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Sodium/hydrogen exchanger 3 (Na( )/H( ) exchanger 3) (NHE-3) (Solute carrier family 9 member 3)

 SL9A3_RABIT             Reviewed;         832 AA.
P26432;
01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
01-AUG-1992, sequence version 1.
23-MAY-2018, entry version 125.
RecName: Full=Sodium/hydrogen exchanger 3;
AltName: Full=Na(+)/H(+) exchanger 3;
Short=NHE-3;
AltName: Full=Solute carrier family 9 member 3;
Name=SLC9A3; Synonyms=NHE3;
Oryctolagus cuniculus (Rabbit).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae;
Oryctolagus.
NCBI_TaxID=9986;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=New Zealand white; TISSUE=Ileal villus, and Kidney cortex;
PubMed=1374392;
Tse C.-M., Brant S.R., Walker S.S., Pouyssegur J., Donowitz M.;
"Cloning and sequencing of a rabbit cDNA encoding an intestinal and
kidney-specific Na+/H+ exchanger isoform (NHE-3).";
J. Biol. Chem. 267:9340-9346(1992).
[2]
INTERACTION WITH SLC9A3R1 AND SLC9A3R2.
PubMed=9096337; DOI=10.1073/pnas.94.7.3010;
Yun C.H.C., Oh S., Zizak M., Steplock D., Tsao S., Tse C.-M.,
Weinman E.J., Donowitz M.;
"cAMP-mediated inhibition of the epithelial brush border Na+/H+
exchanger, NHE3, requires an associated regulatory protein.";
Proc. Natl. Acad. Sci. U.S.A. 94:3010-3015(1997).
[3]
PHOSPHORYLATION AT SER-663 BY SGK1, AND SUBCELLULAR LOCATION.
PubMed=15888551; DOI=10.1152/ajpcell.00597.2004;
Wang D., Sun H., Lang F., Yun C.C.;
"Activation of NHE3 by dexamethasone requires phosphorylation of NHE3
at Ser663 by SGK1.";
Am. J. Physiol. 289:C802-C810(2005).
[4]
INTERACTION WITH PDZK1.
PubMed=16141316; DOI=10.1073/pnas.0506578102;
Thomson R.B., Wang T., Thomson B.R., Tarrats L., Girardi A.,
Mentone S., Soleimani M., Kocher O., Aronson P.S.;
"Role of PDZK1 in membrane expression of renal brush border ion
exchangers.";
Proc. Natl. Acad. Sci. U.S.A. 102:13331-13336(2005).
[5]
INTERACTION WITH PDZD3.
PubMed=19088451; DOI=10.1159/000185553;
Zachos N.C., Hodson C., Kovbasnjuk O., Li X., Thelin W.R., Cha B.,
Milgram S., Donowitz M.;
"Elevated intracellular calcium stimulates NHE3 activity by an IKEPP
(NHERF4) dependent mechanism.";
Cell. Physiol. Biochem. 22:693-704(2008).
[6]
INTERACTION WITH AHCYL1, AND FUNCTION.
PubMed=18829453; DOI=10.1074/jbc.M805534200;
He P., Zhang H., Yun C.C.;
"IRBIT, inositol 1,4,5-triphosphate (IP3) receptor-binding protein
released with IP3, binds Na+/H+ exchanger NHE3 and activates NHE3
activity in response to calcium.";
J. Biol. Chem. 283:33544-33553(2008).
-!- FUNCTION: Involved in pH regulation to eliminate acids generated
by active metabolism or to counter adverse environmental
conditions. Major proton extruding system driven by the inward
sodium ion chemical gradient. Plays an important role in signal
transduction. {ECO:0000250|UniProtKB:P48764}.
-!- SUBUNIT: Interacts with CHP1, CHP2 and SHANK2 (By similarity).
Interacts with PDZD3 and interactions decrease in response to
elevated calcium ion levels. Binds SLC9A3R1 and SLC9A3R2.
Interacts with PDZK1 (via C-terminal PDZ domain). Interacts with
AHCYL1; the interaction is required for SLC9A3 activity
(PubMed:18829453). {ECO:0000250|UniProtKB:P26433,
ECO:0000250|UniProtKB:P48764, ECO:0000250|UniProtKB:Q28362,
ECO:0000269|PubMed:16141316, ECO:0000269|PubMed:18829453,
ECO:0000269|PubMed:19088451, ECO:0000269|PubMed:9096337}.
-!- SUBCELLULAR LOCATION: Apical cell membrane
{ECO:0000269|PubMed:15888551}; Multi-pass membrane protein
{ECO:0000269|PubMed:15888551}. Note=In intestinal epithelial
cells, localizes to the ileal brush border (By similarity).
Phosphorylation at Ser-663 by SGK1 is associated with increased
abundance at the cell membrane. Angiotensin-2 enhances apical
expression (By similarity). {ECO:0000250|UniProtKB:P48764,
ECO:0000250|UniProtKB:Q28362}.
-!- TISSUE SPECIFICITY: Intestinal and kidney specific. Most abundant
in kidney cortex, followed equally by ileum and ascending colon,
then kidney medulla and jejunum. Is absent from duodenum and
descending colon.
-!- PTM: Phosphorylated by PKA, which inhibits activity (By
similarity). Phosphorylation at Ser-663 by SGK1 is associated with
increased abundance at the cell membrane.
{ECO:0000250|UniProtKB:P26433, ECO:0000269|PubMed:15888551}.
-!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1
(CPA1) transporter (TC 2.A.36) family. {ECO:0000305}.
-!- CAUTION: The number, localization and denomination of hydrophobic
domains in the Na(+)/H(+) exchangers vary among authors.
{ECO:0000305}.
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EMBL; M87007; AAA31420.1; -; mRNA.
PIR; A40205; A40205.
RefSeq; NP_001076166.1; NM_001082697.1.
UniGene; Ocu.1936; -.
ProteinModelPortal; P26432; -.
SMR; P26432; -.
STRING; 9986.ENSOCUP00000024686; -.
ChEMBL; CHEMBL2096985; -.
iPTMnet; P26432; -.
PRIDE; P26432; -.
GeneID; 100009430; -.
KEGG; ocu:100009430; -.
CTD; 6550; -.
eggNOG; KOG1966; Eukaryota.
eggNOG; COG0025; LUCA.
HOGENOM; HOG000247044; -.
HOVERGEN; HBG052615; -.
InParanoid; P26432; -.
KO; K12040; -.
PRO; PR:P26432; -.
Proteomes; UP000001811; Unplaced.
GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
GO; GO:0005903; C:brush border; IDA:UniProtKB.
GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
GO; GO:0009986; C:cell surface; IDA:UniProtKB.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
GO; GO:0015385; F:sodium:proton antiporter activity; IDA:UniProtKB.
GO; GO:0006885; P:regulation of pH; IEA:InterPro.
GO; GO:0098719; P:sodium ion import across plasma membrane; ISS:UniProtKB.
InterPro; IPR006153; Cation/H_exchanger.
InterPro; IPR018422; Cation/H_exchanger_CPA1.
InterPro; IPR018410; Na/H_exchanger_3/5.
InterPro; IPR004709; NaH_exchanger.
PANTHER; PTHR10110; PTHR10110; 1.
Pfam; PF00999; Na_H_Exchanger; 1.
PRINTS; PR01084; NAHEXCHNGR.
PRINTS; PR01087; NAHEXCHNGR3.
TIGRFAMs; TIGR00840; b_cpa1; 1.
1: Evidence at protein level;
Antiport; Cell membrane; Complete proteome; Glycoprotein;
Ion transport; Membrane; Phosphoprotein; Polymorphism;
Reference proteome; Sodium; Sodium transport; Transmembrane;
Transmembrane helix; Transport.
CHAIN 1 832 Sodium/hydrogen exchanger 3.
/FTId=PRO_0000052357.
TOPO_DOM 1 11 Cytoplasmic. {ECO:0000255}.
TRANSMEM 12 27 Helical; Name=M1. {ECO:0000255}.
TOPO_DOM 28 59 Extracellular. {ECO:0000255}.
TRANSMEM 60 79 Helical; Name=M2. {ECO:0000255}.
TOPO_DOM 80 81 Cytoplasmic. {ECO:0000255}.
TRANSMEM 82 101 Helical; Name=M3. {ECO:0000255}.
TOPO_DOM 102 110 Extracellular. {ECO:0000255}.
TRANSMEM 111 130 Helical; Name=M4. {ECO:0000255}.
TOPO_DOM 131 134 Cytoplasmic. {ECO:0000255}.
TRANSMEM 135 154 Helical; Name=M5. {ECO:0000255}.
TOPO_DOM 155 180 Extracellular. {ECO:0000255}.
TRANSMEM 181 200 Helical; Name=M5A. {ECO:0000255}.
TOPO_DOM 201 209 Cytoplasmic. {ECO:0000255}.
TRANSMEM 210 229 Helical; Name=M5B. {ECO:0000255}.
TOPO_DOM 230 249 Extracellular. {ECO:0000255}.
TRANSMEM 250 269 Helical; Name=M6. {ECO:0000255}.
TOPO_DOM 270 298 Cytoplasmic. {ECO:0000255}.
TRANSMEM 299 319 Helical; Name=M7. {ECO:0000255}.
TOPO_DOM 320 339 Extracellular. {ECO:0000255}.
TRANSMEM 340 359 Helical; Name=M8. {ECO:0000255}.
TOPO_DOM 360 366 Cytoplasmic. {ECO:0000255}.
TRANSMEM 367 385 Helical; Name=M9. {ECO:0000255}.
TOPO_DOM 386 435 Extracellular. {ECO:0000255}.
TRANSMEM 436 455 Helical; Name=M10. {ECO:0000255}.
TOPO_DOM 456 832 Cytoplasmic. {ECO:0000255}.
REGION 590 667 Interaction with PDZD3.
{ECO:0000269|PubMed:19088451}.
REGION 591 696 Interaction with AHCYL1.
{ECO:0000269|PubMed:18829453}.
MOD_RES 554 554 Phosphoserine.
{ECO:0000250|UniProtKB:P26433}.
MOD_RES 562 562 Phosphoserine.
{ECO:0000250|UniProtKB:P26433}.
MOD_RES 592 592 Phosphoserine.
{ECO:0000250|UniProtKB:G3X939}.
MOD_RES 607 607 Phosphoserine.
{ECO:0000250|UniProtKB:P26433}.
MOD_RES 663 663 Phosphoserine; by SGK1.
{ECO:0000269|PubMed:15888551}.
MOD_RES 813 813 Phosphoserine.
{ECO:0000250|UniProtKB:G3X939}.
MOD_RES 816 816 Phosphoserine.
{ECO:0000250|UniProtKB:G3X939}.
CARBOHYD 325 325 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
VARIANT 144 144 L -> P.
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


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