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 28-JAN-2026, entry version 149. 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}; 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; 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; CCDS47742.2; -. [Q8NHE4-2] DR CCDS; CCDS55181.2; -. [Q8NHE4-1] DR CCDS; CCDS94229.1; -. [Q8NHE4-3] DR RefSeq; NP_001094062.2; NM_001100592.3. [Q8NHE4-2] DR RefSeq; NP_001276919.2; NM_001289990.2. [Q8NHE4-3] DR RefSeq; NP_001354718.2; NM_001367789.2. [Q8NHE4-1] DR RefSeq; NP_660265.3; NM_145230.4. [Q8NHE4-1] DR AlphaFoldDB; Q8NHE4; -. DR SMR; Q8NHE4; -. DR BioGRID; 127575; 4. 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 FunCoup; Q8NHE4; 457. DR IntAct; Q8NHE4; 1. DR MINT; Q8NHE4; -. DR STRING; 9606.ENSP00000411672; -. DR DrugBank; DB01133; Tiludronic acid. DR GlyCosmos; Q8NHE4; 1 site, No reported glycans. DR GlyGen; Q8NHE4; 2 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; Q8NHE4; -. DR PhosphoSitePlus; Q8NHE4; -. DR BioMuta; ATP6V0E2; -. DR DMDM; 74715659; -. DR MassIVE; Q8NHE4; -. DR PeptideAtlas; Q8NHE4; -. DR Antibodypedia; 46340; 29 antibodies from 9 providers. DR DNASU; 155066; -. DR Ensembl; ENST00000421974.7; ENSP00000411672.3; ENSG00000171130.20. [Q8NHE4-2] DR Ensembl; ENST00000425642.3; ENSP00000396148.2; ENSG00000171130.20. [Q8NHE4-1] DR Ensembl; ENST00000456496.7; ENSP00000410220.3; ENSG00000171130.20. [Q8NHE4-1] DR Ensembl; ENST00000464662.5; ENSP00000475645.1; ENSG00000171130.20. [Q8NHE4-1] DR Ensembl; ENST00000471877.5; ENSP00000420679.1; ENSG00000171130.20. [Q8NHE4-1] DR Ensembl; ENST00000479613.5; ENSP00000417939.1; ENSG00000171130.20. [Q8NHE4-3] DR Ensembl; ENST00000606024.5; ENSP00000475904.1; ENSG00000171130.20. [Q8NHE4-2] DR Ensembl; ENST00000649866.2; ENSP00000497146.2; ENSG00000171130.20. [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 AGR; HGNC:21723; -. DR ClinPGx; PA162377277; -. DR CTD; 155066; -. DR DisGeNET; 155066; -. DR GeneCards; ATP6V0E2; -. DR HGNC; HGNC:21723; ATP6V0E2. DR HPA; ENSG00000171130; Tissue enhanced (brain). DR MIM; 611019; gene. DR OpenTargets; ENSG00000171130; -. DR VEuPathDB; HostDB:ENSG00000171130; -. DR GeneTree; ENSGT00940000162476; -. DR HOGENOM; CLU_170555_0_1_1; -. DR InParanoid; Q8NHE4; -. DR OrthoDB; 1508846at2759; -. DR PAN-GO; Q8NHE4; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q8NHE4; -. DR BioCyc; MetaCyc:HS15951-MONOMER; -. 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 SIGNOR; Q8NHE4; -. DR Agora; ENSG00000171130; -. DR BioGRID-ORCS; 155066; 10 hits in 1149 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 205 other cell types or tissues. DR ExpressionAtlas; Q8NHE4; baseline and differential. DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. 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:SF2; V-TYPE PROTON ATPASE SUBUNIT E 2; 1. DR PANTHER; PTHR12263; VACUOLAR ATP SYNTHASE SUBUNIT H; 1. DR Pfam; PF05493; ATP_synt_H; 1. DR PIRSF; PIRSF038097; V-ATP_synth_e1/e2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasmic vesicle; Glycoprotein; KW Hydrogen ion transport; Ion transport; Membrane; Proteomics identification; KW Reference proteome; 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 //