VAS1_MOUSE
ID VAS1_MOUSE Reviewed; 463 AA.
AC Q9R1Q9;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=V-type proton ATPase subunit S1;
DE Short=V-ATPase subunit S1;
DE AltName: Full=Protein C7-1;
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hayashi A., Hattori A., Okaze H., Kozuma S., Seki N., Saito T.;
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
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 [3]
RP PROTEIN SEQUENCE OF 325-338 AND 454-463, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, GLYCOSYLATION, PROTEOLYTIC CLEAVAGE, AND
RP MUTAGENESIS OF 222-ARG--ARG-225.
RX PubMed=18713856; DOI=10.1073/pnas.0800340105;
RA Louagie E., Taylor N.A., Flamez D., Roebroek A.J., Bright N.A.,
RA Meulemans S., Quintens R., Herrera P.L., Schuit F., Van de Ven W.J.,
RA Creemers J.W.;
RT "Role of furin in granular acidification in the endocrine pancreas:
RT identification of the V-ATPase subunit Ac45 as a candidate substrate.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12319-12324(2008).
RN [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-255.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP TISSUE SPECIFICITY, AND GLYCOSYLATION.
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).
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:18713856). 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. Involved in membrane trafficking and Ca(2+)-
CC dependent membrane fusion. May play a role in the assembly of the V-
CC type ATPase complex. 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). In islets of
CC Langerhans cells, may regulate the acidification of dense-core
CC secretory granules (PubMed:18713856). {ECO:0000250|UniProtKB:Q15904,
CC ECO:0000269|PubMed:18713856}.
CC -!- SUBUNIT: Accessory component of the multisubunit proton-transporting
CC vacuolar (V)-ATPase protein pump. Interacts (via N-terminus) with
CC ATP6AP2 (via N-terminus). Interacts with RNASEK (By similarity).
CC {ECO:0000250|UniProtKB:Q15904}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q15904}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q15904}. Endoplasmic reticulum-Golgi
CC intermediate compartment membrane {ECO:0000250|UniProtKB:Q15904}.
CC Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane
CC {ECO:0000250|UniProtKB:O54715}; Single-pass type I membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, clathrin-coated vesicle membrane
CC {ECO:0000250|UniProtKB:O54715}; Single-pass type I membrane protein
CC {ECO:0000305}. Note=Not detected in trans-Golgi network.
CC {ECO:0000250|UniProtKB:Q15904}.
CC -!- TISSUE SPECIFICITY: Expressed in brain cortex (at protein level)
CC (PubMed:27231034). Highly expressed in islets of Langerhans
CC (PubMed:18713856). Expressed in pancreatic acini, pituitary gland,
CC adrenal gland, lung, brain and bone marrow (PubMed:18713856).
CC {ECO:0000269|PubMed:18713856, ECO:0000269|PubMed:27231034}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:18713856}.
CC -!- SIMILARITY: Belongs to the vacuolar ATPase subunit S1 family.
CC {ECO:0000305}.
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DR EMBL; AB031290; BAA83498.1; -; mRNA.
DR EMBL; BC048241; AAH48241.1; -; mRNA.
DR CCDS; CCDS30226.1; -.
DR RefSeq; NP_061264.1; NM_018794.4.
DR AlphaFoldDB; Q9R1Q9; -.
DR SMR; Q9R1Q9; -.
DR BioGRID; 207653; 3.
DR IntAct; Q9R1Q9; 1.
DR MINT; Q9R1Q9; -.
DR STRING; 10090.ENSMUSP00000019231; -.
DR GlyConnect; 2826; 7 N-Linked glycans (4 sites).
DR GlyGen; Q9R1Q9; 8 sites, 7 N-linked glycans (4 sites).
DR iPTMnet; Q9R1Q9; -.
DR PhosphoSitePlus; Q9R1Q9; -.
DR EPD; Q9R1Q9; -.
DR jPOST; Q9R1Q9; -.
DR MaxQB; Q9R1Q9; -.
DR PaxDb; Q9R1Q9; -.
DR PeptideAtlas; Q9R1Q9; -.
DR PRIDE; Q9R1Q9; -.
DR ProteomicsDB; 298272; -.
DR Antibodypedia; 31229; 212 antibodies from 27 providers.
DR DNASU; 54411; -.
DR Ensembl; ENSMUST00000019231; ENSMUSP00000019231; ENSMUSG00000019087.
DR GeneID; 54411; -.
DR KEGG; mmu:54411; -.
DR UCSC; uc009tol.2; mouse.
DR CTD; 537; -.
DR MGI; MGI:109629; Atp6ap1.
DR VEuPathDB; HostDB:ENSMUSG00000019087; -.
DR eggNOG; KOG3868; Eukaryota.
DR GeneTree; ENSGT00940000156650; -.
DR HOGENOM; CLU_039408_1_0_1; -.
DR InParanoid; Q9R1Q9; -.
DR OMA; WFTMEHL; -.
DR OrthoDB; 1111170at2759; -.
DR PhylomeDB; Q9R1Q9; -.
DR TreeFam; TF325819; -.
DR Reactome; R-MMU-77387; Insulin receptor recycling.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-917977; Transferrin endocytosis and recycling.
DR Reactome; R-MMU-983712; Ion channel transport.
DR BioGRID-ORCS; 54411; 22 hits in 72 CRISPR screens.
DR ChiTaRS; Atp6ap1; mouse.
DR PRO; PR:Q9R1Q9; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9R1Q9; protein.
DR Bgee; ENSMUSG00000019087; Expressed in stroma of bone marrow and 270 other tissues.
DR ExpressionAtlas; Q9R1Q9; baseline and differential.
DR Genevisible; Q9R1Q9; MM.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:MGI.
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; IPI:UniProtKB.
DR GO; GO:0008219; P:cell death; ISO:MGI.
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:0099638; P:endosome to plasma membrane protein transport; IMP:UniProtKB.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW.
DR GO; GO:0036035; P:osteoclast development; IMP:UniProtKB.
DR GO; GO:0030641; P:regulation of cellular pH; IBA:GO_Central.
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 Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Hydrogen ion transport; Ion transport;
KW Membrane; Reference proteome; Signal; Synapse; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..463
FT /note="V-type proton ATPase subunit S1"
FT /id="PRO_0000002544"
FT PROPEP 33..225
FT /evidence="ECO:0000269|PubMed:18713856"
FT /id="PRO_0000454042"
FT TOPO_DOM 33..412
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 413..433
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 434..463
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT SITE 225..226
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000269|PubMed:18713856"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 255
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 344
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 351
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 399
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 365..411
FT /evidence="ECO:0000250|UniProtKB:Q15904"
FT MUTAGEN 222..225
FT /note="RVAR->AVAA: Impairs propeptide cleavage."
FT /evidence="ECO:0000269|PubMed:18713856"
SQ SEQUENCE 463 AA; 51008 MW; AE28D99718BA0AC0 CRC64;
MMAATVVSRI RTGTGRAPVM WLSLSLVAVA AAVATEQQVP LVLWSSDRNL WAPVADTHEG
HITSDMQLST YLDPALELGP RNVLLFLQDK LSIEDFTAYG GVFGNKQDSA FSNLENALDL
APSSLVLPAV DWYAISTLTT YLQEKLGASP LHVDLATLKE LKLNASLPAL LLIRLPYTAS
SGLMAPREVL TGNDEVIGQV LSTLKSEDVP YTAALTAVRP SRVARDITMV AGGLGRQLLQ
TQVASPAIHP PVSYNDTAPR ILFWAQNFSV AYKDEWKDLT SLTFGVENLN LTGSFWNDSF
AMLSLTYEPL FGATVTFKFI LASRFYPVSA RYWFAMERLE IHSNGSVAHF NVSQVTGPSI
YSFHCEYVSS VSKKGNLLVT NVPSVWQMTL HNFQIQAFNV TGEQFSYASD CAGFFSPGIW
MGLLTTLFML FIFTYGLHMI LSLKTMDRFD DHKGPTITLT QIV
