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WDR59_DROME
ID   WDR59_DROME             Reviewed;         969 AA.
AC   Q9VKK2; B5RIT6; Q7KTE5; Q8T9F8;
DT   20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT   18-SEP-2013, sequence version 3.
DT   03-AUG-2022, entry version 144.
DE   RecName: Full=GATOR complex protein Wdr59 {ECO:0000303|PubMed:23723238};
GN   Name=Wdr59 {ECO:0000303|PubMed:23723238, ECO:0000312|FlyBase:FBgn0032339};
GN   ORFNames=CG4705 {ECO:0000312|FlyBase:FBgn0032339};
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 [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   [2]
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   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Embryo;
RA   Stapleton M., Carlson J.W., Booth B., Chavez C., Frise E., George R.A.,
RA   Pacleb J.M., Park S., Wan K.H., Yu C., Celniker S.E.;
RL   Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-373, 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   [6]
RP   FUNCTION.
RX   PubMed=23723238; DOI=10.1126/science.1232044;
RA   Bar-Peled L., Chantranupong L., Cherniack A.D., Chen W.W., Ottina K.A.,
RA   Grabiner B.C., Spear E.D., Carter S.L., Meyerson M., Sabatini D.M.;
RT   "A Tumor suppressor complex with GAP activity for the Rag GTPases that
RT   signal amino acid sufficiency to mTORC1.";
RL   Science 340:1100-1106(2013).
RN   [7]
RP   IDENTIFICATION IN THE GATOR COMPLEX.
RX   PubMed=27166823; DOI=10.1371/journal.pgen.1006036;
RA   Cai W., Wei Y., Jarnik M., Reich J., Lilly M.A.;
RT   "The GATOR2 component Wdr24 regulates TORC1 activity and lysosome
RT   function.";
RL   PLoS Genet. 12:E1006036-E1006036(2016).
CC   -!- FUNCTION: A component of the GATOR subcomplex GATOR2 which functions as
CC       an activator of the amino acid-sensing branch of the TORC1 signaling
CC       pathway. The two GATOR subcomplexes, GATOR1 and GATOR2, regulate the
CC       TORC1 pathway in order to mediate metabolic homeostasis, female
CC       gametogenesis and the response to amino acid limitation and complete
CC       starvation. GATOR2 activates the TORC1 signaling pathway through the
CC       inhibition of the GATOR1 subcomplex, controlling the switch to cell
CC       proliferation and growth under nutrient replete conditions and during
CC       female oocyte development. {ECO:0000269|PubMed:23723238}.
CC   -!- SUBUNIT: Component of the GATOR complex consisting of mio, Nup44A/Seh1,
CC       Im11, Nplr3, Nplr2, Wdr24, Wdr59 and Sec13. Within the GATOR complex,
CC       probable component of the GATOR2 subcomplex which is likely composed of
CC       mio, Nup44A/Seh1, Wdr24, Wdr59 and Sec13.
CC       {ECO:0000269|PubMed:27166823}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAL39932.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=AAZ66312.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AE014134; AAS64677.1; -; Genomic_DNA.
DR   EMBL; AY069787; AAL39932.1; ALT_FRAME; mRNA.
DR   EMBL; BT023805; AAZ66312.1; ALT_FRAME; mRNA.
DR   EMBL; BT044210; ACH92275.1; -; mRNA.
DR   RefSeq; NP_609485.4; NM_135641.4.
DR   RefSeq; NP_995682.1; NM_205960.4.
DR   AlphaFoldDB; Q9VKK2; -.
DR   SMR; Q9VKK2; -.
DR   BioGRID; 60602; 1.
DR   STRING; 7227.FBpp0079785; -.
DR   iPTMnet; Q9VKK2; -.
DR   PaxDb; Q9VKK2; -.
DR   PRIDE; Q9VKK2; -.
DR   DNASU; 34540; -.
DR   EnsemblMetazoa; FBtr0080196; FBpp0079785; FBgn0032339.
DR   EnsemblMetazoa; FBtr0343622; FBpp0310217; FBgn0032339.
DR   GeneID; 34540; -.
DR   KEGG; dme:Dmel_CG4705; -.
DR   UCSC; CG4705-RA; d. melanogaster.
DR   CTD; 79726; -.
DR   FlyBase; FBgn0032339; Wdr59.
DR   VEuPathDB; VectorBase:FBgn0032339; -.
DR   eggNOG; KOG0309; Eukaryota.
DR   GeneTree; ENSGT00940000157600; -.
DR   HOGENOM; CLU_009370_0_0_1; -.
DR   InParanoid; Q9VKK2; -.
DR   OMA; HDACIPF; -.
DR   OrthoDB; 590848at2759; -.
DR   PhylomeDB; Q9VKK2; -.
DR   BioGRID-ORCS; 34540; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 34540; -.
DR   PRO; PR:Q9VKK2; -.
DR   Proteomes; UP000000803; Chromosome 2L.
DR   Bgee; FBgn0032339; Expressed in adult Malpighian tubule (Drosophila) and 25 other tissues.
DR   Genevisible; Q9VKK2; DM.
DR   GO; GO:0061700; C:GATOR2 complex; TAS:FlyBase.
DR   GO; GO:0035859; C:Seh1-associated complex; IDA:FlyBase.
DR   GO; GO:0005774; C:vacuolar membrane; IBA:GO_Central.
DR   GO; GO:0035591; F:signaling adaptor activity; IBA:GO_Central.
DR   GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB.
DR   GO; GO:0032008; P:positive regulation of TOR signaling; IMP:UniProtKB.
DR   GO; GO:1904263; P:positive regulation of TORC1 signaling; IBA:GO_Central.
DR   CDD; cd16692; mRING-H2-C3H3C2_WDR59; 1.
DR   Gene3D; 2.130.10.10; -; 1.
DR   InterPro; IPR006575; RWD-domain.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   InterPro; IPR001680; WD40_repeat.
DR   InterPro; IPR019775; WD40_repeat_CS.
DR   InterPro; IPR036322; WD40_repeat_dom_sf.
DR   InterPro; IPR039456; WDR59_mRING-H2-C3H3C2.
DR   Pfam; PF00400; WD40; 2.
DR   SMART; SM00320; WD40; 4.
DR   SUPFAM; SSF50978; SSF50978; 1.
DR   PROSITE; PS50908; RWD; 1.
DR   PROSITE; PS00678; WD_REPEATS_1; 2.
DR   PROSITE; PS50082; WD_REPEATS_2; 4.
DR   PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE   1: Evidence at protein level;
KW   Phosphoprotein; Reference proteome; Repeat; WD repeat.
FT   CHAIN           1..969
FT                   /note="GATOR complex protein Wdr59"
FT                   /id="PRO_0000280724"
FT   REPEAT          127..167
FT                   /note="WD 1"
FT   REPEAT          172..211
FT                   /note="WD 2"
FT   REPEAT          215..255
FT                   /note="WD 3"
FT   REPEAT          258..303
FT                   /note="WD 4"
FT   REPEAT          307..351
FT                   /note="WD 5"
FT   DOMAIN          435..538
FT                   /note="RWD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00179"
FT   REGION          1..24
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         373
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
SQ   SEQUENCE   969 AA;  107969 MW;  B60C97C86C1F1314 CRC64;
     MPPTETLRPG ERGTAGGPGA GAPEQTYIVR QSNKYYEHRD SQATAMSVDY SGQWVLLAGR
     GHLALQRLGQ DDGSLRRHER QSKYEVSVAE FAICPSRKEY CAIATSQHID IVRWGTAEPH
     YEMSLRGHTR TVTDIDWHGK DPNLLVSCSI DTFSHIWDLR EPRKPALSLN AVCMSGATQV
     GFNRVSGNLL AAAHDGDLRI WDIRKGSCPT HYITAHLNRV HGINWSHKRE TCLATASQDG
     TVKYFDVCNP RRAEKIITTM SPVWRARYTP IGNGLVSIVV PHLGRGENSL LLWSNSKQTD
     PICSFVGHTD VILDFAWRPN RESSNEIELV TWSRDRTLRV WKIDDNMLKL CEPSAEEIES
     RFEPDLSELR VPTPPEFLHP RSILVAASLP ISTGDGACNT LPMARSPSFG GGYYRREEPH
     IARSLTDQPT CSLHHEFSLL NTNMPHVEVD TLDAIKRYAC FKICAGGHTV ILQVTFTTSY
     PSPSAPPDFQ LCQGTTLSSE VSGVLLKVLR CNALQRVKKS RTCLEQCLRA LVAAMKKKVA
     AVGGADRSQL LLQSPRLEGA LSSTLHDACI PYPRTSGVHF NAIGMLTTFA QPVNNKRLTL
     RQHTALTPRT FSSINGSGLL GNVMATAQRE ANASFYLQER MISGKPGKQR AIRQMNGSPV
     VHVYDTSSLL HISRRMAREF SLDKCNIAET CRKNGEICRQ HGRLDLVPVW LLAELIATPQ
     IPHETLNDLL FYKDPFKKSL LESLIMHYAI SGDIQTAVLL ACLFDKCPTG GGAIMEKTVR
     LPPQLNSQIS PYHTVLPLDV KSSSSSNTWQ QLKQLRSNSW SDSLDLEIKQ IQSDAYACSL
     IRRTKMPLFD QFKRAYAEIL FGWQLLSKRA LILKHTQNTP PPVQGVEFVT ECRKCAKPKR
     TPKCEPCKRP VLFCVLCRLP VKGAANACLA CGHGGHIDHM MQWFEKHNVC ATCGCKCLER
     TSELLALLS
 
 
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