WDR24_DROME
ID WDR24_DROME Reviewed; 776 AA.
AC Q9XZ25;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=GATOR complex protein WDR24 {ECO:0000305};
DE AltName: Full=WD repeat-containing protein 24 {ECO:0000303|PubMed:27166823};
GN Name=Wdr24 {ECO:0000303|PubMed:27166823};
GN ORFNames=CG7609 {ECO:0000312|FlyBase:FBgn0027518};
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:AAD34769.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAD34769.1};
RX PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA Harvey D.A.;
RT "A Drosophila complementary DNA resource.";
RL Science 287:2222-2224(2000).
RN [4]
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 [5] {ECO:0000305}
RP FUNCTION, IDENTIFICATION IN THE GATOR COMPLEX, INTERACTION WITH MIO; NPRL3
RP AND NUP44A, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
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: An essential component of the GATOR subcomplex GATOR2 which
CC functions as an activator of the amino acid-sensing branch of the TORC1
CC signaling pathway (PubMed:27166823, PubMed:23723238). The two GATOR
CC subcomplexes, GATOR1 and GATOR2, regulate the TORC1 pathway in order to
CC mediate metabolic homeostasis, female gametogenesis and the response to
CC amino acid limitation and complete starvation (PubMed:27166823,
CC PubMed:23723238). GATOR2 activates the TORC1 signaling pathway through
CC the inhibition of the GATOR1 subcomplex, controlling the switch to cell
CC proliferation and growth under nutrient replete conditions and during
CC female oocyte development (PubMed:27166823, PubMed:23723238). This
CC GATOR2 component is required for activating TORC1 and promoting cell
CC growth in both germline and somatic cells (PubMed:27166823,
CC PubMed:23723238). In addition to its role in regulation of the TORC1
CC complex, functions independently of TORC1 to promote the acidification
CC of lysosomes and facilitates autophagic flux (PubMed:27166823).
CC {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:27166823}.
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 (PubMed:27166823). Interacts
CC with Nup44A/Seh1 (PubMed:27166823). Interacts with mio
CC (PubMed:27166823). Interacts with Nplr3 (PubMed:27166823).
CC {ECO:0000269|PubMed:27166823}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:27166823}.
CC Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:27166823}.
CC Note=Localizes to lysosomes and autolysosomes under fed and starved
CC conditions (PubMed:27166823). In female egg chambers, localizes
CC primarily to autophagosomes and autolysosomes during amino-acid
CC starvation (PubMed:27166823). {ECO:0000269|PubMed:27166823}.
CC -!- DISRUPTION PHENOTYPE: No effect on viability. Decreased TORC1 complex
CC activity. Decreased body size and weight. Mutant females have small
CC ovaries, reduced egg chamber growth and exhibit a 90% reduction in eggs
CC laid per day. Activation of autophagy and accumulation of autolysosomes
CC independent of nutritional status. {ECO:0000269|PubMed:27166823}.
CC -!- SIMILARITY: Belongs to the WD repeat WDR24 family. {ECO:0000305}.
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DR EMBL; AE014297; AAN14184.1; -; Genomic_DNA.
DR EMBL; AF132181; AAD34769.1; -; mRNA.
DR RefSeq; NP_651720.3; NM_143463.5.
DR AlphaFoldDB; Q9XZ25; -.
DR SMR; Q9XZ25; -.
DR IntAct; Q9XZ25; 1.
DR STRING; 7227.FBpp0303329; -.
DR DNASU; 43505; -.
DR EnsemblMetazoa; FBtr0085543; FBpp0084909; FBgn0027518.
DR GeneID; 43505; -.
DR KEGG; dme:Dmel_CG7609; -.
DR UCSC; CG7609-RB; d. melanogaster.
DR CTD; 84219; -.
DR FlyBase; FBgn0027518; Wdr24.
DR VEuPathDB; VectorBase:FBgn0027518; -.
DR eggNOG; KOG0269; Eukaryota.
DR GeneTree; ENSGT00940000159396; -.
DR HOGENOM; CLU_010233_0_0_1; -.
DR InParanoid; Q9XZ25; -.
DR PhylomeDB; Q9XZ25; -.
DR BioGRID-ORCS; 43505; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 43505; -.
DR PRO; PR:Q9XZ25; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0027518; Expressed in egg chamber and 22 other tissues.
DR ExpressionAtlas; Q9XZ25; baseline and differential.
DR GO; GO:0044754; C:autolysosome; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0061700; C:GATOR2 complex; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0035859; C:Seh1-associated complex; IDA:FlyBase.
DR GO; GO:0005774; C:vacuolar membrane; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IBA:GO_Central.
DR GO; GO:0007042; P:lysosomal lumen acidification; IMP:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:FlyBase.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:FlyBase.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; -; 2.
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; IPR037590; WDR24.
DR PANTHER; PTHR46200; PTHR46200; 2.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 3.
DR PROSITE; PS50082; WD_REPEATS_2; 3.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Autophagy; Cell cycle; Cell division; Cytoplasmic vesicle; Lysosome;
KW Mitosis; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..776
FT /note="GATOR complex protein WDR24"
FT /evidence="ECO:0000305"
FT /id="PRO_0000437416"
FT REPEAT 63..103
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 109..149
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 152..192
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 196..235
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 238..280
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 284..326
FT /note="WD 6"
FT /evidence="ECO:0000255"
FT REGION 466..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 776 AA; 87066 MW; F77AE45525D2ED62 CRC64;
MPDSVEDTST ISLRICLEGH ANALALNKDN NQIALAGRSL LKVYSINSNG FTESCNMRGK
NQNLSYSAND VAWSTLDSNL LATAATNGVV SVWDLSKFGR QKQLLVYNEH ERTAHTVTFH
SSEPNILISG SQDGTIKCFD IRSDKSINTY FCNSESVRDV KFSPHTQNIF SAVSENGTVQ
LWDMRKWDKC MVQFTAHYGP VYTCDWHPTR NWLATGSRDK QIKVWNMDGR PGLEHTIHTI
AVVGRVKWRP ERTYHIASCA LVVDYSVHVW DIRRPYIPFA SFNEHTNVTT GIAWQGSDSH
CLLSISKDST IYKHAFKDAT RPALKANAQG ASLGRFGDIS FANKIKEYEP KTSGASNTKS
SSFIRRKTNV AGSIQFHLDH SKMYKFMVND TFSGYPLSES VSRPTQEHES FIGCARELVI
SGKKLSELCE HNAEVSKKYG KHNATTLWNF IKLFYGSNHF EPPFEHRSSF SNQKNPMNSR
RATQVASDWP QQRTELGQDL NGNTPETAHE IDVANVDDDT LGSSGVEHPP TSSVILSETQ
IISEITFDNF ELLRNGFIYV GPTECPKALA FPALHHDVQA ARPQLDLKAS DHEKSPPPHV
PTVLKVSHVP PIPMWEPHKF VSDALMLMND VGDVQTALTV LIALGEARKL LPIDDALVEH
WFYTYVDQLH RYELWNEACE VINRSWLRSV QQLNQHSTAM HTNCGECGRP MGGKVGWYCD
KCKSMQSAKC CVCGLIVRGV YAWCQGCSHG GHIEHLQKYF AKHSKCPKCG HLCAYS
