VPP2_MOUSE
ID VPP2_MOUSE Reviewed; 856 AA.
AC P15920; A4FU82; Q3U2X3; Q8VHU0; Q9JHJ2;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=V-type proton ATPase 116 kDa subunit a 2;
DE Short=V-ATPase 116 kDa subunit a 2;
DE AltName: Full=Immune suppressor factor J6B7;
DE Short=ISF;
DE AltName: Full=Lysosomal H(+)-transporting ATPase V0 subunit a 2;
DE AltName: Full=ShIF;
DE AltName: Full=Vacuolar proton translocating ATPase 116 kDa subunit a isoform 2;
GN Name=Atp6v0a2; Synonyms=Atp6n1b, Tj6;
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] (ISOFORM 1).
RX PubMed=2247090; DOI=10.1016/0161-5890(90)90102-6;
RA Lee C.-K., Ghoshal K., Beaman K.D.;
RT "Cloning of a cDNA for a T cell produced molecule with a putative immune
RT regulatory role.";
RL Mol. Immunol. 27:1137-1144(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10722719; DOI=10.1074/jbc.275.12.8760;
RA Toyomura T., Oka T., Yamaguchi C., Wada Y., Futai M.;
RT "Three subunit a isoforms of mouse vacuolar H+-ATPase. Preferential
RT expression of the a3 isoform during osteoclast differentiation.";
RL J. Biol. Chem. 275:8760-8765(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Heart;
RX PubMed=10702241; DOI=10.1074/jbc.275.10.6824;
RA Nishi T., Forgac M.;
RT "Molecular cloning and expression of three isoforms of the 100-kDa a
RT subunit of the mouse vacuolar proton-translocating ATPase.";
RL J. Biol. Chem. 275:6824-6830(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=NOD; TISSUE=Dendritic cell, and Wolffian duct;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary tumor;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 569-856, AND TISSUE SPECIFICITY.
RX PubMed=11375395; DOI=10.1074/jbc.m101781200;
RA Tulin E.E., Onoda N., Maeda M., Hasegawa M., Nosaka T., Nomura H.,
RA Asano S., Kitamura T.;
RT "A novel secreted form of immune suppressor factor with high homology to
RT vacuolar ATPases identified by a forward genetic approach of functional
RT screening based on cell proliferation.";
RL J. Biol. Chem. 276:27519-27526(2001).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PSCD2.
RX PubMed=16415858; DOI=10.1038/ncb1348;
RA Hurtado-Lorenzo A., Skinner M., El Annan J., Futai M., Sun-Wada G.-H.,
RA Bourgoin S., Casanova J., Wildeman A., Bechoua S., Ausiello D.A., Brown D.,
RA Marshansky V.;
RT "V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the
RT protein degradative pathway.";
RL Nat. Cell Biol. 8:124-136(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-695 AND SER-700, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-695 AND SER-700, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, 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).
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 (By similarity). 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). Essential
CC component of the endosomal pH-sensing machinery (PubMed:16415858). May
CC play a role in maintaining the Golgi functions, such as glycosylation
CC maturation, by controlling the Golgi pH (By similarity). In aerobic
CC conditions, involved in intracellular iron homeostasis, thus triggering
CC the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to
CC HIF1A hydroxylation and subsequent proteasomal degradation (By
CC similarity). {ECO:0000250|UniProtKB:Q29466,
CC ECO:0000250|UniProtKB:Q93050, ECO:0000250|UniProtKB:Q9Y487,
CC ECO:0000269|PubMed:16415858}.
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 (By similarity). The V1 complex consists of three catalytic
CC AB heterodimers that form a heterohexamer, three peripheral stalks each
CC consisting of EG heterodimers, one central rotor including subunits D
CC and F, and the regulatory subunits C and H (By similarity). The proton
CC translocation complex V0 consists of the proton transport subunit a, a
CC ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f,
CC and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By
CC similarity). Directly interacts with PSCD2 through its N-terminal
CC cytosolic tail in an intra-endosomal acidification-dependent manner
CC (PubMed:16415858). Disruption of this interaction results in the
CC inhibition of endocytosis (PubMed:16415858). Interacts with SPAAR (By
CC similarity). {ECO:0000250|UniProtKB:Q93050,
CC ECO:0000250|UniProtKB:Q9Y487, ECO:0000269|PubMed:16415858}.
CC -!- INTERACTION:
CC P15920; P63034: Cyth2; NbExp=5; IntAct=EBI-988456, EBI-988425;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16415858};
CC Multi-pass membrane protein {ECO:0000269|PubMed:16415858}. Endosome
CC membrane {ECO:0000269|PubMed:16415858}. Note=In kidney proximal
CC tubules, detected in subapical early endosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P15920-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P15920-2; Sequence=VSP_032088;
CC -!- TISSUE SPECIFICITY: Relatively high expression in kidney and liver.
CC Lower levels in the spleen, testis, and skeletal muscle. Also expressed
CC in the thymus. {ECO:0000269|PubMed:11375395}.
CC -!- SIMILARITY: Belongs to the V-ATPase 116 kDa subunit family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL57303.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M31226; AAA39336.1; -; mRNA.
DR EMBL; X55184; CAA38968.1; -; mRNA.
DR EMBL; AB022323; BAA93007.1; -; mRNA.
DR EMBL; AF218252; AAF59921.1; -; mRNA.
DR EMBL; AK032909; BAC28081.1; -; mRNA.
DR EMBL; AK155055; BAE33017.1; -; mRNA.
DR EMBL; BC108991; AAI08992.1; -; mRNA.
DR EMBL; BC108992; AAI08993.1; -; mRNA.
DR EMBL; BC112905; AAI12906.1; -; mRNA.
DR EMBL; AF388674; AAL57303.1; ALT_INIT; mRNA.
DR CCDS; CCDS84963.1; -. [P15920-1]
DR PIR; JH0287; JH0287.
DR RefSeq; NP_035726.2; NM_011596.5. [P15920-1]
DR PDB; 2LX4; NMR; -; A=1-17.
DR PDBsum; 2LX4; -.
DR AlphaFoldDB; P15920; -.
DR BMRB; P15920; -.
DR SMR; P15920; -.
DR BioGRID; 204208; 1.
DR IntAct; P15920; 1.
DR STRING; 10090.ENSMUSP00000039737; -.
DR TCDB; 3.A.2.2.6; the h(+)- or na(+)-translocating f-type, v-type and a-type atpase (f-atpase) superfamily.
DR iPTMnet; P15920; -.
DR PhosphoSitePlus; P15920; -.
DR SwissPalm; P15920; -.
DR EPD; P15920; -.
DR jPOST; P15920; -.
DR MaxQB; P15920; -.
DR PaxDb; P15920; -.
DR PeptideAtlas; P15920; -.
DR PRIDE; P15920; -.
DR ProteomicsDB; 300181; -. [P15920-1]
DR ProteomicsDB; 300182; -. [P15920-2]
DR Antibodypedia; 31833; 115 antibodies from 25 providers.
DR DNASU; 21871; -.
DR Ensembl; ENSMUST00000037865; ENSMUSP00000039737; ENSMUSG00000038023. [P15920-1]
DR GeneID; 21871; -.
DR KEGG; mmu:21871; -.
DR UCSC; uc008zqn.2; mouse. [P15920-2]
DR UCSC; uc029voj.2; mouse. [P15920-1]
DR CTD; 23545; -.
DR MGI; MGI:104855; Atp6v0a2.
DR VEuPathDB; HostDB:ENSMUSG00000038023; -.
DR eggNOG; KOG2189; Eukaryota.
DR GeneTree; ENSGT00950000182881; -.
DR HOGENOM; CLU_005230_0_0_1; -.
DR InParanoid; P15920; -.
DR OMA; MIFFKWL; -.
DR OrthoDB; 181796at2759; -.
DR PhylomeDB; P15920; -.
DR TreeFam; TF300346; -.
DR Reactome; R-MMU-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-MMU-77387; Insulin receptor recycling.
DR Reactome; R-MMU-917977; Transferrin endocytosis and recycling.
DR Reactome; R-MMU-983712; Ion channel transport.
DR BioGRID-ORCS; 21871; 2 hits in 51 CRISPR screens.
DR ChiTaRS; Atp6v0a2; mouse.
DR PRO; PR:P15920; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P15920; protein.
DR Bgee; ENSMUSG00000038023; Expressed in choroid plexus of fourth ventricle and 283 other tissues.
DR ExpressionAtlas; P15920; baseline and differential.
DR Genevisible; P15920; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:MGI.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0043229; C:intracellular organelle; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0016471; C:vacuolar proton-transporting V-type ATPase complex; IBA:GO_Central.
DR GO; GO:0000220; C:vacuolar proton-transporting V-type ATPase, V0 domain; IEA:InterPro.
DR GO; GO:0051117; F:ATPase binding; IBA:GO_Central.
DR GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; IEA:InterPro.
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:0007035; P:vacuolar acidification; IBA:GO_Central.
DR InterPro; IPR002490; V-ATPase_116kDa_su.
DR InterPro; IPR026028; V-type_ATPase_116kDa_su_euka.
DR PANTHER; PTHR11629; PTHR11629; 1.
DR Pfam; PF01496; V_ATPase_I; 1.
DR PIRSF; PIRSF001293; ATP6V0A1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Endosome;
KW Hydrogen ion transport; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..856
FT /note="V-type proton ATPase 116 kDa subunit a 2"
FT /id="PRO_0000119217"
FT TOPO_DOM 1..393
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 394..412
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 413..414
FT /note="Vacuolar"
FT /evidence="ECO:0000255"
FT TRANSMEM 415..431
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 432..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..475
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 476..549
FT /note="Vacuolar"
FT /evidence="ECO:0000255"
FT TRANSMEM 550..569
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 570..587
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 588..608
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 609..651
FT /note="Vacuolar"
FT /evidence="ECO:0000255"
FT TRANSMEM 652..671
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 672..739
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 740..764
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 765..785
FT /note="Vacuolar"
FT /evidence="ECO:0000255"
FT TRANSMEM 786..824
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 825..856
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 700
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..593
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_032088"
FT CONFLICT 486
FT /note="S -> C (in Ref. 1; AAA39336/CAA38968)"
FT /evidence="ECO:0000305"
FT CONFLICT 791
FT /note="Missing (in Ref. 1; AAA39336/CAA38968)"
FT /evidence="ECO:0000305"
FT HELIX 4..16
FT /evidence="ECO:0007829|PDB:2LX4"
SQ SEQUENCE 856 AA; 98145 MW; 6A0D593F6F401E22 CRC64;
MGSLFRSESM CLAQLFLQSG TAYECLSALG EKGLVQFRDL NQNVSSFQRK FVGEVKRCEE
LERILVYLVQ EITRADIPLP EGEASPPAPP LKHVLEMQEQ LQKLEVELRE VTKNKEKLRK
NLLELVEYTH MLRVTKTFLK RNVEFEPTYE EFPALENDSL LDYSCMQRLG AKLGFVSGLI
QQGRVEAFER MLWRACKGYT IVTYAELDEC LEDPETGEVI KWYVFLISFW GEQIGHKVKK
ICDCYHCHIY PYPNTAEERR EIQEGLNTRI QDLYTVLHKT EDYLRQVLCK AAESVCSRVV
QVRKMKAIYH MLNMCSFDVT NKCLIAEVWC PEVDLPGLRR ALEEGSRESG ATIPSFMNTI
PTKETPPTLI RTNKFTEGFQ NIVDAYGVGS YREVNPALFT IITFPFLFAV MFGDFGHGFV
MFLFALLLVL NENHPRLSQS QEILRMFFDG RYILLLMGLF SVYTGLIYND CFSKSVNLFG
SGWNVSAMYS SSHSPEEQRK MVLWNDSTIR HSRTLQLDPN IPGVFRGPYP FGIDPIWNLA
TNRLTFLNSF KMKMSVILGI FHMTFGVVLG IFNHLHFRKK FNVYLVSVPE ILFMLCIFGY
LIFMIIYKWL AYSAETSREA PSILIEFINM FLFPTSKTHG LYPGQAHVQR VLVALTVLAV
PVLFLGKPLF LLWLHNGRNC FGMSRSGYTL VRKDSEEEVS LLGNQDIEEG NSRMEEGCRE
VTCEEFNFGE ILMTQAIHSI EYCLGCISNT ASYLRLWALS LAHAQLSDVL WAMLMRVGLR
VDTTYGVLLL LPVMAFFAVL TIFILLVMEG LSAFLHAIRL HWVEFQNKFY VGAGTKFVPF
SFSLLSSKFS NDDSIA
