NHX2_CAEEL
ID NHX2_CAEEL Reviewed; 644 AA.
AC Q8T5S1; Q09432;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Na(+)/H(+) exchanger protein 2 {ECO:0000303|PubMed:12021279};
DE AltName: Full=Na(+)/H(+) antiporter nhx-2 {ECO:0000303|PubMed:12021279};
GN Name=nhx-2 {ECO:0000312|EMBL:AAM18102.1, ECO:0000312|WormBase:B0495.4};
GN ORFNames=B0495.4;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAM18102.1}
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=12021279; DOI=10.1074/jbc.m203200200;
RA Nehrke K., Melvin J.E.;
RT "The NHX family of Na+-H+ exchangers in Caenorhabditis elegans.";
RL J. Biol. Chem. 277:29036-29044(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=12939266; DOI=10.1074/jbc.m307351200;
RA Nehrke K.;
RT "A reduction in intestinal cell pHi due to loss of the Caenorhabditis
RT elegans Na+/H+ exchanger NHX-2 increases life span.";
RL J. Biol. Chem. 278:44657-44666(2003).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18291648; DOI=10.1016/j.cub.2008.01.054;
RA Pfeiffer J., Johnson D., Nehrke K.;
RT "Oscillatory transepithelial H(+) flux regulates a rhythmic behavior in C.
RT elegans.";
RL Curr. Biol. 18:297-302(2008).
RN [5] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=19627265; DOI=10.1111/j.1474-9726.2009.00473.x;
RA Park S.K., Tedesco P.M., Johnson T.E.;
RT "Oxidative stress and longevity in Caenorhabditis elegans as mediated by
RT SKN-1.";
RL Aging Cell 8:258-269(2009).
RN [6] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=19621081; DOI=10.1371/journal.pone.0006279;
RA Spanier B., Lasch K., Marsch S., Benner J., Liao W., Hu H., Kienberger H.,
RA Eisenreich W., Daniel H.;
RT "How the intestinal peptide transporter PEPT-1 contributes to an obesity
RT phenotype in Caenorhabditits elegans.";
RL PLoS ONE 4:E6279-E6279(2009).
CC -!- FUNCTION: Na(+)/H(+) antiporter that promotes normal di- or tripeptide
CC transporter function, recovery following the peptide-induced
CC acidification of the intestinal cytoplasm and maintenance of the
CC peptide-dependent intestinal pH homeostasis. Regulator of free fatty
CC acid uptake from the diet together with the dipeptide transporter pept-
CC 1. May play a timekeeper role in defecation cycle but is not necessary
CC for pbo-4-dependent proton release. May play a role in the regulation
CC of lifespan independent of the stress response pathway.
CC {ECO:0000269|PubMed:12939266, ECO:0000269|PubMed:18291648}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:12021279, ECO:0000269|PubMed:12939266}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:12021279,
CC ECO:0000269|PubMed:12939266}; Lumenal side
CC {ECO:0000269|PubMed:12021279, ECO:0000269|PubMed:12939266}.
CC Note=Colocalizes with pept-1 along the apical membrane of the
CC intestinal cells. {ECO:0000269|PubMed:12021279,
CC ECO:0000269|PubMed:12939266}.
CC -!- TISSUE SPECIFICITY: Expressed uniformly in the intestinal epithelial
CC cells. {ECO:0000269|PubMed:12021279, ECO:0000269|PubMed:12939266}.
CC -!- DEVELOPMENTAL STAGE: Biphasic expression pattern with high expression
CC in the L1 and L2 larval stages and gradual decrease through adult
CC stages. {ECO:0000269|PubMed:12021279}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown of the protein causes
CC worms to become extremely lean and transparent. Slower progression
CC through the larval stages, in particular the L1 and L2 stages. Increase
CC in average life span, decreased brood size and loss of fat storage
CC granules in the intestine leading to decreased opacity. Reduced rate of
CC pharyngeal pumping, reduced size of proton pulses inside the cells,
CC increased intracellular acidification, reduced uptake of fatty acids,
CC and doubling of the defecation period. {ECO:0000269|PubMed:12939266,
CC ECO:0000269|PubMed:18291648, ECO:0000269|PubMed:19621081,
CC ECO:0000269|PubMed:19627265}.
CC -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1)
CC transporter (TC 2.A.36) family. {ECO:0000255}.
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DR EMBL; AF497824; AAM18102.1; -; mRNA.
DR EMBL; FO080132; CCD61472.2; -; Genomic_DNA.
DR PIR; H88215; H88215.
DR RefSeq; NP_495614.4; NM_063213.5.
DR AlphaFoldDB; Q8T5S1; -.
DR SMR; Q8T5S1; -.
DR STRING; 6239.B0495.4; -.
DR TCDB; 2.A.36.1.8; the monovalent cation:proton antiporter-1 (cpa1) family.
DR EPD; Q8T5S1; -.
DR PaxDb; Q8T5S1; -.
DR PeptideAtlas; Q8T5S1; -.
DR EnsemblMetazoa; B0495.4.1; B0495.4.1; WBGene00003730.
DR GeneID; 174242; -.
DR KEGG; cel:CELE_B0495.4; -.
DR UCSC; B0495.4; c. elegans.
DR CTD; 174242; -.
DR WormBase; B0495.4; CE48832; WBGene00003730; nhx-2.
DR eggNOG; KOG1966; Eukaryota.
DR GeneTree; ENSGT00970000196622; -.
DR HOGENOM; CLU_005912_4_3_1; -.
DR OMA; LESEVFM; -.
DR OrthoDB; 389547at2759; -.
DR Reactome; R-CEL-2160916; Hyaluronan uptake and degradation.
DR Reactome; R-CEL-425986; Sodium/Proton exchangers.
DR PRO; PR:Q8T5S1; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00003730; Expressed in larva and 3 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IDA:WormBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IMP:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0019915; P:lipid storage; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:2000193; P:positive regulation of fatty acid transport; IMP:WormBase.
DR GO; GO:0040010; P:positive regulation of growth rate; IMP:WormBase.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:WormBase.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0051453; P:regulation of intracellular pH; IBA:GO_Central.
DR GO; GO:0090087; P:regulation of peptide transport; IMP:WormBase.
DR GO; GO:0006885; P:regulation of pH; IMP:WormBase.
DR GO; GO:0043051; P:regulation of pharyngeal pumping; IMP:WormBase.
DR GO; GO:0000003; P:reproduction; IMP:WormBase.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; IBA:GO_Central.
DR InterPro; IPR006153; Cation/H_exchanger.
DR InterPro; IPR018422; Cation/H_exchanger_CPA1.
DR InterPro; IPR004709; NaH_exchanger.
DR PANTHER; PTHR10110; PTHR10110; 1.
DR Pfam; PF00999; Na_H_Exchanger; 1.
DR PRINTS; PR01084; NAHEXCHNGR.
DR TIGRFAMs; TIGR00840; b_cpa1; 1.
PE 2: Evidence at transcript level;
KW Antiport; Cell membrane; Ion transport; Membrane; Reference proteome;
KW Sodium; Sodium transport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..644
FT /note="Na(+)/H(+) exchanger protein 2"
FT /id="PRO_0000424423"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..51
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 52..72
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 73..78
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 79..99
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 100..107
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..128
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 129..137
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 138..158
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 159..173
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 195..201
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..244
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..294
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 316..333
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 334..354
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 355..364
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 365..385
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 386..401
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 402..422
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 423..429
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..450
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 451..644
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 621..644
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 644 AA; 72611 MW; BB32044A0E39F6A8 CRC64;
MSLLRRPWVL VVGLLLIMSY VGAECEEEEK EYPSRYPIAY FEWENVKIPM TICLWLIGAS
IAKIIFNLIP HLNELFPDSA LLIMIGLIIG IIFKLIGVNK NAFFLESEVF MLYLLPPLVF
DAGYFMPARQ FFDNFGSILC FAMIGTSFNI VAIALSLWAI SLTGLFSVET PLMHMLLFGS
VAADVDPVAV IVIFEELKVN EVLFIAVFGE SLLNDGVAVV LYRMFLTFSE IGTENLITSD
YINGGVSFLV VAFGGIGIGL LFAFLTSLVT RFARDEEVKV LNSVFILILP YTCYLCGELF
GLSSIMAIVF CGAAMRQYCR ENVDPDTVKA TESFIKVLSL ASETVIFVFL GLSTVSSNHH
WDTSFIVLTV VFCLIYRTLG VVVMCYFLNK YRLNKYTKVD QFIMAYGGLR GAIAYGLVVA
IPDFIPGKNM FVTSCIIVIY FTVFLQGITL KPIAEFLQVE KKNVHSKNMI EHIYSELIDT
TMAGMEDIAG FKGHHWIRDS WNALNNNYLR PILVNKNNMK EMDKTKLVRK YKHLVDEDAK
KIARGDLNSN MVFTKALIEH TRSRTNTMID GVSSTSKIDF TKHMKENFGV TVYDDHSTVP
MTPTHLFQET TEVEYSVRSE INDNDGFEND GYESDESGSF HERV
