ID SL9A9_HUMAN Reviewed; 645 AA. AC Q8IVB4; A6NMQ9; Q3LIC2; Q5JPI6; Q5WA58; Q8NAB9; DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 27-MAR-2024, entry version 171. DE RecName: Full=Sodium/hydrogen exchanger 9; DE AltName: Full=Na(+)/H(+) exchanger 9; DE Short=NHE-9; DE AltName: Full=Solute carrier family 9 member 9; GN Name=SLC9A9 {ECO:0000312|HGNC:HGNC:20653}; Synonyms=NHE9; GN ORFNames=Nbla00118; 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], TISSUE SPECIFICITY, AND CHROMOSOMAL RP REARRANGEMENT. RX PubMed=14569117; DOI=10.1136/jmg.40.10.733; RA De Silva M.G., Elliott K., Dahl H.-H.M., Fitzpatrick E., Wilcox S., RA Delatycki M., Williamson R., Efron D., Lynch M., Forrest S.; RT "Disruption of a novel member of a sodium/hydrogen exchanger family and RT DOCK3 is associated with an attention deficit hyperactivity disorder-like RT phenotype."; RL J. Med. Genet. 40:733-740(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR RP 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-589. RC TISSUE=Lymph node; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 248-645. RC TISSUE=Spleen; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 431-645. RC TISSUE=Neuroblastoma; RX PubMed=12880961; DOI=10.1016/s0304-3835(03)00085-5; RA Ohira M., Morohashi A., Nakamura Y., Isogai E., Furuya K., Hamano S., RA Machida T., Aoyama M., Fukumura M., Miyazaki K., Suzuki Y., Sugano S., RA Hirato J., Nakagawara A.; RT "Neuroblastoma oligo-capping cDNA project: toward the understanding of the RT genesis and biology of neuroblastoma."; RL Cancer Lett. 197:63-68(2003). RN [8] RP INTERACTION WITH RACK1. RX PubMed=18057008; DOI=10.1074/jbc.m705146200; RA Ohgaki R., Fukura N., Matsushita M., Mitsui K., Kanazawa H.; RT "Cell surface levels of organellar Na+/H+ exchanger isoform 6 are regulated RT by interaction with RACK1."; RL J. Biol. Chem. 283:4417-4429(2008). RN [9] RP INVOLVEMENT IN AUTS16, AND VARIANT AUTS16 423-ARG--ASN-645 DEL. RX PubMed=18621663; DOI=10.1126/science.1157657; RA Morrow E.M., Yoo S.-Y., Flavell S.W., Kim T.-K., Lin Y., Hill R.S., RA Mukaddes N.M., Balkhy S., Gascon G., Hashmi A., Al-Saad S., Ware J., RA Joseph R.M., Greenblatt R., Gleason D., Ertelt J.A., Apse K.A., Bodell A., RA Partlow J.N., Barry B., Yao H., Markianos K., Ferland R.J., Greenberg M.E., RA Walsh C.A.; RT "Identifying autism loci and genes by tracing recent shared ancestry."; RL Science 321:218-223(2008). RN [10] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-96. 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 [11] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF VAL-176; LEU-236 AND RP SER-438. RX PubMed=24065030; DOI=10.1038/ncomms3510; RA Kondapalli K.C., Hack A., Schushan M., Landau M., Ben-Tal N., Rao R.; RT "Functional evaluation of autism-associated mutations in NHE9."; RL Nat. Commun. 4:2510-2510(2013). RN [12] 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 [13] RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=28130443; DOI=10.1074/jbc.m116.769240; RA Beydoun R., Hamood M.A., Gomez Zubieta D.M., Kondapalli K.C.; RT "Na+/H+ exchanger 9 regulates iron mobilization at the blood-brain barrier RT in response to iron starvation."; RL J. Biol. Chem. 292:4293-4301(2017). CC -!- FUNCTION: Endosomal Na(+), K(+)/H(+) antiporter. Mediates the CC electroneutral exchange of endosomal luminal H(+) for a cytosolic Na(+) CC or K(+) (Probable). By facilitating proton efflux, SLC9A9 counteracts CC the acidity generated by vacuolar (V)-ATPase, thereby limiting luminal CC acidification. Regulates organellar pH and consequently, e.g., endosome CC maturation and endocytic trafficking of plasma membrane receptors and CC neurotransporters (PubMed:28130443, PubMed:15522866, PubMed:24065030). CC Promotes the recycling of transferrin receptors back to the cell CC surface to facilitate additional iron uptake in the brain CC (PubMed:28130443). Regulates synaptic transmission by regulating the CC luminal pH of axonal endosomes (By similarity). Regulates phagosome CC lumenal pH, thus affecting phagosome maturation, and consequently, CC microbicidal activity in macrophages (By similarity). Can also be CC active at the cell surface of specialized cells, e.g., in the inner ear CC hair bundles uses the high K(+) of the endolymph to regulate CC intracelular pH (By similarity). {ECO:0000250|UniProtKB:Q8BZ00, CC ECO:0000269|PubMed:15522866, ECO:0000269|PubMed:24065030, CC ECO:0000269|PubMed:28130443, ECO:0000305|PubMed:15522866}. 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:0000305|PubMed:15522866}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+)(out) + K(+)(in) = H(+)(in) + K(+)(out); CC Xref=Rhea:RHEA:29467, ChEBI:CHEBI:15378, ChEBI:CHEBI:29103; CC Evidence={ECO:0000250|UniProtKB:Q8BZ00}; CC -!- SUBUNIT: Homodimer; phosphatidylinositol-4,5-bisphosphate (PIP2) and CC phosphatidylinositol 3,4,5-trisphosphate (PIP3) could be involved in CC the dimer stabilization (By similarity). Interacts (via the C-terminus) CC with RACK1 (PubMed:18057008). Interacts with CHP1 (By similarity). CC {ECO:0000250|UniProtKB:D4A7H1, ECO:0000250|UniProtKB:F7B113, CC ECO:0000269|PubMed:18057008}. CC -!- INTERACTION: CC Q8IVB4; Q8IUH5: ZDHHC17; NbExp=2; IntAct=EBI-9092184, EBI-524753; CC -!- SUBCELLULAR LOCATION: Late endosome membrane CC {ECO:0000269|PubMed:15522866}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:F7B113}. Early endosome membrane CC {ECO:0000269|PubMed:24065030, ECO:0000269|PubMed:28130443}; Multi-pass CC membrane protein {ECO:0000250|UniProtKB:F7B113}. Recycling endosome CC membrane {ECO:0000269|PubMed:15522866, ECO:0000269|PubMed:24065030, CC ECO:0000269|PubMed:28130443}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:F7B113}. Cell membrane CC {ECO:0000250|UniProtKB:Q8BZ00}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:F7B113}. Cytoplasmic vesicle, phagosome membrane CC {ECO:0000250|UniProtKB:Q8BZ00}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:F7B113}. Note=Localized to the plasma membrane CC in inner ear hair cell bundle. {ECO:0000250|UniProtKB:Q8BZ00}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissues tested. CC Expressed at highest levels in heart and skeletal muscle, followed by CC placenta, kidney, and liver. Expressed in the brain, in the medulla and CC spinal cord. {ECO:0000269|PubMed:14569117, CC ECO:0000269|PubMed:15522866}. CC -!- INDUCTION: Conditioned medium from iron-depleted astrocytes increases CC SLC9A9 levels in human blood-brain barrier endothelial cells (hBMVECs). CC {ECO:0000269|PubMed:15522866}. CC -!- DISEASE: Note=A chromosomal aberration involving SLC9A9 has been found CC in a family with early-onset behavioral/developmental disorder with CC features of attention deficit-hyperactivity disorder and intellectual CC disability. Inversion inv(3)(p14:q21). The inversion disrupts DOCK3 and CC SLC9A9. {ECO:0000269|PubMed:14569117}. CC -!- DISEASE: Autism 16 (AUTS16) [MIM:613410]: A complex multifactorial, CC pervasive developmental disorder characterized by impairments in CC reciprocal social interaction and communication, restricted and CC stereotyped patterns of interests and activities, and the presence of CC developmental abnormalities by 3 years of age. Most individuals with CC autism also manifest moderate intellectual disability. AUTS16 can be CC associated with epilepsy. {ECO:0000269|PubMed:18621663}. Note=Disease CC susceptibility is associated with variants affecting the gene CC 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 -!- SEQUENCE CAUTION: CC Sequence=BAC04005.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AY254100; AAP80573.1; -; mRNA. DR EMBL; AB089794; BAD69592.1; -; mRNA. DR EMBL; AL832304; CAI46158.1; -; mRNA. DR EMBL; AC131210; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC035779; AAH35779.1; -; mRNA. DR EMBL; AK092932; BAC04005.1; ALT_INIT; mRNA. DR EMBL; AB075486; BAE45746.1; -; mRNA. DR CCDS; CCDS33872.1; -. DR RefSeq; NP_775924.1; NM_173653.3. DR AlphaFoldDB; Q8IVB4; -. DR SMR; Q8IVB4; -. DR BioGRID; 130044; 3. DR IntAct; Q8IVB4; 3. DR MINT; Q8IVB4; -. DR STRING; 9606.ENSP00000320246; -. DR TCDB; 2.A.36.1.19; the monovalent cation:proton antiporter-1 (cpa1) family. DR GlyCosmos; Q8IVB4; 1 site, No reported glycans. DR GlyGen; Q8IVB4; 1 site. DR iPTMnet; Q8IVB4; -. DR PhosphoSitePlus; Q8IVB4; -. DR SwissPalm; Q8IVB4; -. DR BioMuta; SLC9A9; -. DR DMDM; 44888222; -. DR EPD; Q8IVB4; -. DR jPOST; Q8IVB4; -. DR MassIVE; Q8IVB4; -. DR PaxDb; 9606-ENSP00000320246; -. DR PeptideAtlas; Q8IVB4; -. DR ProteomicsDB; 70678; -. DR Antibodypedia; 18118; 249 antibodies from 27 providers. DR DNASU; 285195; -. DR Ensembl; ENST00000316549.11; ENSP00000320246.6; ENSG00000181804.15. DR GeneID; 285195; -. DR KEGG; hsa:285195; -. DR MANE-Select; ENST00000316549.11; ENSP00000320246.6; NM_173653.4; NP_775924.1. DR UCSC; uc003evn.3; human. DR AGR; HGNC:20653; -. DR CTD; 285195; -. DR DisGeNET; 285195; -. DR GeneCards; SLC9A9; -. DR HGNC; HGNC:20653; SLC9A9. DR HPA; ENSG00000181804; Low tissue specificity. DR MalaCards; SLC9A9; -. DR MIM; 608396; gene. DR MIM; 613410; phenotype. DR neXtProt; NX_Q8IVB4; -. DR OpenTargets; ENSG00000181804; -. DR Orphanet; 106; NON RARE IN EUROPE: Autism. DR PharmGKB; PA134889062; -. DR VEuPathDB; HostDB:ENSG00000181804; -. DR eggNOG; KOG1965; Eukaryota. DR GeneTree; ENSGT00940000160094; -. DR HOGENOM; CLU_005912_7_0_1; -. DR InParanoid; Q8IVB4; -. DR OMA; FVKAMIY; -. DR OrthoDB; 1065060at2759; -. DR PhylomeDB; Q8IVB4; -. DR TreeFam; TF318755; -. DR PathwayCommons; Q8IVB4; -. DR Reactome; R-HSA-425986; Sodium/Proton exchangers. DR Reactome; R-HSA-5619052; Defective SLC9A9 causes autism 16 (AUTS16). DR SignaLink; Q8IVB4; -. DR SIGNOR; Q8IVB4; -. DR BioGRID-ORCS; 285195; 10 hits in 1153 CRISPR screens. DR ChiTaRS; SLC9A9; human. DR GenomeRNAi; 285195; -. DR Pharos; Q8IVB4; Tbio. DR PRO; PR:Q8IVB4; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q8IVB4; Protein. DR Bgee; ENSG00000181804; Expressed in calcaneal tendon and 173 other cell types or tissues. DR ExpressionAtlas; Q8IVB4; baseline and differential. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0032009; C:early phagosome; IEA:Ensembl. DR GO; GO:0031902; C:late endosome membrane; TAS:Reactome. DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB. DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB. DR GO; GO:0015386; F:potassium:proton antiporter activity; ISS:UniProtKB. DR GO; GO:0015385; F:sodium:proton antiporter activity; IBA:GO_Central. DR GO; GO:0042742; P:defense response to bacterium; IEA:Ensembl. DR GO; GO:0006811; P:monoatomic ion transport; TAS:Reactome. DR GO; GO:0090382; P:phagosome maturation; IEA:Ensembl. DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB. DR GO; GO:0051453; P:regulation of intracellular pH; IDA:UniProtKB. DR GO; GO:0098719; P:sodium ion import across plasma membrane; IBA:GO_Central. 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 InterPro; IPR002090; NHE-6/7/9. DR NCBIfam; TIGR00840; b_cpa1; 1. DR PANTHER; PTHR10110; SODIUM/HYDROGEN EXCHANGER; 1. DR PANTHER; PTHR10110:SF61; SODIUM_HYDROGEN EXCHANGER 9; 1. DR Pfam; PF00999; Na_H_Exchanger; 1. DR PRINTS; PR01084; NAHEXCHNGR. DR PRINTS; PR01088; NAHEXCHNGR6. DR Genevisible; Q8IVB4; HS. PE 1: Evidence at protein level; KW Antiport; Autism; Autism spectrum disorder; Cell membrane; KW Chromosomal rearrangement; Cytoplasmic vesicle; Disease variant; Endosome; KW Glycoprotein; Ion transport; Membrane; Reference proteome; Sodium; KW Sodium transport; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..645 FT /note="Sodium/hydrogen exchanger 9" FT /id="PRO_0000052367" FT TOPO_DOM 1..20 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 21..41 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 42..45 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 46..66 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 67..126 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 127..147 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 148..164 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 165..185 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 186..203 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 204..224 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 225..235 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 236..256 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 257..277 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 278..298 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 299..301 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 302..322 FT /note="Helical; Name=8" FT /evidence="ECO:0000255" FT TRANSMEM 323..343 FT /note="Helical; Name=9" FT /evidence="ECO:0000255" FT TOPO_DOM 344..364 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 365..385 FT /note="Helical; Name=10" FT /evidence="ECO:0000255" FT TOPO_DOM 386 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 387..407 FT /note="Helical; Name=11" FT /evidence="ECO:0000255" FT TOPO_DOM 408..429 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 430..450 FT /note="Helical; Name=12" FT /evidence="ECO:0000255" FT TOPO_DOM 451..465 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:F7B113" FT TRANSMEM 466..486 FT /note="Helical; Name=13" FT /evidence="ECO:0000255" FT TOPO_DOM 487..645 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:18057008" FT REGION 594..622 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 96 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT VARIANT 423..645 FT /note="Missing (in AUTS16)" FT /evidence="ECO:0000269|PubMed:18621663" FT /id="VAR_087549" FT VARIANT 540 FT /note="I -> V (in dbSNP:rs16853300)" FT /id="VAR_050232" FT VARIANT 589 FT /note="I -> V (in dbSNP:rs2289491)" FT /evidence="ECO:0000269|PubMed:17974005" FT /id="VAR_022114" FT MUTAGEN 176 FT /note="V->I: Normal protein expression. Does not affect FT endosomal localizatiion. Fails to alkalinizes endosomal FT lumen." FT /evidence="ECO:0000269|PubMed:24065030" FT MUTAGEN 236 FT /note="L->S: Normal protein expression. Fails to FT alkalinizes endosomal lumen. Does not affect endosomal FT localizatiion." FT /evidence="ECO:0000269|PubMed:24065030" FT MUTAGEN 438 FT /note="S->P: Normal protein expression. Fails to FT alkalinizes endosomal lumen. Does not affect endosomal FT localizatiion." FT /evidence="ECO:0000269|PubMed:24065030" SQ SEQUENCE 645 AA; 72565 MW; E23F7385D0B3ACAB CRC64; MERQSRVMSE KDEYQFQHQG AVELLVFNFL LILTILTIWL FKNHRFRFLH ETGGAMVYGL IMGLILRYAT APTDIESGTV YDCVKLTFSP STLLVNITDQ VYEYKYKREI SQHNINPHQG NAILEKMTFD PEIFFNVLLP PIIFHAGYSL KKRHFFQNLG SILTYAFLGT AISCIVIGLI MYGFVKAMIH AGQLKNGDFH FTDCLFFGSL MSATDPVTVL AIFHELHVDP DLYTLLFGES VLNDAVAIVL TYSISIYSPK ENPNAFDAAA FFQSVGNFLG IFAGSFAMGS AYAIITALLT KFTKLCEFPM LETGLFFLLS WSAFLSAEAA GLTGIVAVLF CGVTQAHYTY NNLSSDSKIR TKQLFEFMNF LAENVIFCYM GLALFTFQNH IFNALFILGA FLAIFVARAC NIYPLSFLLN LGRKQKIPWN FQHMMMFSGL RGAIAFALAI RNTESQPKQM MFTTTLLLVF FTVWVFGGGT TPMLTWLQIR VGVDLDENLK EDPSSQHQEA NNLDKNMTKA ESARLFRMWY SFDHKYLKPI LTHSGPPLTT TLPEWCGPIS RLLTSPQAYG EQLKEDDVEC IVNQDELAIN YQEQASSPCS PPARLGLDQK ASPQTPGKEN IYEGDLGLGG YELKLEQTLG QSQLN //