ID   VATL_HUMAN              Reviewed;         155 AA.
AC   P27449; Q6FH26;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   18-JUN-2025, entry version 221.
DE   RecName: Full=V-type proton ATPase 16 kDa proteolipid subunit c {ECO:0000305};
DE            Short=V-ATPase 16 kDa proteolipid subunit c {ECO:0000305};
DE   AltName: Full=Vacuolar proton pump 16 kDa proteolipid subunit c {ECO:0000305};
GN   Name=ATP6V0C; Synonyms=ATP6C, ATP6L, ATPL;
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].
RX   PubMed=1709739; DOI=10.1073/pnas.88.10.4289;
RA   Gillespie G.A.J., Somlo S., Germino G.G., Weinstat-Saslow D., Reeders S.T.;
RT   "CpG island in the region of an autosomal dominant polycystic kidney
RT   disease locus defines the 5' end of a gene encoding a putative proton
RT   channel.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:4289-4293(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, Muscle, and Skin;
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   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 28-155.
RX   PubMed=1532310; DOI=10.1016/0006-291x(92)90562-y;
RA   Hasebe M., Hanada H., Moriyama Y., Maeda M., Futai M.;
RT   "Vacuolar type H(+)-ATPase genes: presence of four genes including
RT   pseudogenes for the 16-kDa proteolipid subunit in the human genome.";
RL   Biochem. Biophys. Res. Commun. 183:856-863(1992).
RN   [6]
RP   INTERACTION WITH HTLV-1 ACCESSORY PROTEIN P12I (MICROBIAL INFECTION).
RX   PubMed=7636472; DOI=10.1099/0022-1317-76-8-1909;
RA   Koralnik I.J., Mulloy J.C., Andresson T., Fullen J., Franchini G.;
RT   "Mapping of the intermolecular association of human T cell
RT   leukaemia/lymphotropic virus type I p12I and the vacuolar H+-ATPase 16 kDa
RT   subunit protein.";
RL   J. Gen. Virol. 76:1909-1916(1995).
RN   [7]
RP   INTERACTION WITH LASS2.
RX   PubMed=11543633; DOI=10.1006/geno.2001.6614;
RA   Pan H., Qin W.-X., Huo K.-K., Wan D.-F., Yu Y., Xu Z.-G., Hu Q.-D.,
RA   Gu K.T., Zhou X.-M., Jiang H.-Q., Zhang P.-P., Huang Y., Li Y.-Y.,
RA   Gu J.-R.;
RT   "Cloning, mapping, and characterization of a human homologue of the yeast
RT   longevity assurance gene LAG1.";
RL   Genomics 77:58-64(2001).
RN   [8]
RP   INTERACTION WITH RNF182, AND UBIQUITINATION.
RX   PubMed=18298843; DOI=10.1186/1750-1326-3-4;
RA   Liu Q.Y., Lei J.X., Sikorska M., Liu R.;
RT   "A novel brain-enriched E3 ubiquitin ligase RNF182 is up regulated in the
RT   brains of Alzheimer's patients and targets ATP6V0C for degradation.";
RL   Mol. Neurodegener. 3:4-4(2008).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [11]
RP   INVOLVEMENT IN EPEO3.
RX   PubMed=33190975; DOI=10.1016/j.braindev.2020.10.016;
RA   Ittiwut C., Poonmaksatit S., Boonsimma P., Desudchit T., Suphapeetiporn K.,
RA   Ittiwut R., Shotelersuk V.;
RT   "Novel de novo mutation substantiates ATP6V0C as a gene causing epilepsy
RT   with intellectual disability.";
RL   Brain Dev. 43:490-494(2021).
RN   [12] {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   [13]
RP   VARIANT EPEO3 THR-22, AND INVOLVEMENT IN EPEO3.
RX   PubMed=35600075; DOI=10.3389/fnmol.2022.889534;
RA   Tian Y., Zhai Q.X., Li X.J., Shi Z., Cheng C.F., Fan C.X., Tang B.,
RA   Zhang Y., He Y.Y., Li W.B., Luo S., Hou C., Chen W.X., Liao W.P., Wang J.;
RT   "ATP6V0C Is Associated With Febrile Seizures and Epilepsy With Febrile
RT   Seizures Plus.";
RL   Front. Mol. Neurosci. 15:889534-889534(2022).
RN   [14]
RP   VARIANTS EPEO3 SER-29; PRO-48; ARG-53; ALA-58; ALA-63; PHE-74; THR-95;
RP   PRO-95; VAL-95; ARG-98; ASN-132; LEU-137; PRO-138; ASP-142; THR-147;
RP   THR-149; PHE-150 AND PRO-150, CHARACTERIZATION OF VARIANTS EPEO3 SER-29;
RP   PRO-48; ALA-63; PHE-74; THR-95; PRO-95; ARG-98; LEU-137; PRO-138; THR-149;
RP   PHE-150 AND PRO-150, CHARACTERIZATION OF VARIANTS TRP-48; SER-103 AND
RP   ILE-131, AND MUTAGENESIS OF GLU-139.
RX   PubMed=36074901; DOI=10.1093/brain/awac330;
RG   Genomics England Research Consortium;
RA   Mattison K.A., Tossing G., Mulroe F., Simmons C., Butler K.M.,
RA   Schreiber A., Alsadah A., Neilson D.E., Naess K., Wedell A., Wredenberg A.,
RA   Sorlin A., McCann E., Burghel G.J., Menendez B., Hoganson G.E., Botto L.D.,
RA   Filloux F.M., Aledo-Serrano A., Gil-Nagel A., Tatton-Brown K.,
RA   Verbeek N.E., van der Zwaag B., Aleck K.A., Fazenbaker A.C.,
RA   Balciuniene J., Dubbs H.A., Marsh E.D., Garber K., Ek J., Duno M.,
RA   Hoei-Hansen C.E., Deardorff M.A., Raca G., Quindipan C., van Hirtum-Das M.,
RA   Breckpot J., Hammer T.B., Moeller R.S., Whitney A., Douglas A.G.L.,
RA   Kharbanda M., Brunetti-Pierri N., Morleo M., Nigro V., May H.J., Tao J.X.,
RA   Argilli E., Sherr E.H., Dobyns W.B., Baines R.A., Warwicker J.,
RA   Parker J.A., Banka S., Campeau P.M., Escayg A.;
RT   "ATP6V0C variants impair V-ATPase function causing a neurodevelopmental
RT   disorder often associated with epilepsy.";
RL   Brain 146:1357-1372(2023).
RN   [15]
RP   VARIANTS EPEO3 99-VAL--SER-102 DEL AND TRP-119.
RX   PubMed=37161035; DOI=10.1038/s10038-023-01145-1;
RA   Zhao S., Zhang X., Yang L., Wang Y., Jia S., Li X., Wang Z., Yang F.,
RA   Liang M., Wang X., Wang D.;
RT   "ATP6V0C gene variants were identified in individuals with epilepsy, with
RT   or without developmental delay.";
RL   J. Hum. Genet. 68:589-597(2023).
CC   -!- FUNCTION: Proton-conducting pore forming subunit 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,
CC       PubMed:36074901). V-ATPase is responsible for acidifying and
CC       maintaining the pH of intracellular compartments, and in some cell
CC       types, it is targeted to the plasma membrane, where it is responsible
CC       for acidifying the extracellular environment (By similarity).
CC       {ECO:0000250|UniProtKB:P23956, ECO:0000269|PubMed:33065002,
CC       ECO:0000269|PubMed:36074901}.
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 the V0
CC       complex V-ATPase subunit a4 ATP6V0A4 (By similarity). Interacts with
CC       LASS2 (PubMed:11543633). Interacts with RNF182; this interaction leads
CC       to ubiquitination and degradation via the proteasome pathway
CC       (PubMed:18298843). {ECO:0000250|UniProtKB:P63082,
CC       ECO:0000269|PubMed:11543633, ECO:0000269|PubMed:18298843,
CC       ECO:0000269|PubMed:33065002}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with HTLV-1 accessory protein
CC       p12I. {ECO:0000269|PubMed:7636472}.
CC   -!- INTERACTION:
CC       P27449; Q13520: AQP6; NbExp=3; IntAct=EBI-721179, EBI-13059134;
CC       P27449; P07307-3: ASGR2; NbExp=3; IntAct=EBI-721179, EBI-12808270;
CC       P27449; P19397: CD53; NbExp=3; IntAct=EBI-721179, EBI-6657396;
CC       P27449; Q07108: CD69; NbExp=3; IntAct=EBI-721179, EBI-2836595;
CC       P27449; P11912: CD79A; NbExp=3; IntAct=EBI-721179, EBI-7797864;
CC       P27449; Q96G23: CERS2; NbExp=4; IntAct=EBI-721179, EBI-1057080;
CC       P27449; Q86T13: CLEC14A; NbExp=3; IntAct=EBI-721179, EBI-17710733;
CC       P27449; Q6ZS10: CLEC17A; NbExp=3; IntAct=EBI-721179, EBI-11977093;
CC       P27449; Q9UHP7-3: CLEC2D; NbExp=3; IntAct=EBI-721179, EBI-11749983;
CC       P27449; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-721179, EBI-18013275;
CC       P27449; Q9NR28: DIABLO; NbExp=3; IntAct=EBI-721179, EBI-517508;
CC       P27449; Q96KC8: DNAJC1; NbExp=3; IntAct=EBI-721179, EBI-296550;
CC       P27449; Q92838: EDA; NbExp=4; IntAct=EBI-721179, EBI-529425;
CC       P27449; Q9HAV5: EDA2R; NbExp=3; IntAct=EBI-721179, EBI-526033;
CC       P27449; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-721179, EBI-781551;
CC       P27449; P84090: ERH; NbExp=3; IntAct=EBI-721179, EBI-711389;
CC       P27449; P22794: EVI2A; NbExp=3; IntAct=EBI-721179, EBI-2870359;
CC       P27449; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-721179, EBI-18938272;
CC       P27449; O15552: FFAR2; NbExp=3; IntAct=EBI-721179, EBI-2833872;
CC       P27449; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-721179, EBI-12142257;
CC       P27449; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-721179, EBI-13345167;
CC       P27449; O00155: GPR25; NbExp=3; IntAct=EBI-721179, EBI-10178951;
CC       P27449; O15529: GPR42; NbExp=3; IntAct=EBI-721179, EBI-18076404;
CC       P27449; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-721179, EBI-18053395;
CC       P27449; Q13651: IL10RA; NbExp=3; IntAct=EBI-721179, EBI-1031656;
CC       P27449; P16871: IL7R; NbExp=3; IntAct=EBI-721179, EBI-80490;
CC       P27449; Q92876: KLK6; NbExp=3; IntAct=EBI-721179, EBI-2432309;
CC       P27449; P26715: KLRC1; NbExp=3; IntAct=EBI-721179, EBI-9018187;
CC       P27449; Q8N386: LRRC25; NbExp=3; IntAct=EBI-721179, EBI-11304917;
CC       P27449; Q8IX19: MCEMP1; NbExp=5; IntAct=EBI-721179, EBI-2816356;
CC       P27449; P21757: MSR1; NbExp=6; IntAct=EBI-721179, EBI-1776976;
CC       P27449; Q6P499: NIPAL3; NbExp=3; IntAct=EBI-721179, EBI-10252783;
CC       P27449; P35372-10: OPRM1; NbExp=3; IntAct=EBI-721179, EBI-12807478;
CC       P27449; Q9BQ51: PDCD1LG2; NbExp=3; IntAct=EBI-721179, EBI-16427978;
CC       P27449; Q6UXB8: PI16; NbExp=3; IntAct=EBI-721179, EBI-12810028;
CC       P27449; P25788: PSMA3; NbExp=3; IntAct=EBI-721179, EBI-348380;
CC       P27449; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-721179, EBI-7545592;
CC       P27449; Q86VR2: RETREG3; NbExp=4; IntAct=EBI-721179, EBI-10192441;
CC       P27449; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-721179, EBI-17247926;
CC       P27449; Q7Z769: SLC35E3; NbExp=3; IntAct=EBI-721179, EBI-13389236;
CC       P27449; P30825: SLC7A1; NbExp=3; IntAct=EBI-721179, EBI-4289564;
CC       P27449; Q9BZL3: SMIM3; NbExp=6; IntAct=EBI-721179, EBI-741850;
CC       P27449; Q9HBV2: SPACA1; NbExp=3; IntAct=EBI-721179, EBI-17498703;
CC       P27449; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-721179, EBI-17280858;
CC       P27449; P27105: STOM; NbExp=3; IntAct=EBI-721179, EBI-1211440;
CC       P27449; Q96L08: SUSD3; NbExp=3; IntAct=EBI-721179, EBI-18194029;
CC       P27449; Q8IV31: TMEM139; NbExp=3; IntAct=EBI-721179, EBI-7238458;
CC       P27449; Q9P0T7: TMEM9; NbExp=3; IntAct=EBI-721179, EBI-723976;
CC       P27449; Q9H7M9: VSIR; NbExp=3; IntAct=EBI-721179, EBI-744988;
CC       P27449; Q6PEW1: ZCCHC12; NbExp=3; IntAct=EBI-721179, EBI-748373;
CC       P27449; P0CK45: E5; Xeno; NbExp=2; IntAct=EBI-721179, EBI-7015490;
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle
CC       membrane {ECO:0000250|UniProtKB:P63081}; Multi-pass membrane protein
CC       {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC       membrane {ECO:0000250|UniProtKB:P63081}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- PTM: Ubiquitinated by RNF182, leading to its degradation via the
CC       ubiquitin-proteasome pathway. {ECO:0000269|PubMed:18298843}.
CC   -!- DISEASE: Epilepsy, early-onset, 3, with or without developmental delay
CC       (EPEO3) [MIM:620465]: An autosomal dominant neurologic disorder
CC       characterized by various types of seizures with onset in the first
CC       months or years of life. Many patients present with febrile seizures
CC       and later develop afebrile seizures. Some affected individuals have
CC       global developmental delay or regression, impaired intellectual
CC       development, poor or absent speech, and motor delay. Additional
CC       variable features include hypotonia, gait ataxia, behavioral
CC       abnormalities, and anomalies on brain imaging.
CC       {ECO:0000269|PubMed:33190975, ECO:0000269|PubMed:35600075,
CC       ECO:0000269|PubMed:36074901, ECO:0000269|PubMed:37161035}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the V-ATPase proteolipid subunit family.
CC       {ECO:0000305}.
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DR   EMBL; M62762; AAA60039.1; -; mRNA.
DR   EMBL; CR541930; CAG46728.1; -; mRNA.
DR   EMBL; CR541951; CAG46749.1; -; mRNA.
DR   EMBL; BT007155; AAP35819.1; -; mRNA.
DR   EMBL; BC004537; AAH04537.1; -; mRNA.
DR   EMBL; BC007389; AAH07389.1; -; mRNA.
DR   EMBL; BC007759; AAH07759.1; -; mRNA.
DR   EMBL; BC009290; AAH09290.1; -; mRNA.
DR   CCDS; CCDS10470.1; -.
DR   PIR; A39367; A39367.
DR   RefSeq; NP_001185498.1; NM_001198569.2.
DR   RefSeq; NP_001685.1; NM_001694.4.
DR   PDB; 6WLW; EM; 3.00 A; 1/2/3/4/5/6/7/8/9=1-155.
DR   PDB; 6WM2; EM; 3.10 A; 1/2/3/4/5/6/7/8/9=1-155.
DR   PDB; 6WM3; EM; 3.40 A; 1/2/3/4/5/6/7/8/9=1-155.
DR   PDB; 6WM4; EM; 3.60 A; 1/2/3/4/5/6/7/8/9=1-155.
DR   PDB; 7U4T; EM; 3.60 A; 1/2/3/4/5/6/7/8/9=1-155.
DR   PDB; 7UNF; EM; 4.08 A; 0/2/3/4/5/6/7/8/9=1-155.
DR   PDBsum; 6WLW; -.
DR   PDBsum; 6WM2; -.
DR   PDBsum; 6WM3; -.
DR   PDBsum; 6WM4; -.
DR   PDBsum; 7U4T; -.
DR   PDBsum; 7UNF; -.
DR   AlphaFoldDB; P27449; -.
DR   EMDB; EMD-21844; -.
DR   EMDB; EMD-21847; -.
DR   EMDB; EMD-21848; -.
DR   EMDB; EMD-21849; -.
DR   EMDB; EMD-26334; -.
DR   EMDB; EMD-26623; -.
DR   SMR; P27449; -.
DR   BioGRID; 107010; 151.
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   CORUM; P27449; -.
DR   FunCoup; P27449; 1503.
DR   IntAct; P27449; 127.
DR   MINT; P27449; -.
DR   STRING; 9606.ENSP00000329757; -.
DR   DrugBank; DB01133; Tiludronic acid.
DR   GlyGen; P27449; 3 sites, 1 O-linked glycan (3 sites).
DR   iPTMnet; P27449; -.
DR   PhosphoSitePlus; P27449; -.
DR   BioMuta; ATP6V0C; -.
DR   DMDM; 137479; -.
DR   jPOST; P27449; -.
DR   MassIVE; P27449; -.
DR   PaxDb; 9606-ENSP00000329757; -.
DR   PeptideAtlas; P27449; -.
DR   ProteomicsDB; 54393; -.
DR   Pumba; P27449; -.
DR   TopDownProteomics; P27449; -.
DR   Antibodypedia; 23806; 84 antibodies from 19 providers.
DR   DNASU; 527; -.
DR   Ensembl; ENST00000330398.9; ENSP00000329757.4; ENSG00000185883.12.
DR   GeneID; 527; -.
DR   KEGG; hsa:527; -.
DR   MANE-Select; ENST00000330398.9; ENSP00000329757.4; NM_001694.4; NP_001685.1.
DR   UCSC; uc002cqn.4; human.
DR   AGR; HGNC:855; -.
DR   CTD; 527; -.
DR   DisGeNET; 527; -.
DR   GeneCards; ATP6V0C; -.
DR   HGNC; HGNC:855; ATP6V0C.
DR   HPA; ENSG00000185883; Low tissue specificity.
DR   MalaCards; ATP6V0C; -.
DR   MIM; 108745; gene.
DR   MIM; 620465; phenotype.
DR   OpenTargets; ENSG00000185883; -.
DR   VEuPathDB; HostDB:ENSG00000185883; -.
DR   eggNOG; KOG0232; Eukaryota.
DR   GeneTree; ENSGT00550000074873; -.
DR   HOGENOM; CLU_085752_1_2_1; -.
DR   InParanoid; P27449; -.
DR   OMA; MGVMKPD; -.
DR   OrthoDB; 1744869at2759; -.
DR   PAN-GO; P27449; 1 GO annotation based on evolutionary models.
DR   PhylomeDB; P27449; -.
DR   BioCyc; MetaCyc:MONOMER66-34368; -.
DR   PathwayCommons; P27449; -.
DR   Reactome; R-HSA-1222556; ROS and RNS production in phagocytes.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
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   Reactome; R-HSA-9857377; Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy.
DR   SignaLink; P27449; -.
DR   SIGNOR; P27449; -.
DR   BioGRID-ORCS; 527; 866 hits in 1175 CRISPR screens.
DR   ChiTaRS; ATP6V0C; human.
DR   GeneWiki; ATP6V0C; -.
DR   GenomeRNAi; 527; -.
DR   Pharos; P27449; Tbio.
DR   PRO; PR:P27449; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; P27449; protein.
DR   Bgee; ENSG00000185883; Expressed in superior frontal gyrus and 95 other cell types or tissues.
DR   ExpressionAtlas; P27449; baseline and differential.
DR   GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR   GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR   GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR   GO; GO:0000139; C:Golgi membrane; NAS:ComplexPortal.
DR   GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
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; TAS:Reactome.
DR   GO; GO:0033176; C:proton-transporting V-type ATPase complex; NAS:ComplexPortal.
DR   GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR   GO; GO:0000220; C:vacuolar proton-transporting V-type ATPase, V0 domain; ISS:UniProtKB.
DR   GO; GO:0046933; F:proton-transporting ATP synthase activity, rotational mechanism; TAS:UniProtKB.
DR   GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; TAS:ProtInc.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR   GO; GO:0048388; P:endosomal lumen acidification; NAS:ComplexPortal.
DR   GO; GO:0061795; P:Golgi lumen acidification; NAS:ComplexPortal.
DR   GO; GO:0051452; P:intracellular pH reduction; NAS:ComplexPortal.
DR   GO; GO:0007042; P:lysosomal lumen acidification; NAS:ComplexPortal.
DR   GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IMP:UniProtKB.
DR   GO; GO:1902600; P:proton transmembrane transport; TAS:ProtInc.
DR   GO; GO:0016241; P:regulation of macroautophagy; NAS:ParkinsonsUK-UCL.
DR   GO; GO:0097401; P:synaptic vesicle lumen acidification; IEA:Ensembl.
DR   GO; GO:0007035; P:vacuolar acidification; NAS:ComplexPortal.
DR   CDD; cd18175; ATP-synt_Vo_c_ATP6C_rpt1; 1.
DR   CDD; cd18176; ATP-synt_Vo_c_ATP6C_rpt2; 1.
DR   FunFam; 1.20.120.610:FF:000001; V-type proton ATPase proteolipid subunit; 1.
DR   Gene3D; 1.20.120.610; lithium bound rotor ring of v- atpase; 1.
DR   InterPro; IPR002379; ATPase_proteolipid_c-like_dom.
DR   InterPro; IPR000245; ATPase_proteolipid_csu.
DR   InterPro; IPR011555; ATPase_proteolipid_su_C_euk.
DR   InterPro; IPR035921; F/V-ATP_Csub_sf.
DR   NCBIfam; TIGR01100; V_ATP_synt_C; 1.
DR   PANTHER; PTHR10263; V-TYPE PROTON ATPASE PROTEOLIPID SUBUNIT; 1.
DR   Pfam; PF00137; ATP-synt_C; 2.
DR   PRINTS; PR00122; VACATPASE.
DR   SUPFAM; SSF81333; F1F0 ATP synthase subunit C; 2.
DR   neXtProt; NX_P27449; -.
DR   PharmGKB; PA25149; -.
DR   TreeFam; TF300025; -.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasmic vesicle; Disease variant; Epilepsy;
KW   Host-virus interaction; Hydrogen ion transport; Ion transport; Membrane;
KW   Proteomics identification; Reference proteome; Synapse; Transmembrane;
KW   Transmembrane helix; Transport; Ubl conjugation.
FT   CHAIN           1..155
FT                   /note="V-type proton ATPase 16 kDa proteolipid subunit c"
FT                   /id="PRO_0000071743"
FT   TOPO_DOM        1..10
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        11..33
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        34..55
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        56..76
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        77..92
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        93..114
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        115..131
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        132..152
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        153..155
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   SITE            139
FT                   /note="Essential for proton translocation"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT   VARIANT         22
FT                   /note="A -> T (in EPEO3; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:35600075"
FT                   /id="VAR_088818"
FT   VARIANT         29
FT                   /note="G -> S (in EPEO3; uncertain significance; decreased
FT                   function in proton transmembrane transport)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088819"
FT   VARIANT         48
FT                   /note="R -> P (in EPEO3; likely pathogenic; decreased
FT                   function in proton transmembrane transport)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088820"
FT   VARIANT         48
FT                   /note="R -> W (sligthly decreased function in proton
FT                   transmembrane transport; dbSNP:rs770613842)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088821"
FT   VARIANT         53
FT                   /note="M -> R (in EPEO3; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088822"
FT   VARIANT         58
FT                   /note="P -> A (in EPEO3; uncertain significance;
FT                   dbSNP:rs2065895527)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088823"
FT   VARIANT         63
FT                   /note="G -> A (in EPEO3; uncertain significance; sligthly
FT                   decreased function in proton transmembrane transport)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088824"
FT   VARIANT         74
FT                   /note="V -> F (in EPEO3; uncertain significance; decreased
FT                   function in proton transmembrane transport)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088825"
FT   VARIANT         95
FT                   /note="A -> P (in EPEO3; likely pathogenic; loss of
FT                   function in proton transmembrane transport)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088826"
FT   VARIANT         95
FT                   /note="A -> T (in EPEO3; likely pathogenic; decreased
FT                   function in proton transmembrane transport)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088827"
FT   VARIANT         95
FT                   /note="A -> V (in EPEO3; likely pathogenic)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088828"
FT   VARIANT         98
FT                   /note="S -> R (in EPEO3; uncertain significance; severely
FT                   decreased function in proton transmembrane transport)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088829"
FT   VARIANT         99..102
FT                   /note="Missing (in EPEO3; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:37161035"
FT                   /id="VAR_088830"
FT   VARIANT         103
FT                   /note="G -> S (sligthly decreased function in proton
FT                   transmembrane transport; dbSNP:rs754740949)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088831"
FT   VARIANT         119
FT                   /note="R -> W (in EPEO3; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:37161035"
FT                   /id="VAR_088832"
FT   VARIANT         131
FT                   /note="M -> I (sligthly decreased function in proton
FT                   transmembrane transport; dbSNP:rs1490539690)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088833"
FT   VARIANT         132
FT                   /note="I -> N (in EPEO3; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088834"
FT   VARIANT         137
FT                   /note="F -> L (in EPEO3; uncertain significance; unaffected
FT                   function in proton transmembrane transport)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088835"
FT   VARIANT         138
FT                   /note="A -> P (in EPEO3; likely pathogenic; decreased
FT                   function in proton transmembrane transport;
FT                   dbSNP:rs2065898758)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088836"
FT   VARIANT         142
FT                   /note="G -> D (in EPEO3; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088837"
FT   VARIANT         147
FT                   /note="I -> T (in EPEO3; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088838"
FT   VARIANT         149
FT                   /note="A -> T (in EPEO3; likely pathogenic; severely
FT                   decreased function in proton transmembrane transport)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088839"
FT   VARIANT         150
FT                   /note="L -> F (in EPEO3; likely pathogenic; sligthly
FT                   decreased function in proton transmembrane transport)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088840"
FT   VARIANT         150
FT                   /note="L -> P (in EPEO3; likely pathogenic; severely
FT                   decreased function in proton transmembrane transport)"
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT                   /id="VAR_088841"
FT   MUTAGEN         139
FT                   /note="E->A: Severely decreased proton transmembrane
FT                   transport."
FT                   /evidence="ECO:0000269|PubMed:36074901"
FT   HELIX           9..12
FT                   /evidence="ECO:0007829|PDB:6WLW"
FT   HELIX           13..45
FT                   /evidence="ECO:0007829|PDB:6WLW"
FT   HELIX           49..51
FT                   /evidence="ECO:0007829|PDB:6WLW"
FT   HELIX           54..56
FT                   /evidence="ECO:0007829|PDB:6WLW"
FT   HELIX           57..76
FT                   /evidence="ECO:0007829|PDB:6WLW"
FT   HELIX           86..123
FT                   /evidence="ECO:0007829|PDB:6WLW"
FT   HELIX           125..127
FT                   /evidence="ECO:0007829|PDB:6WLW"
FT   HELIX           128..137
FT                   /evidence="ECO:0007829|PDB:6WLW"
FT   HELIX           140..152
FT                   /evidence="ECO:0007829|PDB:6WLW"
SQ   SEQUENCE   155 AA;  15736 MW;  91141854A0492A5B CRC64;
     MSESKSGPEY ASFFAVMGAS AAMVFSALGA AYGTAKSGTG IAAMSVMRPE QIMKSIIPVV
     MAGIIAIYGL VVAVLIANSL NDDISLYKSF LQLGAGLSVG LSGLAAGFAI GIVGDAGVRG
     TAQQPRLFVG MILILIFAEV LGLYGLIVAL ILSTK
//