VATA_BOVIN
ID VATA_BOVIN Reviewed; 617 AA.
AC P31404; Q3MHQ8;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=V-type proton ATPase catalytic subunit A;
DE Short=V-ATPase subunit A;
DE EC=7.1.2.2 {ECO:0000269|PubMed:32764564};
DE AltName: Full=V-ATPase 69 kDa subunit;
DE AltName: Full=Vacuolar proton pump subunit alpha;
GN Name=ATP6V1A; Synonyms=ATP6A1, ATP6V1A1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1722207; DOI=10.1016/s0021-9258(18)54266-6;
RA Puopolo K., Kumamoto C., Adachi I., Forgac M.;
RT "A single gene encodes the catalytic 'A' subunit of the bovine vacuolar
RT H(+)-ATPase.";
RL J. Biol. Chem. 266:24564-24572(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal medulla;
RX PubMed=1835703; DOI=10.1016/0014-5793(91)81158-5;
RA Pan Y.X., Xu J., Strasser J.E., Howell M., Dean G.E.;
RT "Structure and expression of subunit A from the bovine chromaffin cell
RT vacuolar ATPase.";
RL FEBS Lett. 293:89-92(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0007744|PDB:6XBW, ECO:0007744|PDB:6XBY}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.37 ANGSTROMS) IN COMPLEX WITH ADP,
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, IDENTIFICATION IN THE
RP V-ATPASE COMPLEX, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND TISSUE SPECIFICITY.
RX PubMed=32764564; DOI=10.1038/s41467-020-17762-9;
RA Wang R., Long T., Hassan A., Wang J., Sun Y., Xie X.S., Li X.;
RT "Cryo-EM structures of intact V-ATPase from bovine brain.";
RL Nat. Commun. 11:3921-3921(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:32764564). 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:32764564). 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 (By similarity). May play a role in
CC neurite development and synaptic connectivity (By similarity).
CC {ECO:0000250|UniProtKB:P38606, ECO:0000269|PubMed:32764564}.
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:0000269|PubMed:32764564};
CC -!- ACTIVITY REGULATION: ATP hydrolysis occurs at the interface between the
CC nucleotide-binding domains of subunits A and B (Probable). ATP
CC hydrolysis triggers a conformational change in the subunits D and F,
CC which induces a shift of subunit d (Probable). The c-ring is
CC subsequently rotated and results in a continuous proton translocation
CC across the membrane (Probable). The V-ATPase is inhibited by
CC bafilomycin A (PubMed:32764564). {ECO:0000269|PubMed:32764564,
CC ECO:0000305|PubMed:32764564}.
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:32764564). 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:32764564). 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:32764564). Interacts with the V0
CC complex V-ATPase subunit a4 ATP6V0A4 (By similarity). Interacts with
CC WFS1 (By similarity). Interacts with alpha-crystallin B chain/CRYAB and
CC with MTOR, forming a ternary complex (By similarity).
CC {ECO:0000250|UniProtKB:P38606, ECO:0000250|UniProtKB:P50516,
CC ECO:0000269|PubMed:32764564}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P38606}.
CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:P50516}. Cytoplasmic vesicle,
CC secretory vesicle {ECO:0000250|UniProtKB:P38606}. Cytoplasmic vesicle,
CC clathrin-coated vesicle membrane {ECO:0000269|PubMed:32764564};
CC Peripheral membrane protein {ECO:0000305}. Lysosome
CC {ECO:0000250|UniProtKB:P50516}. Note=Co-localizes with WFS1 in the
CC secretory granules in neuroblastoma cell lines.
CC {ECO:0000250|UniProtKB:P38606}.
CC -!- TISSUE SPECIFICITY: Expressed in brain (at protein level).
CC {ECO:0000269|PubMed:32764564}.
CC -!- PTM: Phosphorylation at Ser-384 by AMPK down-regulates its enzyme
CC activity. {ECO:0000250|UniProtKB:P50516}.
CC -!- SIMILARITY: Belongs to the ATPase alpha/beta chains family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI05146.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA41276.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M80430; AAA30392.1; -; mRNA.
DR EMBL; X58386; CAA41276.1; ALT_INIT; mRNA.
DR EMBL; BC105145; AAI05146.1; ALT_INIT; mRNA.
DR PIR; S19659; S19659.
DR RefSeq; NP_776929.1; NM_174504.2.
DR RefSeq; XP_015326478.1; XM_015470992.1.
DR PDB; 6XBW; EM; 3.37 A; A/B/C=1-617.
DR PDB; 6XBY; EM; 3.79 A; A/B/C=1-617.
DR PDB; 7KHR; EM; 3.62 A; A/B/C=1-617.
DR PDBsum; 6XBW; -.
DR PDBsum; 6XBY; -.
DR PDBsum; 7KHR; -.
DR AlphaFoldDB; P31404; -.
DR SMR; P31404; -.
DR CORUM; P31404; -.
DR STRING; 9913.ENSBTAP00000050728; -.
DR PaxDb; P31404; -.
DR PeptideAtlas; P31404; -.
DR PRIDE; P31404; -.
DR Ensembl; ENSBTAT00000068126; ENSBTAP00000070089; ENSBTAG00000002703.
DR GeneID; 282147; -.
DR KEGG; bta:282147; -.
DR CTD; 523; -.
DR VEuPathDB; HostDB:ENSBTAG00000002703; -.
DR VGNC; VGNC:26316; ATP6V1A.
DR eggNOG; KOG1352; Eukaryota.
DR GeneTree; ENSGT00550000074787; -.
DR HOGENOM; CLU_008162_3_1_1; -.
DR InParanoid; P31404; -.
DR OMA; RIVKTFW; -.
DR OrthoDB; 241249at2759; -.
DR TreeFam; TF300811; -.
DR Proteomes; UP000009136; Chromosome 1.
DR Bgee; ENSBTAG00000002703; Expressed in occipital lobe and 105 other tissues.
DR ExpressionAtlas; P31404; baseline and differential.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS: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; ISS:UniProtKB.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISS:UniProtKB.
DR GO; GO:0036295; P:cellular response to increased oxygen levels; ISS:UniProtKB.
DR GO; GO:0045851; P:pH reduction; IC:UniProtKB.
DR GO; GO:1902600; P:proton transmembrane transport; IBA:GO_Central.
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; ATP-binding; Cytoplasm; Cytoplasmic vesicle;
KW Hydrogen ion transport; Ion transport; Lysosome; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Translocase;
KW Transport.
FT CHAIN 1..617
FT /note="V-type proton ATPase catalytic subunit A"
FT /id="PRO_0000144559"
FT BINDING 250..257
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:32764564,
FT ECO:0007744|PDB:6XBW, ECO:0007744|PDB:6XBY"
FT MOD_RES 136
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P38606"
FT MOD_RES 384
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:P50516"
FT CONFLICT 91
FT /note="G -> C (in Ref. 1; AAA30392)"
FT /evidence="ECO:0000305"
FT STRAND 18..20
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:6XBW"
FT TURN 46..49
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 50..58
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 79..93
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 106..113
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 152..157
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 174..179
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 207..213
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 232..236
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 252..255
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 256..265
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 270..278
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 283..290
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 305..308
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 309..314
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 320..338
FT /evidence="ECO:0007829|PDB:6XBW"
FT TURN 339..341
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 343..349
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 351..364
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 378..386
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 395..398
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 401..410
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 413..415
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 422..426
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 437..441
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 454..456
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 458..468
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 473..495
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 503..518
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 527..529
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 534..555
FT /evidence="ECO:0007829|PDB:6XBW"
FT STRAND 560..562
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 567..573
FT /evidence="ECO:0007829|PDB:6XBW"
FT TURN 574..576
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 577..581
FT /evidence="ECO:0007829|PDB:6XBW"
FT TURN 582..585
FT /evidence="ECO:0007829|PDB:6XBW"
FT HELIX 594..608
FT /evidence="ECO:0007829|PDB:6XBW"
FT TURN 609..611
FT /evidence="ECO:0007829|PDB:6XBW"
SQ SEQUENCE 617 AA; 68344 MW; EF27E9DB67B6CB9C CRC64;
MDFSKLPKIR DEDKESTFGY VHGVSGPVVT ACDMAGAAMY ELVRVGHSEL VGEIIRLEGD
MATIQVYEET SGVSVGDPVL RTGKPLSVEL GPGIMGAIFD GIQRPLSDIS SQTQSIYIPR
GVNVSALSRD VKWDFTPCKN LRVGSHITGG DIYGIVNENS LIKHKIMLPP RNRGTVTYIA
PPGNYDTSDV VLELEFEGIK EKFSMVQVWP 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 REHMGEILYK LSSMKFKDPV KDGEAKIKAD
YAQLLEDMQN AFRSLED
