VPS18_CAEEL
ID VPS18_CAEEL Reviewed; 1026 AA.
AC Q23194; G4SQH0;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 4.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Vacuolar protein sorting-associated protein 18 homolog {ECO:0000305};
GN Name=vps-18 {ECO:0000312|WormBase:W06B4.3};
GN ORFNames=W06B4.3 {ECO:0000312|WormBase:W06B4.3};
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|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 [2]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-923 AND HIS-925.
RX PubMed=18923146; DOI=10.1091/mbc.e08-04-0441;
RA Xiao H., Chen D., Fang Z., Xu J., Sun X., Song S., Liu J., Yang C.;
RT "Lysosome biogenesis mediated by vps-18 affects apoptotic cell degradation
RT in Caenorhabditis elegans.";
RL Mol. Biol. Cell 20:21-32(2009).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24501423; DOI=10.1091/mbc.e13-09-0521;
RA Delahaye J.L., Foster O.K., Vine A., Saxton D.S., Curtin T.P., Somhegyi H.,
RA Salesky R., Hermann G.J.;
RT "Caenorhabditis elegans HOPS and CCZ-1 mediate trafficking to lysosome-
RT related organelles independently of RAB-7 and SAND-1.";
RL Mol. Biol. Cell 25:1073-1096(2014).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25273556; DOI=10.1091/mbc.e13-12-0710;
RA Solinger J.A., Spang A.;
RT "Loss of the Sec1/Munc18-family proteins VPS-33.2 and VPS-33.1 bypasses a
RT block in endosome maturation in Caenorhabditis elegans.";
RL Mol. Biol. Cell 25:3909-3925(2014).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26783301; DOI=10.1083/jcb.201506081;
RA Liu K., Jian Y., Sun X., Yang C., Gao Z., Zhang Z., Liu X., Li Y., Xu J.,
RA Jing Y., Mitani S., He S., Yang C.;
RT "Negative regulation of phosphatidylinositol 3-phosphate levels in early-
RT to-late endosome conversion.";
RL J. Cell Biol. 212:181-198(2016).
RN [6]
RP ERRATUM OF PUBMED:26783301.
RX PubMed=26975852; DOI=10.1083/jcb.20150608103012016c;
RA Liu K., Jian Y., Sun X., Yang C., Gao Z., Zhang Z., Liu X., Li Y., Xu J.,
RA Jing Y., Mitani S., He S., Yang C.;
RT "Correction: Negative regulation of phosphatidylinositol 3-phosphate levels
RT in early-to-late endosome conversion.";
RL J. Cell Biol. 212:739-739(2016).
CC -!- FUNCTION: Plays a role in vesicle-mediated protein trafficking to
CC lysosomal compartments including the endocytic membrane transport and
CC autophagic pathways (PubMed:25273556, PubMed:26783301). Believed to act
CC as a core component of the putative HOPS and CORVET endosomal tethering
CC complexes which are proposed to be involved in the rab-5-to-rab-7
CC endosome conversion probably implicating sand-1, and via binding SNAREs
CC and SNARE complexes to mediate tethering and docking events during
CC SNARE-mediated membrane fusion (By similarity). The HOPS complex is
CC proposed to be recruited to rab-7 on the late endosomal membrane and to
CC regulate late endocytic, phagocytic and autophagic traffic towards
CC lysosomes (By similarity). Within the HOPS complex, contributes to the
CC normal development of gut granules in intestinal cells of the embryo,
CC and also promotes the trafficking of embryonic intestinal gut granules
CC away from lysosomes (PubMed:24501423, PubMed:25273556). The CORVET
CC complex is proposed to function as a rab-5 effector to mediate early
CC endosome fusion probably in specific endosome subpopulations (By
CC similarity). Required for fusion of endosomes and autophagosomes with
CC lysosomes (PubMed:18923146, PubMed:26783301). Plays a role in the
CC degradation of apoptotic cells during programmed cell death
CC (PubMed:18923146). {ECO:0000250|UniProtKB:Q9P253,
CC ECO:0000269|PubMed:18923146, ECO:0000269|PubMed:24501423,
CC ECO:0000269|PubMed:25273556, ECO:0000269|PubMed:26783301}.
CC -!- SUBUNIT: Probable core component of at least two putative endosomal
CC tethering complexes, the homotypic fusion and vacuole protein sorting
CC (HOPS) complex and the class C core vacuole/endosome tethering (CORVET)
CC complex. Their common core is composed of the class C Vps proteins vps-
CC 11, vps-16 and vps-18, which in HOPS further associates with vps-33.1,
CC vps-39 and vps-41 and in CORVET with vps-8 and vps-33.2.
CC {ECO:0000250|UniProtKB:Q9P253}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18923146}. Late
CC endosome membrane {ECO:0000250|UniProtKB:Q9P253}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q9P253}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9P253}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9P253}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9P253}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9P253}. Early endosome
CC {ECO:0000250|UniProtKB:Q9P253}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:Q9P253}. Cytoplasmic vesicle, clathrin-coated
CC vesicle {ECO:0000250|UniProtKB:Q9P253}.
CC -!- TISSUE SPECIFICITY: In hermaphrodites, expressed in coelomocytes and
CC gonadal sheath cells. {ECO:0000269|PubMed:18923146}.
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in embryos. In early
CC larvae, expressed in hypodermal cells, seam cells and body wall muscle
CC cells. {ECO:0000269|PubMed:18923146}.
CC -!- DISRUPTION PHENOTYPE: Temperature-sensitive defects in the formation of
CC gut granules during embryogenesis (PubMed:24501423). At 15 degrees
CC Celsius, pretzel-stage embryos have a reduced number of gut granules in
CC intestinal cells, and at 22 degrees Celsius, pretzel-stage embryos
CC completely lack gut granules in intestinal cells (PubMed:24501423). At
CC 25 degrees Celsius, many embryos arrest by the pre-bean stage before
CC elongation, and 76% of these embryos contain gut granules irregularly
CC distributed throughout the embryo (PubMed:24501423). Defective
CC apoptotic germ cell corpse digestion with delayed degradation of
CC chromatin in late germ cell corpses (PubMed:18923146). This results in
CC increased numbers of germ cell corpses at 20 degrees Celsius during
CC embryogenesis and post the L4 stage of larval development, and
CC furthermore the retention of cell corpses for a longer duration of time
CC (PubMed:18923146). Impaired formation of endosomes and lysosomes in
CC coelomocytes, in particular there is impaired formation of recycling
CC endosomes (PubMed:18923146). In addition, there are endosome/lysosome
CC fusion defects in coelomocytes (PubMed:18923146, PubMed:26783301).
CC RNAi-mediated knockdown results in defective endosome maturation with
CC the accumulation of small vesicles near the gut lumen and large
CC endosomes/lysosomes on the basal side of the cell (PubMed:25273556).
CC Double knockout with either sorf-1 or sorf-2, results in larger
CC endosomes and larger lysosomes and thus suppresses the
CC endosome/lysosome fusion defect in the vps-18 single mutant
CC (PubMed:26783301). {ECO:0000269|PubMed:18923146,
CC ECO:0000269|PubMed:24501423, ECO:0000269|PubMed:25273556,
CC ECO:0000269|PubMed:26783301}.
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DR EMBL; BX284602; CCD73641.1; -; Genomic_DNA.
DR RefSeq; NP_494788.3; NM_062387.5.
DR AlphaFoldDB; Q23194; -.
DR ComplexPortal; CPX-1136; HOPS complex.
DR ComplexPortal; CPX-1137; CORVET complex.
DR STRING; 6239.W06B4.3; -.
DR EPD; Q23194; -.
DR PaxDb; Q23194; -.
DR PeptideAtlas; Q23194; -.
DR PRIDE; Q23194; -.
DR EnsemblMetazoa; W06B4.3.1; W06B4.3.1; WBGene00021058.
DR GeneID; 173783; -.
DR KEGG; cel:CELE_W06B4.3; -.
DR UCSC; W06B4.3; c. elegans.
DR CTD; 173783; -.
DR WormBase; W06B4.3; CE43757; WBGene00021058; vps-18.
DR eggNOG; KOG2034; Eukaryota.
DR GeneTree; ENSGT00940000153635; -.
DR HOGENOM; CLU_003488_1_0_1; -.
DR InParanoid; Q23194; -.
DR OMA; LFADWKK; -.
DR OrthoDB; 87842at2759; -.
DR PhylomeDB; Q23194; -.
DR PRO; PR:Q23194; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00021058; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0033263; C:CORVET complex; IC:ComplexPortal.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0031901; C:early endosome membrane; IC:ComplexPortal.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0030897; C:HOPS complex; ISS:WormBase.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0007032; P:endosome organization; IMP:WormBase.
DR GO; GO:0008333; P:endosome to lysosome transport; IBA:GO_Central.
DR GO; GO:0007040; P:lysosome organization; IMP:WormBase.
DR GO; GO:0048284; P:organelle fusion; IMP:UniProtKB.
DR GO; GO:0090389; P:phagosome-lysosome fusion involved in apoptotic cell clearance; IMP:WormBase.
DR GO; GO:0051036; P:regulation of endosome size; IGI:UniProtKB.
DR GO; GO:0032889; P:regulation of vacuole fusion, non-autophagic; IC:ComplexPortal.
DR GO; GO:0042144; P:vacuole fusion, non-autophagic; IC:ComplexPortal.
DR GO; GO:0007033; P:vacuole organization; IBA:GO_Central.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IBA:GO_Central.
DR GO; GO:0099022; P:vesicle tethering; IC:ComplexPortal.
DR InterPro; IPR007810; Pep3_Vps18.
DR Pfam; PF05131; Pep3_Vps18; 1.
PE 1: Evidence at protein level;
KW Autophagy; Coiled coil; Cytoplasm; Cytoplasmic vesicle; Endosome; Lysosome;
KW Membrane; Metal-binding; Reference proteome; Transport; Zinc; Zinc-finger.
FT CHAIN 1..1026
FT /note="Vacuolar protein sorting-associated protein 18
FT homolog"
FT /evidence="ECO:0000305"
FT /id="PRO_0000441274"
FT ZN_FING 906..932
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT COILED 858..896
FT /evidence="ECO:0000255"
FT MUTAGEN 923
FT /note="C->A: Fails to rescue the defects in germ cell
FT corpse clearance in the vps-18 (tm1125) deletion mutant;
FT when associated with A-925."
FT /evidence="ECO:0000269|PubMed:18923146"
FT MUTAGEN 925
FT /note="H->A: Fails to rescue the defects in germ cell
FT corpse clearance in the vps-18 (tm1125) deletion mutant;
FT when associated with A-923."
FT /evidence="ECO:0000269|PubMed:18923146"
SQ SEQUENCE 1026 AA; 116669 MW; 17BBBA4CC4E6A8A2 CRC64;
MIKNTAKNKN GIITRATIDL KKDLKFVKLT AVSNLAVQNG EMLAAVTEKL LVHYSEGTGE
RHQEMSLPLN GPDHVAYIHL SRTGFHAIVS SKLGHNFYIH LKSNAFHHLK KLRCVVTAVG
WNPDYSKETD TTGPILLGTA QGSIIELNVG STGMMTTLKE LTSQVAQIAE QRITSAPSPA
AAITDIQLFQ LADDDPKNKK WMVIIAQMAR LIVLITDNEP APVVKLGGFT SSASLQAGLM
NLATEQAPST TFHSFFTSPN TLQHTISSSK FSEKFKNHGF LTMHPTIAEP KRYAWLSPDG
ISIGNVNIYA ERIQDVLVEE FNIEHRLIEG RLEPPTGIAL TDYHVLLAYS SRVLALSLLP
PHDVIFEDPW NPELGGALGF VSDNVAEFVW LYTQTFAMKY GTNDEARYIW KTYLDRGEYQ
KALQIARTRV AIEPDALEMV LRKQADFYIQ EKNFTAAAEI LAQSSEPFES VVLKFLTNSS
ERKMGLKTLL DKKLERLTRH EDKIRRDALV MWLLNVQLEE LAEMRRLKNS NPDPAFVEKL
RDTTDHVQRY FMRKNVIESI QTNRDAVYRM CVAHADFEMQ LFFANAVKDL RTVIDILMLR
EQYFEVLEVL KNQRISELTY EMCPLLIEHI PKQVIVYLIQ NQDQISPQKL TPCLSLCVKN
MEMAIPAIKY LEAQFKGTQT ISQNPQNLAN LHNIYIHLMA KFRREKLLGY LESHGTIRSD
LPYELDFAMR TCEQFKIEPC VVYLFCVAGM FGDAVEKALG FDVDLAKKCA LMMEEAEANF
AWLEGMEDPA ATSYIRQKLD EKAKKAIWLK IGQYYVTQEN NVDKCIELIN ESNHLLTIQD
LLPIIPKFTR VGALKPIIVD FLKRNKQRLE KLERSMKEAT EIASEIRDKQ EKLKNRTTVV
KPSDVCSHCA RPISGRAFNV HSCRHFFHRE CLEIAMISFL SQEEVEKMKT LIIDEERVLS
QMKAEQLAGN QKGFIEKQEK YLKIAAFISN IVGAECPLCG NIAISQIDKQ FLSDEEFAAD
LNTWLL
