ID VAS1_HUMAN Reviewed; 470 AA. AC Q15904; A6ZKI4; Q8NBT4; Q9H0C7; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2001, sequence version 2. DT 27-MAR-2024, entry version 213. DE RecName: Full=V-type proton ATPase subunit S1; DE Short=V-ATPase subunit S1; DE AltName: Full=Protein XAP-3; DE AltName: Full=V-ATPase Ac45 subunit; DE AltName: Full=V-ATPase S1 accessory protein; DE AltName: Full=Vacuolar proton pump subunit S1; DE Flags: Precursor; GN Name=ATP6AP1; Synonyms=ATP6IP1, ATP6S1, VATPS1, XAP3; 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 [GENOMIC DNA / MRNA]. RX PubMed=8733135; DOI=10.1093/hmg/5.5.659; RA Chen E.Y., Zollo M., Mazzarella R.A., Ciccodicola A., Chen C.-N., Zuo L., RA Heiner C., Burough F.W., Ripetto M., Schlessinger D., D'Urso M.; RT "Long-range sequence analysis in Xq28: thirteen known and six candidate RT genes in 219.4 kb of high GC DNA between the RCP/GCP and G6PD loci."; RL Hum. Mol. Genet. 5:659-668(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT libraries."; RL DNA Res. 12:117-126(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). 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]. 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 NUCLEOTIDE SEQUENCE [MRNA] OF 97-470. RC TISSUE=Brain; RX PubMed=8034313; DOI=10.1006/geno.1994.1194; RA Yokoi H., Hadano S., Kogi M., Kang X., Wakasa K., Ikeda J.; RT "Isolation of expressed sequences encoded by the human Xq terminal portion RT using microclone probes generated by laser microdissection."; RL Genomics 20:404-411(1994). RN [9] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-261 AND ASN-273. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [10] 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-465, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 INTERACTION WITH RNASEK. RX PubMed=26212330; DOI=10.1016/j.celrep.2015.06.076; RA Perreira J.M., Aker A.M., Savidis G., Chin C.R., McDougall W.M., RA Portmann J.M., Meraner P., Smith M.C., Rahman M., Baker R.E., Gauthier A., RA Franti M., Brass A.L.; RT "RNASEK Is a V-ATPase-Associated Factor Required for Endocytosis and the RT Replication of Rhinovirus, Influenza A Virus, and Dengue Virus."; RL Cell Rep. 12:850-863(2015). RN [13] RP INVOLVEMENT IN IMD47, VARIANTS IMD47 PRO-144; CYS-313; LYS-346 AND ILE-428, RP CHARACTERIZATION OF VARIANTS IMD47 CYS-313; LYS-346 AND ILE-428, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, AND MUTAGENESIS OF RP VAL-470. RX PubMed=27231034; DOI=10.1038/ncomms11600; RA Jansen E.J., Timal S., Ryan M., Ashikov A., van Scherpenzeel M., RA Graham L.A., Mandel H., Hoischen A., Iancu T.C., Raymond K., RA Steenbergen G., Gilissen C., Huijben K., van Bakel N.H., Maeda Y., RA Rodenburg R.J., Adamowicz M., Crushell E., Koenen H., Adams D., RA Vodopiutz J., Greber-Platzer S., Mueller T., Dueckers G., Morava E., RA Sykut-Cegielska J., Martens G.J., Wevers R.A., Niehues T., Huynen M.A., RA Veltman J.A., Stevens T.H., Lefeber D.J.; RT "ATP6AP1 deficiency causes an immunodeficiency with hepatopathy, cognitive RT impairment and abnormal protein glycosylation."; RL Nat. Commun. 7:11600-11600(2016). RN [14] 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 [15] RP INTERACTION WITH ATP6AP2. RX PubMed=29127204; DOI=10.1084/jem.20170453; RA Rujano M.A., Cannata Serio M., Panasyuk G., Peanne R., Reunert J., RA Rymen D., Hauser V., Park J.H., Freisinger P., Souche E., Guida M.C., RA Maier E.M., Wada Y., Jaeger S., Krogan N.J., Kretz O., Nobre S., Garcia P., RA Quelhas D., Bird T.D., Raskind W.H., Schwake M., Duvet S., Foulquier F., RA Matthijs G., Marquardt T., Simons M.; RT "Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with RT autophagic defects."; RL J. Exp. Med. 214:3707-3729(2017). RN [16] RP INTERACTION WITH TMEM106B. RX PubMed=28728022; DOI=10.1016/j.neuron.2017.06.026; RA Klein Z.A., Takahashi H., Ma M., Stagi M., Zhou M., Lam T.T., RA Strittmatter S.M.; RT "Loss of TMEM106B ameliorates lysosomal and frontotemporal dementia-related RT phenotypes in progranulin-deficient mice."; RL Neuron 95:281-296(2017). RN [17] {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, IDENTIFICATION RP IN THE V-ATPASE COMPLEX, GLYCOSYLATION AT ASN-261; ASN-273; ASN-296; RP ASN-303; ASN-350 AND ASN-357, AND DISULFIDE BONDS. 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: Accessory subunit of the proton-transporting vacuolar (V)- CC ATPase protein pump, which is required for luminal acidification of CC secretory vesicles (PubMed:33065002). Guides the V-type ATPase into CC specialized subcellular compartments, such as neuroendocrine regulated CC secretory vesicles or the ruffled border of the osteoclast, thereby CC regulating its activity (PubMed:27231034). Involved in membrane CC trafficking and Ca(2+)-dependent membrane fusion (PubMed:27231034). May CC play a role in the assembly of the V-type ATPase complex (Probable). In CC aerobic conditions, involved in intracellular iron homeostasis, thus CC triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and CC leading to HIF1A hydroxylation and subsequent proteasomal degradation CC (PubMed:28296633). In islets of Langerhans cells, may regulate the CC acidification of dense-core secretory granules (By similarity). CC {ECO:0000250|UniProtKB:Q9R1Q9, ECO:0000269|PubMed:28296633, CC ECO:0000269|PubMed:33065002, ECO:0000303|PubMed:27231034, CC ECO:0000305|PubMed:33065002}. CC -!- SUBUNIT: Accessory component of the multisubunit proton-transporting CC vacuolar (V)-ATPase protein pump (PubMed:33065002). Interacts (via N- CC terminus) with ATP6AP2 (via N-terminus) (PubMed:33065002, CC PubMed:29127204). Interacts with RNASEK (PubMed:26212330). Interacts CC with TMEM106B (via C-terminus) (PubMed:28728022). CC {ECO:0000269|PubMed:26212330, ECO:0000269|PubMed:28728022, CC ECO:0000269|PubMed:29127204, ECO:0000269|PubMed:33065002}. CC -!- INTERACTION: CC Q15904; P42858: HTT; NbExp=3; IntAct=EBI-714667, EBI-466029; CC Q15904; PRO_0000449624 [P0DTD1]: rep; Xeno; NbExp=12; IntAct=EBI-714667, EBI-25475868; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:27231034}; Single-pass type I membrane protein CC {ECO:0000305}. Endoplasmic reticulum-Golgi intermediate compartment CC membrane {ECO:0000269|PubMed:27231034}. Cytoplasmic vesicle, secretory CC vesicle, synaptic vesicle membrane {ECO:0000250|UniProtKB:O54715}; CC Single-pass type I membrane protein {ECO:0000305}. Cytoplasmic vesicle, CC clathrin-coated vesicle membrane {ECO:0000250|UniProtKB:O54715}; CC Single-pass type I membrane protein {ECO:0000305}. Note=Not detected in CC trans-Golgi network. {ECO:0000269|PubMed:27231034}. CC -!- TISSUE SPECIFICITY: widely expressed, with highest levels in brain and CC lowest in liver and duodenum. {ECO:0000269|PubMed:27231034}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:27231034}. CC -!- DISEASE: Immunodeficiency 47 (IMD47) [MIM:300972]: A complex CC immunodeficiency syndrome characterized by hypogammaglobulinemia, CC recurrent bacterial infections, defective glycosylation of serum CC proteins, and liver disease with neonatal jaundice and CC hepatosplenomegaly. Some patients may also have neurologic features, CC including seizures, mild intellectual disability, and behavioral CC abnormalities. Inheritance is X-linked recessive. CC {ECO:0000269|PubMed:27231034}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the vacuolar ATPase subunit S1 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA03938.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAB66785.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; L44140; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL136851; CAB66785.1; ALT_INIT; mRNA. DR EMBL; AK026519; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK289452; BAF82141.1; -; mRNA. DR EMBL; AK075284; BAC11520.1; -; mRNA. DR EMBL; BX936347; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BX936385; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471172; EAW72715.1; -; Genomic_DNA. DR EMBL; BC000724; AAH00724.1; -; mRNA. DR EMBL; D16469; BAA03938.1; ALT_INIT; mRNA. DR CCDS; CCDS35451.1; -. DR RefSeq; NP_001174.2; NM_001183.5. DR RefSeq; XP_011529481.1; XM_011531179.1. DR PDB; 6WLW; EM; 3.00 A; U=1-470. DR PDB; 6WM2; EM; 3.10 A; U=1-470. DR PDB; 6WM3; EM; 3.40 A; U=1-470. DR PDB; 6WM4; EM; 3.60 A; U=1-470. DR PDB; 7U4T; EM; 3.60 A; U=1-470. DR PDB; 7UNF; EM; 4.08 A; s=1-470. DR PDBsum; 6WLW; -. DR PDBsum; 6WM2; -. DR PDBsum; 6WM3; -. DR PDBsum; 6WM4; -. DR PDBsum; 7U4T; -. DR PDBsum; 7UNF; -. DR AlphaFoldDB; Q15904; -. DR EMDB; EMD-21844; -. DR EMDB; EMD-21847; -. DR EMDB; EMD-21848; -. DR EMDB; EMD-21849; -. DR EMDB; EMD-26334; -. DR EMDB; EMD-26623; -. DR SMR; Q15904; -. DR BioGRID; 107019; 182. 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 IntAct; Q15904; 43. DR MINT; Q15904; -. DR STRING; 9606.ENSP00000358777; -. DR BindingDB; Q15904; -. DR ChEMBL; CHEMBL4790; -. DR DrugBank; DB01133; Tiludronic acid. DR TCDB; 8.A.107.1.1; the v-type atpase assembly factor, atp6ap1 (atp6ap1) family. DR GlyConnect; 1900; 5 N-Linked glycans (2 sites). DR GlyCosmos; Q15904; 7 sites, 5 glycans. DR GlyGen; Q15904; 10 sites, 5 N-linked glycans (2 sites), 2 O-linked glycans (3 sites). DR iPTMnet; Q15904; -. DR PhosphoSitePlus; Q15904; -. DR BioMuta; ATP6AP1; -. DR DMDM; 12230759; -. DR EPD; Q15904; -. DR jPOST; Q15904; -. DR MassIVE; Q15904; -. DR MaxQB; Q15904; -. DR PaxDb; 9606-ENSP00000358777; -. DR PeptideAtlas; Q15904; -. DR ProteomicsDB; 60806; -. DR Pumba; Q15904; -. DR Antibodypedia; 31229; 227 antibodies from 27 providers. DR DNASU; 537; -. DR Ensembl; ENST00000369762.7; ENSP00000358777.2; ENSG00000071553.18. DR GeneID; 537; -. DR KEGG; hsa:537; -. DR MANE-Select; ENST00000369762.7; ENSP00000358777.2; NM_001183.6; NP_001174.2. DR UCSC; uc004flf.3; human. DR AGR; HGNC:868; -. DR DisGeNET; 537; -. DR GeneCards; ATP6AP1; -. DR HGNC; HGNC:868; ATP6AP1. DR HPA; ENSG00000071553; Low tissue specificity. DR MalaCards; ATP6AP1; -. DR MIM; 300197; gene. DR MIM; 300972; phenotype. DR neXtProt; NX_Q15904; -. DR OpenTargets; ENSG00000071553; -. DR PharmGKB; PA25145; -. DR VEuPathDB; HostDB:ENSG00000071553; -. DR eggNOG; KOG3868; Eukaryota. DR GeneTree; ENSGT00940000156650; -. DR HOGENOM; CLU_039408_1_0_1; -. DR InParanoid; Q15904; -. DR OMA; WFTMEHL; -. DR OrthoDB; 2878970at2759; -. DR PhylomeDB; Q15904; -. DR TreeFam; TF325819; -. DR BioCyc; MetaCyc:HS01034-MONOMER; -. DR PathwayCommons; Q15904; -. DR Reactome; R-HSA-77387; Insulin receptor recycling. DR Reactome; R-HSA-8980692; RHOA GTPase cycle. DR Reactome; R-HSA-917977; Transferrin endocytosis and recycling. DR Reactome; R-HSA-983712; Ion channel transport. DR SignaLink; Q15904; -. DR SIGNOR; Q15904; -. DR BioGRID-ORCS; 537; 322 hits in 810 CRISPR screens. DR ChiTaRS; ATP6AP1; human. DR GeneWiki; ATP6AP1; -. DR GenomeRNAi; 537; -. DR Pharos; Q15904; Tchem. DR PRO; PR:Q15904; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q15904; Protein. DR Bgee; ENSG00000071553; Expressed in endometrium epithelium and 204 other cell types or tissues. DR ExpressionAtlas; Q15904; baseline and differential. DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; NAS:ComplexPortal. DR GO; GO:0005765; C:lysosomal membrane; NAS:ComplexPortal. DR GO; GO:0016020; C:membrane; IDA:ComplexPortal. DR GO; GO:0005886; C:plasma membrane; NAS:ComplexPortal. DR GO; GO:0016469; C:proton-transporting two-sector ATPase complex; TAS:ProtInc. DR GO; GO:0033176; C:proton-transporting V-type ATPase complex; IBA:GO_Central. DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0001671; F:ATPase activator activity; IEA:Ensembl. DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB. DR GO; GO:0141109; F:transporter activator activity; IEA:Ensembl. 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:0099638; P:endosome to plasma membrane protein transport; ISS:UniProtKB. 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:0036035; P:osteoclast development; ISS:CAFA. DR GO; GO:1902600; P:proton transmembrane transport; NAS:ComplexPortal. DR GO; GO:0030641; P:regulation of cellular pH; IBA:GO_Central. DR GO; GO:0097401; P:synaptic vesicle lumen acidification; IEA:Ensembl. DR GO; GO:0007035; P:vacuolar acidification; NAS:ComplexPortal. DR Gene3D; 2.40.160.110; -; 1. DR InterPro; IPR008388; Ac45_acc_su. DR InterPro; IPR046756; VAS1/VOA1_TM. DR InterPro; IPR046755; VAS1_LD. DR PANTHER; PTHR12471:SF2; V-TYPE PROTON ATPASE SUBUNIT S1; 1. DR PANTHER; PTHR12471; VACUOLAR ATP SYNTHASE SUBUNIT S1; 1. DR Pfam; PF20520; Ac45-VOA1_TM; 1. DR Pfam; PF05827; VAS1_LD; 1. DR Genevisible; Q15904; HS. PE 1: Evidence at protein level; KW 3D-structure; Congenital disorder of glycosylation; Cytoplasmic vesicle; KW Disease variant; Disulfide bond; Endoplasmic reticulum; Glycoprotein; KW Hydrogen ion transport; Ion transport; Membrane; Phosphoprotein; KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix; KW Transport. FT SIGNAL 1..41 FT /evidence="ECO:0000255" FT CHAIN 42..470 FT /note="V-type proton ATPase subunit S1" FT /id="PRO_0000002543" FT PROPEP 42..231 FT /evidence="ECO:0000250|UniProtKB:Q9R1Q9" FT /id="PRO_0000454041" FT TOPO_DOM 42..419 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 420..440 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 441..470 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT SITE 231..232 FT /note="Cleavage; by furin" FT /evidence="ECO:0000250|UniProtKB:Q9R1Q9" FT MOD_RES 465 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CARBOHYD 170 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 261 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:33065002, ECO:0007744|PDB:6WLW, FT ECO:0007744|PDB:6WM2, ECO:0007744|PDB:6WM3, FT ECO:0007744|PDB:6WM4" FT CARBOHYD 273 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:33065002, ECO:0007744|PDB:6WLW, FT ECO:0007744|PDB:6WM2, ECO:0007744|PDB:6WM3, FT ECO:0007744|PDB:6WM4" FT CARBOHYD 296 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255, ECO:0000269|PubMed:33065002, FT ECO:0007744|PDB:6WM3, ECO:0007744|PDB:6WM4" FT CARBOHYD 303 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:33065002, FT ECO:0007744|PDB:6WLW, ECO:0007744|PDB:6WM2, FT ECO:0007744|PDB:6WM3, ECO:0007744|PDB:6WM4" FT CARBOHYD 350 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:33065002, FT ECO:0007744|PDB:6WLW, ECO:0007744|PDB:6WM2, FT ECO:0007744|PDB:6WM3, ECO:0007744|PDB:6WM4" FT CARBOHYD 357 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:33065002, FT ECO:0007744|PDB:6WM3, ECO:0007744|PDB:6WM4" FT DISULFID 371..418 FT /evidence="ECO:0000269|PubMed:33065002, FT ECO:0007744|PDB:6WLW, ECO:0007744|PDB:6WM2, FT ECO:0007744|PDB:6WM3, ECO:0007744|PDB:6WM4" FT VARIANT 144 FT /note="L -> P (in IMD47; dbSNP:rs878853276)" FT /evidence="ECO:0000269|PubMed:27231034" FT /id="VAR_077021" FT VARIANT 313 FT /note="Y -> C (in IMD47; probable loss of FT proton-transporting V-type ATPase complex assembly in FT yeast; unable to restore V-ATPase-dependent growth in Voa1 FT mutant yeast; dbSNP:rs878853278)" FT /evidence="ECO:0000269|PubMed:27231034" FT /id="VAR_077022" FT VARIANT 346 FT /note="E -> K (in IMD47; probable loss of FT proton-transporting V-type ATPase complex assembly in FT yeast; unable to restore V-ATPase-dependent growth in Voa1 FT mutant yeast; dbSNP:rs878853277)" FT /evidence="ECO:0000269|PubMed:27231034" FT /id="VAR_077023" FT VARIANT 428 FT /note="M -> I (in IMD47; restores V-ATPase-dependent growth FT in Voa1 mutant yeast; dbSNP:rs878853275)" FT /evidence="ECO:0000269|PubMed:27231034" FT /id="VAR_077024" FT MUTAGEN 470 FT /note="V->VKKNN: Retained in the endoplasmic reticulum when FT transfected into yeast cells. Restores V-ATPase-dependent FT growth in Voa1 mutant yeast." FT /evidence="ECO:0000269|PubMed:27231034" FT CONFLICT 68 FT /note="I -> V (in Ref. 4; BAC11520)" FT /evidence="ECO:0000305" FT CONFLICT 74 FT /note="L -> P (in Ref. 4; BAC11520)" FT /evidence="ECO:0000305" FT CONFLICT 229 FT /note="V -> A (in Ref. 3; AK026519)" FT /evidence="ECO:0000305" FT CONFLICT 307 FT /note="A -> T (in Ref. 3; AK026519)" FT /evidence="ECO:0000305" FT CONFLICT 335 FT /note="S -> F (in Ref. 3; AK026519)" FT /evidence="ECO:0000305" FT STRAND 258..270 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 272..280 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 282..284 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 286..289 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 304..316 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 319..332 FT /evidence="ECO:0007829|PDB:6WLW" FT TURN 333..336 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 337..348 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 353..357 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 365..376 FT /evidence="ECO:0007829|PDB:6WLW" FT TURN 378..381 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 385..390 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 392..403 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 409..411 FT /evidence="ECO:0007829|PDB:6WLW" FT STRAND 415..418 FT /evidence="ECO:0007829|PDB:6WLW" FT HELIX 424..448 FT /evidence="ECO:0007829|PDB:6WLW" SQ SEQUENCE 470 AA; 52026 MW; A71C7EF0E90D0652 CRC64; MMAAMATARV RMGPRCAQAL WRMPWLPVFL SLAAAAAAAA AEQQVPLVLW SSDRDLWAPA ADTHEGHITS DLQLSTYLDP ALELGPRNVL LFLQDKLSIE DFTAYGGVFG NKQDSAFSNL ENALDLAPSS LVLPAVDWYA VSTLTTYLQE KLGASPLHVD LATLRELKLN ASLPALLLIR LPYTASSGLM APREVLTGND EVIGQVLSTL KSEDVPYTAA LTAVRPSRVA RDVAVVAGGL GRQLLQKQPV SPVIHPPVSY NDTAPRILFW AQNFSVAYKD QWEDLTPLTF GVQELNLTGS FWNDSFARLS LTYERLFGTT VTFKFILANR LYPVSARHWF TMERLEVHSN GSVAYFNASQ VTGPSIYSFH CEYVSSLSKK GSLLVARTQP SPWQMMLQDF QIQAFNVMGE QFSYASDCAS FFSPGIWMGL LTSLFMLFIF TYGLHMILSL KTMDRFDDHK GPTISLTQIV //