SL9A3_RABIT
ID SL9A3_RABIT Reviewed; 832 AA.
AC P26432;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 25-MAY-2022, entry version 135.
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 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, and Kidney cortex;
RX PubMed=1374392; DOI=10.1016/s0021-9258(19)50429-x;
RA Tse C.-M., Brant S.R., Walker S.S., Pouyssegur J., Donowitz M.;
RT "Cloning and sequencing of a rabbit cDNA encoding an intestinal and kidney-
RT specific Na+/H+ exchanger isoform (NHE-3).";
RL J. Biol. Chem. 267:9340-9346(1992).
RN [2]
RP INTERACTION WITH SLC9A3R1 AND SLC9A3R2.
RX PubMed=9096337; DOI=10.1073/pnas.94.7.3010;
RA Yun C.H.C., Oh S., Zizak M., Steplock D., Tsao S., Tse C.-M., Weinman E.J.,
RA Donowitz M.;
RT "cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger,
RT NHE3, requires an associated regulatory protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:3010-3015(1997).
RN [3]
RP PHOSPHORYLATION AT SER-663 BY SGK1, AND SUBCELLULAR LOCATION.
RX PubMed=15888551; DOI=10.1152/ajpcell.00597.2004;
RA Wang D., Sun H., Lang F., Yun C.C.;
RT "Activation of NHE3 by dexamethasone requires phosphorylation of NHE3 at
RT Ser663 by SGK1.";
RL Am. J. Physiol. 289:C802-C810(2005).
RN [4]
RP INTERACTION WITH PDZK1.
RX PubMed=16141316; DOI=10.1073/pnas.0506578102;
RA Thomson R.B., Wang T., Thomson B.R., Tarrats L., Girardi A., Mentone S.,
RA Soleimani M., Kocher O., Aronson P.S.;
RT "Role of PDZK1 in membrane expression of renal brush border ion
RT exchangers.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:13331-13336(2005).
RN [5]
RP INTERACTION WITH PDZD3.
RX PubMed=19088451; DOI=10.1159/000185553;
RA Zachos N.C., Hodson C., Kovbasnjuk O., Li X., Thelin W.R., Cha B.,
RA Milgram S., Donowitz M.;
RT "Elevated intracellular calcium stimulates NHE3 activity by an IKEPP
RT (NHERF4) dependent mechanism.";
RL Cell. Physiol. Biochem. 22:693-704(2008).
RN [6]
RP INTERACTION WITH AHCYL1, AND FUNCTION.
RX PubMed=18829453; DOI=10.1074/jbc.m805534200;
RA He P., Zhang H., Yun C.C.;
RT "IRBIT, inositol 1,4,5-triphosphate (IP3) receptor-binding protein released
RT with IP3, binds Na+/H+ exchanger NHE3 and activates NHE3 activity in
RT response to calcium.";
RL J. Biol. Chem. 283:33544-33553(2008).
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: Interacts with CHP1, CHP2 and SHANK2 (By similarity).
CC Interacts with PDZD3 and interactions decrease in response to elevated
CC calcium ion levels. Binds SLC9A3R1 and SLC9A3R2. Interacts with PDZK1
CC (via C-terminal PDZ domain). Interacts with AHCYL1; the interaction is
CC required for SLC9A3 activity (PubMed:18829453).
CC {ECO:0000250|UniProtKB:P26433, ECO:0000250|UniProtKB:P48764,
CC ECO:0000250|UniProtKB:Q28362, ECO:0000269|PubMed:16141316,
CC ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:19088451,
CC ECO:0000269|PubMed:9096337}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:15888551}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15888551}. Note=In intestinal epithelial cells,
CC localizes to the ileal brush border (By similarity). Phosphorylation at
CC Ser-663 by SGK1 is associated with increased abundance at the cell
CC membrane. Angiotensin-2 enhances apical expression (By similarity).
CC {ECO:0000250|UniProtKB:P48764, ECO:0000250|UniProtKB:Q28362}.
CC -!- TISSUE SPECIFICITY: Intestinal and kidney specific. Most abundant in
CC kidney cortex, followed equally by ileum and ascending colon, then
CC kidney medulla and jejunum. Is absent from duodenum and descending
CC colon.
CC -!- PTM: Phosphorylated by PKA, which inhibits activity (By similarity).
CC Phosphorylation at Ser-663 by SGK1 is associated with increased
CC abundance at the cell membrane. {ECO:0000250|UniProtKB:P26433,
CC ECO:0000269|PubMed:15888551}.
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; M87007; AAA31420.1; -; mRNA.
DR PIR; A40205; A40205.
DR RefSeq; NP_001076166.1; NM_001082697.1.
DR AlphaFoldDB; P26432; -.
DR SMR; P26432; -.
DR STRING; 9986.ENSOCUP00000024686; -.
DR BindingDB; P26432; -.
DR ChEMBL; CHEMBL2096985; -.
DR iPTMnet; P26432; -.
DR PRIDE; P26432; -.
DR GeneID; 100009430; -.
DR KEGG; ocu:100009430; -.
DR CTD; 6550; -.
DR eggNOG; KOG1966; Eukaryota.
DR InParanoid; P26432; -.
DR OrthoDB; 389547at2759; -.
DR PRO; PR:P26432; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005903; C:brush border; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
DR GO; GO:0015385; F:sodium:proton antiporter activity; IDA:UniProtKB.
DR GO; GO:0006885; P:regulation of pH; IEA:InterPro.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; ISS:UniProtKB.
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..832
FT /note="Sodium/hydrogen exchanger 3"
FT /id="PRO_0000052357"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..27
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..59
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..79
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 80..81
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..101
FT /note="Helical; Name=M3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 102..110
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..130
FT /note="Helical; Name=M4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 131..134
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 135..154
FT /note="Helical; Name=M5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 155..180
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..200
FT /note="Helical; Name=M5A"
FT /evidence="ECO:0000255"
FT TOPO_DOM 201..209
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 210..229
FT /note="Helical; Name=M5B"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..249
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..269
FT /note="Helical; Name=M6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..298
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 299..319
FT /note="Helical; Name=M7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..339
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 340..359
FT /note="Helical; Name=M8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 360..366
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 367..385
FT /note="Helical; Name=M9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 386..435
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 436..455
FT /note="Helical; Name=M10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 456..832
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 590..667
FT /note="Interaction with PDZD3"
FT /evidence="ECO:0000269|PubMed:19088451"
FT REGION 591..696
FT /note="Interaction with AHCYL1"
FT /evidence="ECO:0000269|PubMed:18829453"
FT REGION 664..706
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 554
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26433"
FT MOD_RES 562
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26433"
FT MOD_RES 592
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G3X939"
FT MOD_RES 607
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26433"
FT MOD_RES 663
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000269|PubMed:15888551"
FT MOD_RES 813
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G3X939"
FT MOD_RES 816
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G3X939"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 144
FT /note="L -> P"
SQ SEQUENCE 832 AA; 92749 MW; 8C8BB7C296CF8740 CRC64;
MSGRGGCGPC WGLLLALVLA LGALPWTQGA EQEHHDEIQG FQIVTFKWHH VQDPYIIALW
VLVASLAKIV FHLSHKVTSV VPESALLIVL GLVLGGIVLA ADHIASFTLT PTVFFFYLLP
PIVLDAGYFM PNRLFFSNLG SILLYAVVGT VWNAATTGLS LYGVFLSGIM GELKIGLLDF
LLFGSLIAAV DPVAVLAVFE EVHVNEVLFI IVFGESLLND AVTVVLYNVF QSFVTLGGDK
VTGVDCVKGI VSFFVVSLGG TLVGVVFAFL LSLVTRFTKH VRVIEPGFVF IISYLSYLTS
EMLSLSSILA ITFCGICCQK YVKANISEQS ATTVRYTMKM LASGAETIIF MFLGISAVDP
LIWTWNTAFV LLTLLFVSVF RAIGVVLQTW LLNRYRMVQL ELIDQVVMSY GGLRGAVAFA
LVALLDGNKV KEKNLFVSTT IIVVFFTVIF QGLTIKPLVQ WLKVKRSEHR EPKLNEKLHG
RAFDHILSAI EDISGQIGHN YLRDKWANFD RRFLSKLLMR QSAQKSRDRI LNVFHELNLK
DAISYVTEGE RRGSLAFIRS PSTDNMVNVD FSTPRPSTVE ASVSYLLRES ASAVCLDMQS
LEQRRRSVRD AEDVITHHTL QQYLYKPRQE YKHLYSRHVL SPSEDEKQDK EIFHRTMRKR
LESFKSAKLG LGQSKKATKH KRERERAQKR RNSSVPNGKL PLDSPAYGLT LKERELELSD
PEEAPDYYEA EKMSGGIEFL ASVTKDTTSD SPAGIDNPVF SPDEDLAPSL LARVPPWLSP
GEAVVPSQRA RVQIPYSPGN FRRLAPFRLS NKSVDSFLLA EDGAEHPEST HM
