VATO_HUMAN
ID VATO_HUMAN Reviewed; 205 AA.
AC Q99437; D3DPY5; Q6IB32;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=V-type proton ATPase 21 kDa proteolipid subunit c'' {ECO:0000305};
DE Short=V-ATPase 21 kDa proteolipid subunit c'' {ECO:0000305};
DE AltName: Full=Vacuolar proton pump 21 kDa proteolipid subunit c'' {ECO:0000305};
DE AltName: Full=hATPL;
GN Name=ATP6V0B; Synonyms=ATP6F;
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).
RC TISSUE=Kidney;
RX PubMed=9653649; DOI=10.1006/geno.1998.5310;
RA Nishigori H., Yamada S., Tomura H., Fernald A.A., le Beau M.M.,
RA Takeuchi T., Takeda J.;
RT "Identification and characterization of the gene encoding a second
RT proteolipid subunit of human vacuolar H(+)-ATPase (ATP6F).";
RL Genomics 50:222-228(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [7] {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, AND
RP IDENTIFICATION IN THE V-ATPASE COMPLEX.
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).
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] MET-155.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Proton-conducting pore forming of the V0 complex of
CC vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a
CC peripheral complex (V1) that hydrolyzes ATP and a membrane integral
CC complex (V0) that translocates protons (PubMed:33065002). V-ATPase is
CC responsible for acidifying and maintaining the pH of intracellular
CC compartments and in some cell types, is targeted to the plasma
CC membrane, where it is responsible for acidifying the extracellular
CC environment (By similarity). {ECO:0000250|UniProtKB:Q2TA24,
CC ECO:0000269|PubMed:33065002}.
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 (PubMed:33065002). The V1 complex consists of three
CC catalytic AB heterodimers that form a heterohexamer, three peripheral
CC stalks each consisting of EG heterodimers, one central rotor including
CC subunits D and F, and the regulatory subunits C and H
CC (PubMed:33065002). The proton translocation complex V0 consists of the
CC proton transport subunit a, a ring of proteolipid subunits c9c'',
CC rotary subunit d, subunits e and f, and the accessory subunits
CC ATP6AP1/Ac45 and ATP6AP2/PRR (PubMed:33065002). Interacts with IFITM3
CC (By similarity). {ECO:0000250|UniProtKB:Q91V37,
CC ECO:0000269|PubMed:33065002}.
CC -!- INTERACTION:
CC Q99437; Q86Y34: ADGRG3; NbExp=3; IntAct=EBI-3904417, EBI-17979264;
CC Q99437; P05090: APOD; NbExp=3; IntAct=EBI-3904417, EBI-715495;
CC Q99437; P29400-2: COL4A5; NbExp=3; IntAct=EBI-3904417, EBI-12211159;
CC Q99437; P54849: EMP1; NbExp=3; IntAct=EBI-3904417, EBI-4319440;
CC Q99437; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-3904417, EBI-18938272;
CC Q99437; P48165: GJA8; NbExp=3; IntAct=EBI-3904417, EBI-17458373;
CC Q99437; O15529: GPR42; NbExp=3; IntAct=EBI-3904417, EBI-18076404;
CC Q99437; Q9BZJ8: GPR61; NbExp=3; IntAct=EBI-3904417, EBI-12808020;
CC Q99437; Q9Y5U4: INSIG2; NbExp=3; IntAct=EBI-3904417, EBI-8503746;
CC Q99437; P26715: KLRC1; NbExp=3; IntAct=EBI-3904417, EBI-9018187;
CC Q99437; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-3904417, EBI-11956541;
CC Q99437; P30301: MIP; NbExp=3; IntAct=EBI-3904417, EBI-8449636;
CC Q99437; Q96HJ5: MS4A3; NbExp=5; IntAct=EBI-3904417, EBI-12806656;
CC Q99437; Q8IXM6: NRM; NbExp=3; IntAct=EBI-3904417, EBI-10262547;
CC Q99437; Q14973: SLC10A1; NbExp=3; IntAct=EBI-3904417, EBI-3923031;
CC Q99437; P22732: SLC2A5; NbExp=3; IntAct=EBI-3904417, EBI-2825135;
CC Q99437; Q9HBV2: SPACA1; NbExp=3; IntAct=EBI-3904417, EBI-17498703;
CC Q99437; P27105: STOM; NbExp=3; IntAct=EBI-3904417, EBI-1211440;
CC Q99437; Q96DZ7: TM4SF19; NbExp=3; IntAct=EBI-3904417, EBI-6448756;
CC Q99437; Q9NWH2: TMEM242; NbExp=3; IntAct=EBI-3904417, EBI-10315004;
CC Q99437; Q3ZAQ7: VMA21; NbExp=3; IntAct=EBI-3904417, EBI-1055364;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle
CC membrane {ECO:0000250|UniProtKB:Q2TA24}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99437-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99437-2; Sequence=VSP_046288;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the V-ATPase proteolipid subunit family.
CC {ECO:0000305}.
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DR EMBL; D89052; BAA13753.1; -; mRNA.
DR EMBL; BT007151; AAP35815.1; -; mRNA.
DR EMBL; CR456972; CAG33253.1; -; mRNA.
DR EMBL; AL357079; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07066.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07067.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07068.1; -; Genomic_DNA.
DR EMBL; BC000423; AAH00423.1; -; mRNA.
DR EMBL; BC005876; AAH05876.1; -; mRNA.
DR CCDS; CCDS41315.1; -. [Q99437-2]
DR CCDS; CCDS505.1; -. [Q99437-1]
DR RefSeq; NP_001034546.1; NM_001039457.2. [Q99437-2]
DR RefSeq; NP_004038.1; NM_004047.4. [Q99437-1]
DR PDB; 6WLW; EM; 3.00 A; 0=1-205.
DR PDB; 6WM2; EM; 3.10 A; 0=1-205.
DR PDB; 6WM3; EM; 3.40 A; 0=1-205.
DR PDB; 6WM4; EM; 3.60 A; 0=1-205.
DR PDBsum; 6WLW; -.
DR PDBsum; 6WM2; -.
DR PDBsum; 6WM3; -.
DR PDBsum; 6WM4; -.
DR AlphaFoldDB; Q99437; -.
DR SMR; Q99437; -.
DR BioGRID; 107016; 33.
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; Q99437; 26.
DR MINT; Q99437; -.
DR STRING; 9606.ENSP00000434729; -.
DR DrugBank; DB01133; Tiludronic acid.
DR iPTMnet; Q99437; -.
DR PhosphoSitePlus; Q99437; -.
DR BioMuta; ATP6V0B; -.
DR DMDM; 6136172; -.
DR MassIVE; Q99437; -.
DR PaxDb; Q99437; -.
DR PeptideAtlas; Q99437; -.
DR PRIDE; Q99437; -.
DR Antibodypedia; 32422; 86 antibodies from 18 providers.
DR DNASU; 533; -.
DR Ensembl; ENST00000236067.8; ENSP00000236067.4; ENSG00000117410.14. [Q99437-2]
DR Ensembl; ENST00000472174.7; ENSP00000431605.1; ENSG00000117410.14. [Q99437-1]
DR Ensembl; ENST00000498664.1; ENSP00000434094.1; ENSG00000117410.14. [Q99437-2]
DR GeneID; 533; -.
DR KEGG; hsa:533; -.
DR MANE-Select; ENST00000472174.7; ENSP00000431605.1; NM_004047.5; NP_004038.1.
DR UCSC; uc001cld.4; human. [Q99437-1]
DR CTD; 533; -.
DR DisGeNET; 533; -.
DR GeneCards; ATP6V0B; -.
DR HGNC; HGNC:861; ATP6V0B.
DR HPA; ENSG00000117410; Low tissue specificity.
DR MIM; 603717; gene.
DR neXtProt; NX_Q99437; -.
DR OpenTargets; ENSG00000117410; -.
DR PharmGKB; PA25148; -.
DR VEuPathDB; HostDB:ENSG00000117410; -.
DR eggNOG; KOG0233; Eukaryota.
DR GeneTree; ENSGT00550000075120; -.
DR HOGENOM; CLU_085752_0_0_1; -.
DR InParanoid; Q99437; -.
DR OMA; PYAWAST; -.
DR PhylomeDB; Q99437; -.
DR TreeFam; TF314946; -.
DR BioCyc; MetaCyc:ENSG00000117410-MON; -.
DR PathwayCommons; Q99437; -.
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; Q99437; -.
DR BioGRID-ORCS; 533; 673 hits in 1084 CRISPR screens.
DR ChiTaRS; ATP6V0B; human.
DR GeneWiki; ATP6V0B; -.
DR GenomeRNAi; 533; -.
DR Pharos; Q99437; Tbio.
DR PRO; PR:Q99437; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q99437; protein.
DR Bgee; ENSG00000117410; Expressed in granulocyte and 200 other tissues.
DR ExpressionAtlas; Q99437; baseline and differential.
DR Genevisible; Q99437; HS.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; IC:ComplexPortal.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IDA:ComplexPortal.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0033176; C:proton-transporting V-type ATPase complex; IC:ComplexPortal.
DR GO; GO:0000220; C:vacuolar proton-transporting V-type ATPase, V0 domain; ISS:UniProtKB.
DR GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; TAS:ProtInc.
DR GO; GO:0048388; P:endosomal lumen acidification; IC:ComplexPortal.
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:1902600; P:proton transmembrane transport; TAS:ProtInc.
DR GO; GO:0016241; P:regulation of macroautophagy; NAS:ParkinsonsUK-UCL.
DR GO; GO:0007035; P:vacuolar acidification; IC:ComplexPortal.
DR Gene3D; 1.20.120.610; -; 1.
DR InterPro; IPR002379; ATPase_proteolipid_c-like_dom.
DR InterPro; IPR000245; ATPase_proteolipid_csu.
DR InterPro; IPR035921; F/V-ATP_Csub_sf.
DR Pfam; PF00137; ATP-synt_C; 2.
DR PRINTS; PR00122; VACATPASE.
DR SUPFAM; SSF81333; SSF81333; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasmic vesicle;
KW Hydrogen ion transport; Ion transport; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..205
FT /note="V-type proton ATPase 21 kDa proteolipid subunit c''"
FT /id="PRO_0000071777"
FT TOPO_DOM 1..3
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..51
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 52..72
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 73..90
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 91..111
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 112..137
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 138..158
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 159..175
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 197..205
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT SITE 98
FT /note="Essential for proton translocation"
FT /evidence="ECO:0000250|UniProtKB:Q2TA24"
FT VAR_SEQ 1..47
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_046288"
FT VARIANT 155
FT /note="V -> M (in a breast cancer sample; somatic mutation;
FT dbSNP:rs373883976)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035703"
FT HELIX 3..28
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 37..43
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 46..79
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 91..111
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 123..168
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:6WLW"
FT HELIX 173..197
FT /evidence="ECO:0007829|PDB:6WLW"
SQ SEQUENCE 205 AA; 21406 MW; F17C688D068A2785 CRC64;
MTGLALLYSG VFVAFWACAL AVGVCYTIFD LGFRFDVAWF LTETSPFMWS NLGIGLAISL
SVVGAAWGIY ITGSSIIGGG VKAPRIKTKN LVSIIFCEAV AIYGIIMAIV ISNMAEPFSA
TDPKAIGHRN YHAGYSMFGA GLTVGLSNLF CGVCVGIVGS GAALADAQNP SLFVKILIVE
IFGSAIGLFG VIVAILQTSR VKMGD
