SL9A5_HUMAN
ID SL9A5_HUMAN Reviewed; 896 AA.
AC Q14940; A5PKY7; Q9Y626;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Sodium/hydrogen exchanger 5;
DE AltName: Full=Na(+)/H(+) exchanger 5;
DE Short=NHE-5;
DE AltName: Full=Solute carrier family 9 member 5;
GN Name=SLC9A5; Synonyms=NHE5;
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=Brain;
RX PubMed=9933641; DOI=10.1074/jbc.274.7.4377;
RA Baird N.R., Orlowski J., Szabo E.Z., Zaun H.C., Schultheis P.J.,
RA Menon A.G., Shull G.E.;
RT "Molecular cloning, genomic organization, and functional expression of
RT Na+/H+ exchanger isoform 5 (NHE5) from human brain.";
RL J. Biol. Chem. 274:4377-4382(1999).
RN [2]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 64-218.
RX PubMed=7759094; DOI=10.1016/0888-7543(95)80002-4;
RA Klanke C.A., Su Y.R., Callen D.F., Wang Z., Meneton P., Baird N.,
RA Kandasamy R.A., Orlowski J., Otterud B.E., Leppert M., Shull G.E.,
RA Menon A.G.;
RT "Molecular cloning and physical and genetic mapping of a novel human Na+/H+
RT exchanger (NHE5/SLC9A5) to chromosome 16q22.1.";
RL Genomics 25:615-622(1995).
RN [5]
RP INTERACTION WITH ARRB2.
RX PubMed=15699339; DOI=10.1073/pnas.0407444102;
RA Szabo E.Z., Numata M., Lukashova V., Iannuzzi P., Orlowski J.;
RT "beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+
RT exchanger NHE5 isoform.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:2790-2795(2005).
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 (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with CHP1 and CHP2 (By similarity). Interacts with
CC ARRB2. {ECO:0000250, ECO:0000269|PubMed:15699339}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in brain, testis, spleen, and skeletal
CC muscle.
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; AF111173; AAC98696.1; -; mRNA.
DR EMBL; CH471092; EAW83114.1; -; Genomic_DNA.
DR EMBL; BC142671; AAI42672.1; -; mRNA.
DR EMBL; U08607; AAA87678.1; -; Genomic_DNA.
DR CCDS; CCDS42178.1; -.
DR RefSeq; NP_004585.1; NM_004594.2.
DR AlphaFoldDB; Q14940; -.
DR SMR; Q14940; -.
DR BioGRID; 112442; 22.
DR IntAct; Q14940; 1.
DR STRING; 9606.ENSP00000299798; -.
DR BindingDB; Q14940; -.
DR ChEMBL; CHEMBL3058; -.
DR DrugCentral; Q14940; -.
DR GuidetoPHARMACOLOGY; 952; -.
DR TCDB; 2.A.36.1.16; the monovalent cation:proton antiporter-1 (cpa1) family.
DR GlyGen; Q14940; 2 sites.
DR iPTMnet; Q14940; -.
DR PhosphoSitePlus; Q14940; -.
DR BioMuta; SLC9A5; -.
DR DMDM; 12644417; -.
DR MassIVE; Q14940; -.
DR PaxDb; Q14940; -.
DR PeptideAtlas; Q14940; -.
DR PRIDE; Q14940; -.
DR ProteomicsDB; 60252; -.
DR Antibodypedia; 44267; 61 antibodies from 20 providers.
DR DNASU; 6553; -.
DR Ensembl; ENST00000299798.16; ENSP00000299798.11; ENSG00000135740.17.
DR GeneID; 6553; -.
DR KEGG; hsa:6553; -.
DR MANE-Select; ENST00000299798.16; ENSP00000299798.11; NM_004594.3; NP_004585.1.
DR UCSC; uc002esm.4; human.
DR CTD; 6553; -.
DR DisGeNET; 6553; -.
DR GeneCards; SLC9A5; -.
DR HGNC; HGNC:11078; SLC9A5.
DR HPA; ENSG00000135740; Tissue enhanced (brain, lymphoid tissue).
DR MIM; 600477; gene.
DR neXtProt; NX_Q14940; -.
DR OpenTargets; ENSG00000135740; -.
DR PharmGKB; PA35934; -.
DR VEuPathDB; HostDB:ENSG00000135740; -.
DR eggNOG; KOG1966; Eukaryota.
DR GeneTree; ENSGT00940000159190; -.
DR HOGENOM; CLU_005912_4_2_1; -.
DR InParanoid; Q14940; -.
DR OMA; PWKGDQA; -.
DR OrthoDB; 389547at2759; -.
DR PhylomeDB; Q14940; -.
DR TreeFam; TF317212; -.
DR PathwayCommons; Q14940; -.
DR Reactome; R-HSA-425986; Sodium/Proton exchangers.
DR SignaLink; Q14940; -.
DR SIGNOR; Q14940; -.
DR BioGRID-ORCS; 6553; 7 hits in 1074 CRISPR screens.
DR GeneWiki; SLC9A5; -.
DR GenomeRNAi; 6553; -.
DR Pharos; Q14940; Tchem.
DR PRO; PR:Q14940; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q14940; protein.
DR Bgee; ENSG00000135740; Expressed in right hemisphere of cerebellum and 105 other tissues.
DR ExpressionAtlas; Q14940; baseline and differential.
DR Genevisible; Q14940; 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: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; 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; Glycoprotein; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Sodium; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..896
FT /note="Sodium/hydrogen exchanger 5"
FT /id="PRO_0000052360"
FT TRANSMEM 46..66
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 74..94
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 135..155
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 247..267
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 277..297
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 332..352
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 361..381
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 399..419
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 429..449
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 658..686
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 701..720
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 818..864
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 701..717
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 849..863
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 202
FT /note="L -> V (in Ref. 4; AAA87678)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 896 AA; 99011 MW; B9D234BFE0922269 CRC64;
MLRAALSLLA LPLAGAAEEP TQKPESPGEP PPGLELFRWQ WHEVEAPYLV ALWILVASLA
KIVFHLSRKV TSLVPESCLL ILLGLVLGGI VLAVAKKAEY QLEPGTFFLF LLPPIVLDSG
YFMPSRLFFD NLGAILTYAV VGTLWNAFTT GAALWGLQQA GLVAPRVQAG LLDFLLFGSL
ISAVDPVAVL AVFEEVHVNE TLFIIVFGES LLNDAVTVVL YKVCNSFVEM GSANVQATDY
LKGVASLFVV SLGGAAVGLV FAFLLALTTR FTKRVRIIEP LLVFLLAYAA YLTAEMASLS
AILAVTMCGL GCKKYVEANI SHKSRTTVKY TMKTLASCAE TVIFMLLGIS AVDSSKWAWD
SGLVLGTLIF ILFFRALGVV LQTWVLNQFR LVPLDKIDQV VMSYGGLRGA VAFALVILLD
RTKVPAKDYF VATTIVVVFF TVIVQGLTIK PLVKWLKVKR SEHHKPTLNQ ELHEHTFDHI
LAAVEDVVGH HGYHYWRDRW EQFDKKYLSQ LLMRRSAYRI RDQIWDVYYR LNIRDAISFV
DQGGHVLSST GLTLPSMPSR NSVAETSVTN LLRESGSGAC LDLQVIDTVR SGRDREDAVM
HHLLCGGLYK PRRRYKASCS RHFISEDAQE RQDKEVFQQN MKRRLESFKS TKHNICFTKS
KPRPRKTGRR KKDGVANAEA TNGKHRGLGF QDTAAVILTV ESEEEEEESD SSETEKEDDE
GIIFVARATS EVLQEGKVSG SLEVCPSPRI IPPSPTCAEK ELPWKSGQGD LAVYVSSETT
KIVPVDMQTG WNQSISSLES LASPPCNQAP ILTCLPPHPR GTEEPQVPLH LPSDPRSSFA
FPPSLAKAGR SRSESSADLP QQQELQPLMG HKDHTHLSPG TATSHWCIQF NRGSRL
