VPS41_CAEEL
ID VPS41_CAEEL Reviewed; 901 AA.
AC Q19954; A3RMR9; A3RMS0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 4.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Vacuolar protein sorting-associated protein 41 homolog;
GN Name=vps-41 {ECO:0000312|WormBase:F32A6.3c};
GN ORFNames=F32A6.3 {ECO:0000312|WormBase:F32A6.3c};
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], AND ALTERNATIVE SPLICING.
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 [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15837622; DOI=10.1016/j.ccr.2005.03.024;
RA Lackner M.R., Kindt R.M., Carroll P.M., Brown K., Cancilla M.R., Chen C.,
RA de Silva H., Franke Y., Guan B., Heuer T., Hung T., Keegan K., Lee J.M.,
RA Manne V., O'Brien C., Parry D., Perez-Villar J.J., Reddy R.K., Xiao H.,
RA Zhan H., Cockett M., Plowman G., Fitzgerald K., Costa M.,
RA Ross-Macdonald P.;
RT "Chemical genetics identifies Rab geranylgeranyl transferase as an
RT apoptotic target of farnesyl transferase inhibitors.";
RL Cancer Cell 7:325-336(2005).
RN [3]
RP FUNCTION.
RX PubMed=16862146; DOI=10.1038/ncbl439;
RA Saleh M.-C., van Rij R.P., Hekele A., Gillis A., Foley E., O'Farrell P.H.,
RA Andino R.;
RT "The endocytic pathway mediates cell entry of dsRNA to induce RNAi
RT silencing.";
RL Nat. Cell Biol. 8:793-802(2006).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24374177; DOI=10.1016/j.devcel.2013.11.022;
RA Manil-Segalen M., Lefebvre C., Jenzer C., Trichet M., Boulogne C.,
RA Satiat-Jeunemaitre B., Legouis R.;
RT "The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by
RT interacting with the HOPS subunit VPS39.";
RL Dev. Cell 28:43-55(2014).
RN [5]
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 [6]
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 [7]
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 [8]
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
CC pathways (PubMed:26783301). Believed to act in part as a core component
CC of the putative HOPS endosomal tethering complex which is proposed to
CC be involved in the rab-5-to-rab-7 endosome conversion probably
CC implicating sand-1, and via binding SNAREs and SNARE complexes to
CC mediate tethering and docking events during SNARE-mediated membrane
CC fusion (PubMed:25273556). The HOPS complex is proposed to be recruited
CC to rab-7 on the late endosomal membrane and to regulate late endocytic,
CC phagocytic and autophagic traffic towards lysosomes (By similarity).
CC Within the HOPS complex, contributes to the normal development of gut
CC granules in the adult intestine (PubMed:24501423). May mediate the
CC tethering of autophagosomes with lysosomes (PubMed:24374177). Has a
CC role in the negative regulation of apoptosis (PubMed:15837622).
CC Required for uptake of exogenous dsRNA which is used in experimental
CC RNA silencing (PubMed:16862146). {ECO:0000250|UniProtKB:P49754,
CC ECO:0000269|PubMed:15837622, ECO:0000269|PubMed:16862146,
CC ECO:0000269|PubMed:24501423, ECO:0000269|PubMed:25273556,
CC ECO:0000269|PubMed:26783301, ECO:0000305|PubMed:24374177}.
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. {ECO:0000250|UniProtKB:P49754}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:P49754};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P49754}. Late
CC endosome membrane {ECO:0000250|UniProtKB:P49754}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:P49754}. Early endosome membrane
CC {ECO:0000250|UniProtKB:P49754}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P49754}. Lysosome membrane
CC {ECO:0000250|UniProtKB:P49754}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P49754}. Golgi apparatus, trans-Golgi network
CC {ECO:0000250|UniProtKB:P49754}. Cytoplasmic vesicle, clathrin-coated
CC vesicle {ECO:0000250|UniProtKB:P49754}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P49754}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=c;
CC IsoId=Q19954-1; Sequence=Displayed;
CC Name=a;
CC IsoId=Q19954-2; Sequence=VSP_027445;
CC Name=b;
CC IsoId=Q19954-3; Sequence=VSP_027445, VSP_027446, VSP_027447;
CC -!- DISRUPTION PHENOTYPE: In 1-cell to 20-cell stage embryos, there is
CC defective autophagosome degradation with an accumulation of lgg-1- and
CC lgg-2-positive autophagosomes and paternal mitochondria close to the
CC nuclei (PubMed:24374177). Clusters of cell corpses in the distal region
CC of the body and show no dsRNA uptake (PubMed:15837622). Reduced number
CC of gut granules in the adult intestine (PubMed:24501423).
CC Endosome/lysosome fusion defects in coelomocytes (PubMed:26783301).
CC Double knockout with either sorf-1 or sorf-2 RNAi results in larger
CC endosomes and larger lysosomes and thus suppresses the
CC endosome/lysosome fusion defects in coelomocytes in the vps-41 single
CC mutant (PubMed:26783301). RNAi-mediated knockdown results in a reduced
CC number of gut granules in embryonic intestinal cells (PubMed:24501423).
CC RNAi-mediated knockdown results in the formation of large late
CC endosomes/lysosomes, but with simultaneous expression of rab-5- and
CC rab-7-positive vesicles on the basal side of gut cells
CC (PubMed:25273556). {ECO:0000269|PubMed:15837622,
CC ECO:0000269|PubMed:24374177, ECO:0000269|PubMed:24501423,
CC ECO:0000269|PubMed:25273556, ECO:0000269|PubMed:26783301}.
CC -!- SIMILARITY: Belongs to the VPS41 family. {ECO:0000305}.
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DR EMBL; FO080679; CCD65714.1; -; Genomic_DNA.
DR EMBL; FO080679; CCD65718.1; -; Genomic_DNA.
DR EMBL; FO080679; CCD65724.1; -; Genomic_DNA.
DR EMBL; FO081274; CCD70397.1; -; Genomic_DNA.
DR PIR; T16236; T16236.
DR RefSeq; NP_001033544.1; NM_001038455.3.
DR RefSeq; NP_001033545.2; NM_001038456.3.
DR RefSeq; NP_001123142.1; NM_001129670.2.
DR AlphaFoldDB; Q19954; -.
DR BioGRID; 45734; 1.
DR ComplexPortal; CPX-1136; HOPS complex.
DR STRING; 6239.F32A6.3c; -.
DR EPD; Q19954; -.
DR PaxDb; Q19954; -.
DR PeptideAtlas; Q19954; -.
DR EnsemblMetazoa; F32A6.3a.1; F32A6.3a.1; WBGene00017974. [Q19954-2]
DR EnsemblMetazoa; F32A6.3b.1; F32A6.3b.1; WBGene00017974. [Q19954-3]
DR EnsemblMetazoa; F32A6.3c.1; F32A6.3c.1; WBGene00017974. [Q19954-1]
DR UCSC; F32A6.3b; c. elegans. [Q19954-1]
DR WormBase; F32A6.3a; CE37009; WBGene00017974; vps-41. [Q19954-2]
DR WormBase; F32A6.3b; CE40762; WBGene00017974; vps-41. [Q19954-3]
DR WormBase; F32A6.3c; CE40763; WBGene00017974; vps-41. [Q19954-1]
DR eggNOG; KOG2066; Eukaryota.
DR GeneTree; ENSGT00390000000481; -.
DR HOGENOM; CLU_001285_2_2_1; -.
DR InParanoid; Q19954; -.
DR OMA; KFKYQRI; -.
DR OrthoDB; 722805at2759; -.
DR PhylomeDB; Q19954; -.
DR PRO; PR:Q19954; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00017974; Expressed in embryo and 3 other tissues.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0030897; C:HOPS complex; ISS:UniProtKB.
DR GO; GO:0005770; C:late endosome; IBA:GO_Central.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005773; C:vacuole; IC:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0009267; P:cellular response to starvation; IBA:GO_Central.
DR GO; GO:0034058; P:endosomal vesicle fusion; IBA:GO_Central.
DR GO; GO:0016236; P:macroautophagy; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0006623; P:protein targeting to vacuole; IBA:GO_Central.
DR GO; GO:0006624; P:vacuolar protein processing; IMP:UniProtKB.
DR GO; GO:0007034; P:vacuolar transport; IMP:UniProtKB.
DR GO; GO:0042144; P:vacuole fusion, non-autophagic; IC:ComplexPortal.
DR GO; GO:0016192; P:vesicle-mediated transport; ISS:UniProtKB.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000547; Clathrin_H-chain/VPS_repeat.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR016902; VPS41.
DR InterPro; IPR045111; Vps41/Vps8.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR PANTHER; PTHR12616; PTHR12616; 1.
DR Pfam; PF00637; Clathrin; 1.
DR PIRSF; PIRSF028921; VPS41; 1.
DR SMART; SM00299; CLH; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50236; CHCR; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 3: Inferred from homology;
KW Alternative splicing; Apoptosis; Cytoplasm; Cytoplasmic vesicle; Endosome;
KW Golgi apparatus; Lysosome; Membrane; Metal-binding; Protein transport;
KW Reference proteome; Transport; Zinc; Zinc-finger.
FT CHAIN 1..901
FT /note="Vacuolar protein sorting-associated protein 41
FT homolog"
FT /id="PRO_0000212824"
FT REPEAT 618..760
FT /note="CHCR"
FT ZN_FING 839..893
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..142
FT /note="Missing (in isoform a and isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_027445"
FT VAR_SEQ 808..823
FT /note="CYDSTLNDLNVLTQGL -> TFGYFYFAGGLKVEHR (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_027446"
FT VAR_SEQ 824..901
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_027447"
SQ SEQUENCE 901 AA; 102579 MW; 6C81730B21CD5DF0 CRC64;
MDETHENEAS DSFDPVFENS YHDDVTFNTE DDDEPPLEPR FKYERLKGEE TLPFMKTATF
TSIDLHDKFI AIGTATGLIY ILDHHGYGNF DSVPPLKPHR CAVSKVKFDE TGSYVLSCAN
DSKIVVSGVG NDKLCCTINI QVMPKSIYFS PDFIRQQSGH CFIMGERNLV LYEKRMFQYK
ASSLYSGSER DGFIHCCSWN ENLIAFTNDT GTRVYERGAE RIITSVQPSH DVDRVRSSRS
PPKHTWMPEN NLVIGWADTV TILKIRDDDG VKKGEVHHIF HVSMFICGIS YIPESGIDNM
ELFLVGLQLE GEDFDDCASV ISTVTTLTAL ESSACTILKT SVIRPLGLKE FELQSEDMIE
SVKLSNHTLP YMIHGLGIPY LATYFILTTK HIIMAVPYGP EDGIRWRLKY KLYDEALDMA
KHNADLLSKT DLSPKKVGRM IIEGYLTGKR ARAAASRLPL ICGECKEEWE WAVNQFEEVK
LCTLLAEVLP DGTPTLDPEC YQKVLIACLF NNVKQFRKLV QTWSPDLYMT SFIIDRTQWR
IQQISKSGNL ADVDETERVL MDALAHLYLY ERKYESALKI LMSCQDFQIF NVIDKHQLFD
LVKDQITELM NINSERALRL LLDNADSVEP SFVMEKIGRQ PKLQLAYLTK LMSRNEGTEF
ADKAVQLYAE YDQKKLLPFL RKNANYNVNK ARKLCSDKGY IEETIYLLAK SGNHYDAVKM
MVREYRNMEK VIDYCKDQND PDLWIHLLGV VAEFPAHFSQ LIIEASNCLD PLLIMDKLPD
DSDIPNLSEA LDKLLVDYTN HAELQQCCYD STLNDLNVLT QGLISAADES VSVNIVSRCS
LCAQIIINSN QETTKKFSDI KVFKCGHIFH LACSTSEMER RQSIEEGLCI ACSDQIELIN
V
