VAS1_HUMAN
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 03-AUG-2022, entry version 204.
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] {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).
CC {ECO:0000269|PubMed:26212330, ECO:0000269|PubMed:29127204,
CC ECO:0000269|PubMed:33065002}.
CC -!- INTERACTION:
CC Q15904; P42858: HTT; NbExp=3; IntAct=EBI-714667, EBI-466029;
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};
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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 PDBsum; 6WLW; -.
DR PDBsum; 6WM2; -.
DR PDBsum; 6WM3; -.
DR PDBsum; 6WM4; -.
DR AlphaFoldDB; Q15904; -.
DR SMR; Q15904; -.
DR BioGRID; 107019; 161.
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; 40.
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 GlyGen; Q15904; 8 sites, 5 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
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; Q15904; -.
DR PeptideAtlas; Q15904; -.
DR PRIDE; Q15904; -.
DR ProteomicsDB; 60806; -.
DR Antibodypedia; 31229; 212 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 CTD; 537; -.
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; 1111170at2759; -.
DR PhylomeDB; Q15904; -.
DR TreeFam; TF325819; -.
DR BioCyc; MetaCyc:HS01034-MON; -.
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; 304 hits in 727 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 202 other tissues.
DR ExpressionAtlas; Q15904; baseline and differential.
DR Genevisible; Q15904; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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; IC:ComplexPortal.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IC:ComplexPortal.
DR GO; GO:0016020; C:membrane; IDA:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IC: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:0031267; F:small GTPase binding; ISS:UniProtKB.
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:0099638; P:endosome to plasma membrane protein transport; ISS:UniProtKB.
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:0036035; P:osteoclast development; ISS:CAFA.
DR GO; GO:1902600; P:proton transmembrane transport; IC:ComplexPortal.
DR GO; GO:0030641; P:regulation of cellular pH; IBA:GO_Central.
DR GO; GO:0007035; P:vacuolar acidification; IC:ComplexPortal.
DR InterPro; IPR008388; Ac45_acc_su.
DR PANTHER; PTHR12471; PTHR12471; 1.
DR Pfam; PF05827; ATP-synt_S1; 1.
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 proton-
FT transporting V-type ATPase complex assembly in yeast;
FT unable to restore V-ATPase-dependent growth in Voa1 mutant
FT 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 proton-
FT transporting V-type ATPase complex assembly in yeast;
FT unable to restore V-ATPase-dependent growth in Voa1 mutant
FT 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
