SL9A3_RAT
ID SL9A3_RAT Reviewed; 831 AA.
AC P26433;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 25-MAY-2022, entry version 156.
DE RecName: Full=Sodium/hydrogen exchanger 3;
DE AltName: Full=Na(+)/H(+) exchanger 3;
DE Short=NHE-3;
DE AltName: Full=Solute carrier family 9 member 3;
GN Name=Slc9a3; Synonyms=Nhe3;
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=Kidney;
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 PHOSPHORYLATION AT SER-552 AND SER-605.
RX PubMed=9933588; DOI=10.1074/jbc.274.7.3978;
RA Zhao H., Wiederkehr M.R., Fan L., Collazo R.L., Crowder L.A., Moe O.W.;
RT "Acute inhibition of Na/H exchanger NHE-3 by cAMP. Role of protein kinase a
RT and NHE-3 phosphoserines 552 and 605.";
RL J. Biol. Chem. 274:3978-3987(1999).
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 SHANK2.
RX PubMed=16293618; DOI=10.1074/jbc.m509786200;
RA Han W., Kim K.H., Jo M.J., Lee J.H., Yang J., Doctor R.B., Moe O.W.,
RA Lee J., Kim E., Lee M.G.;
RT "Shank2 associates with and regulates Na+/H+ exchanger 3.";
RL J. Biol. Chem. 281:1461-1469(2006).
RN [5]
RP TISSUE SPECIFICITY, INTERACTION WITH AHCYL1, AND SUBCELLULAR LOCATION.
RX PubMed=20584908; DOI=10.1074/jbc.m110.133066;
RA He P., Klein J., Yun C.C.;
RT "Activation of Na+/H+ exchanger NHE3 by angiotensin II is mediated by
RT inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with
RT IP3 (IRBIT) and Ca2+/calmodulin-dependent protein kinase II.";
RL J. Biol. Chem. 285:27869-27878(2010).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-552; SER-560 AND SER-807, 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 {ECO:0000250|UniProtKB:P48764}.
CC -!- SUBUNIT: Binds SLC9A3R1 and SLC9A3R2. Interacts with PDZD3 and
CC interactions decrease in response to elevated calcium ion levels.
CC Interacts with PDZK1 (via C-terminal PDZ domain) (By similarity).
CC Interacts with CHP1, CHP2 and SHANK2 (PubMed:12576672,
CC PubMed:16293618). Interacts with AHCYL1; the interaction is required
CC for SLC9A3 activity (PubMed:20584908). {ECO:0000250|UniProtKB:P48764,
CC ECO:0000250|UniProtKB:Q28362, ECO:0000269|PubMed:12576672,
CC ECO:0000269|PubMed:16293618, ECO:0000269|PubMed:20584908}.
CC -!- INTERACTION:
CC P26433; Q810D1: Chp2; NbExp=3; IntAct=EBI-961694, EBI-6146708;
CC P26433; Q9QX74: Shank2; NbExp=2; IntAct=EBI-961694, EBI-397902;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:20584908}; Multi-pass membrane protein. Note=In
CC intestinal epithelial cells, localizes to the ileal brush border.
CC Phosphorylation at Ser-661 by SGK1 is associated with increased
CC abundance at the cell membrane. Angiotensin-2 enhances apical
CC expression (By similarity). {ECO:0000250|UniProtKB:P48764,
CC ECO:0000250|UniProtKB:Q28362}.
CC -!- TISSUE SPECIFICITY: Most abundant in colon and small intestine,
CC followed by kidney and stomach. In kidney, expressed in proximal
CC tubules and outer medulla (at protein level) (PubMed:20584908).
CC {ECO:0000269|PubMed:20584908}.
CC -!- PTM: Phosphorylated by PKA, which inhibits activity (PubMed:9933588).
CC Phosphorylation at Ser-661 by SGK1 is associated with increased
CC abundance at the cell membrane (By similarity).
CC {ECO:0000250|UniProtKB:P26432, ECO:0000269|PubMed:9933588}.
CC -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1)
CC transporter (TC 2.A.36) family. {ECO:0000305}.
CC -!- CAUTION: The number, localization and denomination of hydrophobic
CC domains in the Na(+)/H(+) exchangers vary among authors. {ECO:0000305}.
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DR EMBL; M85300; AAA41702.1; -; mRNA.
DR PIR; B40204; B40204.
DR RefSeq; NP_036786.1; NM_012654.1.
DR AlphaFoldDB; P26433; -.
DR SMR; P26433; -.
DR BioGRID; 246908; 1.
DR IntAct; P26433; 5.
DR MINT; P26433; -.
DR STRING; 10116.ENSRNOP00000020711; -.
DR BindingDB; P26433; -.
DR ChEMBL; CHEMBL3879842; -.
DR GuidetoPHARMACOLOGY; 950; -.
DR TCDB; 2.A.36.1.2; the monovalent cation:proton antiporter-1 (cpa1) family.
DR GlyGen; P26433; 1 site.
DR iPTMnet; P26433; -.
DR PhosphoSitePlus; P26433; -.
DR PaxDb; P26433; -.
DR PRIDE; P26433; -.
DR DNASU; 24784; -.
DR GeneID; 24784; -.
DR KEGG; rno:24784; -.
DR UCSC; RGD:3720; rat.
DR CTD; 6550; -.
DR RGD; 3720; Slc9a3.
DR eggNOG; KOG1966; Eukaryota.
DR InParanoid; P26433; -.
DR OrthoDB; 389547at2759; -.
DR PhylomeDB; P26433; -.
DR Reactome; R-RNO-425986; Sodium/Proton exchangers.
DR PRO; PR:P26433; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005903; C:brush border; IDA:RGD.
DR GO; GO:0031526; C:brush border membrane; IDA:RGD.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0031982; C:vesicle; ISO:RGD.
DR GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
DR GO; GO:0015386; F:potassium:proton antiporter activity; IBA:GO_Central.
DR GO; GO:0015385; F:sodium:proton antiporter activity; IDA:RGD.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IMP:RGD.
DR GO; GO:0051453; P:regulation of intracellular pH; IBA:GO_Central.
DR GO; GO:0006885; P:regulation of pH; IDA:RGD.
DR GO; GO:0002028; P:regulation of sodium ion transport; IMP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0006814; P:sodium ion transport; IDA:RGD.
DR InterPro; IPR006153; Cation/H_exchanger.
DR InterPro; IPR018422; Cation/H_exchanger_CPA1.
DR InterPro; IPR018410; Na/H_exchanger_3/5.
DR InterPro; IPR004709; NaH_exchanger.
DR PANTHER; PTHR10110; PTHR10110; 1.
DR Pfam; PF00999; Na_H_Exchanger; 1.
DR PRINTS; PR01084; NAHEXCHNGR.
DR PRINTS; PR01087; NAHEXCHNGR3.
DR TIGRFAMs; TIGR00840; b_cpa1; 1.
PE 1: Evidence at protein level;
KW Antiport; Cell membrane; Glycoprotein; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Sodium; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..831
FT /note="Sodium/hydrogen exchanger 3"
FT /id="PRO_0000052358"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 12..25
FT /note="Name=A/M1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 26..51
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 52..70
FT /note="Name=B/M2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 71..76
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..96
FT /note="Helical; Name=C/M3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 97..109
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 110..130
FT /note="Helical; Name=D/M4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 131..136
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..157
FT /note="Helical; Name=E/M5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 158..177
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..199
FT /note="Helical; Name=F/M5A"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..207
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 208..229
FT /note="Helical; Name=G/M5B"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..249
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..271
FT /note="Helical; Name=H/M6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..287
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..306
FT /note="Helical; Name=I/M7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 307..337
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..359
FT /note="Helical; Name=J/M8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 360..366
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 367..387
FT /note="Helical; Name=K/M9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 388..402
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 403..423
FT /note="Name=L"
FT /evidence="ECO:0000255"
FT TOPO_DOM 424..432
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 433..453
FT /note="Helical; Name=M/M10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 454..831
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 588..665
FT /note="Interaction with PDZD3"
FT /evidence="ECO:0000250"
FT REGION 808..831
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 552
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9933588,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 560
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 590
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G3X939"
FT MOD_RES 605
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9933588"
FT MOD_RES 661
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000250|UniProtKB:P26432"
FT MOD_RES 807
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 810
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G3X939"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 831 AA; 93105 MW; 77A4BF10DFF99E3F CRC64;
MWHPALGPGW KPLLALAVAV TSLRGVRGIE EEPNSGGSFQ IVTFKWHHVQ DPYIIALWIL
VASLAKIVFH LSHKVTSVVP ESALLIVLGL VLGGIVWAAD HIASFTLTPT LFFFYLLPPI
VLDAGYFMPN RLFFGNLGTI LLYAVIGTIW NAATTGLSLY GVFLSGLMGE LKIGLLDFLL
FGSLIAAVDP VAVLAVFEEV HVNEVLFIIV FGESLLNDAV TVVLYNVFES FVTLGGDAVT
GVDCVKGIVS FFVVSLGGTL VGVIFAFLLS LVTRFTKHVR IIEPGFVFVI SYLSYLTSEM
LSLSAILAIT FCGICCQKYV KANISEQSAT TVRYTMKMLA SGAETIIFMF LGISAVDPVI
WTWNTAFVLL TLVFISVYRA IGVVLQTWIL NRYRMVQLET IDQVVMSYGG LRGAVAYALV
VLLDEKKVKE KNLFVSTTLI VVFFTVIFQG LTIKPLVQWL KVKRSEQREP KLNEKLHGRA
FDHILSAIED ISGQIGHNYL RDKWSNFDRK FLSKVLMRRS AQKSRDRILN VFHELNLKDA
ISYVAEGERR GSLAFIRSPS TDNMVNVDFS TPRPSTVEAS VSYFLRENVS AVCLDMQSLE
QRRRSIRDTE DMVTHHTLQQ YLYKPRQEYK HLYSRHELTP NEDEKQDKEI FHRTMRKRLE
SFKSAKLGIN QNKKAAKLYK RERAQKRRNS SIPNGKLPME NLAHNFTIKE KDLELSEPEE
ATNYEEISGG IEFLASVTKD VASDSGAGID NPVFSPDEDL DPSILSRVPP WLSPGETVVP
SQRARVQIPN SPSNFRRLTP FRLSNKSVDS FLQADGPEEQ LQPASPESTH M
