SL9A2_HUMAN
ID SL9A2_HUMAN Reviewed; 812 AA.
AC Q9UBY0; B2RMS2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Sodium/hydrogen exchanger 2;
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Colon;
RX PubMed=10444453; DOI=10.1152/ajpgi.1999.277.2.g383;
RA Malakooti J., Dahdal R.Y., Schmidt L., Layden T.J., Dudeja P.K.,
RA Ramaswamy K.;
RT "Molecular cloning, tissue distribution, and functional expression of the
RT human Na(+)/H(+) exchanger NHE2.";
RL Am. J. Physiol. 277:G383-G390(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-299 AND GLN-806.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
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. Seems to play an important role in colonic sodium absorption.
CC -!- SUBUNIT: Interacts with CHP1 and CHP2. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, colon and kidney.
CC Lower levels in the testis, prostate, ovary, and small intestine.
CC -!- PTM: Phosphorylated (Possible).
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 ---------------------------------------------------------------------------
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; AF073299; AAD41635.1; -; mRNA.
DR EMBL; AC007239; AAF19248.1; -; Genomic_DNA.
DR EMBL; CH471127; EAX01789.1; -; Genomic_DNA.
DR EMBL; BC136377; AAI36378.1; -; mRNA.
DR EMBL; BC136378; AAI36379.1; -; mRNA.
DR CCDS; CCDS2062.1; -.
DR RefSeq; NP_003039.2; NM_003048.5.
DR AlphaFoldDB; Q9UBY0; -.
DR SMR; Q9UBY0; -.
DR BioGRID; 112439; 7.
DR IntAct; Q9UBY0; 3.
DR STRING; 9606.ENSP00000233969; -.
DR BindingDB; Q9UBY0; -.
DR ChEMBL; CHEMBL3133; -.
DR TCDB; 2.A.36.1.17; the monovalent cation:proton antiporter-1 (cpa1) family.
DR GlyGen; Q9UBY0; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UBY0; -.
DR PhosphoSitePlus; Q9UBY0; -.
DR BioMuta; SLC9A2; -.
DR DMDM; 19924293; -.
DR jPOST; Q9UBY0; -.
DR MassIVE; Q9UBY0; -.
DR MaxQB; Q9UBY0; -.
DR PaxDb; Q9UBY0; -.
DR PeptideAtlas; Q9UBY0; -.
DR PRIDE; Q9UBY0; -.
DR ProteomicsDB; 84098; -.
DR Antibodypedia; 32970; 90 antibodies from 21 providers.
DR DNASU; 6549; -.
DR Ensembl; ENST00000233969.3; ENSP00000233969.2; ENSG00000115616.3.
DR GeneID; 6549; -.
DR KEGG; hsa:6549; -.
DR MANE-Select; ENST00000233969.3; ENSP00000233969.2; NM_003048.6; NP_003039.2.
DR UCSC; uc002tca.4; human.
DR CTD; 6549; -.
DR DisGeNET; 6549; -.
DR GeneCards; SLC9A2; -.
DR HGNC; HGNC:11072; SLC9A2.
DR HPA; ENSG00000115616; Tissue enhanced (intestine, stomach).
DR MIM; 600530; gene.
DR neXtProt; NX_Q9UBY0; -.
DR OpenTargets; ENSG00000115616; -.
DR PharmGKB; PA35929; -.
DR VEuPathDB; HostDB:ENSG00000115616; -.
DR eggNOG; KOG1966; Eukaryota.
DR GeneTree; ENSGT00940000156807; -.
DR HOGENOM; CLU_005912_4_3_1; -.
DR InParanoid; Q9UBY0; -.
DR OMA; DDHETMS; -.
DR OrthoDB; 316731at2759; -.
DR PhylomeDB; Q9UBY0; -.
DR TreeFam; TF317212; -.
DR PathwayCommons; Q9UBY0; -.
DR Reactome; R-HSA-425986; Sodium/Proton exchangers.
DR SignaLink; Q9UBY0; -.
DR SIGNOR; Q9UBY0; -.
DR BioGRID-ORCS; 6549; 9 hits in 1070 CRISPR screens.
DR GeneWiki; SLC9A2; -.
DR GenomeRNAi; 6549; -.
DR Pharos; Q9UBY0; Tchem.
DR PRO; PR:Q9UBY0; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9UBY0; protein.
DR Bgee; ENSG00000115616; Expressed in rectum and 94 other tissues.
DR Genevisible; Q9UBY0; HS.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
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; IBA:GO_Central.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0051453; P:regulation of intracellular pH; IBA:GO_Central.
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 InterPro; IPR001953; NHE-2/4.
DR InterPro; IPR032103; NHE_CaM-bd.
DR PANTHER; PTHR10110; PTHR10110; 1.
DR Pfam; PF00999; Na_H_Exchanger; 1.
DR Pfam; PF16644; NEXCaM_BD; 1.
DR PRINTS; PR01084; NAHEXCHNGR.
DR PRINTS; PR01086; NAHEXCHNGR2.
DR TIGRFAMs; TIGR00840; b_cpa1; 1.
PE 2: Evidence at transcript level;
KW Antiport; Glycoprotein; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Sodium; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..812
FT /note="Sodium/hydrogen exchanger 2"
FT /id="PRO_0000052352"
FT TOPO_DOM 1..13
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 14..33
FT /note="Name=A/M1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 34..79
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 80..100
FT /note="Name=B/M2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 101..106
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 107..127
FT /note="Helical; Name=C/M3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..138
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical; Name=D/M4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 160..168
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical; Name=E/M5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..208
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..229
FT /note="Helical; Name=F/M5A"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..236
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..257
FT /note="Helical; Name=G/M5B"
FT /evidence="ECO:0000255"
FT TOPO_DOM 258..277
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 278..298
FT /note="Helical; Name=H/M6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 299..307
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 308..328
FT /note="Helical; Name=I/M7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 329..360
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 361..381
FT /note="Helical; Name=J/M8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 382..391
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 392..412
FT /note="Helical; Name=K/M9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 413..429
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 430..450
FT /note="Name=L"
FT /evidence="ECO:0000250"
FT TOPO_DOM 451..458
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 459..479
FT /note="Helical; Name=M13"
FT /evidence="ECO:0000255"
FT TOPO_DOM 480..812
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 648..701
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 733..812
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 686..701
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 750..771
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 299
FT /note="T -> S (in a breast cancer sample; somatic mutation;
FT dbSNP:rs1386751319)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035964"
FT VARIANT 806
FT /note="R -> Q (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035965"
SQ SEQUENCE 812 AA; 91520 MW; 17EE177DC3830D0A CRC64;
MEPLGNWRSL RAPLPPMLLL LLLQVAGPVG ALAETLLNAP RAMGTSSSPP SPASVVAPGT
TLFEESRLPV FTLDYPHVQI PFEITLWILL ASLAKIGFHL YHKLPTIVPE SCLLIMVGLL
LGGIIFGVDE KSPPAMKTDV FFLYLLPPIV LDAGYFMPTR PFFENIGTIF WYAVVGTLWN
SIGIGVSLFG ICQIEAFGLS DITLLQNLLF GSLISAVDPV AVLAVFENIH VNEQLYILVF
GESLLNDAVT VVLYNLFKSF CQMKTIETID VFAGIANFFV VGIGGVLIGI FLGFIAAFTT
RFTHNIRVIE PLFVFLYSYL SYITAEMFHL SGIMAITACA MTMNKYVEEN VSQKSYTTIK
YFMKMLSSVS ETLIFIFMGV STVGKNHEWN WAFVCFTLAF CLMWRALGVF VLTQVINRFR
TIPLTFKDQF IIAYGGLRGA ICFALVFLLP AAVFPRKKLF ITAAIVVIFF TVFILGITIR
PLVEFLDVKR SNKKQQAVSE EIYCRLFDHV KTGIEDVCGH WGHNFWRDKF KKFDDKYLRK
LLIRENQPKS SIVSLYKKLE IKHAIEMAET GMISTVPTFA SLNDCREEKI RKVTSSETDE
IRELLSRNLY QIRQRTLSYN RHSLTADTSE RQAKEILIRR RHSLRESIRK DSSLNREHRA
STSTSRYLSL PKNTKLPEKL QKRRTISIAD GNSSDSDADA GTTVLNLQPR ARRFLPEQFS
KKSPQSYKME WKNEVDVDSG RDMPSTPPTP HSREKGTQTS GLLQQPLLSK DQSGSEREDS
LTEGIPPKPP PRLVWRASEP GSRKARFGSE KP
