VP33A_CAEEL
ID VP33A_CAEEL Reviewed; 603 AA.
AC P34260;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 16-JAN-2004, sequence version 4.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Vacuolar protein sorting-associated protein 33A;
DE AltName: Full=Protein slp-1;
GN Name=vps-33.1 {ECO:0000312|WormBase:B0303.9};
GN Synonyms=slp-1 {ECO:0000303|PubMed:19109425};
GN ORFNames=B0303.9 {ECO:0000312|WormBase:B0303.9};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=1538779; DOI=10.1038/356037a0;
RA Sulston J., Du Z., Thomas K., Wilson R., Hillier L., Staden R.,
RA Halloran N., Green P., Thierry-Mieg J., Qiu L., Dear S., Coulson A.,
RA Craxton M., Durbin R., Berks M., Metzstein M., Hawkins T., Ainscough R.,
RA Waterston R.;
RT "The C. elegans genome sequencing project: a beginning.";
RL Nature 356:37-41(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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]
RP INTERACTION WITH SPE-39.
RX PubMed=19109425; DOI=10.1091/mbc.e08-07-0728;
RA Zhu G.D., Salazar G., Zlatic S.A., Fiza B., Doucette M.M., Heilman C.J.,
RA Levey A.I., Faundez V., L'hernault S.W.;
RT "SPE-39 family proteins interact with the HOPS complex and function in
RT lysosomal delivery.";
RL Mol. Biol. Cell 20:1223-1240(2009).
RN [4]
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP 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 [6]
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 [7]
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).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=27558849; DOI=10.1111/tra.12430;
RA Gengyo-Ando K., Kage-Nakadai E., Yoshina S., Otori M., Kagawa-Nagamura Y.,
RA Nakai J., Mitani S.;
RT "Distinct roles of the two VPS33 proteins in the endolysosomal system in
RT Caenorhabditis elegans.";
RL Traffic 17:1197-1213(2016).
CC -!- FUNCTION: Plays a role in vesicle-mediated protein trafficking to
CC lysosomal compartments including the endocytic membrane transport
CC pathways (PubMed:25273556, PubMed:26783301, PubMed:27558849). Believed
CC to act as a component of the putative HOPS endosomal tethering complex
CC which is proposed to be involved in the rab-5-to-rab-7 endosome
CC conversion probably implicating sand-1, and via binding SNAREs and
CC SNARE complexes to mediate tethering and docking events during SNARE-
CC mediated membrane fusion (PubMed:25273556). 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 embryonic and adult intestinal
CC cells (PubMed:24501423, PubMed:25273556). Required for
CC endosome/lysosome fusion (PubMed:26783301, PubMed:27558849). Required
CC for early embryonic development (PubMed:27558849).
CC {ECO:0000250|UniProtKB:Q96AX1, ECO:0000269|PubMed:24501423,
CC ECO:0000269|PubMed:25273556, ECO:0000269|PubMed:26783301,
CC ECO:0000269|PubMed:27558849}.
CC -!- SUBUNIT: Probable component of the homotypic fusion and vacuole protein
CC sorting (HOPS) complex consisting of the core class C Vps proteins vps-
CC 11, vps-16, vps-18, and which further associates with vps-33.1, vps-39
CC and vps-41 (PubMed:24501423, PubMed:25273556). Interacts with spe-39
CC (PubMed:19109425). {ECO:0000269|PubMed:19109425,
CC ECO:0000305|PubMed:24501423, ECO:0000305|PubMed:25273556}.
CC -!- INTERACTION:
CC P34260; Q93934: adk-1; NbExp=2; IntAct=EBI-312046, EBI-312052;
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:25273556}. Early
CC endosome {ECO:0000269|PubMed:27558849}. Late endosome
CC {ECO:0000269|PubMed:25273556, ECO:0000269|PubMed:27558849}. Apical cell
CC membrane {ECO:0000269|PubMed:25273556}; Peripheral membrane protein
CC {ECO:0000269|PubMed:25273556}. Note=Localizes to lysosome-related gut
CC granules. {ECO:0000269|PubMed:25273556}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed at high levels in somatic
CC tissues including the pharynx, muscles, hypodermis, neurons,
CC coelomocytes and spermatheca (PubMed:27558849). Expressed in the
CC intestine (PubMed:25273556, PubMed:27558849).
CC {ECO:0000269|PubMed:25273556, ECO:0000269|PubMed:27558849}.
CC -!- DISRUPTION PHENOTYPE: Viable, and develop into fertile adults, but
CC their progeny arrest before embryonic morphogenesis (PubMed:27558849).
CC Defective endosome/lysosome size and fusion, and delayed endocytic
CC trafficking to lysosomes in coelomocytes (PubMed:26783301,
CC PubMed:27558849). Reduced number of gut granules in the adult intestine
CC (PubMed:24501423, PubMed:27558849). RNAi-mediated knockdown results in
CC a reduced number of gut granules in embryonic intestinal cells
CC (PubMed:24501423). RNAi-mediated knockdown results in the accumulation
CC of lysosomal proteins such as lmp-1 in early endocytic compartments,
CC and the formation of large late endosomes/lysosomes, but with
CC simultaneous expression of rab-5- and rab-7-positive vesicles on the
CC basal side of gut cells (PubMed:25273556). Double RNAi-mediated
CC knockdown together with vsp-33.2 results in defective protein
CC trafficking to lysosomal compartments, and an irregular distribution of
CC vesicles of various sizes throughout the gut cells. RNAi-mediated
CC knockdown in a sand-1 mutant background results in no viable offspring
CC (PubMed:25273556). Double RNAi-mediated knockdown together with vsp-
CC 33.1 in a sand-1 mutant background rescues the large endosome phenotype
CC and the defective protein trafficking to lysosomal compartments in the
CC sand-1 single mutant, but still results in lethality (PubMed:25273556).
CC Double knockout with tbc-2 or single knockout in a constitutively
CC active rab-5 mutant background, rescues the large endosome formation
CC defect in coelomocytes in the individual tbc-2 single and
CC constitutively active rab-5 mutants (PubMed:27558849).
CC {ECO:0000269|PubMed:24501423, ECO:0000269|PubMed:25273556,
CC ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27558849}.
CC -!- SIMILARITY: Belongs to the STXBP/unc-18/SEC1 family. {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; FO080163; CCD61712.1; -; Genomic_DNA.
DR PIR; S27790; S27790.
DR RefSeq; NP_498920.2; NM_066519.4.
DR AlphaFoldDB; P34260; -.
DR SMR; P34260; -.
DR BioGRID; 41424; 2.
DR ComplexPortal; CPX-1136; HOPS complex.
DR IntAct; P34260; 2.
DR STRING; 6239.B0303.9; -.
DR EPD; P34260; -.
DR PaxDb; P34260; -.
DR PeptideAtlas; P34260; -.
DR EnsemblMetazoa; B0303.9.1; B0303.9.1; WBGene00015130.
DR GeneID; 176221; -.
DR KEGG; cel:CELE_B0303.9; -.
DR CTD; 176221; -.
DR WormBase; B0303.9; CE00539; WBGene00015130; vps-33.1.
DR eggNOG; KOG1302; Eukaryota.
DR GeneTree; ENSGT00940000155165; -.
DR HOGENOM; CLU_026398_0_0_1; -.
DR InParanoid; P34260; -.
DR OMA; FHIFFVP; -.
DR OrthoDB; 406738at2759; -.
DR PhylomeDB; P34260; -.
DR PRO; PR:P34260; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00015130; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033263; C:CORVET complex; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030897; C:HOPS complex; ISS:WormBase.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0005773; C:vacuole; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0042144; P:vacuole fusion, non-autophagic; IC:ComplexPortal.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR Gene3D; 1.25.40.850; -; 1.
DR Gene3D; 3.40.50.1910; -; 1.
DR Gene3D; 3.40.50.2060; -; 1.
DR Gene3D; 3.90.830.10; -; 1.
DR InterPro; IPR043154; Sec-1-like_dom1.
DR InterPro; IPR043127; Sec-1-like_dom3a.
DR InterPro; IPR001619; Sec1-like.
DR InterPro; IPR027482; Sec1-like_dom2.
DR InterPro; IPR036045; Sec1-like_sf.
DR InterPro; IPR027121; VPS33.
DR InterPro; IPR043155; VPS33_dom3b.
DR PANTHER; PTHR11679; PTHR11679; 1.
DR PANTHER; PTHR11679:SF1; PTHR11679:SF1; 1.
DR Pfam; PF00995; Sec1; 1.
DR PIRSF; PIRSF005715; VPS45_Sec1; 1.
DR SUPFAM; SSF56815; SSF56815; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Endosome; Lysosome; Membrane; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..603
FT /note="Vacuolar protein sorting-associated protein 33A"
FT /id="PRO_0000071960"
SQ SEQUENCE 603 AA; 68166 MW; FF959FE7A617BD6A CRC64;
MAANEDRDDA AAILNWEGTS EIKSANEYSR NLLFSVLDSL DGNKTIVWDR DRSVMHRVNL
FAGASVLAAH GVVANHSIET KKSASTPHVV FFLAPTMVSL DLLCDYIDNV RNDSKILYQV
FFIPEAWFVV RESLKTRAEG KYWERLESVK EIPLCWLPRD GECLSLSSPQ IAARLLINGD
WTHLHKCAVA LNQLIDMCRG RSSSSNQRPM SIYAKGKWAS DVAKMMGKIR NSAEADSMTK
NLDPIEGLLK INRIVLIDRW MDPLTPMLSQ LTFYGLLDEI YGIGMVNSVK VPEMEFKNEK
DGDPFQEKEV YLIDEVYHRL KHSHINAVSI EASKVLAEIR DDEQFDRDKM SVAEYSVLVK
KMPKIINRKK MIEVHMRLAE MIQSHVYCKQ SDSIKLERDL LEYSDSDKAI PLIEDLIFDA
SPLNAVLRLI SVHSLTCGGL KPSVLQHYRR IVNQSYGSSA LNKVLKMQKM GLIREKGGGG
KMQCEYAQMM FQQMKKNHDM LPEEFSEAKL DDMAYAYSGF SPLLCKMLEE GDRVKWVGWP
KTVIGDKSDL IAERDGRGTC VFVIGGLTRS ELAIIRENLP NVALITTSAL ITGDKLLNNI
TNI