SL9A6_HUMAN
ID SL9A6_HUMAN Reviewed; 669 AA.
AC Q92581; A6NIQ9; A8K160; B4DU30; B7ZAE0; Q3ZCW7; Q5JPP8; Q5JPP9; Q86VS0;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Sodium/hydrogen exchanger 6;
DE AltName: Full=Na(+)/H(+) exchanger 6;
DE Short=NHE-6;
DE AltName: Full=Solute carrier family 9 member 6;
GN Name=SLC9A6; Synonyms=KIAA0267, NHE6;
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] (ISOFORM 1).
RX PubMed=9507001; DOI=10.1074/jbc.273.12.6951;
RA Numata M., Petrecca K., Lake N., Orlowski J.;
RT "Identification of a mitochondrial Na+/H+ exchanger.";
RL J. Biol. Chem. 273:6951-6959(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-669 (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=11940519; DOI=10.1152/ajpcell.00420.2001;
RA Brett C.L., Wei Y., Donowitz M., Rao R.;
RT "Human Na(+)/H(+) exchanger isoform 6 is found in recycling endosomes of
RT cells, not in mitochondria.";
RL Am. J. Physiol. 282:C1031-C1041(2002).
RN [7]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-443, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Mammary cancer;
RX PubMed=17370265; DOI=10.1002/pmic.200600410;
RA Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.;
RT "Tryptic digestion of ubiquitin standards reveals an improved strategy for
RT identifying ubiquitinated proteins by mass spectrometry.";
RL Proteomics 7:868-874(2007).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP INVOLVEMENT IN MRXSCH.
RX PubMed=18342287; DOI=10.1016/j.ajhg.2008.01.013;
RA Gilfillan G.D., Selmer K.K., Roxrud I., Smith R., Kyllerman M., Eiklid K.,
RA Kroken M., Mattingsdal M., Egeland T., Stenmark H., Sjoholm H., Server A.,
RA Samuelsson L., Christianson A., Tarpey P., Whibley A., Stratton M.R.,
RA Futreal P.A., Teague J., Edkins S., Gecz J., Turner G., Raymond F.L.,
RA Schwartz C., Stevenson R.E., Undlien D.E., Stromme P.;
RT "SLC9A6 mutations cause X-linked mental retardation, microcephaly,
RT epilepsy, and ataxia, a phenotype mimicking Angelman syndrome.";
RL Am. J. Hum. Genet. 82:1003-1010(2008).
RN [11]
RP INVOLVEMENT IN MRXSCH.
RX PubMed=24123876; DOI=10.1136/jmedgenet-2013-101644;
RA Schuurs-Hoeijmakers J.H., Vulto-van Silfhout A.T., Vissers L.E.,
RA van de Vondervoort I.I., van Bon B.W., de Ligt J., Gilissen C.,
RA Hehir-Kwa J.Y., Neveling K., del Rosario M., Hira G., Reitano S.,
RA Vitello A., Failla P., Greco D., Fichera M., Galesi O., Kleefstra T.,
RA Greally M.T., Ockeloen C.W., Willemsen M.H., Bongers E.M., Janssen I.M.,
RA Pfundt R., Veltman J.A., Romano C., Willemsen M.A., van Bokhoven H.,
RA Brunner H.G., de Vries B.B., de Brouwer A.P.;
RT "Identification of pathogenic gene variants in small families with
RT intellectually disabled siblings by exome sequencing.";
RL J. Med. Genet. 50:802-811(2013).
RN [12]
RP VARIANT MRXSCH ARG-186, CHARACTERIZATION OF VARIANT MRXSCH ARG-186,
RP SUBUNIT, SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=30296617; DOI=10.1016/j.nbd.2018.10.002;
RA Ilie A., Gao A.Y.L., Boucher A., Park J., Berghuis A.M., Hoffer M.J.V.,
RA Hilhorst-Hofstee Y., McKinney R.A., Orlowski J.;
RT "A potential gain-of-function variant of SLC9A6 leads to endosomal
RT alkalinization and neuronal atrophy associated with Christianson
RT Syndrome.";
RL Neurobiol. Dis. 121:187-204(2019).
CC -!- FUNCTION: Electroneutral exchange of protons for Na(+) and K(+) across
CC the early and recycling endosome membranes. Contributes to calcium
CC homeostasis.
CC -!- SUBUNIT: Homodimer (in vitro). {ECO:0000269|PubMed:30296617}.
CC -!- INTERACTION:
CC Q92581-2; P15260: IFNGR1; NbExp=3; IntAct=EBI-17198620, EBI-1030755;
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:11940519};
CC Multi-pass membrane protein {ECO:0000269|PubMed:11940519}. Note=Is
CC present in the recycling compartments including early and recycling
CC endosomes, and only appears transiently on the plasma membrane.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Recycling endosome membrane
CC {ECO:0000269|PubMed:30296617}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q92581-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92581-2; Sequence=VSP_042030;
CC Name=3;
CC IsoId=Q92581-3; Sequence=VSP_044868, VSP_042030;
CC -!- TISSUE SPECIFICITY: Ubiquitous; but is most abundant in mitochondrion-
CC rich tissues such as brain, skeletal muscle and heart.
CC -!- PTM: Ubiquitinated (in vitro). {ECO:0000269|PubMed:30296617}.
CC -!- DISEASE: Intellectual developmental disorder, X-linked, syndromic,
CC Christianson type (MRXSCH) [MIM:300243]: A syndrome characterized by
CC profound intellectual disability, epilepsy, ataxia, and microcephaly.
CC It shows phenotypic overlap with Angelman syndrome.
CC {ECO:0000269|PubMed:18342287, ECO:0000269|PubMed:24123876,
CC ECO:0000269|PubMed:30296617}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1)
CC transporter (TC 2.A.36) family. {ECO:0000305}.
CC -!- CAUTION: Was originally (PubMed:9507001) identified as a mitochondrial
CC inner membrane protein, but was later shown to be localized in early
CC and recycling endosomes and not mitochondria (PubMed:11940519).
CC {ECO:0000305|PubMed:11940519, ECO:0000305|PubMed:9507001}.
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DR EMBL; AF030409; AAC39643.1; -; mRNA.
DR EMBL; AK289775; BAF82464.1; -; mRNA.
DR EMBL; AK300475; BAG62192.1; -; mRNA.
DR EMBL; AK316255; BAH14626.1; -; mRNA.
DR EMBL; AL732579; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035029; AAH35029.1; -; mRNA.
DR EMBL; BC049169; AAH49169.1; -; mRNA.
DR EMBL; D87743; BAA13449.1; -; mRNA.
DR CCDS; CCDS14654.1; -. [Q92581-1]
DR CCDS; CCDS44003.1; -. [Q92581-2]
DR CCDS; CCDS55504.1; -. [Q92581-3]
DR RefSeq; NP_001036002.1; NM_001042537.1. [Q92581-2]
DR RefSeq; NP_001171122.1; NM_001177651.1. [Q92581-3]
DR RefSeq; NP_006350.1; NM_006359.2. [Q92581-1]
DR RefSeq; XP_006724789.1; XM_006724726.3. [Q92581-3]
DR RefSeq; XP_016884712.1; XM_017029223.1. [Q92581-3]
DR RefSeq; XP_016884713.1; XM_017029224.1. [Q92581-3]
DR AlphaFoldDB; Q92581; -.
DR SMR; Q92581; -.
DR BioGRID; 115742; 43.
DR IntAct; Q92581; 29.
DR STRING; 9606.ENSP00000359729; -.
DR TCDB; 2.A.36.1.14; the monovalent cation:proton antiporter-1 (cpa1) family.
DR GlyGen; Q92581; 1 site.
DR iPTMnet; Q92581; -.
DR PhosphoSitePlus; Q92581; -.
DR SwissPalm; Q92581; -.
DR BioMuta; SLC9A6; -.
DR DMDM; 6919937; -.
DR EPD; Q92581; -.
DR jPOST; Q92581; -.
DR MassIVE; Q92581; -.
DR MaxQB; Q92581; -.
DR PaxDb; Q92581; -.
DR PeptideAtlas; Q92581; -.
DR PRIDE; Q92581; -.
DR ProteomicsDB; 63023; -.
DR ProteomicsDB; 75339; -. [Q92581-1]
DR ProteomicsDB; 75340; -. [Q92581-2]
DR Antibodypedia; 30408; 157 antibodies from 26 providers.
DR DNASU; 10479; -.
DR Ensembl; ENST00000370695.8; ENSP00000359729.4; ENSG00000198689.13. [Q92581-2]
DR Ensembl; ENST00000370698.7; ENSP00000359732.3; ENSG00000198689.13. [Q92581-1]
DR Ensembl; ENST00000370701.6; ENSP00000359735.1; ENSG00000198689.13. [Q92581-3]
DR Ensembl; ENST00000636092.1; ENSP00000490406.1; ENSG00000198689.13. [Q92581-3]
DR Ensembl; ENST00000636347.1; ENSP00000490648.1; ENSG00000198689.13. [Q92581-3]
DR Ensembl; ENST00000637234.1; ENSP00000490527.1; ENSG00000198689.13. [Q92581-3]
DR Ensembl; ENST00000637581.1; ENSP00000490731.1; ENSG00000198689.13. [Q92581-3]
DR GeneID; 10479; -.
DR KEGG; hsa:10479; -.
DR UCSC; uc004ezj.3; human. [Q92581-1]
DR CTD; 10479; -.
DR DisGeNET; 10479; -.
DR GeneCards; SLC9A6; -.
DR GeneReviews; SLC9A6; -.
DR HGNC; HGNC:11079; SLC9A6.
DR HPA; ENSG00000198689; Tissue enhanced (brain).
DR MalaCards; SLC9A6; -.
DR MIM; 300231; gene.
DR MIM; 300243; phenotype.
DR neXtProt; NX_Q92581; -.
DR OpenTargets; ENSG00000198689; -.
DR Orphanet; 85278; Christianson syndrome.
DR PharmGKB; PA35935; -.
DR VEuPathDB; HostDB:ENSG00000198689; -.
DR eggNOG; KOG1965; Eukaryota.
DR GeneTree; ENSGT00940000153460; -.
DR HOGENOM; CLU_005912_7_0_1; -.
DR InParanoid; Q92581; -.
DR OrthoDB; 559433at2759; -.
DR PhylomeDB; Q92581; -.
DR TreeFam; TF318755; -.
DR PathwayCommons; Q92581; -.
DR Reactome; R-HSA-425986; Sodium/Proton exchangers.
DR Reactome; R-HSA-5619092; Defective SLC9A6 causes X-linked, syndromic mental retardation, Christianson type (MRXSCH).
DR SignaLink; Q92581; -.
DR SIGNOR; Q92581; -.
DR BioGRID-ORCS; 10479; 10 hits in 704 CRISPR screens.
DR ChiTaRS; SLC9A6; human.
DR GeneWiki; SLC9A6; -.
DR GenomeRNAi; 10479; -.
DR Pharos; Q92581; Tbio.
DR PRO; PR:Q92581; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q92581; protein.
DR Bgee; ENSG00000198689; Expressed in lateral nuclear group of thalamus and 201 other tissues.
DR ExpressionAtlas; Q92581; baseline and differential.
DR Genevisible; Q92581; HS.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IBA:GO_Central.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
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:0048675; P:axon extension; IDA:MGI.
DR GO; GO:0097484; P:dendrite extension; IDA:MGI.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0048812; P:neuron projection morphogenesis; IDA:MGI.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0051453; P:regulation of intracellular pH; IMP:UniProtKB.
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; IPR002090; NHE-6/7/9.
DR PANTHER; PTHR10110; PTHR10110; 2.
DR Pfam; PF00999; Na_H_Exchanger; 1.
DR PRINTS; PR01084; NAHEXCHNGR.
DR PRINTS; PR01088; NAHEXCHNGR6.
DR TIGRFAMs; TIGR00840; b_cpa1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Antiport; Disease variant; Endosome; Epilepsy;
KW Glycoprotein; Intellectual disability; Ion transport; Isopeptide bond;
KW Membrane; Reference proteome; Sodium; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..669
FT /note="Sodium/hydrogen exchanger 6"
FT /id="PRO_0000052362"
FT TRANSMEM 28..48
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 71..91
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 220..240
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 246..266
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 292..312
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 340..360
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 382..402
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 404..424
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 447..467
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 483..503
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CROSSLNK 443
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:17370265"
FT VAR_SEQ 1..52
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044868"
FT VAR_SEQ 144
FT /note="V -> VNVSGKFYEYMLKGEISSHELNNVQDNEMLRKV (in isoform 2
FT and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_042030"
FT VARIANT 186
FT /note="G -> R (in MRXSCH; decreases protein stability;
FT increased ubiquitination; impairs acidification of
FT endosomes; reduces localization to recycling endosomes;
FT impairs trafficking to plasma membrane; reduces uptake of
FT recycling endosomal cargo)"
FT /evidence="ECO:0000269|PubMed:30296617"
FT /id="VAR_083536"
FT CONFLICT 20
FT /note="R -> G (in Ref. 4; AAH35029)"
FT /evidence="ECO:0000305"
FT CONFLICT 92
FT /note="K -> E (in Ref. 2; BAF82464)"
FT /evidence="ECO:0000305"
FT CONFLICT 144
FT /note="V -> I (in Ref. 2; BAH14626)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="A -> T (in Ref. 2; BAH14626)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="T -> M (in Ref. 2; BAF82464)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="E -> G (in Ref. 2; BAG62192)"
FT /evidence="ECO:0000305"
FT CONFLICT 634
FT /note="A -> S (in Ref. 2; BAF82464)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 669 AA; 74162 MW; F6416596229F2639 CRC64;
MARRGWRRAP LRRGVGSSPR ARRLMRPLWL LLAVGVFDWA GASDGGGGEA RAMDEEIVSE
KQAEESHRQD SANLLIFILL LTLTILTIWL FKHRRARFLH ETGLAMIYGL LVGLVLRYGI
HVPSDVNNVT LSCEVQSSPT TLLVTFDPEV FFNILLPPII FYAGYSLKRR HFFRNLGSIL
AYAFLGTAIS CFVIGSIMYG CVTLMKVTGQ LAGDFYFTDC LLFGAIVSAT DPVTVLAIFH
ELQVDVELYA LLFGESVLND AVAIVLSSSI VAYQPAGDNS HTFDVTAMFK SIGIFLGIFS
GSFAMGAATG VVTALVTKFT KLREFQLLET GLFFLMSWST FLLAEAWGFT GVVAVLFCGI
TQAHYTYNNL STESQHRTKQ LFELLNFLAE NFIFSYMGLT LFTFQNHVFN PTFVVGAFVA
IFLGRAANIY PLSLLLNLGR RSKIGSNFQH MMMFAGLRGA MAFALAIRDT ATYARQMMFS
TTLLIVFFTV WVFGGGTTAM LSCLHIRVGV DSDQEHLGVP ENERRTTKAE SAWLFRMWYN
FDHNYLKPLL THSGPPLTTT LPACCGPIAR CLTSPQAYEN QEQLKDDDSD LILNDGDISL
TYGDSTVNTE PATSSAPRRF MGNSSEDALD RELAFGDHEL VIRGTRLVLP MDDSEPPLNL
LDNTRHGPA
