ID   SL9A2_RAT               Reviewed;         813 AA.
AC   P48763; Q16434;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   27-MAR-2024, entry version 164.
DE   RecName: Full=Sodium/hydrogen exchanger 2;
DE   AltName: Full=H7;
DE   AltName: Full=Na(+)/H(+) exchanger 2;
DE            Short=NHE-2;
DE   AltName: Full=Solute carrier family 9 member 2;
GN   Name=Slc9a2; Synonyms=Nhe2;
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] (ISOFORM LONG), AND TISSUE SPECIFICITY.
RC   TISSUE=Stomach;
RX   PubMed=7685026; DOI=10.1016/s0021-9258(19)50288-5;
RA   Wang Z., Orlowski J., Shull G.E.;
RT   "Primary structure and functional expression of a novel gastrointestinal
RT   isoform of the rat Na/H exchanger.";
RL   J. Biol. Chem. 268:11925-11928(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC   STRAIN=Sprague-Dawley; TISSUE=Small intestine;
RX   PubMed=7683411; DOI=10.1073/pnas.90.9.3938;
RA   Collins J.F., Honda T., Knobel S., Bulus N.M., Conary J., Dubois R.,
RA   Ghishan F.K.;
RT   "Molecular cloning, sequencing, tissue distribution, and functional
RT   expression of a Na+/H+ exchanger (NHE-2).";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:3938-3942(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC   TISSUE=Liver;
RX   PubMed=8595899; DOI=10.1006/geno.1995.0004;
RA   Ghishan F.K., Knobel S.M., Summar M.;
RT   "Molecular cloning, sequencing, chromosomal localization, and tissue
RT   distribution of the human Na+/H+ exchanger (SLC9A2).";
RL   Genomics 30:25-30(1995).
RN   [4]
RP   BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, AND TRANSPORTER ACTIVITY.
RX   PubMed=8244988; DOI=10.1016/s0021-9258(19)74423-8;
RA   Levine S.A., Montrose M.H., Tse C.M., Donowitz M.;
RT   "Kinetics and regulation of three cloned mammalian Na+/H+ exchangers stably
RT   expressed in a fibroblast cell line.";
RL   J. Biol. Chem. 268:25527-25535(1993).
RN   [5]
RP   FUNCTION, AND TRANSPORTER ACTIVITY.
RX   PubMed=8244989; DOI=10.1016/s0021-9258(19)74424-x;
RA   Yu F.H., Shull G.E., Orlowski J.;
RT   "Functional properties of the rat Na/H exchanger NHE-2 isoform expressed in
RT   Na/H exchanger-deficient Chinese hamster ovary cells.";
RL   J. Biol. Chem. 268:25536-25541(1993).
RN   [6]
RP   FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP   REGULATION.
RX   PubMed=10678742; DOI=10.1007/s004249900195;
RA   Kobayashi Y., Pang T., Iwamoto T., Wakabayashi S., Shigekawa M.;
RT   "Lithium activates mammalian Na+/H+ exchangers: isoform specificity and
RT   inhibition by genistein.";
RL   Pflugers Arch. 439:455-462(2000).
RN   [7]
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   [8]
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: Plasma membrane Na(+)/H(+) antiporter. Mediates the
CC       electroneutral exchange of intracellular H(+) ions for extracellular
CC       Na(+) (PubMed:10678742, PubMed:8244988, PubMed:8244989). Major apical
CC       Na(+)/H(+) exchanger in the base of the colonic crypt. Controls in the
CC       colonic crypt intracellular pH (pHi) to direct colonic epithelial cell
CC       differentiation into the absorptive enterocyte lineage at the expense
CC       of the secretory lineage (By similarity).
CC       {ECO:0000250|UniProtKB:Q3ZAS0, ECO:0000269|PubMed:10678742,
CC       ECO:0000269|PubMed:8244988, ECO:0000269|PubMed:8244989}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+)(out) + Na(+)(in) = H(+)(in) + Na(+)(out);
CC         Xref=Rhea:RHEA:29419, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:10678742, ECO:0000269|PubMed:8244988,
CC         ECO:0000269|PubMed:8244989};
CC   -!- ACTIVITY REGULATION: Li(+) activates Na(+)/H(+) exchanger.
CC       {ECO:0000269|PubMed:10678742}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=50 mM for mM for Na(+) {ECO:0000269|PubMed:8244988};
CC         KM=27.5 mM for Na(+) {ECO:0000269|PubMed:10678742};
CC   -!- SUBUNIT: Interacts with CHP1 and CHP2. {ECO:0000269|PubMed:12576672}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000250|UniProtKB:Q9UBY0}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Localizes to the brush-border membrane throughout
CC       the intestinal tract. {ECO:0000269|PubMed:7685026}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Long;
CC         IsoId=P48763-1; Sequence=Displayed;
CC       Name=Short;
CC         IsoId=P48763-2; Sequence=VSP_003394;
CC   -!- TISSUE SPECIFICITY: Predominantly in small intestine, colon, and
CC       stomach, with much lower levels in skeletal muscle, kidney, brain,
CC       testis, uterus, heart and lung. {ECO:0000269|PubMed:7685026}.
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}.
CC   -!- CAUTION: PubMed:8595899 sequence was originally thought to originate
CC       from human. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; L11236; AAA72350.1; -; mRNA.
DR   EMBL; L11004; AAA75406.1; -; mRNA.
DR   EMBL; S81591; AAB36180.1; -; mRNA.
DR   PIR; A46748; A46748.
DR   PIR; A57644; A57644.
DR   RefSeq; NP_001106806.1; NM_001113335.1. [P48763-1]
DR   RefSeq; NP_036785.2; NM_012653.2. [P48763-2]
DR   AlphaFoldDB; P48763; -.
DR   SMR; P48763; -.
DR   IntAct; P48763; 2.
DR   STRING; 10116.ENSRNOP00000021270; -.
DR   ChEMBL; CHEMBL3886122; -.
DR   GlyCosmos; P48763; 1 site, No reported glycans.
DR   GlyGen; P48763; 1 site.
DR   iPTMnet; P48763; -.
DR   PhosphoSitePlus; P48763; -.
DR   PaxDb; 10116-ENSRNOP00000021270; -.
DR   Ensembl; ENSRNOT00000021270.7; ENSRNOP00000021270.4; ENSRNOG00000015567.8. [P48763-1]
DR   Ensembl; ENSRNOT00055033870; ENSRNOP00055027509; ENSRNOG00055019822. [P48763-1]
DR   Ensembl; ENSRNOT00060032939; ENSRNOP00060026936; ENSRNOG00060019047. [P48763-1]
DR   Ensembl; ENSRNOT00065051703; ENSRNOP00065042557; ENSRNOG00065029915. [P48763-1]
DR   GeneID; 24783; -.
DR   KEGG; rno:24783; -.
DR   UCSC; RGD:3719; rat. [P48763-1]
DR   AGR; RGD:3719; -.
DR   CTD; 6549; -.
DR   RGD; 3719; Slc9a2.
DR   eggNOG; KOG1966; Eukaryota.
DR   GeneTree; ENSGT00940000156807; -.
DR   HOGENOM; CLU_005912_4_3_1; -.
DR   InParanoid; P48763; -.
DR   OMA; INMFRTI; -.
DR   OrthoDB; 1065060at2759; -.
DR   PhylomeDB; P48763; -.
DR   TreeFam; TF317212; -.
DR   Reactome; R-RNO-425986; Sodium/Proton exchangers.
DR   PRO; PR:P48763; -.
DR   Proteomes; UP000002494; Chromosome 9.
DR   Bgee; ENSRNOG00000015567; Expressed in jejunum and 15 other cell types or tissues.
DR   GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0015386; F:potassium:proton antiporter activity; IBA:GO_Central.
DR   GO; GO:0015385; F:sodium:proton antiporter activity; IDA:UniProtKB.
DR   GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0008104; P:protein localization; ISO:RGD.
DR   GO; GO:0051453; P:regulation of intracellular pH; ISO:RGD.
DR   GO; GO:0006885; P:regulation of pH; ISO:RGD.
DR   GO; GO:0098719; P:sodium ion import across plasma membrane; IBA:GO_Central.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB.
DR   GO; GO:0006814; P:sodium ion transport; ISO:RGD.
DR   Gene3D; 6.10.140.1330; -; 1.
DR   Gene3D; 6.10.250.1040; -; 1.
DR   Gene3D; 6.10.250.2020; -; 1.
DR   InterPro; IPR006153; Cation/H_exchanger.
DR   InterPro; IPR018422; Cation/H_exchanger_CPA1.
DR   InterPro; IPR004709; NaH_exchanger.
DR   InterPro; IPR001953; NHE-2/4.
DR   InterPro; IPR032103; NHE_CaM-bd.
DR   NCBIfam; TIGR00840; b_cpa1; 1.
DR   PANTHER; PTHR10110; SODIUM/HYDROGEN EXCHANGER; 1.
DR   PANTHER; PTHR10110:SF89; SODIUM_HYDROGEN EXCHANGER 2; 1.
DR   Pfam; PF00999; Na_H_Exchanger; 1.
DR   Pfam; PF16644; NEXCaM_BD; 1.
DR   PRINTS; PR01084; NAHEXCHNGR.
DR   PRINTS; PR01086; NAHEXCHNGR2.
DR   Genevisible; P48763; RN.
PE   1: Evidence at protein level;
KW   Alternative splicing; Antiport; Cell membrane; Glycoprotein; Ion transport;
KW   Membrane; Reference proteome; Sodium; Sodium transport; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..813
FT                   /note="Sodium/hydrogen exchanger 2"
FT                   /id="PRO_0000052354"
FT   TRANSMEM        108..128
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        139..159
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        170..190
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        210..230
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        238..258
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        279..299
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        309..329
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        362..382
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        393..413
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        431..451
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        460..480
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          649..709
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          736..813
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        687..704
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        751..765
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        771..786
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        798..813
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        351
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..116
FT                   /note="Missing (in isoform Short)"
FT                   /evidence="ECO:0000303|PubMed:7683411,
FT                   ECO:0000303|PubMed:8595899"
FT                   /id="VSP_003394"
FT   CONFLICT        504
FT                   /note="H -> HW (in Ref. 3; AAB36180)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        610..616
FT                   /note="LYQIRQR -> SLSNPPA (in Ref. 3; AAB36180)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        742
FT                   /note="A -> P (in Ref. 3; AAB36180)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        786
FT                   /note="V -> G (in Ref. 2; AAA75406)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   813 AA;  91403 MW;  29727267D7085845 CRC64;
     MGPSGTAHRM RAPLSWLLLL LLSLQVAVPA GALAETLLDA PGARGASSNP PSPASVVAPG
     TTPFEESRLP VFTLDYPHVQ IPFEITLWIL LASLAKIGFH LYHKLPTIVP ESCLLIMVGL
     LLGGIIFGVD EKSPPAMKTD VFFLYLLPPI VLDAGYFMPT RPFFENLGTI FWYAVVGTLW
     NSIGIGLSLF GICQIEAFGL SDITLLQNLL FGSLISAVDP VAVLAVFENI HVNEQLYILV
     FGESLLNDAV TVVLYNLFKS FCQMKTIQTV DVFAGIANFF VVGIGGVLIG ILLGFIAAFT
     TRFTHNIRVI EPLFVFLYSY LSYITAEMFH LSGIMAITAC AMTMNKYVEE NVSQKSYTTI
     KYFMKMLSSV SETLIFIFMG VSTVGKNHEW NWAFVCFTLA FCLIWRALGV FVLTQVINWF
     RTIPLTFKDQ FIIAYGGLRG AICFALVFLL PATVFPRKKL FITAAIVVIF FTVFILGITI
     RPLVEFLDVK RSNKKQQAVS EEIHCRFFDH VKTGIEDVCG HWGHNFWRDK FKKFDDKYLR
     KLLIRENQPK SSIVSLYKKL EIKHAIEMAE TGMISTVPSF ASLNDCREEK IRKLTPGEMD
     EIREILSRNL YQIRQRTLSY NRHNLTADTS ERQAKEILIR RRHSLRESLR KDNSLNRERR
     ASTSTSRYLS LPKNTKLPEK LQKKNKVSNA DGNSSDSDMD GTTVLNLQPR ARRFLPDQFS
     KKASPAYKME WKNEVDVGSA RAPPSVTPAP RSKEGGTQTP GVLRQPLLSK DQRFGRGRED
     SLTEDVPPKP PPRLVRRASE PGNRKGRLGN EKP
//