ID VATA_HUMAN Reviewed; 617 AA. AC P38606; B2RBR8; B7Z1R5; D3DN75; Q53YD9; Q96DY6; Q9UHY3; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 02-AUG-2002, sequence version 2. DT 28-JAN-2026, entry version 226. DE RecName: Full=V-type proton ATPase catalytic subunit A; DE Short=V-ATPase subunit A; DE EC=7.1.2.2 {ECO:0000250|UniProtKB:P50516}; DE AltName: Full=V-ATPase 69 kDa subunit; DE AltName: Full=Vacuolar ATPase isoform VA68; DE AltName: Full=Vacuolar proton pump subunit alpha; GN Name=ATP6V1A; Synonyms=ATP6A1, ATP6V1A1, VPP2; 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). RC TISSUE=Fetal adrenal gland, and Leukocyte; RX PubMed=8463241; DOI=10.1016/s0021-9258(18)53147-1; RA van Hille B., Richener H., Evans D.B., Green J.R., Bilbe G.; RT "Identification of two subunit A isoforms of the vacuolar H(+)-ATPase in RT human osteoclastoma."; RL J. Biol. Chem. 268:7075-7080(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Hypothalamus; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Amygdala, and Cerebellum; 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]. 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 (ISOFORM 2), CLEAVAGE OF RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 2), AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [10] RP SUBCELLULAR LOCATION, AND INTERACTION WITH WFS1. RX PubMed=23035048; DOI=10.1093/hmg/dds400; RA Gharanei S., Zatyka M., Astuti D., Fenton J., Sik A., Nagy Z., RA Barrett T.G.; RT "Vacuolar-type H+-ATPase V1A subunit is a molecular partner of Wolfram RT syndrome 1 (WFS1) protein, which regulates its expression and stability."; RL Hum. Mol. Genet. 22:203-217(2013). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-136 AND SER-384, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and 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 [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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [14] RP INVOLVEMENT IN ARCL2D, TISSUE SPECIFICITY, AND VARIANTS ARCL2D ASP-72 AND RP CYS-338. RX PubMed=28065471; DOI=10.1016/j.ajhg.2016.12.010; RA Van Damme T., Gardeitchik T., Mohamed M., Guerrero-Castillo S., RA Freisinger P., Guillemyn B., Kariminejad A., Dalloyaux D., van Kraaij S., RA Lefeber D.J., Syx D., Steyaert W., De Rycke R., Hoischen A., Kamsteeg E.J., RA Wong S.Y., van Scherpenzeel M., Jamali P., Brandt U., Nijtmans L., RA Korenke G.C., Chung B.H., Mak C.C., Hausser I., Kornak U., RA Fischer-Zirnsak B., Strom T.M., Meitinger T., Alanay Y., Utine G.E., RA Leung P.K., Ghaderi-Sohi S., Coucke P., Symoens S., De Paepe A., Thiel C., RA Haack T.B., Malfait F., Morava E., Callewaert B., Wevers R.A.; RT "Mutations in ATP6V1E1 or ATP6V1A cause autosomal-recessive cutis laxa."; RL Am. J. Hum. Genet. 100:216-227(2017). RN [15] RP FUNCTION. RX PubMed=28296633; DOI=10.7554/elife.22693; RA Miles A.L., Burr S.P., Grice G.L., Nathan J.A.; RT "The vacuolar-ATPase complex and assembly factors, TMEM199 and CCDC115, RT control HIF1alpha prolyl hydroxylation by regulating cellular iron RT levels."; RL Elife 6:E22693-E22693(2017). RN [16] RP INVOLVEMENT IN IECEE3, VARIANTS IECEE3 ARG-27; TYR-100; ASN-349 AND RP GLY-371, VARIANTS ASN-11 AND ARG-249, CHARACTERIZATION OF VARIANTS IECEE3 RP TYR-100 AND ASN-349, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=29668857; DOI=10.1093/brain/awy092; RA Fassio A., Esposito A., Kato M., Saitsu H., Mei D., Marini C., Conti V., RA Nakashima M., Okamoto N., Olmez Turker A., Albuz B., Semerci Guenduez C.N., RA Yanagihara K., Belmonte E., Maragliano L., Ramsey K., Balak C., Siniard A., RA Narayanan V., Ohba C., Shiina M., Ogata K., Matsumoto N., Benfenati F., RA Guerrini R.; RT "De novo mutations of the ATP6V1A gene cause developmental encephalopathy RT with epilepsy."; RL Brain 141:1703-1718(2018). RN [17] RP INTERACTION WITH CRYAB AND MTOR. RX PubMed=31786107; DOI=10.1016/j.bbagen.2019.129496; RA Cui X., Feng R., Wang J., Du C., Pi X., Chen D., Li J., Li H., Zhang J., RA Zhang J., Mu H., Zhang F., Liu M., Hu Y.; RT "Heat shock factor 4 regulates lysosome activity by modulating the alphaB- RT crystallin-ATP6V1A-mTOR complex in ocular lens."; RL Biochim. Biophys. Acta 1864:129496-129496(2020). RN [18] RP FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, INTERACTION WITH RP RABIES VIRUS PROTEIN M (MICROBIAL INFECTION), AND MUTAGENESIS OF LYS-256 RP AND GLU-279. RX PubMed=33208464; DOI=10.1074/jbc.ra120.014190; RA Liu X., Li F., Zhang J., Wang L., Wang J., Wen Z., Wang Z., Shuai L., RA Wang X., Ge J., Zhao D., Bu Z.; RT "The ATPase ATP6V1A facilitates rabies virus replication by promoting RT virion uncoating and interacting with the viral matrix protein."; RL J. Biol. Chem. 296:100096-100096(2020). RN [19] RP REVIEW. RX PubMed=32001091; DOI=10.1016/j.tibs.2019.12.007; RA Vasanthakumar T., Rubinstein J.L.; RT "Structure and Roles of V-type ATPases."; RL Trends Biochem. Sci. 45:295-307(2020). RN [20] {ECO:0007744|PDB:6WLZ, ECO:0007744|PDB:6WM2, ECO:0007744|PDB:6WM3, ECO:0007744|PDB:6WM4} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) IN COMPLEX WITH ADP, RP FUNCTION, AND IDENTIFICATION IN THE V-ATPASE COMPLEX. 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). CC -!- FUNCTION: Catalytic subunit of the V1 complex of vacuolar(H+)-ATPase CC (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) CC that hydrolyzes ATP and a membrane integral complex (V0) that CC translocates protons (PubMed:8463241). V-ATPase is responsible for CC acidifying and maintaining the pH of intracellular compartments and in CC some cell types, is targeted to the plasma membrane, where it is CC responsible for acidifying the extracellular environment CC (PubMed:32001091). In aerobic conditions, involved in intracellular CC iron homeostasis, thus triggering the activity of Fe(2+) prolyl CC hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and CC subsequent proteasomal degradation (PubMed:28296633). May play a role CC in neurite development and synaptic connectivity (PubMed:29668857). CC {ECO:0000250|UniProtKB:P50516, ECO:0000269|PubMed:28296633, CC ECO:0000269|PubMed:29668857, ECO:0000269|PubMed:8463241, CC ECO:0000303|PubMed:32001091}. CC -!- FUNCTION: (Microbial infection) Plays an important role in virion CC uncoating during Rabies virus replication after membrane fusion. CC Specifically, participates in the dissociation of incoming viral matrix CC M proteins uncoating through direct interaction. CC {ECO:0000269|PubMed:33208464}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O + 4 H(+)(in) = ADP + phosphate + 5 H(+)(out); CC Xref=Rhea:RHEA:57720, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=7.1.2.2; CC Evidence={ECO:0000250|UniProtKB:P50516}; CC -!- ACTIVITY REGULATION: ATP hydrolysis occurs at the interface between the CC nucleotide-binding domains of subunits A and B (By similarity). ATP CC hydrolysis triggers a conformational change in the subunits D and F, CC which induces a shift of subunit d (By similarity). The c-ring is CC subsequently rotated and results in a continuous proton translocation CC across the membrane (By similarity). {ECO:0000250|UniProtKB:P31404}. 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 the V0 CC complex V-ATPase subunit a4 ATP6V0A4 (By similarity). Interacts with CC WFS1 (PubMed:23035048). Interacts with alpha-crystallin B chain/CRYAB CC and with MTOR, forming a ternary complex (PubMed:31786107). CC {ECO:0000250|UniProtKB:P50516, ECO:0000269|PubMed:23035048, CC ECO:0000269|PubMed:31786107, ECO:0000269|PubMed:33065002}. CC -!- SUBUNIT: (Microbial infection) Interacts with Rabies virus protein M; CC this interaction promotes virion uncoating. CC {ECO:0000269|PubMed:33208464}. CC -!- INTERACTION: CC P38606; P0DOF2: M; Xeno; NbExp=10; IntAct=EBI-1054757, EBI-25567776; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:29668857, CC ECO:0000269|PubMed:33208464}. Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P50516}. Cytoplasmic vesicle, secretory vesicle CC {ECO:0000269|PubMed:23035048}. Cytoplasmic vesicle, clathrin-coated CC vesicle membrane {ECO:0000250|UniProtKB:P31404}; Peripheral membrane CC protein {ECO:0000305}. Lysosome {ECO:0000250|UniProtKB:P50516}. CC Note=Co-localizes with WFS1 in the secretory granules in neuroblastoma CC cell lines. {ECO:0000269|PubMed:23035048}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P38606-1; Sequence=Displayed; CC Name=2; CC IsoId=P38606-2; Sequence=VSP_056408; CC -!- TISSUE SPECIFICITY: High expression in the skin. CC {ECO:0000269|PubMed:28065471}. CC -!- PTM: Phosphorylation at Ser-384 by AMPK down-regulates its enzyme CC activity. {ECO:0000250|UniProtKB:P50516}. CC -!- DISEASE: Cutis laxa, autosomal recessive, 2D (ARCL2D) [MIM:617403]: A CC form of cutis laxa, a disorder characterized by an excessive congenital CC skin wrinkling, a large fontanelle with delayed closure, a typical CC facial appearance with downslanting palpebral fissures, and a general CC connective tissue weakness. Most ARCL2D patients exhibit severe CC hypotonia as well as cardiovascular and neurologic involvement. CC {ECO:0000269|PubMed:28065471}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Epileptic encephalopathy, infantile or early childhood, 3 CC (IECEE3) [MIM:618012]: A form of epileptic encephalopathy, a CC heterogeneous group of severe childhood onset epilepsies characterized CC by refractory seizures, neurodevelopmental impairment, and poor CC prognosis. Development is normal prior to seizure onset, after which CC cognitive and motor delays become apparent. IECEE3 is an autosomal CC dominant form characterized by onset of seizures in the first years of CC life. The severity of the phenotype is highly variable: some patients CC may be non-verbal and non-ambulatory with spastic quadriparesis and CC poor eye contact, whereas others have moderate intellectual disability. CC {ECO:0000269|PubMed:29668857}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ATPase alpha/beta chains 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; L09235; AAA83249.1; -; mRNA. DR EMBL; AF113129; AAF14870.1; -; mRNA. DR EMBL; BT006672; AAP35318.1; -; mRNA. DR EMBL; AK293804; BAH11601.1; -; mRNA. DR EMBL; AK314779; BAG37315.1; -; mRNA. DR EMBL; AC079944; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC108693; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW79625.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79626.1; -; Genomic_DNA. DR EMBL; BC013138; AAH13138.1; -; mRNA. DR CCDS; CCDS2976.1; -. [P38606-1] DR PIR; B46091; B46091. DR RefSeq; NP_001681.2; NM_001690.3. [P38606-1] DR RefSeq; XP_047304261.1; XM_047448305.1. [P38606-1] DR RefSeq; XP_047304262.1; XM_047448306.1. [P38606-1] DR RefSeq; XP_054202813.1; XM_054346838.1. [P38606-1] DR RefSeq; XP_054202814.1; XM_054346839.1. [P38606-1] DR RefSeq; XP_054202815.1; XM_054346840.1. [P38606-1] DR PDB; 6WLZ; EM; 2.90 A; A/B/C=1-617. DR PDB; 6WM2; EM; 3.10 A; A/B/C=1-617. DR PDB; 6WM3; EM; 3.40 A; A/B/C=1-617. DR PDB; 6WM4; EM; 3.60 A; A/B/C=1-617. DR PDB; 7U4T; EM; 3.60 A; A/B/C=1-617. DR PDB; 7UNF; EM; 4.08 A; L/M/N=1-617. DR PDB; 9CF8; EM; 3.46 A; A/B/C=1-617. DR PDB; 9CFC; EM; 3.47 A; A/B/C=1-617. DR PDBsum; 6WLZ; -. DR PDBsum; 6WM2; -. DR PDBsum; 6WM3; -. DR PDBsum; 6WM4; -. DR PDBsum; 7U4T; -. DR PDBsum; 7UNF; -. DR PDBsum; 9CF8; -. DR PDBsum; 9CFC; -. DR AlphaFoldDB; P38606; -. DR EMDB; EMD-21845; -. DR EMDB; EMD-21847; -. DR EMDB; EMD-21848; -. DR EMDB; EMD-21849; -. DR EMDB; EMD-26334; -. DR EMDB; EMD-26623; -. DR EMDB; EMD-45533; -. DR EMDB; EMD-45536; -. DR SMR; P38606; -. DR BioGRID; 107007; 315. DR ComplexPortal; CPX-2470; Vacuolar proton translocating ATPase complex, ATP6V0A1 variant. DR ComplexPortal; CPX-6904; Vacuolar proton translocating ATPase complex, ATP6V0A2 variant. DR ComplexPortal; CPX-6905; Vacuolar proton translocating ATPase complex, ATP6V0A3 variant. DR ComplexPortal; CPX-6912; Vacuolar proton translocating ATPase complex, ATP6V0A4 variant. DR CORUM; P38606; -. DR FunCoup; P38606; 3081. DR IntAct; P38606; 181. DR MINT; P38606; -. DR STRING; 9606.ENSP00000273398; -. DR ChEMBL; CHEMBL4295756; -. DR DrugBank; DB00630; Alendronic acid. DR DrugBank; DB06733; Bafilomycin A1. DR DrugBank; DB06734; Bafilomycin B1. DR DrugBank; DB01077; Etidronic acid. 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; P38606; 2 sites, 1 glycan. DR GlyGen; P38606; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; P38606; -. DR MetOSite; P38606; -. DR PhosphoSitePlus; P38606; -. DR SwissPalm; P38606; -. DR BioMuta; ATP6V1A; -. DR DMDM; 22096378; -. DR jPOST; P38606; -. DR MassIVE; P38606; -. DR PaxDb; 9606-ENSP00000273398; -. DR PeptideAtlas; P38606; -. DR PRIDE; P38606; -. DR ProteomicsDB; 55303; -. [P38606-1] DR ProteomicsDB; 6360; -. DR Pumba; P38606; -. DR Antibodypedia; 32600; 209 antibodies from 34 providers. DR DNASU; 523; -. DR Ensembl; ENST00000273398.8; ENSP00000273398.3; ENSG00000114573.13. [P38606-1] DR Ensembl; ENST00000496747.6; ENSP00000417545.2; ENSG00000114573.13. [P38606-2] DR Ensembl; ENST00000703904.2; ENSP00000515542.1; ENSG00000114573.13. [P38606-1] DR Ensembl; ENST00000703910.1; ENSP00000515547.1; ENSG00000114573.13. [P38606-1] DR Ensembl; ENST00000703911.1; ENSP00000515548.1; ENSG00000114573.13. [P38606-1] DR GeneID; 523; -. DR KEGG; hsa:523; -. DR MANE-Select; ENST00000273398.8; ENSP00000273398.3; NM_001690.4; NP_001681.2. DR UCSC; uc003eao.4; human. [P38606-1] DR AGR; HGNC:851; -. DR ClinPGx; PA25152; -. DR CTD; 523; -. DR DisGeNET; 523; -. DR GeneCards; ATP6V1A; -. DR HGNC; HGNC:851; ATP6V1A. DR HPA; ENSG00000114573; Low tissue specificity. DR MalaCards; ATP6V1A; -. DR MIM; 607027; gene. DR MIM; 617403; phenotype. DR MIM; 618012; phenotype. DR OpenTargets; ENSG00000114573; -. DR Orphanet; 357074; Autosomal recessive cutis laxa type 2, classic type. DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy. DR VEuPathDB; HostDB:ENSG00000114573; -. DR eggNOG; KOG1352; Eukaryota. DR GeneTree; ENSGT00550000074787; -. DR HOGENOM; CLU_008162_3_1_1; -. DR InParanoid; P38606; -. DR OMA; RIVKTFW; -. DR OrthoDB; 1676488at2759; -. DR PAN-GO; P38606; 2 GO annotations based on evolutionary models. DR PhylomeDB; P38606; -. DR BioCyc; MetaCyc:HS03781-MONOMER; -. DR PathwayCommons; P38606; -. DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes. DR Reactome; R-HSA-77387; Insulin receptor recycling. DR Reactome; R-HSA-917977; Transferrin endocytosis and recycling. DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1. DR Reactome; R-HSA-983712; Ion channel transport. DR Reactome; R-HSA-9857377; Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy. DR SignaLink; P38606; -. DR SIGNOR; P38606; -. DR Agora; ENSG00000114573; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 523; 821 hits in 1186 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; ATP6V1A; human. DR GeneWiki; ATP6V1A; -. DR GenomeRNAi; 523; -. DR Pharos; P38606; Tbio. DR PRO; PR:P38606; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P38606; protein. DR Bgee; ENSG00000114573; Expressed in Brodmann (1909) area 23 and 207 other cell types or tissues. DR ExpressionAtlas; P38606; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. 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; NAS:ComplexPortal. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0098850; C:extrinsic component of synaptic vesicle membrane; IEA:Ensembl. DR GO; GO:0000139; C:Golgi membrane; NAS:ComplexPortal. DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:ComplexPortal. DR GO; GO:0005902; C:microvillus; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0016469; C:proton-transporting two-sector ATPase complex; TAS:ProtInc. DR GO; GO:0033176; C:proton-transporting V-type ATPase complex; NAS:ComplexPortal. DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB. DR GO; GO:0000221; C:vacuolar proton-transporting V-type ATPase, V1 domain; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; IBA:GO_Central. DR GO; GO:0046034; P:ATP metabolic process; IEA:InterPro. DR GO; GO:0036295; P:cellular response to increased oxygen levels; IMP:UniProtKB. DR GO; GO:0048388; P:endosomal lumen acidification; NAS:ComplexPortal. DR GO; GO:0061795; P:Golgi lumen acidification; NAS:ComplexPortal. DR GO; GO:0006879; P:intracellular iron ion homeostasis; IMP:UniProtKB. DR GO; GO:0051452; P:intracellular pH reduction; NAS:ComplexPortal. DR GO; GO:0007042; P:lysosomal lumen acidification; NAS:ComplexPortal. DR GO; GO:1902600; P:proton transmembrane transport; IBA:GO_Central. DR GO; GO:0016241; P:regulation of macroautophagy; NAS:ParkinsonsUK-UCL. DR GO; GO:0097401; P:synaptic vesicle lumen acidification; IEA:Ensembl. DR GO; GO:0007035; P:vacuolar acidification; NAS:ComplexPortal. DR CDD; cd18111; ATP-synt_V_A-type_alpha_C; 1. DR CDD; cd18119; ATP-synt_V_A-type_alpha_N; 1. DR CDD; cd01134; V_A-ATPase_A; 1. DR FunFam; 1.10.1140.10:FF:000002; V-type proton ATPase catalytic subunit A; 1. DR FunFam; 2.40.30.20:FF:000002; V-type proton ATPase catalytic subunit A; 1. DR FunFam; 2.40.50.100:FF:000008; V-type proton ATPase catalytic subunit A; 1. DR FunFam; 3.40.50.300:FF:000052; V-type proton ATPase catalytic subunit A; 1. DR Gene3D; 2.40.30.20; -; 1. DR Gene3D; 2.40.50.100; -; 1. DR Gene3D; 1.10.1140.10; Bovine Mitochondrial F1-atpase, Atp Synthase Beta Chain, Chain D, domain 3; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR HAMAP; MF_00309; ATP_synth_A_arch; 1. DR InterPro; IPR055190; ATP-synt_VA_C. DR InterPro; IPR031686; ATP-synth_a_Xtn. DR InterPro; IPR023366; ATP_synth_asu-like_sf. DR InterPro; IPR020003; ATPase_a/bsu_AS. DR InterPro; IPR004100; ATPase_F1/V1/A1_a/bsu_N. DR InterPro; IPR036121; ATPase_F1/V1/A1_a/bsu_N_sf. DR InterPro; IPR000194; ATPase_F1/V1/A1_a/bsu_nucl-bd. DR InterPro; IPR024034; ATPase_F1/V1_b/a_C. DR InterPro; IPR005725; ATPase_V1-cplx_asu. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR022878; V-ATPase_asu. DR NCBIfam; NF003220; PRK04192.1; 1. DR NCBIfam; TIGR01042; V-ATPase_V1_A; 1. DR PANTHER; PTHR43607; V-TYPE PROTON ATPASE CATALYTIC SUBUNIT A; 1. DR PANTHER; PTHR43607:SF9; V-TYPE PROTON ATPASE CATALYTIC SUBUNIT A; 1. DR Pfam; PF00006; ATP-synt_ab; 1. DR Pfam; PF02874; ATP-synt_ab_N; 1. DR Pfam; PF16886; ATP-synt_ab_Xtn; 1. DR Pfam; PF22919; ATP-synt_VA_C; 1. DR SUPFAM; SSF47917; C-terminal domain of alpha and beta subunits of F1 ATP synthase; 1. DR SUPFAM; SSF50615; N-terminal domain of alpha and beta subunits of F1 ATP synthase; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00152; ATPASE_ALPHA_BETA; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm; KW Cytoplasmic vesicle; Disease variant; Epilepsy; Hydrogen ion transport; KW Ion transport; Lysosome; Membrane; Nucleotide-binding; Phosphoprotein; KW Proteomics identification; Reference proteome; Translocase; Transport. FT CHAIN 1..617 FT /note="V-type proton ATPase catalytic subunit A" FT /id="PRO_0000144560" FT BINDING 250..257 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305|PubMed:33065002, FT ECO:0000312|PDB:6WLZ, ECO:0007744|PDB:6WM2, FT ECO:0007744|PDB:6WM3, ECO:0007744|PDB:6WM4" FT MOD_RES 136 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 384 FT /note="Phosphoserine; by AMPK" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..33 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056408" FT VARIANT 11 FT /note="D -> N (found in a patient with autism spectrum FT disorder; uncertain significance; dbSNP:rs746407800)" FT /evidence="ECO:0000269|PubMed:29668857" FT /id="VAR_080994" FT VARIANT 27 FT /note="P -> R (in IECEE3; uncertain significance; FT dbSNP:rs1553709380)" FT /evidence="ECO:0000269|PubMed:29668857" FT /id="VAR_080995" FT VARIANT 72 FT /note="G -> D (in ARCL2D; dbSNP:rs1060505037)" FT /evidence="ECO:0000269|PubMed:28065471" FT /id="VAR_078606" FT VARIANT 100 FT /note="D -> Y (in IECEE3; loss-of-function variant leading FT to increased pH in intracellular organelles; affects FT neurite arborization and impairs the formation and FT maintenance of excitatory synapses, when tested in a FT heterologous system; not effect on subcellular location; FT dbSNP:rs1553709855)" FT /evidence="ECO:0000269|PubMed:29668857" FT /id="VAR_080996" FT VARIANT 249 FT /note="P -> R (found in a patient with severe developmental FT disorder; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29668857" FT /id="VAR_080997" FT VARIANT 338 FT /note="R -> C (in ARCL2D; dbSNP:rs1060505036)" FT /evidence="ECO:0000269|PubMed:28065471" FT /id="VAR_078607" FT VARIANT 349 FT /note="D -> N (in IECEE3; gain-of-function variant leading FT to decreased pH in intracellular organelles; affects FT neurite arborization and impairs the formation and FT maintenance of excitatory synapses, when tested in a FT heterologous system; not effect on subcellular location; FT dbSNP:rs1553710664)" FT /evidence="ECO:0000269|PubMed:29668857" FT /id="VAR_080998" FT VARIANT 371 FT /note="D -> G (in IECEE3; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29668857" FT /id="VAR_080999" FT MUTAGEN 256 FT /note="K->Q: Complete loss of interaction with Rabies virus FT protein M; when associated with Q-279." FT /evidence="ECO:0000269|PubMed:33208464" FT MUTAGEN 279 FT /note="E->Q: Complete loss of interaction with Rabies virus FT protein M; when associated with Q-256." FT /evidence="ECO:0000269|PubMed:33208464" FT CONFLICT 71 FT /note="S -> C (in Ref. 1; AAA83249)" FT /evidence="ECO:0000305" FT CONFLICT 89..90 FT /note="EL -> DV (in Ref. 1; AAA83249)" FT /evidence="ECO:0000305" FT CONFLICT 211 FT /note="V -> A (in Ref. 1; AAA83249 and 2; AAF14870)" FT /evidence="ECO:0000305" FT STRAND 18..25 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 28..32 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 42..45 FT /evidence="ECO:0007829|PDB:6WLZ" FT TURN 46..49 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 50..58 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 61..68 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 78..81 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 86..93 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 106..113 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 115..117 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 129..131 FT /evidence="ECO:0007829|PDB:6WM3" FT STRAND 133..137 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 146..148 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 152..157 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 159..161 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 163..167 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 173..179 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 182..185 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 192..198 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 200..203 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 207..210 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 218..221 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 232..236 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 245..248 FT /evidence="ECO:0007829|PDB:6WLZ" FT TURN 252..255 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 256..265 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 266..268 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 270..279 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 281..290 FT /evidence="ECO:0007829|PDB:6WLZ" FT TURN 291..293 FT /evidence="ECO:0007829|PDB:6WM3" FT STRAND 295..298 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 301..304 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 305..307 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 308..312 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 320..323 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 326..338 FT /evidence="ECO:0007829|PDB:6WLZ" FT TURN 339..341 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 343..349 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 352..364 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 369..371 FT /evidence="ECO:0007829|PDB:6WM3" FT HELIX 378..386 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 390..393 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 395..398 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 402..409 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 413..415 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 420..425 FT /evidence="ECO:0007829|PDB:6WLZ" FT TURN 426..428 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 430..432 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 437..441 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 450..452 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 454..456 FT /evidence="ECO:0007829|PDB:6WLZ" FT TURN 458..461 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 462..468 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 472..493 FT /evidence="ECO:0007829|PDB:6WLZ" FT TURN 494..496 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 498..500 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 503..518 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 526..531 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 534..557 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 559..563 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 568..571 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 574..576 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 577..580 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 584..586 FT /evidence="ECO:0007829|PDB:6WLZ" FT TURN 589..591 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 594..615 FT /evidence="ECO:0007829|PDB:6WLZ" FT INIT_MET P38606-2:1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES P38606-2:2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" SQ SEQUENCE 617 AA; 68304 MW; DB409A8731D772CB CRC64; MDFSKLPKIL DEDKESTFGY VHGVSGPVVT ACDMAGAAMY ELVRVGHSEL VGEIIRLEGD MATIQVYEET SGVSVGDPVL RTGKPLSVEL GPGIMGAIFD GIQRPLSDIS SQTQSIYIPR GVNVSALSRD IKWDFTPCKN LRVGSHITGG DIYGIVSENS LIKHKIMLPP RNRGTVTYIA PPGNYDTSDV VLELEFEGVK EKFTMVQVWP VRQVRPVTEK LPANHPLLTG QRVLDALFPC VQGGTTAIPG AFGCGKTVIS QSLSKYSNSD VIIYVGCGER GNEMSEVLRD FPELTMEVDG KVESIMKRTA LVANTSNMPV AAREASIYTG ITLSEYFRDM GYHVSMMADS TSRWAEALRE ISGRLAEMPA DSGYPAYLGA RLASFYERAG RVKCLGNPER EGSVSIVGAV SPPGGDFSDP VTSATLGIVQ VFWGLDKKLA QRKHFPSVNW LISYSKYMRA LDEYYDKHFT EFVPLRTKAK EILQEEEDLA EIVQLVGKAS LAETDKITLE VAKLIKDDFL QQNGYTPYDR FCPFYKTVGM LSNMIAFYDM ARRAVETTAQ SDNKITWSII REHMGDILYK LSSMKFKDPL KDGEAKIKSD YAQLLEDMQN AFRSLED //