VPP2_CAEEL
ID VPP2_CAEEL Reviewed; 873 AA.
AC G5EEK9;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=V-type proton ATPase 116 kDa subunit a 2 {ECO:0000305};
DE Short=V-ATPase 116 kDa isoform a 2 {ECO:0000305};
DE AltName: Full=Rod-like larval lethality and dye-filling defective protein 1 {ECO:0000303|PubMed:17179093};
GN Name=vha-5 {ECO:0000303|PubMed:11441002, ECO:0000312|WormBase:F35H10.4};
GN Synonyms=rdy-1 {ECO:0000303|PubMed:17179093};
GN ORFNames=F35H10.4 {ECO:0000312|EMBL:CCD69637.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:BAB62291.1}
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH VHA-11, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=11441002; DOI=10.1074/jbc.m101652200;
RA Oka T., Toyomura T., Honjo K., Wada Y., Futai M.;
RT "Four subunit a isoforms of Caenorhabditis elegans vacuolar H+-ATPase.
RT Cell-specific expression during development.";
RL J. Biol. Chem. 276:33079-33085(2001).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF TRP-190; ARG-191; TRP-327; LEU-786; GLU-830 AND VAL-844.
RX PubMed=16785323; DOI=10.1083/jcb.200511072;
RA Liegeois S., Benedetto A., Garnier J.M., Schwab Y., Labouesse M.;
RT "The V0-ATPase mediates apical secretion of exosomes containing Hedgehog-
RT related proteins in Caenorhabditis elegans.";
RL J. Cell Biol. 173:949-961(2006).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP LEU-786.
RX PubMed=17179093; DOI=10.1534/genetics.106.066035;
RA Liegeois S., Benedetto A., Michaux G., Belliard G., Labouesse M.;
RT "Genes required for osmoregulation and apical secretion in Caenorhabditis
RT elegans.";
RL Genetics 175:709-724(2007).
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). Involved in
CC the assembly of the V-ATPase complex (PubMed:17179093). The V-ATPase is
CC required for the function of the excretory canal (PubMed:16785323,
CC PubMed:17179093). Independently of the V1 complex, the V0 complex of
CC the V-ATPase is required for multivesicular body membrane fusion with
CC the apical membrane of the epidermal cells during exosome release and
CC thus regulates the release of cuticle components such as Hedgehog-
CC related peptide wrt-2 but not collagen (PubMed:16785323). Also, in the
CC epidermis, regulates the trafficking of che-14 and rdy-2
CC (PubMed:17179093). Regulates the secretion of granular material found
CC in the amphid channel and in controlling osmoregulation in the amphid
CC pocket (PubMed:17179093). {ECO:0000250|UniProtKB:G5EGP4,
CC ECO:0000250|UniProtKB:Q29466, ECO:0000269|PubMed:16785323,
CC ECO:0000269|PubMed:17179093}.
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 vah-19/Ac45 and vah-20/PRR (By similarity).
CC Interacts with V-type proton ATPase subunit C vha-11 (PubMed:11441002).
CC {ECO:0000250|UniProtKB:Q29466, ECO:0000269|PubMed:11441002}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:11441002, ECO:0000269|PubMed:16785323}; Multi-pass
CC membrane protein {ECO:0000255}. Endosome, multivesicular body membrane
CC {ECO:0000269|PubMed:16785323}; Multi-pass membrane protein
CC {ECO:0000255}. Note=In embryos, localizes to dot-like compartments or
CC in cup-shaped structures (PubMed:11441002). Localizes to multivesicular
CC body membranes in the epidermis (PubMed:16785323). Colocalizes with
CC vha-8 to stacked sheets of the apical cell membrane of syncytial
CC hypodermal cells (PubMed:16785323). In the epidermis, localizes to
CC dispersed spots during intermolts which becomes aligned and colocalizes
CC with actin bundles during the molts (PubMed:17179093).
CC {ECO:0000269|PubMed:11441002, ECO:0000269|PubMed:16785323,
CC ECO:0000269|PubMed:17179093}.
CC -!- TISSUE SPECIFICITY: Expressed in the H-shaped excretory cell (at
CC protein level) (PubMed:11441002, PubMed:16785323, PubMed:17179093).
CC Expressed in hypodermal cells around the vulva (PubMed:11441002).
CC Expressed in the main epidermal syncytium (PubMed:16785323,
CC PubMed:17179093). Expressed in the sheath cells associated with head
CC and tail sensory organs; specifically, expressed in the apical sheath
CC cells of the amphids and CEP neuron and in the sheath cells of the OLQ
CC sensory organ (PubMed:17179093). {ECO:0000269|PubMed:11441002,
CC ECO:0000269|PubMed:16785323, ECO:0000269|PubMed:17179093}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos (at protein level)
CC (PubMed:11441002). Expressed in the H-shaped excretory cell and pharynx
CC in L2 larvae and adults (PubMed:11441002).
CC {ECO:0000269|PubMed:11441002}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes larval lethality
CC at the L2 stage (PubMed:11441002, PubMed:16785323). RNAi-mediated
CC knockdown causes defects in alae formation in L1 larvae and in the few
CC surviving adults (PubMed:16785323). Shorter body length
CC (PubMed:16785323). {ECO:0000269|PubMed:11441002,
CC ECO:0000269|PubMed:16785323}.
CC -!- SIMILARITY: Belongs to the V-ATPase 116 kDa subunit family.
CC {ECO:0000255|RuleBase:RU361189}.
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DR EMBL; AB055110; BAB62291.1; -; mRNA.
DR EMBL; BX284604; CCD69637.1; -; Genomic_DNA.
DR PIR; T16282; T16282.
DR RefSeq; NP_501399.1; NM_068998.7.
DR AlphaFoldDB; G5EEK9; -.
DR SMR; G5EEK9; -.
DR STRING; 6239.F35H10.4.1; -.
DR TCDB; 3.A.2.2.7; the h(+)- or na(+)-translocating f-type, v-type and a-type atpase (f-atpase) superfamily.
DR EPD; G5EEK9; -.
DR PaxDb; G5EEK9; -.
DR PeptideAtlas; G5EEK9; -.
DR EnsemblMetazoa; F35H10.4.1; F35H10.4.1; WBGene00006914.
DR EnsemblMetazoa; F35H10.4.2; F35H10.4.2; WBGene00006914.
DR EnsemblMetazoa; F35H10.4.3; F35H10.4.3; WBGene00006914.
DR GeneID; 177626; -.
DR KEGG; cel:CELE_F35H10.4; -.
DR CTD; 177626; -.
DR WormBase; F35H10.4; CE04504; WBGene00006914; vha-5.
DR eggNOG; KOG2189; Eukaryota.
DR GeneTree; ENSGT00950000182881; -.
DR HOGENOM; CLU_005230_0_0_1; -.
DR InParanoid; G5EEK9; -.
DR OMA; MFMFKDR; -.
DR OrthoDB; 181796at2759; -.
DR PhylomeDB; G5EEK9; -.
DR Reactome; R-CEL-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR Reactome; R-CEL-77387; Insulin receptor recycling.
DR Reactome; R-CEL-917977; Transferrin endocytosis and recycling.
DR Reactome; R-CEL-9639288; Amino acids regulate mTORC1.
DR Reactome; R-CEL-983712; Ion channel transport.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00006914; Expressed in larva and 6 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IDA:WormBase.
DR GO; GO:0044298; C:cell body membrane; IDA:WormBase.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:WormBase.
DR GO; GO:0070382; C:exocytic vesicle; IDA:WormBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005771; C:multivesicular body; IDA:WormBase.
DR GO; GO:0032585; C:multivesicular body membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016471; C:vacuolar proton-transporting V-type ATPase complex; IPI:WormBase.
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:0040002; P:collagen and cuticulin-based cuticle development; IMP:WormBase.
DR GO; GO:1990182; P:exosomal secretion; IDA:WormBase.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0051046; P:regulation of secretion; IMP:WormBase.
DR GO; GO:0007035; P:vacuolar acidification; IBA:GO_Central.
DR GO; GO:0030104; P:water homeostasis; IMP:WormBase.
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 Cell membrane; Endosome; Glycoprotein; Hydrogen ion transport;
KW Ion transport; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..873
FT /note="V-type proton ATPase 116 kDa subunit a 2"
FT /id="PRO_0000454081"
FT TOPO_DOM 1..407
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 408..428
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 429..445
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 446..466
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 467..543
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 544..564
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 565..574
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 575..595
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 596..614
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 615..635
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 636..668
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 669..689
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 690..785
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 786..806
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 807
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 808..828
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 829..873
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT CARBOHYD 565
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 569
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 190
FT /note="W->A: Section of excretory canal is increased with
FT multiple lumens and abnormal whorls. No defect in collagen
FT secretion."
FT /evidence="ECO:0000269|PubMed:16785323"
FT MUTAGEN 191
FT /note="R->A: Section of excretory canal is increased with
FT multiple lumens and abnormal whorls."
FT /evidence="ECO:0000269|PubMed:16785323"
FT MUTAGEN 327
FT /note="W->A: Section of excretory canal is increased with
FT multiple lumens and abnormal whorls. Impaired alae
FT formation. Accumulation of multivesicular bodies in the
FT epidermis. Animals are shorter and dumpier."
FT /evidence="ECO:0000269|PubMed:16785323"
FT MUTAGEN 786
FT /note="L->S: Impaired alae formation. Animals are shorter
FT and dumpier. Accumulation of multivesicular bodies in the
FT epidermis. Impaired secretion of Hedgehog-related peptides
FT such as wrt-2 in the epidermis. Accumulates together with
FT che-14 and rdy-2 in multivesicular bodies but not in amphid
FT sheath cells."
FT /evidence="ECO:0000269|PubMed:16785323,
FT ECO:0000269|PubMed:17179093"
FT MUTAGEN 830
FT /note="E->Q: Impaired alae formation. Animals are shorter
FT and dumpier. Accumulation of multivesicular bodies in the
FT epidermis. Impaired secretion of Hedgehog-related peptides
FT such as wrt-2 in the epidermis."
FT /evidence="ECO:0000269|PubMed:16785323"
FT MUTAGEN 844
FT /note="V->F: Impaired alae formation. Animals are shorter
FT and dumpier. Accumulation of multivesicular bodies in the
FT epidermis. No defect in collagen secretion."
FT /evidence="ECO:0000269|PubMed:16785323"
SQ SEQUENCE 873 AA; 99313 MW; 930CD7223847E2A4 CRC64;
MGSLSRSEEM RFCQLIVEKD AAFNIVAEIG KQPYVQFKDL NPNVNSFQRT FVKDIRRYDE
MERKLRFLES QIVKDEIVIP GRVDTGDYTI LPTSELNTLE GTLTELEKDV KSMNDSDSQL
KANFMDLKEW DAVLDKTDEF FQGGVDDQAQ EELENLDEEG AVPRVEKGPV NYLVGIIRRE
RLNGFERVLW RACHHTAYIR SSDIEEELED PGTGEKVHKS VFIIFLKGDR MRSIVEKVCD
GFKAKLFKNC PKTFKERQSA RNDVRARIQD LQTVLGQTRE HRFRVLQAAA NNHHQWLKQV
RMIKTVFHML NLFTFDGIGR FFVGECWIPL KHVEDVRKAI EVGAERSGSS VKPVLNILET
SVTPPTYNET NKFTAVFQGI VDSYGIATYR ELNPAPYTII TFPFLFSCMF GDLGHGCIML
MAGLWFVLRE KNLQARNIKD EIFNMFFGGR YIILLMGLFS IHAGIIYNDM FAKSFNIFGS
GWKNPYNASE IEGWINRTEH GKEMLVELAP EDAYDHAGGP YSFGVDPIWN IAENKLNFLN
SMKMKLSVIL GISQMTFGVI LSFFNHTYNK SKIDIFTVFI PQMLFMGCIF MYLCLQIILK
WLFFWTKEAT VFGQIYPGSH CAPSLLIGLI NMFMMKDRNA GFVVDGGKVN GEYREVETCY
LSQWYPGQSV IEMILVVIAV ICVPVMLFGK PIHHVMQQKK KAKELHGNAT VRANVVSDSS
EIVLNGGSKK EGAAHEEHGH GGHEDESFGD IMVHQAIHTI EYVLGCVSHT ASYLRLWALS
LAHAQLSEVL WHMVFVTGGL GISGTAGFIA VYVVFFIFFV LTISILVLME GLSAFLHTLR
LHWVEFQSKF YLGLGYPFVP YSFKTALQEA EAA
