VA0D1_HUMAN
ID VA0D1_HUMAN Reviewed; 351 AA.
AC P61421; P12953; Q02547;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=V-type proton ATPase subunit d 1;
DE Short=V-ATPase subunit d 1;
DE AltName: Full=32 kDa accessory protein;
DE AltName: Full=V-ATPase 40 kDa accessory protein;
DE AltName: Full=V-ATPase AC39 subunit;
DE Short=p39;
DE AltName: Full=Vacuolar proton pump subunit d 1;
GN Name=ATP6V0D1 {ECO:0000312|HGNC:HGNC:13724}; Synonyms=ATP6D, VPATPD;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Osteoclastoma;
RX PubMed=8250920; DOI=10.1006/bbrc.1993.2434;
RA van Hille B., Vanek M., Richener H., Green J.R., Bilbe G.;
RT "Cloning and tissue distribution of subunits C, D, and E of the human
RT vacuolar H(+)-ATPase.";
RL Biochem. Biophys. Res. Commun. 197:15-21(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11118322; DOI=10.1006/bbrc.2000.4003;
RA Agarwal A.K., White P.C.;
RT "Structure of the VPATPD gene encoding subunit D of the human vacuolar
RT proton ATPase.";
RL Biochem. Biophys. Res. Commun. 279:543-547(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 264-351.
RA Bhat K.S.;
RT "Expressed sequence tags from a human cell line.";
RL Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=12384298; DOI=10.1016/s0378-1119(02)00884-3;
RA Smith A.N., Borthwick K.J., Karet F.E.;
RT "Molecular cloning and characterization of novel tissue-specific isoforms
RT of the human vacuolar H(+)-ATPase C, G and d subunits, and their evaluation
RT in autosomal recessive distal renal tubular acidosis.";
RL Gene 297:169-177(2002).
RN [6]
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 [7]
RP SUBCELLULAR LOCATION.
RX PubMed=21844891; DOI=10.1038/cr.2011.134;
RA Chen Y., Wu B., Xu L., Li H., Xia J., Yin W., Li Z., Shi D., Li S., Lin S.,
RA Shu X., Pei D.;
RT "A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo.";
RL Cell Res. 22:333-345(2012).
RN [8]
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 [9]
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 [10]
RP INTERACTION WITH PIP4P1.
RX PubMed=29644770; DOI=10.1111/gtc.12583;
RA Hashimoto Y., Shirane M., Nakayama K.I.;
RT "TMEM55B contributes to lysosomal homeostasis and amino acid-induced mTORC1
RT activation.";
RL Genes Cells 23:418-434(2018).
RN [11]
RP FUNCTION, INTERACTION WITH TMEM9 AND ATP6AP2, AND SUBCELLULAR LOCATION.
RX PubMed=30374053; DOI=10.1038/s41556-018-0219-8;
RA Jung Y.S., Jun S., Kim M.J., Lee S.H., Suh H.N., Lien E.M., Jung H.Y.,
RA Lee S., Zhang J., Yang J.I., Ji H., Wu J.Y., Wang W., Miller R.K., Chen J.,
RA McCrea P.D., Kopetz S., Park J.I.;
RT "TMEM9 promotes intestinal tumorigenesis through vacuolar-ATPase-activated
RT Wnt/beta-catenin signalling.";
RL Nat. Cell Biol. 20:1421-1433(2018).
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, AND
RP 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: 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 translocates
CC protons (PubMed:33065002, PubMed:28296633, PubMed:30374053). V-ATPase
CC is responsible for acidifying and maintaining the pH of intracellular
CC compartments and in some cell types, is targeted to the plasma
CC membrane, where it is responsible for acidifying the extracellular
CC environment (PubMed:30374053). May play a role in coupling of proton
CC transport and ATP hydrolysis (By similarity). In aerobic conditions,
CC involved in intracellular iron homeostasis, thus triggering the
CC activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to
CC HIF1A hydroxylation and subsequent proteasomal degradation
CC (PubMed:28296633). May play a role in cilium biogenesis through
CC regulation of the transport and the localization of proteins to the
CC cilium (By similarity). {ECO:0000250|UniProtKB:P51863,
CC ECO:0000250|UniProtKB:Q6PGV1, ECO:0000269|PubMed:28296633,
CC ECO:0000269|PubMed:30374053, ECO:0000269|PubMed:33065002}.
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 ATP6AP2;
CC ATP6AP2 is a V-ATPase accessory protein and the interaction promotes v-
CC ATPase complex assembly (PubMed:30374053). Interacts with TMEM9; TMEM9
CC is a v-ATPase assembly regulator and the interaction induces the
CC interaction with ATP6AP2 (PubMed:30374053). Interacts with PIP4P1
CC (PubMed:29644770). {ECO:0000269|PubMed:29644770,
CC ECO:0000269|PubMed:30374053, ECO:0000269|PubMed:33065002}.
CC -!- INTERACTION:
CC P61421; P54253: ATXN1; NbExp=7; IntAct=EBI-954063, EBI-930964;
CC P61421; Q9NQL9: DMRT3; NbExp=3; IntAct=EBI-954063, EBI-9679045;
CC P61421; P42858: HTT; NbExp=6; IntAct=EBI-954063, EBI-466029;
CC P61421; O43711: TLX3; NbExp=3; IntAct=EBI-954063, EBI-3939165;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:21844891};
CC Peripheral membrane protein {ECO:0000305|PubMed:21844891}; Cytoplasmic
CC side {ECO:0000305|PubMed:21844891}. Lysosome membrane
CC {ECO:0000305|PubMed:30374053}; Peripheral membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, clathrin-coated vesicle membrane
CC {ECO:0000250|UniProtKB:P61420}; Peripheral membrane protein
CC {ECO:0000305}. Note=Localizes to centrosome and the base of the cilium.
CC {ECO:0000250|UniProtKB:Q6PGV1}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:12384298,
CC ECO:0000269|PubMed:8250920}.
CC -!- SIMILARITY: Belongs to the V-ATPase V0D/AC39 subunit family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA50591.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X71490; CAA50591.1; ALT_FRAME; mRNA.
DR EMBL; BC008861; AAH08861.1; -; mRNA.
DR EMBL; L05087; AAC15852.1; -; mRNA.
DR CCDS; CCDS10838.1; -.
DR RefSeq; NP_004682.2; NM_004691.4.
DR PDB; 6WLW; EM; 3.00 A; Q=1-351.
DR PDB; 6WM2; EM; 3.10 A; Q=1-351.
DR PDB; 6WM3; EM; 3.40 A; Q=1-351.
DR PDB; 6WM4; EM; 3.60 A; Q=1-351.
DR PDBsum; 6WLW; -.
DR PDBsum; 6WM2; -.
DR PDBsum; 6WM3; -.
DR PDBsum; 6WM4; -.
DR AlphaFoldDB; P61421; -.
DR SMR; P61421; -.
DR BioGRID; 114564; 181.
DR CORUM; P61421; -.
DR DIP; DIP-47435N; -.
DR IntAct; P61421; 98.
DR MINT; P61421; -.
DR STRING; 9606.ENSP00000290949; -.
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; P61421; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P61421; -.
DR PhosphoSitePlus; P61421; -.
DR SwissPalm; P61421; -.
DR BioMuta; ATP6V0D1; -.
DR DMDM; 47606646; -.
DR EPD; P61421; -.
DR jPOST; P61421; -.
DR MassIVE; P61421; -.
DR MaxQB; P61421; -.
DR PaxDb; P61421; -.
DR PeptideAtlas; P61421; -.
DR PRIDE; P61421; -.
DR ProteomicsDB; 57300; -.
DR Antibodypedia; 2185; 198 antibodies from 26 providers.
DR DNASU; 9114; -.
DR Ensembl; ENST00000290949.8; ENSP00000290949.3; ENSG00000159720.13.
DR GeneID; 9114; -.
DR KEGG; hsa:9114; -.
DR MANE-Select; ENST00000290949.8; ENSP00000290949.3; NM_004691.5; NP_004682.2.
DR UCSC; uc002ete.2; human.
DR CTD; 9114; -.
DR DisGeNET; 9114; -.
DR GeneCards; ATP6V0D1; -.
DR HGNC; HGNC:13724; ATP6V0D1.
DR HPA; ENSG00000159720; Low tissue specificity.
DR MIM; 607028; gene.
DR neXtProt; NX_P61421; -.
DR OpenTargets; ENSG00000159720; -.
DR PharmGKB; PA25150; -.
DR VEuPathDB; HostDB:ENSG00000159720; -.
DR eggNOG; KOG2957; Eukaryota.
DR GeneTree; ENSGT00390000002200; -.
DR HOGENOM; CLU_051277_0_0_1; -.
DR InParanoid; P61421; -.
DR OrthoDB; 910004at2759; -.
DR PhylomeDB; P61421; -.
DR TreeFam; TF300857; -.
DR BioCyc; MetaCyc:HS08417-MON; -.
DR PathwayCommons; P61421; -.
DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
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; P61421; -.
DR BioGRID-ORCS; 9114; 586 hits in 1080 CRISPR screens.
DR ChiTaRS; ATP6V0D1; human.
DR GeneWiki; ATP6V0D1; -.
DR GenomeRNAi; 9114; -.
DR Pharos; P61421; Tbio.
DR PRO; PR:P61421; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P61421; protein.
DR Bgee; ENSG00000159720; Expressed in mucosa of transverse colon and 203 other tissues.
DR ExpressionAtlas; P61421; baseline and differential.
DR Genevisible; P61421; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IBA:GO_Central.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0033181; C:plasma membrane proton-transporting V-type ATPase complex; IBA:GO_Central.
DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl.
DR GO; GO:0016471; C:vacuolar proton-transporting V-type ATPase complex; IDA:UniProtKB.
DR GO; GO:0000220; C:vacuolar proton-transporting V-type ATPase, V0 domain; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
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:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:1902600; P:proton transmembrane transport; NAS:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; NAS:ParkinsonsUK-UCL.
DR GO; GO:0007035; P:vacuolar acidification; IBA:GO_Central.
DR GO; GO:0007034; P:vacuolar transport; IBA:GO_Central.
DR Gene3D; 1.10.132.50; -; 1.
DR Gene3D; 1.20.1690.10; -; 2.
DR InterPro; IPR036079; ATPase_su_c/d_sf.
DR InterPro; IPR002843; ATPase_V0-cplx_csu/dsu.
DR InterPro; IPR016727; ATPase_V0-cplx_dsu.
DR InterPro; IPR044911; V-type_ATPase_su_c/d_dom_3.
DR InterPro; IPR035067; V-type_ATPase_suC/d.
DR PANTHER; PTHR11028; PTHR11028; 1.
DR Pfam; PF01992; vATP-synt_AC39; 1.
DR PIRSF; PIRSF018497; V-ATP_synth_D; 1.
DR SUPFAM; SSF103486; SSF103486; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cilium biogenesis/degradation; Cytoplasmic vesicle;
KW Hydrogen ion transport; Ion transport; Lysosome; Membrane; Phosphoprotein;
KW Reference proteome; Transport.
FT CHAIN 1..351
FT /note="V-type proton ATPase subunit d 1"
FT /id="PRO_0000119350"
FT MOD_RES 270
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P51863"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51863"
FT CONFLICT 27
FT /note="V -> E (in Ref. 1; CAA50591)"
FT /evidence="ECO:0000305"
FT CONFLICT 266..267
FT /note="NV -> KL (in Ref. 1; CAA50591)"
FT /evidence="ECO:0000305"
FT TURN 5..8
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 9..11
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 16..24
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 30..33
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 34..38
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 42..48
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 50..54
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 67..85
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 86..88
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 91..99
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 100..105
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 106..116
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:6WM2"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:6WM3"
FT TURN 136..143
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 147..156
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 161..164
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 165..167
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 172..175
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 178..197
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 202..208
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 209..225
FT /evidence="ECO:0007829|PDB:6WLW"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 234..237
FT /evidence="ECO:0007829|PDB:6WLW"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 252..256
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 264..267
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 272..277
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 290..292
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 294..303
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:6WLW"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 313..325
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 326..328
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 329..336
FT /evidence="ECO:0007829|PDB:6WLW"
FT TURN 337..339
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 343..346
FT /evidence="ECO:0007829|PDB:6WM3"
SQ SEQUENCE 351 AA; 40329 MW; A720F8A87511203C CRC64;
MSFFPELYFN VDNGYLEGLV RGLKAGVLSQ ADYLNLVQCE TLEDLKLHLQ STDYGNFLAN
EASPLTVSVI DDRLKEKMVV EFRHMRNHAY EPLASFLDFI TYSYMIDNVI LLITGTLHQR
SIAELVPKCH PLGSFEQMEA VNIAQTPAEL YNAILVDTPL AAFFQDCISE QDLDEMNIEI
IRNTLYKAYL ESFYKFCTLL GGTTADAMCP ILEFEADRRA FIITINSFGT ELSKEDRAKL
FPHCGRLYPE GLAQLARADD YEQVKNVADY YPEYKLLFEG AGSNPGDKTL EDRFFEHEVK
LNKLAFLNQF HFGVFYAFVK LKEQECRNIV WIAECIAQRH RAKIDNYIPI F
