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VPS8_DROME
ID   VPS8_DROME              Reviewed;        1229 AA.
AC   Q9VRX2; B7FNP6; C5WLL9; D0IQG0;
DT   18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   03-AUG-2022, entry version 170.
DE   RecName: Full=Vacuolar protein sorting-associated protein 8 homolog {ECO:0000250|UniProtKB:Q8N3P4};
DE   AltName: Full=Vacuolar protein sorting 8 {ECO:0000312|FlyBase:FBgn0035704};
GN   Name=Vps8 {ECO:0000312|FlyBase:FBgn0035704};
GN   ORFNames=CG10144 {ECO:0000312|FlyBase:FBgn0035704};
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 {ECO:0000312|Proteomes:UP000000803};
RN   [1] {ECO:0000312|Proteomes:UP000000803}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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   [2] {ECO:0000312|Proteomes:UP000000803}
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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   [3] {ECO:0000312|EMBL:ACS54286.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley {ECO:0000312|EMBL:ACS54286.1};
RC   TISSUE=Embryo {ECO:0000312|EMBL:ACK77654.1}, and
RC   Testis {ECO:0000312|EMBL:ACS54286.1, ECO:0000312|EMBL:ACY40032.1};
RA   Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL   Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN   [4] {ECO:0000305}
RP   FUNCTION, IDENTIFICATION IN THE CORVET COMPLEX, DISRUPTION PHENOTYPE, AND
RP   IDENTIFICATION BY MASS 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. Specifically required for
CC       endocytic trafficking in a subset of cells, such as hemocytes and
CC       nephrocytes, which are highly active in endocytosis.
CC       {ECO:0000269|PubMed:27253064}.
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. {ECO:0000269|PubMed:27253064}.
CC   -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000269|PubMed:27253064}.
CC       Note=Localization to the early endosome is dependent on Rab5 and class
CC       C core vacuole/endosome tethering (CORVET) complex subunits such as
CC       dor/Vps18, car/Vps33A and Vps16A. {ECO:0000269|PubMed:27253064}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in the larva, in the pupal wings and the
CC       adult fly (at protein level). High levels of expression are found in
CC       larval hemocytes and garland nephrocytes (at protein level).
CC       {ECO:0000269|PubMed:27253064}.
CC   -!- DISRUPTION PHENOTYPE: Semilethal: animals can complete metamorphosis,
CC       but most of them die as pharate adults unable to emerge from the pupal
CC       case; surviving flies are weak, fail to unfold their wings properly and
CC       die within 24 hr. The eye color is similar to wild type flies. In
CC       larvae, results in the development of hemocyte-derived melanotic tumors
CC       in body cavities, accumulation of crystal cells and lamellocytes and
CC       disorganization of the sessile hemocyte compartment which might be
CC       connected to the abnormal increase of circulating hemocytes. In garland
CC       cells, uptake from the hemolymph, endosome formation and endo-lysosomal
CC       trafficking are defective and result in enlarged cells; late endosomes
CC       and endolysosomes are fragmented and erroneously distributed in the
CC       cytoplasm instead of being found in a layer directly beneath peripheral
CC       early endosomes. In hemocytes, acidification of endocytic vacuoles
CC       containing bacteria is defective. In wing imaginal disks, there are no
CC       endosome defects. {ECO:0000269|PubMed:27253064}.
CC   -!- SIMILARITY: Belongs to the VPS8 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=ACK77654.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=ACY40032.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing at the N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AE014296; AAF50660.1; -; Genomic_DNA.
DR   EMBL; BT053736; ACK77654.1; ALT_FRAME; mRNA.
DR   EMBL; BT088834; ACS54286.1; -; mRNA.
DR   EMBL; BT100198; ACY40032.1; ALT_SEQ; mRNA.
DR   RefSeq; NP_648048.1; NM_139791.3.
DR   AlphaFoldDB; Q9VRX2; -.
DR   IntAct; Q9VRX2; 1.
DR   STRING; 7227.FBpp0076695; -.
DR   PaxDb; Q9VRX2; -.
DR   EnsemblMetazoa; FBtr0076986; FBpp0076695; FBgn0035704.
DR   GeneID; 38735; -.
DR   KEGG; dme:Dmel_CG10144; -.
DR   UCSC; CG10144-RA; d. melanogaster.
DR   CTD; 23355; -.
DR   FlyBase; FBgn0035704; Vps8.
DR   VEuPathDB; VectorBase:FBgn0035704; -.
DR   eggNOG; KOG2079; Eukaryota.
DR   GeneTree; ENSGT00390000010672; -.
DR   HOGENOM; CLU_000917_1_2_1; -.
DR   InParanoid; Q9VRX2; -.
DR   OMA; WAHQDKH; -.
DR   OrthoDB; 22166at2759; -.
DR   PhylomeDB; Q9VRX2; -.
DR   BioGRID-ORCS; 38735; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 38735; -.
DR   PRO; PR:Q9VRX2; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0035704; Expressed in embryonic/larval hemocyte (Drosophila) and 25 other tissues.
DR   Genevisible; Q9VRX2; DM.
DR   GO; GO:0033263; C:CORVET complex; IDA:UniProtKB.
DR   GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR   GO; GO:0030897; C:HOPS complex; IBA:GO_Central.
DR   GO; GO:0005770; C:late endosome; IBA:GO_Central.
DR   GO; GO:0051020; F:GTPase binding; ISS:FlyBase.
DR   GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR   GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR   GO; GO:0016197; P:endosomal transport; ISS:FlyBase.
DR   GO; GO:0034058; P:endosomal vesicle fusion; IDA:UniProtKB.
DR   GO; GO:0007032; P:endosome organization; IDA:UniProtKB.
DR   GO; GO:0006623; P:protein targeting to vacuole; IBA:GO_Central.
DR   Gene3D; 2.130.10.10; -; 1.
DR   Gene3D; 3.30.40.10; -; 1.
DR   InterPro; IPR000547; Clathrin_H-chain/VPS_repeat.
DR   InterPro; IPR011047; Quinoprotein_ADH-like_supfam.
DR   InterPro; IPR045111; Vps41/Vps8.
DR   InterPro; IPR025941; Vps8_central_dom.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   InterPro; IPR001841; Znf_RING.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   PANTHER; PTHR12616; PTHR12616; 1.
DR   Pfam; PF00637; Clathrin; 1.
DR   Pfam; PF12816; Vps8; 1.
DR   SUPFAM; SSF50998; SSF50998; 1.
DR   PROSITE; PS50236; CHCR; 1.
DR   PROSITE; PS50089; ZF_RING_2; 1.
PE   1: Evidence at protein level;
KW   Endosome; Metal-binding; Protein transport; Reference proteome; Transport;
KW   Zinc; Zinc-finger.
FT   CHAIN           1..1229
FT                   /note="Vacuolar protein sorting-associated protein 8
FT                   homolog"
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000444757"
FT   REPEAT          901..1063
FT                   /note="CHCR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01006"
FT   ZN_FING         1148..1189
FT                   /note="RING-type; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT   REGION          67..89
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        460
FT                   /note="V -> L (in Ref. 3; ACS54286/ACY40032)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        554
FT                   /note="L -> H (in Ref. 3; ACS54286/ACY40032)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        646
FT                   /note="D -> E (in Ref. 3; ACS54286/ACY40032)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        666
FT                   /note="E -> G (in Ref. 3; ACS54286/ACY40032)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        857
FT                   /note="S -> C (in Ref. 3; ACS54286/ACY40032)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        930
FT                   /note="L -> V (in Ref. 3; ACS54286/ACY40032)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        960
FT                   /note="S -> A (in Ref. 3; ACS54286/ACY40032)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1229 AA;  137922 MW;  256B978BC5B4B71F CRC64;
     MSELKAPSLQ SLLESERGST DSLLAESLQL DFEDLDDAEF AIPPTDVLPT LEAVLSEFEA
     DSDVASEFGM PVPHATPTPS IGEDSTIRTD GRGGGGSIMR YTLLHGISAQ LSSAAERVNA
     GAASSCAVAA FIAIGTSHGH ILNFDVTQTL RWAHQDKHGQ GAVASLAFNA DSTRLLAGFS
     RGLVAMLDTH TGDVLRELFD VITPNTGVLH VKWTSRSSLA LCADAGGSVW SLSFTRKLGI
     RGCQSRCLFS GARGEVCAVE PLIMDSQGRH ELDQYCIVAL ATLSKYFIVT VRPRLRVIKY
     HVLQGPPDCL PLLAWHLVLI QAADTSRSVD PVIVVGRGNQ LFFHQLFVSN GRITLLYLRH
     VQLQGSLLSA HWLGPKCVAS LDTAEILHLV DVRSSKELEC MDMANAGLVY GSAQFKGLAT
     GGNVSPAFAL AGSNACYNSV VSRGTQLYVL GARSLHIIGV RTWSERISFL VKHHRWQEAC
     QLALDGYIAS VDRPRKRAQA KERIIMLFKE YIANSARAPE YCLGAIVNCL ITVGELDLLW
     TQLWEKLHNS STELFLQHIS EHIEKETIHS VNPVISQALV DYWLEHSPAK LEQLILKLDW
     MCLDLNQVLK AVKKHRLFRA QIYLNTQALN DYTAALTELL PLVTPDETDL GNCLLVYVSS
     CLAGREYPSG EIPVELVHQV KHDVLRCLTS QHSKENAGDE LPYPYLRALL KFDTRETLNV
     ISLAFQEREF SNELGISHRK RIINLLLEIM SPENATWAEI GCLLNFIAQQ ISMQCLPRDR
     QLLERVLSHL AQEEIANESS RQHSERENAW HELLSSNCLA EISSDEEQLR LAEKAKCYCV
     VEYLLEKLER YDTILDSYIR NEARHETMFA YMERHVASPK RSIFRQLKRN LRELLTINAK
     ETTRLLSLHY PEKINELLDN LRREENLLYL FLKCLNDRKS ELEASQMELL LELYCKMESS
     STVEEFLRSN SGYRLENAIA IAESHHLNRS VIYLYEKQES YAKAFELSME LLKSAAGEEA
     AKEAQTISAL LARSVETLPA QELERCWFAL LQYILPHQEL QSITKSLLHE ASQHIDLHNL
     VQLIMNTHNV STSFGDIKDL LMGMLDSSRH KTEALRASAG ALCQDLHLKF VKRYQHAHRG
     LWVTTTKCSM CRQRLYDHSQ VLIFGGCGHG IHEQCMEESE TQFEECPRCF TAIPDQSIGL
     PRPNKNLISI SSSLEMGALQ LKAPPRRFI
 
 
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