ID SL9A8_MOUSE Reviewed; 576 AA. AC Q8R4D1; A2A465; Q3UPR4; Q5WA59; Q8BIH8; Q8BJ27; DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 27-MAR-2024, entry version 153. 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=Nhe8; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC STRAIN=SWR/J; TISSUE=Kidney; RX PubMed=12409279; DOI=10.1152/ajprenal.00352.2002; RA Goyal S., Vanden Heuvel G., Aronson P.S.; RT "Renal expression of novel Na+/H+ exchanger isoform NHE8."; RL Am. J. Physiol. 284:F467-F473(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=FVB/N; TISSUE=Kidney; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=C57BL/6J; TISSUE=Embryonic spinal ganglion, and Oviduct; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Kidney; 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-505, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [9] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=18209477; DOI=10.1159/000113752; RA Xu H., Chen H., Dong J., Lynch R., Ghishan F.K.; RT "Gastrointestinal distribution and kinetic characterization of the sodium- RT hydrogen exchanger isoform 8 (NHE8)."; RL Cell. Physiol. Biochem. 21:109-116(2008). RN [10] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=22575219; DOI=10.1152/ajpgi.00146.2012; RA Xu H., Zhang B., Li J., Wang C., Chen H., Ghishan F.K.; RT "Impaired mucin synthesis and bicarbonate secretion in the colon of NHE8 RT knockout mice."; RL Am. J. Physiol. 303:G335-G343(2012). RN [11] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=23657568; DOI=10.1152/ajpcell.00101.2013; RA Liu C., Xu H., Zhang B., Johansson M.E., Li J., Hansson G.C., Ghishan F.K.; RT "NHE8 plays an important role in mucosal protection via its effect on RT bacterial adhesion."; RL Am. J. Physiol. 305:C121-C128(2013). RN [12] RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND DISRUPTION RP PHENOTYPE. RX PubMed=23220221; DOI=10.1152/ajpgi.00433.2012; RA Xu H., Li J., Chen H., Wang C., Ghishan F.K.; RT "NHE8 plays important roles in gastric mucosal protection."; RL Am. J. Physiol. 304:G257-G261(2013). RN [13] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=25377091; DOI=10.1152/ajpcell.00296.2014; RA Xu H., Zhao Y., Li J., Wang M., Lian F., Gao M., Ghishan F.K.; RT "Loss of NHE8 expression impairs ocular surface function in mice."; RL Am. J. Physiol. 308:C79-C87(2015). RN [14] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=25472965; DOI=10.1152/ajpcell.00289.2014; RA Xu H., Chen H., Li J., Zhao Y., Ghishan F.K.; RT "Disruption of NHE8 expression impairs Leydig cell function in the RT testes."; RL Am. J. Physiol. 308:C330-C338(2015). RN [15] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=26505975; DOI=10.1152/ajpgi.00278.2015; RA Wang A., Li J., Zhao Y., Johansson M.E., Xu H., Ghishan F.K.; RT "Loss of NHE8 expression impairs intestinal mucosal integrity."; RL Am. J. Physiol. 309:G855-G864(2015). RN [16] RP DISRUPTION PHENOTYPE, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=28476888; DOI=10.1074/jbc.m117.784108; RA Oberheide K., Puchkov D., Jentsch T.J.; RT "Loss of the Na+/H+ exchanger NHE8 causes male infertility in mice by RT disrupting acrosome formation."; RL J. Biol. Chem. 292:10845-10854(2017). RN [17] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=29958869; DOI=10.1016/j.exer.2018.06.026; RA Xia C.H., Ferguson I., Li M., Kim A., Onishi A., Li L., Su B., Gong X.; RT "Essential function of NHE8 in mouse retina demonstrated by AAV-mediated RT CRISPR/Cas9 knockdown."; RL Exp. Eye Res. 176:29-39(2018). CC -!- FUNCTION: Na(+)/H(+) antiporter. Mediates the electoneutral exchange of CC intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry. CC Acts as an Na(+)/H(+) exchanger in the trans-Golgi. Contributes to the CC regulation of pH regulation of Golgi apparatus, and consequently, in CC protein trafficking and endosomal morphology (By similarity). Plays a CC crucial role in germ cells in acrosome biogenesis and sperm CC development, probably by playing a role in the fusion of the Golgi- CC derived vesicles that form the acrosomal cap (PubMed:28476888, CC PubMed:25472965). Can also be active at the cell surface of specialized CC cells. In the small intestine, plays a major physiological role in CC transepithelial absorption of Na(+). Regulates intracellular pH CC homeostasis of intestinal epithelial cells (By similarity). Acts as an CC important regulator of mucosal integrity in the intestine and in the CC stomach, could mediate the pH fluctuation necessary for mucin CC exocytosis or assist membrane trafficking of other proteins CC (PubMed:26505975, PubMed:23657568, PubMed:23220221). Plays a role in CC photoreceptor survival and in the maintenance of intracellular pH CC homeostasis in retinal pigment epithelium (RPE cells) (PubMed:29958869, CC PubMed:25377091). {ECO:0000250|UniProtKB:Q9Y2E8, CC ECO:0000269|PubMed:23220221, ECO:0000269|PubMed:23657568, CC ECO:0000269|PubMed:25377091, ECO:0000269|PubMed:25472965, CC ECO:0000269|PubMed:26505975, ECO:0000269|PubMed:28476888, CC ECO:0000269|PubMed:29958869}. 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:0000250|UniProtKB:Q9Y2E8}; CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000250|UniProtKB:Q9Y2E8}; Multi-pass membrane protein CC {ECO:0000255}. Golgi apparatus, trans-Golgi network membrane CC {ECO:0000250|UniProtKB:Q9Y2E8}; Multi-pass membrane protein CC {ECO:0000255}. Endosome, multivesicular body membrane CC {ECO:0000250|UniProtKB:Q9Y2E8}; Multi-pass membrane protein CC {ECO:0000255}. Apical cell membrane {ECO:0000269|PubMed:23220221}; CC Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, CC secretory vesicle, acrosome {ECO:0000269|PubMed:28476888}. Note=Mainly CC localized to the mid- to trans-Golgi compartments but a proportion is CC also localized to multivesicular bodies (By similarity). Localized at CC the apical membrane in the gastrointestinal tract (By similarity). CC Recruitment to the plasma membrane upon acid stimulation (By CC similarity). {ECO:0000250|UniProtKB:Q4L208, CC ECO:0000250|UniProtKB:Q9Y2E8}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8R4D1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8R4D1-2; Sequence=VSP_009500; CC Name=3; CC IsoId=Q8R4D1-4; Sequence=VSP_009503, VSP_009504; CC -!- TISSUE SPECIFICITY: Predominantly expressed in the liver, skeletal CC muscle, kidney, and testis (PubMed:12409279). Expressed in both renal CC cortex and medulla (PubMed:12409279). Detected throughout the entire CC gastrointestinal tract, with high expression detected in stomach, CC duodenum and ascending colon (PubMed:18209477). In gastric epithelium; CC expressed in the glands within the fundus and pylorus regions CC (PubMed:23220221). {ECO:0000269|PubMed:12409279, CC ECO:0000269|PubMed:18209477, ECO:0000269|PubMed:23220221}. CC -!- DEVELOPMENTAL STAGE: Expression is much higher in the stomach and CC jejunum in young mice compared with adult mice. CC {ECO:0000269|PubMed:18209477}. CC -!- DISRUPTION PHENOTYPE: The deficient mice have no obvious intestinal CC phenotype, show no defect in Na(+)-absorption, have normal serum Na(+) CC levels and no signs of diarrhea. Apically expressed Slc9a2 and Slc9a3 CC are increased in the small intestine of the Slc9a8-deficient mice in CC compensation (PubMed:22575219). Deficient mice have a reduced gastric CC mucosal surface pH, a higher incidence of developing gastric ulcer, and CC a decreased of mucin-2 (Muc2) expression (PubMed:23657568, CC PubMed:23220221). The intestinal mucosa in Slc9a8-deficient mice is CC prone to bacterial adhesion and penetration, which in turn promotes CC inflammation (PubMed:26505975, PubMed:23220221). Male knockout mice are CC infertile, have small testis, low testosterone levels, normal LH and CC FSH serum levels, however LH receptor (Lhcgr) is approximately 50% CC reduced. The spermatogenesise is also affected, deficient mice have CC round-headed spermatozoa and lack acrosomes (PubMed:25472965, CC PubMed:28476888). Knockout mice exhibit reduced tear production and CC increased corneal staining (PubMed:25377091). Knockdown Slc9a8 in adult CC retina leads to photoreceptor cell death (PubMed:25377091, CC PubMed:29958869). {ECO:0000269|PubMed:22575219, CC ECO:0000269|PubMed:23220221, ECO:0000269|PubMed:23657568, CC ECO:0000269|PubMed:25377091, ECO:0000269|PubMed:25472965, CC ECO:0000269|PubMed:26505975, ECO:0000269|PubMed:28476888, CC ECO:0000269|PubMed:29958869}. CC -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1) CC transporter (TC 2.A.36) family. {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; AF482993; AAL89753.1; -; mRNA. DR EMBL; AB089793; BAD69591.1; -; mRNA. DR EMBL; AK051791; BAC34770.1; -; mRNA. DR EMBL; AK129013; BAC87669.1; -; mRNA. DR EMBL; AK143281; BAE25331.1; -; mRNA. DR EMBL; AL589870; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL591762; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH466551; EDL06513.1; -; Genomic_DNA. DR EMBL; BC030879; AAH30879.1; -; mRNA. DR EMBL; BC058947; AAH58947.1; -; mRNA. DR CCDS; CCDS38339.1; -. [Q8R4D1-1] DR RefSeq; NP_001291469.1; NM_001304540.1. DR RefSeq; NP_001291471.1; NM_001304542.1. DR RefSeq; NP_683731.1; NM_148929.3. [Q8R4D1-1] DR AlphaFoldDB; Q8R4D1; -. DR SMR; Q8R4D1; -. DR BioGRID; 218469; 1. DR STRING; 10090.ENSMUSP00000044185; -. DR iPTMnet; Q8R4D1; -. DR PhosphoSitePlus; Q8R4D1; -. DR MaxQB; Q8R4D1; -. DR PaxDb; 10090-ENSMUSP00000044185; -. DR ProteomicsDB; 257038; -. [Q8R4D1-1] DR ProteomicsDB; 257039; -. [Q8R4D1-2] DR ProteomicsDB; 257040; -. [Q8R4D1-4] DR Pumba; Q8R4D1; -. DR Antibodypedia; 28505; 177 antibodies from 24 providers. DR DNASU; 77031; -. DR Ensembl; ENSMUST00000047815.13; ENSMUSP00000044185.7; ENSMUSG00000039463.15. [Q8R4D1-1] DR Ensembl; ENSMUST00000073873.5; ENSMUSP00000073536.4; ENSMUSG00000039463.15. [Q8R4D1-2] DR GeneID; 77031; -. DR KEGG; mmu:77031; -. DR UCSC; uc008nzp.2; mouse. [Q8R4D1-1] DR UCSC; uc008nzr.2; mouse. [Q8R4D1-4] DR AGR; MGI:1924281; -. DR CTD; 23315; -. DR MGI; MGI:1924281; Slc9a8. DR VEuPathDB; HostDB:ENSMUSG00000039463; -. DR eggNOG; KOG1965; Eukaryota. DR GeneTree; ENSGT00940000157210; -. DR InParanoid; Q8R4D1; -. DR OMA; ETVVMWW; -. DR OrthoDB; 1065060at2759; -. DR PhylomeDB; Q8R4D1; -. DR TreeFam; TF354313; -. DR Reactome; R-MMU-425986; Sodium/Proton exchangers. DR BioGRID-ORCS; 77031; 1 hit in 63 CRISPR screens. DR ChiTaRS; Slc9a8; mouse. DR PRO; PR:Q8R4D1; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; Q8R4D1; Protein. DR Bgee; ENSMUSG00000039463; Expressed in right kidney and 226 other cell types or tissues. DR ExpressionAtlas; Q8R4D1; baseline and differential. DR GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB. DR GO; GO:0032585; C:multivesicular body membrane; ISO:MGI. DR GO; GO:0032588; C:trans-Golgi network membrane; ISO:MGI. DR GO; GO:0015386; F:potassium:proton antiporter activity; ISO:MGI. DR GO; GO:0015385; F:sodium:proton antiporter activity; ISS:UniProtKB. DR GO; GO:0001675; P:acrosome assembly; IMP:UniProtKB. DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central. DR GO; GO:1902600; P:proton transmembrane transport; ISS:UniProtKB. DR GO; GO:1905526; P:regulation of Golgi lumen acidification; ISO:MGI. DR GO; GO:0051453; P:regulation of intracellular pH; IDA:UniProtKB. DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB. DR Gene3D; 6.10.140.1330; -; 1. DR InterPro; IPR006153; Cation/H_exchanger. DR InterPro; IPR018422; Cation/H_exchanger_CPA1. DR InterPro; IPR004709; NaH_exchanger. DR NCBIfam; TIGR00840; b_cpa1; 1. DR PANTHER; PTHR10110; SODIUM/HYDROGEN EXCHANGER; 1. DR PANTHER; PTHR10110:SF201; SODIUM_HYDROGEN EXCHANGER 8; 1. DR Pfam; PF00999; Na_H_Exchanger; 1. DR PRINTS; PR01084; NAHEXCHNGR. DR Genevisible; Q8R4D1; MM. PE 1: Evidence at protein level; KW Alternative splicing; Antiport; Cell membrane; Cytoplasmic vesicle; KW Differentiation; Endosome; Golgi apparatus; Ion transport; Membrane; KW Phosphoprotein; Reference proteome; Sodium; Sodium transport; KW Spermatogenesis; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..576 FT /note="Sodium/hydrogen exchanger 8" FT /id="PRO_0000052366" FT TRANSMEM 55..75 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 79..99 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 118..138 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 151..171 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 186..206 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 256..276 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 306..326 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 349..369 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 374..394 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 412..432 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 446..466 FT /note="Helical" FT /evidence="ECO:0000255" FT MOD_RES 505 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 566 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y2E8" FT MOD_RES 568 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Y2E8" FT VAR_SEQ 1..289 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_009503" FT VAR_SEQ 65..91 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_009500" FT VAR_SEQ 290..315 FT /note="PSLEFGMMIIFAYLPYGLAEGISLSG -> MWTLCSTCWCLEKAFSTMQSPS FT SSPS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_009504" FT CONFLICT 247 FT /note="S -> R (in Ref. 3; BAE25331)" FT /evidence="ECO:0000305" FT CONFLICT 280..283 FT /note="Missing (in Ref. 3; BAC34770)" FT /evidence="ECO:0000305" FT CONFLICT 542 FT /note="D -> E (in Ref. 3; BAE25331)" FT /evidence="ECO:0000305" SQ SEQUENCE 576 AA; 64737 MW; 8322845FDBAC1F8D CRC64; MAEEEFSNTT HETFNFTLHT TLGVTTKLVL PTPAKPILPV QTGEQAQQEE QSSGMTIFFS LLVLAICIIL VHLLIRYRLH FLPESVAVVS LGILMGAVIK VIEFKKLANW KEEEMFRPNM FFLLLLPPII FESGYSLHKG NFFQNIGSIT LFAVFGTAIS AFVVGGGIYF LGQADVISKL NMTDSFAFGS LISAVDPVAT IAIFNALHVD PVLNMLVFGE SILNDAVSIV LTNTAEGLTR KHMSDVSGWQ TFSQALGYFL KMFFGSAALG TLTGLISALV LKHIDLRKTP SLEFGMMIIF AYLPYGLAEG ISLSGIMAIL FSGIVMSHYT HHNLSPVTQI LMQQTLRTVA FLCETCVFAF LGLSIFSFPH KFEISFVIWC IVLVLFGRAV NIFPLSYLLN FFRDHKITPK MMFIMWFSGL RGAIPYALSL HLGLEPMEKR QLIGTTTIVI VLFTILLLGG STMPLIRLVD IEDARARRRS KKDVNLSKTE KMGNAIESEH LSELTEEEYE AHYIRQQDLK GFMWLDAKYL NPFFTRRLTQ EDLHHGRIQM KSLTNKWYEE VRQGPSGSED DEQELF //