VATA_HUMAN
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 03-AUG-2022, entry version 209.
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 + 4 H(+)(in) + H2O = ADP + 5 H(+)(out) + phosphate;
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}.
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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 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 PDBsum; 6WLZ; -.
DR PDBsum; 6WM2; -.
DR PDBsum; 6WM3; -.
DR PDBsum; 6WM4; -.
DR AlphaFoldDB; P38606; -.
DR SMR; P38606; -.
DR BioGRID; 107007; 207.
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 IntAct; P38606; 109.
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 GlyGen; P38606; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P38606; -.
DR MetOSite; P38606; -.
DR PhosphoSitePlus; P38606; -.
DR SwissPalm; P38606; -.
DR BioMuta; ATP6V1A; -.
DR DMDM; 22096378; -.
DR EPD; P38606; -.
DR jPOST; P38606; -.
DR MassIVE; P38606; -.
DR MaxQB; P38606; -.
DR PaxDb; P38606; -.
DR PeptideAtlas; P38606; -.
DR PRIDE; P38606; -.
DR ProteomicsDB; 55303; -. [P38606-1]
DR ProteomicsDB; 6360; -.
DR Antibodypedia; 32600; 201 antibodies from 31 providers.
DR DNASU; 523; -.
DR Ensembl; ENST00000273398.8; ENSP00000273398.3; ENSG00000114573.10. [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 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 neXtProt; NX_P38606; -.
DR OpenTargets; ENSG00000114573; -.
DR Orphanet; 357074; Autosomal recessive cutis laxa type 2, classic type.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA25152; -.
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; 241249at2759; -.
DR PhylomeDB; P38606; -.
DR TreeFam; TF300811; -.
DR BioCyc; MetaCyc:HS03781-MON; -.
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 SignaLink; P38606; -.
DR SIGNOR; P38606; -.
DR BioGRID-ORCS; 523; 781 hits in 1103 CRISPR screens.
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 205 other tissues.
DR ExpressionAtlas; P38606; baseline and differential.
DR Genevisible; P38606; HS.
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; IC:ComplexPortal.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IC:ComplexPortal.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
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; IC:ComplexPortal.
DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
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:0046933; F:proton-transporting ATP synthase activity, rotational mechanism; IEA:UniProtKB-EC.
DR GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; IBA:GO_Central.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:UniProtKB.
DR GO; GO:0036295; P:cellular response to increased oxygen levels; IMP:UniProtKB.
DR GO; GO:0048388; P:endosomal lumen acidification; IC:ComplexPortal.
DR GO; GO:0061795; P:Golgi lumen acidification; IC:ComplexPortal.
DR GO; GO:0051452; P:intracellular pH reduction; IC:ComplexPortal.
DR GO; GO:0007042; P:lysosomal lumen acidification; IC: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:0007035; P:vacuolar acidification; IC:ComplexPortal.
DR Gene3D; 1.10.1140.10; -; 1.
DR Gene3D; 2.40.30.20; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_00309; ATP_synth_A_arch; 1.
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 PANTHER; PTHR43607; PTHR43607; 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 SUPFAM; SSF50615; SSF50615; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR01042; V-ATPase_V1_A; 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 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; unknown pathological significance;
FT dbSNP:rs746407800)"
FT /evidence="ECO:0000269|PubMed:29668857"
FT /id="VAR_080994"
FT VARIANT 27
FT /note="P -> R (in IECEE3; unknown pathological
FT significance; 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; unknown pathological 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; unknown pathological
FT 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
