7;
RA Hildebrandt F., Pizzonia J.H., Reilly R.F., Reboucas N.A., Sardet C.,
RA Pouyssegur J., Slayman C.W., Aronson P.S., Igarashi P.;
RT "Cloning, sequence, and tissue distribution of a rabbit renal Na+/H+
RT exchanger transcript.";
RL Biochim. Biophys. Acta 1129:105-108(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 472-816.
RC STRAIN=New Zealand white; TISSUE=Heart muscle;
RX PubMed=1704856; DOI=10.1016/0014-5793(91)80241-t;
RA Fliegel L., Sardet C., Pouyssegur J., Barr A.;
RT "Identification of the protein and cDNA of the cardiac Na+/H+ exchanger.";
RL FEBS Lett. 279:25-29(1991).
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 CALM 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 -!- TISSUE SPECIFICITY: Kidney and intestine.
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 503-
CC 545. However, another publication has reported interaction with TESC
CC via residues 633-816, the region of the cytoplasmic C-terminus more
CC distal to the membrane. {ECO:0000305}.
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DR EMBL; X59935; CAA42558.1; -; mRNA.
DR EMBL; X61504; CAA43721.1; -; mRNA.
DR EMBL; X56536; CAA39881.1; -; mRNA.
DR PIR; S16328; S16328.
DR RefSeq; NP_001095191.1; NM_001101721.1.
DR AlphaFoldDB; P23791; -.
DR BMRB; P23791; -.
DR SMR; P23791; -.
DR BioGRID; 1172605; 43.
DR STRING; 9986.ENSOCUP00000022999; -.
DR BindingDB; P23791; -.
DR ChEMBL; CHEMBL2865; -.
DR PRIDE; P23791; -.
DR Ensembl; ENSOCUT00000022296; ENSOCUP00000022999; ENSOCUG00000023061.
DR GeneID; 100009586; -.
DR KEGG; ocu:100009586; -.
DR CTD; 6548; -.
DR eggNOG; KOG1966; Eukaryota.
DR GeneTree; ENSGT00940000156338; -.
DR InParanoid; P23791; -.
DR OrthoDB; 389547at2759; -.
DR PRO; PR:P23791; -.
DR Proteomes; UP000001811; Chromosome 13.
DR Bgee; ENSOCUG00000023061; Expressed in uterus and 18 other tissues.
DR ExpressionAtlas; P23791; baseline.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0090533; C:cation-transporting ATPase complex; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0030346; F:protein phosphatase 2B binding; IEA:Ensembl.
DR GO; GO:0015385; F:sodium:proton antiporter activity; ISS:UniProtKB.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0071468; P:cellular response to acidic pH; ISS:UniProtKB.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; IEA:Ensembl.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IEA:Ensembl.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:1903281; P:positive regulation of calcium:sodium antiporter activity; IEA:Ensembl.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IEA:Ensembl.
DR GO; GO:0098735; P:positive regulation of the force of heart contraction; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB.
DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; IEA:Ensembl.
DR GO; GO:0051453; P:regulation of intracellular pH; ISS:UniProtKB.
DR GO; GO:0006885; P:regulation of pH; ISS:UniProtKB.
DR GO; GO:0086092; P:regulation of the force of heart contraction by cardiac conduction; IEA:Ensembl.
DR GO; GO:0010447; P:response to acidic pH; ISS:UniProtKB.
DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl.
DR GO; GO:0036376; P:sodium ion export across plasma membrane; ISS:UniProtKB.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; IEA:Ensembl.
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 2: Evidence at transcript 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..816
FT /note="Sodium/hydrogen exchanger 1"
FT /id="PRO_0000052350"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..32
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..101
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..127
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..129
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 130..149
FT /note="Helical; Name=M3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 150..154
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..174
FT /note="Helical; Name=M4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 175..191
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 192..211
FT /note="Helical; Name=M5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 212..227
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 228..247
FT /note="Helical; Name=M6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..256
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..276
FT /note="Helical; Name=M7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..294
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical; Name=M8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 316..338
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 339..358
FT /note="Helical; Name=M9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..381
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 382..402
FT /note="Name=H10"
FT /evidence="ECO:0000250"
FT TOPO_DOM 403..410
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 411..430
FT /note="Helical; Name=M10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 431..448
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 449..470
FT /note="Helical; Name=M11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 471..479
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 480..499
FT /note="Helical; Name=M12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 500..816
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 37..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..545
FT /note="Interaction with TESC"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT REGION 515..545
FT /note="Interaction with CHP2"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT REGION 633..816
FT /note="Interaction with CALM1"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT REGION 633..816
FT /note="Interaction with TESC"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT REGION 748..816
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 37..57
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 777..795
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 161
FT /note="Channel pore-lining"
FT /evidence="ECO:0000250"
FT MOD_RES 599
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 602
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 603
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q61165"
FT MOD_RES 605
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 693
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 697
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 703
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 723
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 726
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 729
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 786
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 788
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61165"
FT MOD_RES 797
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26431"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 242
FT /note="V -> A (in Ref. 2; CAA43721)"
FT /evidence="ECO:0000305"
FT CONFLICT 569
FT /note="K -> E (in Ref. 2; CAA43721)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 816 AA; 90717 MW; 336738D267F7F436 CRC64;
MLLWSAVRGL SPPRIVPSLL VVVALAGLLP GLRSHGLQLS PTDSTTPDSQ PSRERSIGDV
TTAPPEVTPE SRPVNRSVTE HGMKPRKAFP VLGIDYTHVR TPFEISLWIL LACLMKIGFH
VIPTISSIVP ESCLLIVVGL LVGGLIKGVG EKPPFLQSEV FFLFLLPPII LDAGYFLPLR
QFTENLGTIL IFAVVGTLWN AFFLGGLMYA VCLVGGEQIN NIGLLDNLLF GSIISAVDPV
AVLAVFEEIH INELLHILVF GESLLNDAVT VVLYHLFEEF ANYDHVGIVD IVLGFLSFFV
VALGGVFVGV VYGVIAAFTS RFTAHIRVIE PLFVFLYSYM AYLSAELFHL SGIMALIASG
VVMRPYVEAN ISHKSHTTIK YFLKMWSSVS ETLIFIFLGV STVAGSHHWN WTFVISTLLF
CLIARVLGVL GLTWFINKFR IVKLTPKDQF IIAYGGLRGA IAFSLGYLLD KKHFPMCDLF
LTAIITVIFF TVFVQGMTIR PLVDLLAVKK KQETKRSINE EIHTQFLDHL LTGIEDICGH
YGHHHWKDKL NRFNKKYVKK CLIAGERSKE PQLIAFYHKM EMKQAIELVE SGGMGKIPSA
VSTVSMQNIH PKALPAERIL PALSKDKEEE IRKILRNNLQ KTRQRLRSYN RHTLVADPYE
EAWNQMLLRR QKARQLEQKI NNYLTVPAHK LDSPTMSRAR IGSDPLAYEP KADLPVITID
PASPQSPESV DLVNEELKGK VLGLSREPRV AEEAAEEDED GGIVMRPKEP SSPGTDDVFS
PAPSDSPSSQ RMQRCLSDPG PHPEPGEGEP FIPKGQ
