SL9A3_DIDVI
ID SL9A3_DIDVI Reviewed; 839 AA.
AC Q28362;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 25-MAY-2022, entry version 106.
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 Didelphis virginiana (North American opossum) (Didelphis marsupialis
OS virginiana).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Metatheria; Didelphimorphia; Didelphidae; Didelphis.
OX NCBI_TaxID=9267;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7631739; DOI=10.1152/ajpcell.1995.269.1.c126;
RA Amemiya M., Yamaji Y., Cano A., Moe O.W., Alpern R.J.;
RT "Acid incubation increases NHE-3 mRNA abundance in OKP cells.";
RL Am. J. Physiol. 269:C126-C133(1995).
RN [2]
RP PHOSPHORYLATION AT SER-669 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 [3]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH AHCYL1.
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).
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 CHP1, CHP2 and
CC SHANK2. Interacts with PDZD3 and interactions decrease in response to
CC elevated calcium ion levels. Interacts with PDZK1 (via C-terminal PDZ
CC domain) (By similarity). Interacts with AHCYL1; the interaction is
CC required for SLC9A3 activity (PubMed:20584908).
CC {ECO:0000250|UniProtKB:P26432, ECO:0000250|UniProtKB:P26433,
CC ECO:0000250|UniProtKB:P48764, ECO:0000269|PubMed:20584908}.
CC -!- INTERACTION:
CC Q28362; Q6P0Q8: MAST2; Xeno; NbExp=2; IntAct=EBI-7817027, EBI-493777;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:15888551, ECO:0000269|PubMed:20584908}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:15888551}. Note=In intestinal
CC epithelial cells, localizes to the ileal brush border (By similarity).
CC Phosphorylation at Ser-669 by SGK1 is associated with increased
CC abundance at the cell membrane. Angiotensin-2 enhances apical
CC expression (PubMed:20584908). {ECO:0000250|UniProtKB:Q9Y6R1,
CC ECO:0000269|PubMed:20584908}.
CC -!- PTM: Phosphorylated by PKA, which inhibits activity (By similarity).
CC Phosphorylation at Ser-669 by SGK1 is associated with increased
CC abundance at the cell membrane. {ECO:0000250|UniProtKB:P26432,
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; L42522; AAA98816.1; -; mRNA.
DR AlphaFoldDB; Q28362; -.
DR SMR; Q28362; -.
DR IntAct; Q28362; 1.
DR MINT; Q28362; -.
DR PRIDE; Q28362; -.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISS: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; ISS: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; Sodium; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..839
FT /note="Sodium/hydrogen exchanger 3"
FT /id="PRO_0000052355"
FT TOPO_DOM 1..13
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 14..31
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..65
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 66..85
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..107
FT /note="Helical; Name=M3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..113
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..133
FT /note="Helical; Name=M4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 134..150
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 151..170
FT /note="Helical; Name=M5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 171..186
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..206
FT /note="Helical; Name=M5A"
FT /evidence="ECO:0000255"
FT TOPO_DOM 207..215
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..235
FT /note="Helical; Name=M5B"
FT /evidence="ECO:0000255"
FT TOPO_DOM 236..255
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..276
FT /note="Helical; Name=M6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..299
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 300..319
FT /note="Helical; Name=M7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..347
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 348..366
FT /note="Helical; Name=M8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 367..372
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 373..392
FT /note="Helical; Name=M9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 393..442
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 443..462
FT /note="Helical; Name=M10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 463..839
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 596..673
FT /note="Interaction with PDZD3"
FT /evidence="ECO:0000250"
FT REGION 688..710
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 560
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26433"
FT MOD_RES 568
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26433"
FT MOD_RES 598
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G3X939"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26433"
FT MOD_RES 669
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000250|UniProtKB:P26432"
FT MOD_RES 815
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G3X939"
FT MOD_RES 818
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G3X939"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 839 AA; 94766 MW; F6F9EF778D5DBBB2 CRC64;
MPLGVRGTRR EFRFPVWGLL LLALWMLPRA LGVEEIPGPD SHEKQGFQIV TFKWHHVQDP
YIIALWILVA SLAKIVFHLS HKVTSVVPES ALLIVLGLIL GGIVWAADHI ASFTLTPTVF
FFYLLPPIVL DAGYFMPNRL FFGNLGTILL YAVIGTVWNA ATTGLSLYGV YLSGIMGDLS
IGLLDFLLFG SLIAAVDPVA VLAVFEEVHV NDVLFIIVFG ESLLNDAVTV VLYNVFDSFV
SLGADKVTGV DCVKGIVSFF VVSLGGTLIG IIFAFLLSLV TRFTKHVRII EPGFVFIISY
LSYLTSEMLS LSAILAITFC GICCQKYVKA NISEQSATTV RYTMKMLASG AETIIFMFLG
ISAVDPAIWT WNTAFILLTL VFISVYRAIG VVLQTWLLNK YRMVQLEIID QVVMSYGGLR
GAVAYALVVL LDEKKVKEKN LFVSTTIIVV FFTVIFQGLT IKPLVQWLKV KKSEHREPKL
NEKLHGRAFD HILSAIEDIS GQIGHNYLRD KWSNFDRKVL SKLLMRRSAQ KSRDRILNVF
HELNLKDAIS YVAEGERRGS LAFIRSPSTD NIVNVDFSTP RPSTVEASVS YLLRENVSTV
CLDMQALEQR RKSIRDTEDT VTHHTLQQYL YKPRQEYKHL YSRHELTSNE DEKQDKEIFH
RTMRKRLESF KSTKLGINQT KKTAKLYKRE RGQKRRNSSI PNGKIPMESP TRDFTFKEKE
LEFSDPEETN EYEAEEMSGG IEFLANVTQD TATDSTTGID NPVFSPEEDQ SIFTKVPPWL
SPEETVVPSQ RARVQIPYSP SNFRRLTPIR LSTKSVDSFL LADSPEERPR SFLPESTHM
