VPS18_DROME
ID VPS18_DROME Reviewed; 1002 AA.
AC Q24314; Q95R67; Q9W570;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Vacuolar protein sorting-associated protein 18 homolog;
DE AltName: Full=Protein deep orange;
GN Name=dor; ORFNames=CG3093;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RC TISSUE=Embryo;
RX PubMed=9065698; DOI=10.1007/s004380050367;
RA Shestopal S.A., Makumin I.V., Belyaeva E.S., Ashburner M.;
RT "Molecular characterization of the deep orange (dor) gene of Drosophila
RT melanogaster.";
RL Mol. Gen. Genet. 253:642-648(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Oregon-R;
RX PubMed=10731137; DOI=10.1126/science.287.5461.2220;
RA Benos P.V., Gatt M.K., Ashburner M., Murphy L., Harris D., Barrell B.G.,
RA Ferraz C., Vidal S., Brun C., Demailles J., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Borkova D., Minana B., Kafatos F.C.,
RA Louis C., Siden-Kiamos I., Bolshakov S., Papagiannakis G., Spanos L.,
RA Cox S., Madueno E., de Pablos B., Modolell J., Peter A., Schoettler P.,
RA Werner M., Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H.,
RA Bucheton A., Callister D.M., Campbell L.A., Darlamitsou A., Henderson N.S.,
RA McMillan P.J., Salles C., Tait E.A., Valenti P., Saunders R.D.C.,
RA Glover D.M.;
RT "From sequence to chromosome: the tip of the X chromosome of D.
RT melanogaster.";
RL Science 287:2220-2222(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP FUNCTION, INTERACTION WITH CAR, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP MUTAGENESIS OF CYS-979, AND DISRUPTION PHENOTYPE.
RX PubMed=10549280; DOI=10.1016/s1097-2765(00)80199-9;
RA Sevrioukov E.A., He J.-P., Moghrabi N., Sunio A., Kraemer H.;
RT "A role for the deep orange and carnation eye color genes in lysosomal
RT delivery in Drosophila.";
RL Mol. Cell 4:479-486(1999).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-344, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [8]
RP INTERACTION WITH EMA.
RX PubMed=20194640; DOI=10.1083/jcb.200911126;
RA Kim S., Wairkar Y.P., Daniels R.W., DiAntonio A.;
RT "The novel endosomal membrane protein Ema interacts with the class C Vps-
RT HOPS complex to promote endosomal maturation.";
RL J. Cell Biol. 188:717-734(2010).
RN [9]
RP FUNCTION.
RX PubMed=22160599; DOI=10.1091/mbc.e11-02-0154;
RA Gailite I., Egger-Adam D., Wodarz A.;
RT "The phosphoinositide-associated protein Rush hour regulates endosomal
RT trafficking in Drosophila.";
RL Mol. Biol. Cell 23:433-447(2012).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF 508-ARG--GLU-1002 AND 551-TRP--GLU-1002.
RX PubMed=25422373; DOI=10.1083/jcb.201406026;
RA Fernandes A.C., Uytterhoeven V., Kuenen S., Wang Y.C., Slabbaert J.R.,
RA Swerts J., Kasprowicz J., Aerts S., Verstreken P.;
RT "Reduced synaptic vesicle protein degradation at lysosomes curbs
RT TBC1D24/sky-induced neurodegeneration.";
RL J. Cell Biol. 207:453-462(2014).
RN [11]
RP FUNCTION, IDENTIFICATION IN THE CORVET COMPLEX, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=27253064; DOI=10.7554/elife.14226;
RA Lorincz P., Lakatos Z., Varga A., Maruzs T., Simon-Vecsei Z., Darula Z.,
RA Benko P., Csordas G., Lippai M., Ando I., Hegedus K., Medzihradszky K.F.,
RA Takats S., Juhasz G.;
RT "MiniCORVET is a Vps8-containing early endosomal tether in Drosophila.";
RL Elife 5:0-0(2016).
CC -!- FUNCTION: Plays a role in vesicle-mediated protein trafficking to
CC lysosomal compartments and in membrane docking/fusion reactions of late
CC endosomes/lysosomes probably as part of the class C core
CC vacuole/endosome tethering (CORVET) complex (PubMed:9065698,
CC PubMed:10549280, PubMed:27253064, PubMed:25422373). In larval
CC neuromuscular junctions, essential for endosomal sorting which traffics
CC old or dysfunctional synaptic vesicle proteins through a degradative
CC endolysosomal route (PubMed:25422373). Required for the biogenesis of
CC eye pigment granules (PubMed:10549280). Required to maintain normal
CC levels of rush, which functions in endosome formation and trafficking
CC (PubMed:22160599). {ECO:0000269|PubMed:10549280,
CC ECO:0000269|PubMed:22160599, ECO:0000269|PubMed:25422373,
CC ECO:0000269|PubMed:27253064, ECO:0000269|PubMed:9065698}.
CC -!- SUBUNIT: Component of the class C core vacuole/endosome tethering
CC (CORVET) complex composed of at least dor/Vps18, Vps16A, Vps8 and
CC car/Vps33A; unlike in other species, Vps11 is not part of the
CC Drosophila complex (PubMed:27253064). Interacts with car
CC (PubMed:10549280). Interacts with ema (PubMed:20194640).
CC {ECO:0000269|PubMed:10549280, ECO:0000269|PubMed:20194640,
CC ECO:0000269|PubMed:27253064}.
CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000305|PubMed:27253064}.
CC Late endosome membrane {ECO:0000269|PubMed:10549280}; Peripheral
CC membrane protein {ECO:0000269|PubMed:10549280}; Cytoplasmic side
CC {ECO:0000269|PubMed:10549280}. Lysosome membrane
CC {ECO:0000269|PubMed:10549280}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10549280}; Cytoplasmic side
CC {ECO:0000269|PubMed:10549280}. Note=Cytoplasmic, peripheral membrane
CC protein associated with late endosomes/lysosomes.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically in all
CC stages of development (PubMed:9065698). Highest expression is in third
CC larval instar (PubMed:9065698, PubMed:10549280). Expressed in the
CC larval Garland nephrocytes and in the adult (at protein level)
CC (PubMed:10549280, PubMed:27253064). {ECO:0000269|PubMed:10549280,
CC ECO:0000269|PubMed:27253064, ECO:0000269|PubMed:9065698}.
CC -!- DISRUPTION PHENOTYPE: Flies display impaired deposition of pigment
CC granules (PubMed:9065698, PubMed:10549280). Member of the 'granule
CC group' of eye color genes as mutants affect deposition in pigment
CC granules of two types of pigments, the ommochromes and drosopterins
CC (PubMed:9065698, PubMed:10549280). RNAi-mediated knockdown results in
CC late endosome fragmentation and mislocalization of Vps8
CC (PubMed:27253064). {ECO:0000269|PubMed:10549280,
CC ECO:0000269|PubMed:27253064, ECO:0000269|PubMed:9065698}.
CC -!- SIMILARITY: Belongs to the VPS18 family. {ECO:0000305}.
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DR EMBL; X86683; CAA60382.1; -; mRNA.
DR EMBL; AE014298; AAF45652.1; -; Genomic_DNA.
DR EMBL; AL021726; CAA16809.1; -; Genomic_DNA.
DR EMBL; AY061592; AAL29140.1; -; mRNA.
DR PIR; S54252; S54252.
DR RefSeq; NP_477286.2; NM_057938.5.
DR AlphaFoldDB; Q24314; -.
DR BioGRID; 57669; 24.
DR IntAct; Q24314; 6.
DR STRING; 7227.FBpp0070259; -.
DR MoonProt; Q24314; -.
DR iPTMnet; Q24314; -.
DR PaxDb; Q24314; -.
DR PeptideAtlas; Q24314; -.
DR PRIDE; Q24314; -.
DR DNASU; 31118; -.
DR EnsemblMetazoa; FBtr0070269; FBpp0070259; FBgn0000482.
DR GeneID; 31118; -.
DR KEGG; dme:Dmel_CG3093; -.
DR CTD; 31118; -.
DR FlyBase; FBgn0000482; dor.
DR VEuPathDB; VectorBase:FBgn0000482; -.
DR eggNOG; KOG2034; Eukaryota.
DR GeneTree; ENSGT00940000153635; -.
DR HOGENOM; CLU_003488_1_0_1; -.
DR InParanoid; Q24314; -.
DR PhylomeDB; Q24314; -.
DR SignaLink; Q24314; -.
DR BioGRID-ORCS; 31118; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 31118; -.
DR PRO; PR:Q24314; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0000482; Expressed in seminal fluid secreting gland and 20 other tissues.
DR ExpressionAtlas; Q24314; baseline and differential.
DR Genevisible; Q24314; DM.
DR GO; GO:0033263; C:CORVET complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA:FlyBase.
DR GO; GO:0030897; C:HOPS complex; IDA:FlyBase.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IMP:FlyBase.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR GO; GO:0097352; P:autophagosome maturation; IMP:FlyBase.
DR GO; GO:0007298; P:border follicle cell migration; IMP:FlyBase.
DR GO; GO:0051301; P:cell division; IMP:FlyBase.
DR GO; GO:0009267; P:cellular response to starvation; IMP:FlyBase.
DR GO; GO:0048072; P:compound eye pigmentation; IMP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:0045022; P:early endosome to late endosome transport; IMP:FlyBase.
DR GO; GO:0032456; P:endocytic recycling; IMP:FlyBase.
DR GO; GO:0006897; P:endocytosis; IMP:FlyBase.
DR GO; GO:0016197; P:endosomal transport; ISS:FlyBase.
DR GO; GO:0034058; P:endosomal vesicle fusion; IMP:UniProtKB.
DR GO; GO:0007032; P:endosome organization; IMP:FlyBase.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:FlyBase.
DR GO; GO:0008057; P:eye pigment granule organization; IMP:UniProtKB.
DR GO; GO:0007041; P:lysosomal transport; IMP:FlyBase.
DR GO; GO:0007040; P:lysosome organization; IBA:GO_Central.
DR GO; GO:0007220; P:Notch receptor processing; IMP:FlyBase.
DR GO; GO:0006727; P:ommochrome biosynthetic process; IMP:FlyBase.
DR GO; GO:0048284; P:organelle fusion; IBA:GO_Central.
DR GO; GO:0061357; P:positive regulation of Wnt protein secretion; IMP:FlyBase.
DR GO; GO:0006622; P:protein targeting to lysosome; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:FlyBase.
DR GO; GO:0006728; P:pteridine biosynthetic process; IMP:FlyBase.
DR GO; GO:0035542; P:regulation of SNARE complex assembly; ISS:FlyBase.
DR GO; GO:0007033; P:vacuole organization; IBA:GO_Central.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR000547; Clathrin_H-chain/VPS_repeat.
DR InterPro; IPR007810; Pep3_Vps18.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF05131; Pep3_Vps18; 1.
DR PROSITE; PS50236; CHCR; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Endosome; Lysosome; Membrane; Metal-binding; Phosphoprotein;
KW Protein transport; Reference proteome; Transport; Zinc; Zinc-finger.
FT CHAIN 1..1002
FT /note="Vacuolar protein sorting-associated protein 18
FT homolog"
FT /id="PRO_0000055905"
FT REPEAT 650..804
FT /note="CHCR"
FT ZN_FING 885..979
FT /note="RING-type"
FT COILED 827..880
FT /evidence="ECO:0000255"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 508..1002
FT /note="Missing: In dor-36; reduced endolysosomal
FT trafficking and thus reduced number of effective vesicles
FT released in response to a nerve impulse (quantal content).
FT This is likely largely due to the reduction in readily
FT releasable vesicles. Accumulation of the mature form of
FT Cp1. Expression in sky mutants partially rescues increased
FT neurotransmitter release at the larval neuromuscular
FT junction and neurodegeneration in the retina. However it
FT does not rescue the excessive recycling of vesicles to
FT endosomal compartments in sky mutants."
FT /evidence="ECO:0000269|PubMed:25422373"
FT MUTAGEN 551..1002
FT /note="Missing: In dor-30; Accumulation of the mature form
FT of Cp1."
FT /evidence="ECO:0000269|PubMed:25422373"
FT MUTAGEN 979
FT /note="C->Y: In dor-1; diminished fertility and an orange
FT eye color."
FT /evidence="ECO:0000269|PubMed:10549280"
FT CONFLICT 40
FT /note="E -> D (in Ref. 2; AAF45652)"
FT /evidence="ECO:0000305"
FT CONFLICT 169
FT /note="A -> P (in Ref. 1; CAA60382)"
FT /evidence="ECO:0000305"
FT CONFLICT 581
FT /note="Q -> H (in Ref. 1; CAA60382)"
FT /evidence="ECO:0000305"
FT CONFLICT 865
FT /note="V -> A (in Ref. 4; CAA16809)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1002 AA; 115334 MW; 02CCACE27795183D CRC64;
MDTSMPNQPK FLPRIEHNSS GATANSYVAT ASGNPFETDE EDEIFSRHKM VLRVPSNCTG
DLMHLAVSRN WLVCLLGTPE RTTLLRFFLP RAIPPGEAVL EKYLSGSGYK ITRMFLDPTG
HHIIIALVPK SATAGVSPDF LYIHCLESPQ AQQLKVRRIE KFKDHEITAV AFNPYHGNES
STGPILLGTS RGLIFETELN PAADGHVQRK QLYDLGLGRP KYPITGLKLL RVPNSSRYII
VVTSPECIYT FQETLKAEER SLQAIFAGYV SGVQEPHCEE RKTDLTFSQL RFFAPPNSKY
PKQWAWLCGE GIRVGELSIE ANSAATLIGN TLINLDFEKT MHLSYGERRL NTPKAFVLTE
YHAVLLYADH VRAICLLNQE QVYQEAFDEA RVGKPLSIER DELTGSIYVY TVKTVFNLRV
TREERNVWRI YLDKGQYELA TAHAAEDPEH LQLVLCQRAD AAFADGSYQV AADYYAETDK
SFEEVCLKFM VLPDKRPIIN YVKKRLSRVT TKPMETDELD EDKMNIIKAL VIWLIDLYLI
QINMPDKDEE WRSSWQTEYD EFMMEAHVLS CTRQNRETVR QLIAEHADPR NMAQFAIAIG
DYDEVVAQQL KAECYAEALQ TLINQRNPEL FYKYAPELIT RLPKPTVDAL MAQGSRLEVE
KLVPTLIIME NREQREQTQR YLEFAIYKLN TTNDAIHNFL LHLYAEHEPK LLMKYLEIQG
RDESLVHYDI YYAHKVCTDL DVKEARVFLE CMLRKWISAV DLALTFDMKL AKETASRPSD
SKIRRKLWLR IAYHDIKGTN DVKKALNLLK ECDLLRIEDL LPFFADFEKI DNFKEAICDA
LRDYNQRIQE LQREMAETTE QTDRVTAELQ QLRQHSLTVE SQDTCEICEM MLLVKPFFIF
ICGHKFHSDC LEKHVVPLLT KEQCRRLGTL KQQLEAEVQT QAQPQSGALS KQQAMELQRK
RAALKTEIED ILAADCLFCG LLISTIDQPF VDDWEQVNVE WE
