ID VATD_HUMAN Reviewed; 247 AA. AC Q9Y5K8; B2RE33; Q9Y688; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 28-JAN-2026, entry version 204. DE RecName: Full=V-type proton ATPase subunit D; DE Short=V-ATPase subunit D; DE AltName: Full=V-ATPase 28 kDa accessory protein; DE AltName: Full=Vacuolar proton pump subunit D; GN Name=ATP6V1D; Synonyms=ATP6M, VATD; 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]. RC TISSUE=Heart; RA Zhao Y., Cao H.Q., Wei Y.J., Jiang Y.X., Zhao X.W., Liu D.Q., Meng X.M., RA Liu Y.Q., Xu Y.Y., Sheng H., Liu S., Qiao M., Hui R.T., Ding J.F.; RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pituitary; 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 [MRNA]. RC TISSUE=Brain; RA Quan L., Hong W., Shizhou A.; RT "cDNA of human vacuolar H-ATPase subunit D (VATD) interacts with Rb."; RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Trachea; 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]. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; 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 [7] 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 [8] RP FUNCTION IN CILIOGENESIS, INTERACTION WITH SNX10, AND 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 [9] 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 [10] {ECO:0007744|PDB:6WLZ, ECO:0007744|PDB:6WM2, ECO:0007744|PDB:6WM3, ECO:0007744|PDB:6WM4} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 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 V1 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). V-ATPase is responsible for acidifying and CC maintaining the pH of intracellular compartments and in some cell CC types, is targeted to the plasma membrane, where it is responsible for CC acidifying the extracellular environment (By similarity). May play a CC role in cilium biogenesis through regulation of the transport and the CC localization of proteins to the cilium (PubMed:21844891). CC {ECO:0000250|UniProtKB:P39942, ECO:0000269|PubMed:21844891, CC 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 SNX10 CC (PubMed:21844891). {ECO:0000269|PubMed:21844891, CC ECO:0000269|PubMed:33065002}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:21844891}; CC Peripheral membrane protein {ECO:0000305|PubMed:21844891}; Cytoplasmic CC side {ECO:0000305|PubMed:21844891}. Cytoplasmic vesicle, clathrin- CC coated vesicle membrane {ECO:0000250|UniProtKB:P39942}; Peripheral CC membrane protein {ECO:0000305}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:21844891}. Cell CC projection, cilium {ECO:0000269|PubMed:21844891}. Note=Localizes to CC centrosome and the base of the cilium. {ECO:0000269|PubMed:21844891}. CC -!- SIMILARITY: Belongs to the V-ATPase D subunit family. {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; AF145316; AAD33953.1; -; mRNA. DR EMBL; AF100741; AAD40384.1; -; mRNA. DR EMBL; AF104629; AAG30726.1; -; mRNA. DR EMBL; AK315784; BAG38130.1; -; mRNA. DR EMBL; CH471061; EAW80931.1; -; Genomic_DNA. DR EMBL; BC001411; AAH01411.1; -; mRNA. DR CCDS; CCDS9780.1; -. DR RefSeq; NP_057078.1; NM_015994.4. DR PDB; 6WLZ; EM; 2.90 A; G=1-247. DR PDB; 6WM2; EM; 3.10 A; G=1-247. DR PDB; 6WM3; EM; 3.40 A; G=1-247. DR PDB; 6WM4; EM; 3.60 A; G=1-247. DR PDB; 7U4T; EM; 3.60 A; G=1-247. DR PDB; 7UNF; EM; 4.08 A; D=1-247. DR PDB; 9CF8; EM; 3.46 A; G=1-247. DR PDB; 9CFC; EM; 3.47 A; G=1-247. 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; Q9Y5K8; -. 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; Q9Y5K8; -. DR BioGRID; 119513; 122. 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 FunCoup; Q9Y5K8; 2015. DR MINT; Q9Y5K8; -. DR STRING; 9606.ENSP00000216442; -. DR DrugBank; DB01133; Tiludronic acid. DR iPTMnet; Q9Y5K8; -. DR PhosphoSitePlus; Q9Y5K8; -. DR SwissPalm; Q9Y5K8; -. DR BioMuta; ATP6V1D; -. DR DMDM; 10720351; -. DR jPOST; Q9Y5K8; -. DR MassIVE; Q9Y5K8; -. DR PaxDb; 9606-ENSP00000216442; -. DR PeptideAtlas; Q9Y5K8; -. DR ProteomicsDB; 86435; -. DR Pumba; Q9Y5K8; -. DR Antibodypedia; 24797; 107 antibodies from 31 providers. DR DNASU; 51382; -. DR Ensembl; ENST00000216442.12; ENSP00000216442.7; ENSG00000100554.12. DR Ensembl; ENST00000554087.5; ENSP00000451167.1; ENSG00000100554.12. DR GeneID; 51382; -. DR KEGG; hsa:51382; -. DR MANE-Select; ENST00000216442.12; ENSP00000216442.7; NM_015994.4; NP_057078.1. DR UCSC; uc001xjf.4; human. DR AGR; HGNC:13527; -. DR ClinPGx; PA25157; -. DR CTD; 51382; -. DR DisGeNET; 51382; -. DR GeneCards; ATP6V1D; -. DR HGNC; HGNC:13527; ATP6V1D. DR HPA; ENSG00000100554; Low tissue specificity. DR MIM; 609398; gene. DR OpenTargets; ENSG00000100554; -. DR VEuPathDB; HostDB:ENSG00000100554; -. DR eggNOG; KOG1647; Eukaryota. DR GeneTree; ENSGT00390000010770; -. DR HOGENOM; CLU_069688_0_0_1; -. DR InParanoid; Q9Y5K8; -. DR OMA; REEFFRM; -. DR OrthoDB; 7676488at2759; -. DR PAN-GO; Q9Y5K8; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q9Y5K8; -. DR BioCyc; MetaCyc:HS02107-MONOMER; -. DR PathwayCommons; Q9Y5K8; -. DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-77387; Insulin receptor recycling. DR Reactome; R-HSA-917977; Transferrin endocytosis and recycling. DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1. DR Reactome; R-HSA-983712; Ion channel transport. DR SignaLink; Q9Y5K8; -. DR SIGNOR; Q9Y5K8; -. DR Agora; ENSG00000100554; -. DR BioGRID-ORCS; 51382; 683 hits in 1169 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; ATP6V1D; human. DR GeneWiki; ATP6V1D; -. DR GenomeRNAi; 51382; -. DR Pharos; Q9Y5K8; Tbio. DR PRO; PR:Q9Y5K8; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q9Y5K8; protein. DR Bgee; ENSG00000100554; Expressed in endothelial cell and 210 other cell types or tissues. DR ExpressionAtlas; Q9Y5K8; baseline and differential. DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell. DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell. DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; TAS:Reactome. 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:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0033176; C:proton-transporting V-type ATPase complex; IDA:UniProtKB. DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome. DR GO; GO:0000221; C:vacuolar proton-transporting V-type ATPase, V1 domain; ISS:UniProtKB. DR GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; IEA:InterPro. DR GO; GO:0060271; P:cilium assembly; 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:0051452; P:intracellular pH reduction; NAS:ComplexPortal. DR GO; GO:0007042; P:lysosomal lumen acidification; NAS:ComplexPortal. DR GO; GO:0061512; P:protein localization to cilium; IMP:UniProtKB. DR GO; GO:1902600; P:proton transmembrane transport; NAS:ComplexPortal. 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 FunFam; 1.10.287.3240:FF:000001; V-type proton ATPase subunit D; 1. DR Gene3D; 1.10.287.3240; -; 1. DR InterPro; IPR002699; V_ATPase_D. DR NCBIfam; TIGR00309; V_ATPase_subD; 1. DR PANTHER; PTHR11671; V-TYPE ATP SYNTHASE SUBUNIT D; 1. DR Pfam; PF01813; ATP-synt_D; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell projection; Cilium biogenesis/degradation; Cytoplasm; KW Cytoplasmic vesicle; Cytoskeleton; Hydrogen ion transport; Ion transport; KW Membrane; Proteomics identification; Reference proteome; Transport. FT CHAIN 1..247 FT /note="V-type proton ATPase subunit D" FT /id="PRO_0000144231" FT CONFLICT 228..235 FT /note="EVLEPANL -> RCWSLLIF (in Ref. 2; AAD40384)" FT /evidence="ECO:0000305" FT HELIX 15..73 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 80..85 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 94..101 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 104..110 FT /evidence="ECO:0007829|PDB:6WLZ" FT STRAND 118..126 FT /evidence="ECO:0007829|PDB:6WM2" FT HELIX 129..174 FT /evidence="ECO:0007829|PDB:6WLZ" FT HELIX 176..215 FT /evidence="ECO:0007829|PDB:6WLZ" SQ SEQUENCE 247 AA; 28263 MW; 4185E5F6A74EFB1C CRC64; MSGKDRIEIF PSRMAQTIMK ARLKGAQTGR NLLKKKSDAL TLRFRQILKK IIETKMLMGE VMREAAFSLA EAKFTAGDFS TTVIQNVNKA QVKIRAKKDN VAGVTLPVFE HYHEGTDSYE LTGLARGGEQ LAKLKRNYAK AVELLVELAS LQTSFVTLDE AIKITNRRVN AIEHVIIPRI ERTLAYIITE LDEREREEFY RLKKIQEKKK ILKEKSEKDL EQRRAAGEVL EPANLLAEEK DEDLLFE //