VA0E2_HUMAN
ID VA0E2_HUMAN Reviewed; 81 AA.
AC Q8NHE4; A2T863; A2T8L7; B5MDP5; J3KQW7; Q6MZW1; Q75L47; Q7Z4R7; Q8N7I8;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=V-type proton ATPase subunit e 2;
DE Short=V-ATPase subunit e 2;
DE AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2;
DE AltName: Full=Vacuolar proton pump subunit e 2;
GN Name=ATP6V0E2; Synonyms=ATP6V0E2L, C7orf32;
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] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 1-61
RP (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=17350184; DOI=10.1016/j.gene.2007.01.020;
RA Blake-Palmer K.G., Su Y., Smith A.N., Karet F.E.;
RT "Molecular cloning and characterization of a novel form of the human
RT vacuolar H+-ATPase e-subunit: an essential proton pump component.";
RL Gene 393:94-100(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Li N., Wan T., Zhang M., Zhang W., Cao X.;
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Placenta;
RA Zan Q., Guo J.H., Yu L.;
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
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).
CC {ECO:0000250|UniProtKB:Q2KIB5}.
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. The V1 complex consists of three catalytic AB heterodimers
CC that form a heterohexamer, three peripheral stalks each consisting of
CC EG heterodimers, one central rotor including subunits D and F, and the
CC regulatory subunits C and H. The proton translocation complex V0
CC consists of the proton transport subunit a, a ring of proteolipid
CC subunits c9c'', rotary subunit d, subunits e and f, and the accessory
CC subunits ATP6AP1/Ac45 and ATP6AP2/PRR. {ECO:0000250|UniProtKB:Q2KIB5}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}. Cytoplasmic vesicle, clathrin-coated vesicle
CC membrane {ECO:0000250|UniProtKB:Q5EB76}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC membrane {ECO:0000250|UniProtKB:Q5EB76}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8NHE4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NHE4-2; Sequence=VSP_027104;
CC Name=3;
CC IsoId=Q8NHE4-3; Sequence=VSP_027105;
CC Name=4;
CC IsoId=Q8NHE4-4; Sequence=VSP_044857;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed at high levels in heart,
CC brain and kidney and also detected in inner ear epithelium, vestibule,
CC testis, epididymis and bladder. Isoform 2 is expressed in heart,
CC kidney, placenta and pancreas. Isoform 2 is not detected in frontal
CC cortex, but is prevalent in all other brain areas.
CC {ECO:0000269|PubMed:17350184}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be due to a competing donor splice
CC site. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the V-ATPase e1/e2 subunit family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP97693.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAQ96859.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAC05292.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAE45916.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; DQ995344; ABK76305.1; -; mRNA.
DR EMBL; DQ989009; ABK88279.1; -; mRNA.
DR EMBL; AY037164; AAK67647.1; -; mRNA.
DR EMBL; AF452639; AAP97693.1; ALT_FRAME; mRNA.
DR EMBL; AK098362; BAC05292.1; ALT_INIT; mRNA.
DR EMBL; BX640846; CAE45916.1; ALT_INIT; mRNA.
DR EMBL; AC093458; AAQ96859.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS47742.1; -. [Q8NHE4-2]
DR CCDS; CCDS55181.1; -. [Q8NHE4-1]
DR RefSeq; NP_001094062.1; NM_001100592.2. [Q8NHE4-2]
DR RefSeq; NP_001276919.1; NM_001289990.1. [Q8NHE4-3]
DR RefSeq; NP_660265.2; NM_145230.3. [Q8NHE4-1]
DR AlphaFoldDB; Q8NHE4; -.
DR SMR; Q8NHE4; -.
DR BioGRID; 127575; 4.
DR IntAct; Q8NHE4; 1.
DR MINT; Q8NHE4; -.
DR DrugBank; DB01133; Tiludronic acid.
DR PhosphoSitePlus; Q8NHE4; -.
DR BioMuta; ATP6V0E2; -.
DR DMDM; 74715659; -.
DR MassIVE; Q8NHE4; -.
DR PeptideAtlas; Q8NHE4; -.
DR PRIDE; Q8NHE4; -.
DR Antibodypedia; 46340; 31 antibodies from 10 providers.
DR DNASU; 155066; -.
DR Ensembl; ENST00000421974.7; ENSP00000411672.3; ENSG00000171130.19. [Q8NHE4-2]
DR Ensembl; ENST00000425642.3; ENSP00000396148.2; ENSG00000171130.19. [Q8NHE4-1]
DR Ensembl; ENST00000456496.7; ENSP00000410220.3; ENSG00000171130.19. [Q8NHE4-1]
DR Ensembl; ENST00000464662.5; ENSP00000475645.1; ENSG00000171130.19. [Q8NHE4-1]
DR Ensembl; ENST00000471877.5; ENSP00000420679.1; ENSG00000171130.19. [Q8NHE4-1]
DR Ensembl; ENST00000479613.5; ENSP00000417939.1; ENSG00000171130.19. [Q8NHE4-3]
DR Ensembl; ENST00000606024.5; ENSP00000475904.1; ENSG00000171130.19. [Q8NHE4-2]
DR Ensembl; ENST00000649866.2; ENSP00000497146.2; ENSG00000171130.19. [Q8NHE4-1]
DR GeneID; 155066; -.
DR KEGG; hsa:155066; -.
DR MANE-Select; ENST00000425642.3; ENSP00000396148.2; NM_145230.4; NP_660265.3.
DR UCSC; uc003wgp.3; human. [Q8NHE4-1]
DR CTD; 155066; -.
DR GeneCards; ATP6V0E2; -.
DR HGNC; HGNC:21723; ATP6V0E2.
DR HPA; ENSG00000171130; Tissue enhanced (brain).
DR MIM; 611019; gene.
DR neXtProt; NX_Q8NHE4; -.
DR OpenTargets; ENSG00000171130; -.
DR PharmGKB; PA162377277; -.
DR VEuPathDB; HostDB:ENSG00000171130; -.
DR GeneTree; ENSGT00940000162476; -.
DR HOGENOM; CLU_170555_0_1_1; -.
DR InParanoid; Q8NHE4; -.
DR OrthoDB; 1613627at2759; -.
DR PhylomeDB; Q8NHE4; -.
DR BioCyc; MetaCyc:HS15951-MON; -.
DR PathwayCommons; Q8NHE4; -.
DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes.
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; Q8NHE4; -.
DR BioGRID-ORCS; 155066; 10 hits in 1073 CRISPR screens.
DR ChiTaRS; ATP6V0E2; human.
DR GenomeRNAi; 155066; -.
DR Pharos; Q8NHE4; Tbio.
DR PRO; PR:Q8NHE4; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q8NHE4; protein.
DR Bgee; ENSG00000171130; Expressed in Brodmann (1909) area 10 and 203 other tissues.
DR ExpressionAtlas; Q8NHE4; baseline and differential.
DR Genevisible; Q8NHE4; 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:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000220; C:vacuolar proton-transporting V-type ATPase, V0 domain; ISS:UniProtKB.
DR GO; GO:0042625; F:ATPase-coupled ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; IGI:UniProtKB.
DR GO; GO:1902600; P:proton transmembrane transport; IGI:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; NAS:ParkinsonsUK-UCL.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0007035; P:vacuolar acidification; ISS:UniProtKB.
DR InterPro; IPR008389; ATPase_V0-cplx_e1/e2_su.
DR InterPro; IPR017385; ATPase_V0-cplx_e1/e2_su_met.
DR PANTHER; PTHR12263; PTHR12263; 1.
DR Pfam; PF05493; ATP_synt_H; 1.
DR PIRSF; PIRSF038097; V-ATP_synth_e1/e2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cytoplasmic vesicle; Glycoprotein;
KW Hydrogen ion transport; Ion transport; Membrane; Reference proteome;
KW Synapse; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..81
FT /note="V-type proton ATPase subunit e 2"
FT /id="PRO_0000270199"
FT TOPO_DOM 1..7
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..35
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 36..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..81
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1
FT /note="M -> MRVRGPARLIASGARLLLRMLSALPGWGPAHLQRPLLGPASCLGILR
FT PAM (in isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_044857"
FT VAR_SEQ 51..81
FT /note="FWLIAILAQLNPLFGPQLKNETIWYVRFLWE -> LCPALGMTVAPLSLTTP
FT SSGPSPTQLCLVTSSLLLAPRDPDPQGLPGSWKSSQSSQPARALGSPGHSSGRGDVLLQ
FT YPHCSGVCPLSQGDAAGELVWVGSFPLQTGQMPGLSPS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17350184"
FT /id="VSP_027104"
FT VAR_SEQ 75..81
FT /note="YVRFLWE -> CPALGMTVAPLSLTTPSSGPSPTQLCLVTSSLLLAPRDPDP
FT QGLPGSWKSSQSSQPARALGSPGHSSGRGDVLLQYPHCSGVCPLSQGDAAGELVWVGSF
FT PLQTGQMPGLSPS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_027105"
SQ SEQUENCE 81 AA; 9184 MW; FACC53CB431BA445 CRC64;
MTAHSFALPV IIFTTFWGLV GIAGPWFVPK GPNRGVIITM LVATAVCCYL FWLIAILAQL
NPLFGPQLKN ETIWYVRFLW E
