ID VPP1_HUMAN Reviewed; 837 AA. AC Q93050; B7Z3B7; Q8N5G7; Q9NSX0; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 15-FEB-2005, sequence version 3. DT 27-MAR-2024, entry version 202. DE RecName: Full=V-type proton ATPase 116 kDa subunit a 1; DE Short=V-ATPase 116 kDa subunit a 1; DE AltName: Full=Clathrin-coated vesicle/synaptic vesicle proton pump 116 kDa subunit; DE AltName: Full=Vacuolar adenosine triphosphatase subunit Ac116; DE AltName: Full=Vacuolar proton pump subunit 1; DE AltName: Full=Vacuolar proton translocating ATPase 116 kDa subunit a isoform 1; GN Name=ATP6V0A1; Synonyms=ATP6N1, ATP6N1A, VPP1; 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 2). RC TISSUE=Pancreas; RA Fehr C.N., Gillies R.J., Wang H.-Y., Ullrich A.; RT "Sequence and alternative splicing in human 115 kDa subunit of vacuolar- RT type H(+)-ATPase."; RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Hippocampus, 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=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 675-837 (ISOFORM 2). RC TISSUE=Testis; 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 [7] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=12643545; DOI=10.1021/pr025562r; RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., RA Appella E.; RT "Proteomic analysis of early melanosomes: identification of novel RT melanosomal proteins."; RL J. Proteome Res. 2:69-79(2003). RN [8] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=17081065; DOI=10.1021/pr060363j; RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; RT "Proteomic and bioinformatic characterization of the biogenesis and RT function of melanosomes."; RL J. Proteome Res. 5:3135-3144(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-360, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [10] 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 [11] RP INTERACTION WITH SPAAR. RX PubMed=28024296; DOI=10.1038/nature21034; RA Matsumoto A., Pasut A., Matsumoto M., Yamashita R., Fung J., Monteleone E., RA Saghatelian A., Nakayama K.I., Clohessy J.G., Pandolfi P.P.; RT "mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR RT polypeptide."; RL Nature 541:228-232(2017). RN [12] {ECO:0007744|PDB:6WLW, ECO:0007744|PDB:6WM2, ECO:0007744|PDB:6WM3, ECO:0007744|PDB:6WM4} RP STRUCTURE BY ELECTRON MICROSCOPY (3.00 ANGSTROMS), FUNCTION, IDENTIFICATION RP IN THE V-ATPASE COMPLEX, AND GLYCOSYLATION AT ASN-488. RX PubMed=33065002; DOI=10.1016/j.molcel.2020.09.029; RA Wang L., Wu D., Robinson C.V., Wu H., Fu T.M.; RT "Structures of a Complete Human V-ATPase Reveal Mechanisms of Its RT Assembly."; RL Mol. Cell 80:501-511.e3(2020). RN [13] RP INVOLVEMENT IN DEE104, VARIANTS DEE104 PRO-477; GLU-551; GLN-740 AND RP HIS-804, CHARACTERIZATION OF VARIANT DEE104 GLN-740, INVOLVEMENT IN NEDEBA, RP VARIANT NEDEBA TRP-495, AND FUNCTION. RX PubMed=34909687; DOI=10.1093/braincomms/fcab245; RG ATPase Consortium; RA Bott L.C., Forouhan M., Lieto M., Sala A.J., Ellerington R., Johnson J.O., RA Speciale A.A., Criscuolo C., Filla A., Chitayat D., Alkhunaizi E., RA Shannon P., Nemeth A.H., Angelucci F., Lim W.F., Striano P., Zara F., RA Helbig I., Muona M., Courage C., Lehesjoki A.E., Berkovic S.F., RA Fischbeck K.H., Brancati F., Morimoto R.I., Wood M.J.A., Rinaldi C.; RT "Variants in ATP6V0A1 cause progressive myoclonus epilepsy and RT developmental and epileptic encephalopathy."; RL Brain Commun. 3:fcab245-fcab245(2021). RN [14] RP INVOLVEMENT IN DEE104, VARIANT DEE104 GLN-740, CHARACTERIZATION OF VARIANT RP DEE104 GLN-740, INVOLVEMENT IN NEDEBA, FUNCTION, VARIANTS NEDEBA PRO-505 RP AND ASP-527, AND CHARACTERIZATION OF VARIANTS NEDEBA PRO-505 AND ASP-527. RX PubMed=33833240; DOI=10.1038/s41467-021-22389-5; RA Aoto K., Kato M., Akita T., Nakashima M., Mutoh H., Akasaka N., Tohyama J., RA Nomura Y., Hoshino K., Ago Y., Tanaka R., Epstein O., Ben-Haim R., RA Heyman E., Miyazaki T., Belal H., Takabayashi S., Ohba C., Takata A., RA Mizuguchi T., Miyatake S., Miyake N., Fukuda A., Matsumoto N., Saitsu H.; RT "ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H+-ATPases RT is essential for brain development in humans and mice."; RL Nat. Commun. 12:2107-2107(2021). CC -!- FUNCTION: Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), CC a multisubunit enzyme composed of a peripheral complex (V1) that CC hydrolyzes ATP and a membrane integral complex (V0) that transports CC protons across cellular membranes. V-ATPase is responsible for the CC acidification of various organelles, such as lysosomes, endosomes, the CC trans-Golgi network, and secretory granules, including synaptic CC vesicles (PubMed:33065002, PubMed:34909687, PubMed:33833240). In CC certain cell types, can be exported to the plasma membrane, where it is CC involved in the acidification of the extracellular environment (By CC similarity). Required for assembly and activity of the vacuolar ATPase CC (By similarity). Through its action on compartment acidification, plays CC an essential role in neuronal development in terms of integrity and CC connectivity of neurons (PubMed:33833240). CC {ECO:0000250|UniProtKB:P32563, ECO:0000250|UniProtKB:Q29466, CC ECO:0000269|PubMed:33065002, ECO:0000269|PubMed:33833240, CC ECO:0000269|PubMed:34909687}. CC -!- SUBUNIT: V-ATPase is a heteromultimeric enzyme made up of two CC complexes: the ATP-hydrolytic V1 complex and the proton translocation CC V0 complex (PubMed:33065002). The V1 complex consists of three CC catalytic AB heterodimers that form a heterohexamer, three peripheral CC stalks each consisting of EG heterodimers, one central rotor including CC subunits D and F, and the regulatory subunits C and H CC (PubMed:33065002). The proton translocation complex V0 consists of the CC proton transport subunit a, a ring of proteolipid subunits c9c'', CC rotary subunit d, subunits e and f, and the accessory subunits CC ATP6AP1/Ac45 and ATP6AP2/PRR (PubMed:33065002). Interacts with SPAAR CC (PubMed:28024296). {ECO:0000269|PubMed:28024296, CC ECO:0000269|PubMed:33065002}. CC -!- INTERACTION: CC Q93050; P06927: E5; Xeno; NbExp=3; IntAct=EBI-2891238, EBI-8561748; CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle CC membrane {ECO:0000250|UniProtKB:P25286}; Multi-pass membrane protein CC {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle CC membrane {ECO:0000250|UniProtKB:P25286}; Multi-pass membrane protein CC {ECO:0000255}. Melanosome {ECO:0000269|PubMed:12643545, CC ECO:0000269|PubMed:17081065}. Note=Identified by mass spectrometry in CC melanosome fractions from stage I to stage IV. CC {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=I; CC IsoId=Q93050-2; Sequence=Displayed; CC Name=2; Synonyms=II; CC IsoId=Q93050-1; Sequence=VSP_012814; CC Name=3; CC IsoId=Q93050-3; Sequence=VSP_043532, VSP_012814; CC -!- DISEASE: Developmental and epileptic encephalopathy 104 (DEE104) CC [MIM:619970]: A form of epileptic encephalopathy, a heterogeneous group CC of early-onset epilepsies characterized by refractory seizures, CC neurodevelopmental impairment, and poor prognosis. Development is CC normal prior to seizure onset, after which cognitive and motor delays CC become apparent. DEE104 is an autosomal dominant form characterized by CC onset of developmental delay and drug-resistant focal and generalized CC tonic-clonic seizures in the first few months of life. CC {ECO:0000269|PubMed:33833240, ECO:0000269|PubMed:34909687}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Neurodevelopmental disorder with epilepsy and brain atrophy CC (NEDEBA) [MIM:619971]: An autosomal recessive disorder characterized by CC global developmental delay, early-onset progressive myoclonus epilepsy CC and ataxia. Brain imaging shows progressive atrophy. CC {ECO:0000269|PubMed:33833240, ECO:0000269|PubMed:34909687}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the V-ATPase 116 kDa subunit family. CC {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; Z71460; CAA96077.1; -; mRNA. DR EMBL; AK295682; BAH12153.1; -; mRNA. DR EMBL; AK316305; BAH14676.1; -; mRNA. DR EMBL; AC067852; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC107993; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471152; EAW60830.1; -; Genomic_DNA. DR EMBL; BC032398; AAH32398.1; -; mRNA. DR EMBL; AL137683; CAB70874.1; -; mRNA. DR CCDS; CCDS11426.1; -. [Q93050-1] DR CCDS; CCDS45683.1; -. [Q93050-3] DR CCDS; CCDS45684.1; -. [Q93050-2] DR PIR; T46449; T46449. DR RefSeq; NP_001123492.1; NM_001130020.1. [Q93050-3] DR RefSeq; NP_001123493.1; NM_001130021.1. [Q93050-2] DR RefSeq; NP_005168.2; NM_005177.3. [Q93050-1] DR PDB; 6WLW; EM; 3.00 A; R=1-837. DR PDB; 6WM2; EM; 3.10 A; R=1-837. DR PDB; 6WM3; EM; 3.40 A; R=1-837. DR PDB; 6WM4; EM; 3.60 A; R=1-837. DR PDB; 7U4T; EM; 3.60 A; R=1-837. DR PDBsum; 6WLW; -. DR PDBsum; 6WM2; -. DR PDBsum; 6WM3; -. DR PDBsum; 6WM4; -. DR PDBsum; 7U4T; -. DR AlphaFoldDB; Q93050; -. DR EMDB; EMD-21844; -. DR EMDB; EMD-21847; -. DR EMDB; EMD-21848; -. DR EMDB; EMD-21849; -. DR EMDB; EMD-26334; -. DR SMR; Q93050; -. DR BioGRID; 107018; 218. DR ComplexPortal; CPX-2470; Vacuolar proton translocating ATPase complex, ATP6V0A1 variant. DR IntAct; Q93050; 71. DR MINT; Q93050; -. DR STRING; 9606.ENSP00000264649; -. DR DrugBank; DB01133; Tiludronic acid. DR TCDB; 3.A.2.2.4; the h+- or na+-translocating f-type, v-type and a-type atpase (f-atpase) superfamily. DR GlyCosmos; Q93050; 1 site, No reported glycans. DR GlyGen; Q93050; 1 site. DR iPTMnet; Q93050; -. DR MetOSite; Q93050; -. DR PhosphoSitePlus; Q93050; -. DR SwissPalm; Q93050; -. DR BioMuta; ATP6V0A1; -. DR DMDM; 59803038; -. DR EPD; Q93050; -. DR jPOST; Q93050; -. DR MassIVE; Q93050; -. DR MaxQB; Q93050; -. DR PaxDb; 9606-ENSP00000264649; -. DR PeptideAtlas; Q93050; -. DR ProteomicsDB; 75687; -. [Q93050-2] DR ProteomicsDB; 75688; -. [Q93050-1] DR ProteomicsDB; 75689; -. [Q93050-3] DR Pumba; Q93050; -. DR Antibodypedia; 16938; 126 antibodies from 21 providers. DR DNASU; 535; -. DR Ensembl; ENST00000264649.10; ENSP00000264649.5; ENSG00000033627.18. [Q93050-3] DR Ensembl; ENST00000343619.9; ENSP00000342951.3; ENSG00000033627.18. [Q93050-2] DR Ensembl; ENST00000393829.6; ENSP00000377415.2; ENSG00000033627.18. [Q93050-1] DR Ensembl; ENST00000703901.1; ENSP00000515539.1; ENSG00000033627.18. [Q93050-2] DR GeneID; 535; -. DR KEGG; hsa:535; -. DR MANE-Select; ENST00000343619.9; ENSP00000342951.3; NM_001130021.3; NP_001123493.1. DR UCSC; uc002hzq.4; human. [Q93050-2] DR AGR; HGNC:865; -. DR CTD; 535; -. DR DisGeNET; 535; -. DR GeneCards; ATP6V0A1; -. DR HGNC; HGNC:865; ATP6V0A1. DR HPA; ENSG00000033627; Tissue enhanced (brain). DR MalaCards; ATP6V0A1; -. DR MIM; 192130; gene. DR MIM; 619970; phenotype. DR MIM; 619971; phenotype. DR neXtProt; NX_Q93050; -. DR OpenTargets; ENSG00000033627; -. DR PharmGKB; PA25146; -. DR VEuPathDB; HostDB:ENSG00000033627; -. DR eggNOG; KOG2189; Eukaryota. DR GeneTree; ENSGT00950000182881; -. DR HOGENOM; CLU_005230_0_1_1; -. DR InParanoid; Q93050; -. DR OMA; FYLWFFL; -. DR OrthoDB; 1967517at2759; -. DR PhylomeDB; Q93050; -. DR TreeFam; TF300346; -. DR BioCyc; MetaCyc:ENSG00000033627-MONOMER; -. DR PathwayCommons; Q93050; -. DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-77387; Insulin receptor recycling. DR Reactome; R-HSA-917977; Transferrin endocytosis and recycling. DR Reactome; R-HSA-983712; Ion channel transport. DR SignaLink; Q93050; -. DR BioGRID-ORCS; 535; 28 hits in 1165 CRISPR screens. DR ChiTaRS; ATP6V0A1; human. DR GeneWiki; ATPase,_H%2B_transporting,_lysosomal_V0_subunit_a1; -. DR GenomeRNAi; 535; -. DR Pharos; Q93050; Tbio. DR PRO; PR:Q93050; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q93050; Protein. DR Bgee; ENSG00000033627; Expressed in right frontal lobe and 201 other cell types or tissues. DR ExpressionAtlas; Q93050; baseline and differential. DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005765; C:lysosomal membrane; TAS:ParkinsonsUK-UCL. DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IDA:ComplexPortal. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0033176; C:proton-transporting V-type ATPase complex; NAS:ComplexPortal. DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome. DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016471; C:vacuolar proton-transporting V-type ATPase complex; IBA:GO_Central. DR GO; GO:0000220; C:vacuolar proton-transporting V-type ATPase, V0 domain; ISS:UniProtKB. DR GO; GO:0051117; F:ATPase binding; IPI:UniProtKB. DR GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; IEA:InterPro. DR GO; GO:0048388; P:endosomal lumen acidification; NAS:ComplexPortal. DR GO; GO:0007042; P:lysosomal lumen acidification; NAS:ComplexPortal. DR GO; GO:1902600; P:proton transmembrane transport; NAS:ComplexPortal. DR GO; GO:0016241; P:regulation of macroautophagy; IMP:ParkinsonsUK-UCL. DR GO; GO:0097401; P:synaptic vesicle lumen acidification; IEA:Ensembl. DR GO; GO:0007035; P:vacuolar acidification; IBA:GO_Central. DR InterPro; IPR002490; V-ATPase_116kDa_su. DR InterPro; IPR026028; V-type_ATPase_116kDa_su_euka. DR PANTHER; PTHR11629:SF68; V-TYPE PROTON ATPASE 116 KDA SUBUNIT A 1; 1. DR PANTHER; PTHR11629; VACUOLAR PROTON ATPASES; 1. DR Pfam; PF01496; V_ATPase_I; 1. DR PIRSF; PIRSF001293; ATP6V0A1; 1. DR Genevisible; Q93050; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasmic vesicle; Disease variant; KW Epilepsy; Glycoprotein; Hydrogen ion transport; Intellectual disability; KW Ion transport; Membrane; Phosphoprotein; Reference proteome; Synapse; KW Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..837 FT /note="V-type proton ATPase 116 kDa subunit a 1" FT /id="PRO_0000119211" FT TOPO_DOM 1..388 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 389..407 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 408..409 FT /note="Vacuolar" FT /evidence="ECO:0000255" FT TRANSMEM 410..426 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 427..441 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 442..471 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 472..534 FT /note="Vacuolar" FT /evidence="ECO:0000255" FT TRANSMEM 535..554 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 555..572 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 573..593 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 594..638 FT /note="Vacuolar" FT /evidence="ECO:0000255" FT TRANSMEM 639..658 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 659..724 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 725..749 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 750..770 FT /note="Vacuolar" FT /evidence="ECO:0000255" FT TRANSMEM 771..809 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 810..837 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT MOD_RES 250 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1G4" FT MOD_RES 360 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 364 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1G4" FT CARBOHYD 488 FT /note="N-linked (GalNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:33065002, FT ECO:0000312|PDB:6WM3, ECO:0000312|PDB:6WM4" FT VAR_SEQ 141 FT /note="E -> EAELHHQQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043532" FT VAR_SEQ 705..710 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:17974005, ECO:0000303|Ref.1" FT /id="VSP_012814" FT VARIANT 477 FT /note="S -> P (in DEE104; uncertain significance)" FT /evidence="ECO:0000269|PubMed:34909687" FT /id="VAR_087489" FT VARIANT 495 FT /note="R -> W (in NEDEBA; uncertain significance; FT dbSNP:rs781278654)" FT /evidence="ECO:0000269|PubMed:34909687" FT /id="VAR_087490" FT VARIANT 505 FT /note="A -> P (in NEDEBA; impaired acidification of FT endolysosomal compartments; when tested in transgenic mice, FT homozygosity leads to body weights lower than in wild-type FT animals, impaired motor function, defects in the neuronal FT development and synapse formation and eventually death at FT about 2 weeks of age)" FT /evidence="ECO:0000269|PubMed:33833240" FT /id="VAR_087491" FT VARIANT 527 FT /note="N -> D (in NEDEBA; uncertain significance; impaired FT acidification of endolysosomal compartments; FT dbSNP:rs766856192)" FT /evidence="ECO:0000269|PubMed:33833240" FT /id="VAR_087492" FT VARIANT 551 FT /note="G -> E (in DEE104; uncertain significance)" FT /evidence="ECO:0000269|PubMed:34909687" FT /id="VAR_087493" FT VARIANT 740 FT /note="R -> Q (in DEE104; impaired acidification of FT endolysosomal compartments; when tested in transgenic mice, FT homozygosity leads to embryonic death at 5 to 6 dpc; FT dbSNP:rs1567871600)" FT /evidence="ECO:0000269|PubMed:33833240, FT ECO:0000269|PubMed:34909687" FT /id="VAR_087494" FT VARIANT 804 FT /note="R -> H (in DEE104)" FT /evidence="ECO:0000269|PubMed:34909687" FT /id="VAR_087495" FT CONFLICT 750..751 FT /note="QL -> HV (in Ref. 1; CAA96077)" FT /evidence="ECO:0000305" FT STRAND 10..18 FT /evidence="ECO:0007829|PDB:6WM2" FT HELIX 19..32 FT /evidence="ECO:0007829|PDB:6WM2" FT STRAND 35..37 FT /evidence="ECO:0007829|PDB:6WM3" FT HELIX 46..49 FT /evidence="ECO:0007829|PDB:6WM2" FT HELIX 52..74 FT /evidence="ECO:0007829|PDB:6WM2" FT HELIX 85..87 FT /evidence="ECO:0007829|PDB:6WM3" FT HELIX 94..132 FT /evidence="ECO:0007829|PDB:6WM2" FT STRAND 177..179 FT /evidence="ECO:0007829|PDB:6WM2" FT HELIX 180..189 FT /evidence="ECO:0007829|PDB:6WM2" FT STRAND 197..202 FT /evidence="ECO:0007829|PDB:6WM2" FT TURN 209..211 FT /evidence="ECO:0007829|PDB:6WM2" FT STRAND 217..222 FT /evidence="ECO:0007829|PDB:6WM2" FT HELIX 227..239 FT /evidence="ECO:0007829|PDB:6WM2" FT HELIX 253..308 FT /evidence="ECO:0007829|PDB:6WM2" FT STRAND 309..312 FT /evidence="ECO:0007829|PDB:6WM2" FT STRAND 314..326 FT /evidence="ECO:0007829|PDB:6WM2" FT HELIX 327..329 FT /evidence="ECO:0007829|PDB:6WM2" FT HELIX 330..343 FT /evidence="ECO:0007829|PDB:6WM2" FT STRAND 352..355 FT /evidence="ECO:0007829|PDB:6WM2" FT HELIX 372..378 FT /evidence="ECO:0007829|PDB:6WLW" FT TURN 379..381 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 392..405 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 410..425 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 427..431 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 438..445 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 447..464 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 484..487 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 491..496 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 498..501 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 515..518 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 520..523 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 528..553 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 556..561 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 565..567 FT /evidence="ECO:0007829|PDB:6WLW" FT TURN 568..571 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 572..582 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 584..596 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 602..604 FT /evidence="ECO:0007829|PDB:6WM3" FT HELIX 608..616 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 622..624 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 632..649 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 653..665 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 713..736 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 737..739 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 740..757 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 758..761 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 768..789 FT /evidence="ECO:0007829|PDB:6WLW" FT TURN 790..792 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 793..807 FT /evidence="ECO:0007829|PDB:6WLW" FT TURN 808..810 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 811..813 FT /evidence="ECO:0007829|PDB:6WLW" SQ SEQUENCE 837 AA; 96413 MW; 80E4842CF6ADEE44 CRC64; MGELFRSEEM TLAQLFLQSE AAYCCVSELG ELGKVQFRDL NPDVNVFQRK FVNEVRRCEE MDRKLRFVEK EIRKANIPIM DTGENPEVPF PRDMIDLEAN FEKIENELKE INTNQEALKR NFLELTELKF ILRKTQQFFD EMADPDLLEE SSSLLEPSEM GRGTPLRLGF VAGVINRERI PTFERMLWRV CRGNVFLRQA EIENPLEDPV TGDYVHKSVF IIFFQGDQLK NRVKKICEGF RASLYPCPET PQERKEMASG VNTRIDDLQM VLNQTEDHRQ RVLQAAAKNI RVWFIKVRKM KAIYHTLNLC NIDVTQKCLI AEVWCPVTDL DSIQFALRRG TEHSGSTVPS ILNRMQTNQT PPTYNKTNKF TYGFQNIVDA YGIGTYREIN PAPYTIITFP FLFAVMFGDF GHGILMTLFA VWMVLRESRI LSQKNENEMF STVFSGRYII LLMGVFSMYT GLIYNDCFSK SLNIFGSSWS VRPMFTYNWT EETLRGNPVL QLNPALPGVF GGPYPFGIDP IWNIATNKLT FLNSFKMKMS VILGIIHMLF GVSLSLFNHI YFKKPLNIYF GFIPEIIFMT SLFGYLVILI FYKWTAYDAH TSENAPSLLI HFINMFLFSY PESGYSMLYS GQKGIQCFLV VVALLCVPWM LLFKPLVLRR QYLRRKHLGT LNFGGIRVGN GPTEEDAEII QHDQLSTHSE DADEPSEDEV FDFGDTMVHQ AIHTIEYCLG CISNTASYLR LWALSLAHAQ LSEVLWTMVI HIGLSVKSLA GGLVLFFFFT AFATLTVAIL LIMEGLSAFL HALRLHWVEF QNKFYSGTGF KFLPFSFEHI REGKFEE //