SL9A8_MOUSE
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 03-AUG-2022, entry version 144.
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).
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 -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Multi-
CC pass membrane protein {ECO:0000250}.
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: Ubiquitously expressed. Expressed in both renal
CC cortex and medulla. In the cortex, present in the majority of cortical
CC tubules. In the medulla, most highly expressed in the proximal tubules
CC (S3) of the outer stripe of the outer medulla.
CC {ECO:0000269|PubMed:12409279}.
CC -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1)
CC transporter (TC 2.A.36) family. {ECO:0000305}.
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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 STRING; 10090.ENSMUSP00000044185; -.
DR iPTMnet; Q8R4D1; -.
DR PhosphoSitePlus; Q8R4D1; -.
DR MaxQB; Q8R4D1; -.
DR PaxDb; Q8R4D1; -.
DR PRIDE; Q8R4D1; -.
DR ProteomicsDB; 257038; -. [Q8R4D1-1]
DR ProteomicsDB; 257039; -. [Q8R4D1-2]
DR ProteomicsDB; 257040; -. [Q8R4D1-4]
DR Antibodypedia; 28505; 164 antibodies from 24 providers.
DR DNASU; 77031; -.
DR Ensembl; ENSMUST00000047815; ENSMUSP00000044185; ENSMUSG00000039463. [Q8R4D1-1]
DR Ensembl; ENSMUST00000073873; ENSMUSP00000073536; ENSMUSG00000039463. [Q8R4D1-2]
DR GeneID; 77031; -.
DR KEGG; mmu:77031; -.
DR UCSC; uc008nzp.2; mouse. [Q8R4D1-1]
DR UCSC; uc008nzr.2; mouse. [Q8R4D1-4]
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; 546232at2759; -.
DR PhylomeDB; Q8R4D1; -.
DR TreeFam; TF354313; -.
DR Reactome; R-MMU-425986; Sodium/Proton exchangers.
DR BioGRID-ORCS; 77031; 1 hit in 60 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 224 other tissues.
DR ExpressionAtlas; Q8R4D1; baseline and differential.
DR Genevisible; Q8R4D1; MM.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
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: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..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 211..231
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
