SL9A8_HUMAN
ID SL9A8_HUMAN Reviewed; 581 AA.
AC Q9Y2E8; B4DTQ8; Q2M1U9; Q68CZ8; Q9BX15; Q9Y507;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 4.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Sodium/hydrogen exchanger 8;
DE AltName: Full=Na(+)/H(+) exchanger 8;
DE Short=NHE-8;
DE AltName: Full=Solute carrier family 9 member 8;
GN Name=SLC9A8; Synonyms=KIAA0939, NHE8;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-155 (ISOFORM 1).
RC TISSUE=Gastric mucosa, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15522866; DOI=10.1074/jbc.m410041200;
RA Nakamura N., Tanaka S., Teko Y., Mitsui K., Kanazawa H.;
RT "Four Na+/H+ exchanger isoforms are distributed to Golgi and post-Golgi
RT Compartments and are involved in organelle pH regulation.";
RL J. Biol. Chem. 280:1561-1572(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-571 AND SER-573, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(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:0000269|PubMed:15522866}.
CC -!- INTERACTION:
CC Q9Y2E8; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-1222746, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:15522866}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15522866}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y2E8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y2E8-2; Sequence=VSP_037686;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Strongly expressed in skeletal muscle
CC and kidney. {ECO:0000269|PubMed:15522866}.
CC -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1)
CC transporter (TC 2.A.36) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76783.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB023156; BAA76783.2; ALT_INIT; mRNA.
DR EMBL; AK131001; BAC85475.1; ALT_TERM; mRNA.
DR EMBL; AK300318; BAG62070.1; -; mRNA.
DR EMBL; CR749638; CAH18432.1; -; mRNA.
DR EMBL; AL162615; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031685; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75649.1; -; Genomic_DNA.
DR EMBL; BC112213; AAI12214.1; -; mRNA.
DR CCDS; CCDS13421.1; -. [Q9Y2E8-1]
DR CCDS; CCDS58774.1; -. [Q9Y2E8-2]
DR RefSeq; NP_001247420.1; NM_001260491.1. [Q9Y2E8-2]
DR RefSeq; NP_056081.1; NM_015266.2. [Q9Y2E8-1]
DR AlphaFoldDB; Q9Y2E8; -.
DR SMR; Q9Y2E8; -.
DR BioGRID; 116906; 29.
DR IntAct; Q9Y2E8; 2.
DR STRING; 9606.ENSP00000416418; -.
DR TCDB; 2.A.36.1.9; the monovalent cation:proton antiporter-1 (cpa1) family.
DR iPTMnet; Q9Y2E8; -.
DR PhosphoSitePlus; Q9Y2E8; -.
DR BioMuta; SLC9A8; -.
DR DMDM; 254763448; -.
DR EPD; Q9Y2E8; -.
DR jPOST; Q9Y2E8; -.
DR MassIVE; Q9Y2E8; -.
DR MaxQB; Q9Y2E8; -.
DR PaxDb; Q9Y2E8; -.
DR PeptideAtlas; Q9Y2E8; -.
DR PRIDE; Q9Y2E8; -.
DR ProteomicsDB; 85751; -. [Q9Y2E8-1]
DR ProteomicsDB; 85752; -. [Q9Y2E8-2]
DR Antibodypedia; 28505; 164 antibodies from 24 providers.
DR DNASU; 23315; -.
DR Ensembl; ENST00000361573.3; ENSP00000354966.2; ENSG00000197818.12. [Q9Y2E8-1]
DR Ensembl; ENST00000417961.5; ENSP00000416418.1; ENSG00000197818.12. [Q9Y2E8-2]
DR GeneID; 23315; -.
DR KEGG; hsa:23315; -.
DR MANE-Select; ENST00000361573.3; ENSP00000354966.2; NM_015266.3; NP_056081.1.
DR UCSC; uc002xuv.3; human. [Q9Y2E8-1]
DR CTD; 23315; -.
DR DisGeNET; 23315; -.
DR GeneCards; SLC9A8; -.
DR HGNC; HGNC:20728; SLC9A8.
DR HPA; ENSG00000197818; Low tissue specificity.
DR MIM; 612730; gene.
DR neXtProt; NX_Q9Y2E8; -.
DR OpenTargets; ENSG00000197818; -.
DR PharmGKB; PA134924114; -.
DR VEuPathDB; HostDB:ENSG00000197818; -.
DR eggNOG; KOG1965; Eukaryota.
DR GeneTree; ENSGT00940000157210; -.
DR HOGENOM; CLU_005912_11_0_1; -.
DR InParanoid; Q9Y2E8; -.
DR OMA; ETVVMWW; -.
DR OrthoDB; 546232at2759; -.
DR PhylomeDB; Q9Y2E8; -.
DR TreeFam; TF354313; -.
DR PathwayCommons; Q9Y2E8; -.
DR Reactome; R-HSA-425986; Sodium/Proton exchangers.
DR SignaLink; Q9Y2E8; -.
DR SIGNOR; Q9Y2E8; -.
DR BioGRID-ORCS; 23315; 13 hits in 1079 CRISPR screens.
DR ChiTaRS; SLC9A8; human.
DR GeneWiki; SLC9A8; -.
DR GenomeRNAi; 23315; -.
DR Pharos; Q9Y2E8; Tbio.
DR PRO; PR:Q9Y2E8; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9Y2E8; protein.
DR Bgee; ENSG00000197818; Expressed in blood and 142 other tissues.
DR Genevisible; Q9Y2E8; HS.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 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 1: Evidence at protein level;
KW Alternative splicing; Antiport; Golgi apparatus; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Sodium; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..581
FT /note="Sodium/hydrogen exchanger 8"
FT /id="PRO_0000052365"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..211
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 354..374
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 379..399
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 417..437
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 451..471
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 510
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8R4D1"
FT MOD_RES 571
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 573
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VAR_SEQ 178
FT /note="Q -> QGFFFVCVCVFVCFILQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037686"
FT CONFLICT 114
FT /note="N -> D (in Ref. 3; BAC85475)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 581 AA; 65422 MW; 7508B62B74D584B1 CRC64;
MGEKMAEEER FPNTTHEGFN VTLHTTLVVT TKLVLPTPGK PILPVQTGEQ AQQEEQSSGM
TIFFSLLVLA ICIILVHLLI RYRLHFLPES VAVVSLGILM GAVIKIIEFK KLANWKEEEM
FRPNMFFLLL LPPIIFESGY SLHKGNFFQN IGSITLFAVF GTAISAFVVG GGIYFLGQAD
VISKLNMTDS FAFGSLISAV DPVATIAIFN ALHVDPVLNM LVFGESILND AVSIVLTNTA
EGLTRKNMSD VSGWQTFLQA LDYFLKMFFG SAALGTLTGL ISALVLKHID LRKTPSLEFG
MMIIFAYLPY GLAEGISLSG IMAILFSGIV MSHYTHHNLS PVTQILMQQT LRTVAFLCET
CVFAFLGLSI FSFPHKFEIS FVIWCIVLVL FGRAVNIFPL SYLLNFFRDH KITPKMMFIM
WFSGLRGAIP YALSLHLDLE PMEKRQLIGT TTIVIVLFTI LLLGGSTMPL IRLMDIEDAK
AHRRNKKDVN LSKTEKMGNT VESEHLSELT EEEYEAHYIR RQDLKGFVWL DAKYLNPFFT
RRLTQEDLHH GRIQMKTLTN KWYEEVRQGP SGSEDDEQEL L
