SL9A1_CRIGR
ID SL9A1_CRIGR Reviewed; 822 AA.
AC P48761;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 121.
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 Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8383540; DOI=10.1016/0167-4781(93)90228-6;
RA Counillon L., Pouyssegur J.;
RT "Nucleotide sequence of the Chinese hamster Na+/H+ exchanger NHE1.";
RL Biochim. Biophys. Acta 1172:343-345(1993).
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 {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}. Cell membrane; Multi-pass
CC membrane protein. Note=Colocalizes with CHP1 and CHP2 at the reticulum
CC endoplasmic and 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 637-822, the region of the cytoplasmic C-terminus more
CC distal to the membrane. {ECO:0000305}.
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DR EMBL; X68970; CAA48771.1; -; mRNA.
DR PIR; S30198; S30198.
DR RefSeq; NP_001233682.1; NM_001246753.1.
DR AlphaFoldDB; P48761; -.
DR BMRB; P48761; -.
DR SMR; P48761; -.
DR STRING; 10029.NP_001233682.1; -.
DR GeneID; 100689320; -.
DR KEGG; cge:100689320; -.
DR CTD; 6548; -.
DR eggNOG; KOG1966; Eukaryota.
DR OrthoDB; 389547at2759; -.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0015385; F:sodium:proton antiporter activity; ISS:UniProtKB.
DR GO; GO:0071468; P:cellular response to acidic pH; ISS:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB.
DR GO; GO:0051453; P:regulation of intracellular pH; ISS:UniProtKB.
DR GO; GO:0006885; P:regulation of pH; ISS:UniProtKB.
DR GO; GO:0010447; P:response to acidic pH; ISS:UniProtKB.
DR GO; GO:0036376; P:sodium ion export across plasma membrane; ISS:UniProtKB.
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; Sodium;
KW Sodium transport; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation.
FT CHAIN 1..822
FT /note="Sodium/hydrogen exchanger 1"
FT /id="PRO_0000052346"
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..822
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 41..73
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..822
FT /note="Interaction with CALM1"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT REGION 637..822
FT /note="Interaction with TESC"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT REGION 752..822
FT /note="Disordered"
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:0000250|UniProtKB:P19634"
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:0000250|UniProtKB:P19634"
FT MOD_RES 697
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 701
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 707
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 727
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 730
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 733
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 756
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q61165"
FT MOD_RES 792
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19634"
FT MOD_RES 794
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61165"
FT MOD_RES 803
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26431"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 822 AA; 92004 MW; E97C1ACD4EB88DAA CRC64;
MMLRWSGIWG LSPPRIFPSL LVVVALVGLL PVLRSHGLQP SPTANTIRGA EPPRERSIGD
VTTAPSEPVH HPDDRNLTNL HIEHGAKTLR KAFPVLDIDY LHVRTPFEIS LWILLACLMK
IGFHVIPTIS SIVPESCLLI VVGLLVGGLI KGVGETPPFL QSDVFFLFLL PPIILDAGYF
LPLRQFTENL GTILIFAVVG TLWNAFFLGG LLYAVCLVGG EQINNIGLLD TLLFGSIISA
VDPVAVVAVF EEIHINELLH ILVFGESLLN DAVTVVLYHL FEEFANYDSI GISDIFLGFL
SFFVVALGGV FVGVVYGVIA AFTSRFTSHI RVIEPLFVFL YSYMAYLSAE LFHLSGIMAL
IASGVVMRPY VEANISHKSH TTIKYFLKMW SSVSETLIFI FLGVSTVAGS HQWNWTFVIS
TLLFCLIARV LGVLVLTWFI NKFRIVKLTP KDQFIIAYGG LRGAIAFSLG YLMDKKHFPM
CDLFLTAIIT VIFFTVFVQG MTIRPLVDLL AVKKKQETKR SINEEIHTQF LDHLLTGIED
ICGHYGHHHW KDKLNRFNKK YVKKCLIAGE RSKEPQLIAF YHKMEMKQAI ELVESGGMGK
IPSAVSTVSM QNIHPKSMAS ERILPALSKD KEEEIRKILR SNLQKTRQRL RSYNRHTLVA
DPYEEAWNQM LLRRQKARQL EQKMSNYLTV PAHKLDSPTM SRARIGSDPL AYEPKADLPV
ITIDPASPQS PESVDLVNEE LKAKVLGVNR DPTRLTRGEE DEDEDEDGVI MMRRKEPSSP
GTDVFTPAPM YSPSSQRIQR CLSDPGPHPE PGEGEPFIPK GE
