MIO_DROME
ID MIO_DROME Reviewed; 867 AA.
AC Q9VQ89; Q95RC2;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=GATOR complex protein MIOS {ECO:0000305};
DE AltName: Full=Missing oocyte protein {ECO:0000303|PubMed:14973288};
GN Name=mio {ECO:0000303|PubMed:14973288, ECO:0000312|FlyBase:FBgn0031399};
GN ORFNames=CG7074 {ECO:0000312|FlyBase:FBgn0031399};
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 FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=14973288; DOI=10.1242/dev.01001;
RA Iida T., Lilly M.A.;
RT "missing oocyte encodes a highly conserved nuclear protein required for the
RT maintenance of the meiotic cycle and oocyte identity in Drosophila.";
RL Development 131:1029-1039(2004).
RN [5]
RP FUNCTION, AND INTERACTION WITH NUP44A.
RX PubMed=21521741; DOI=10.1242/dev.057372;
RA Senger S., Csokmay J., Akbar T., Tanveer A., Jones T.I., Sengupta P.,
RA Lilly M.A.;
RT "The nucleoporin Seh1 forms a complex with Mio and serves an essential
RT tissue-specific function in Drosophila oogenesis.";
RL Development 138:2133-2142(2011).
RN [6]
RP ERRATUM OF PUBMED:21521741.
RA Senger S., Csokmay J., Akbar T., Tanveer A., Jones T.I., Sengupta P.,
RA Lilly M.A.;
RT "The nucleoporin Seh1 forms a complex with Mio and serves an essential
RT tissue-specific function in Drosophila oogenesis.";
RL Development 138:2631-2631(2011).
RN [7]
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 [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 817-TRP--SER-867.
RX PubMed=25512509; DOI=10.1073/pnas.1419156112;
RA Wei Y., Reveal B., Reich J., Laursen W.J., Senger S., Akbar T.,
RA Iida-Jones T., Cai W., Jarnik M., Lilly M.A.;
RT "TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte
RT development in Drosophila.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E5670-E5677(2014).
RN [9]
RP FUNCTION, IDENTIFICATION IN THE GATOR COMPLEX, INTERACTION WITH WDR24, AND
RP MUTAGENESIS OF 817-TRP--SER-867.
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:21521741, PubMed:25512509,
CC PubMed:14973288, PubMed:23723238). This component is required for
CC activating TORC1 specifically in germline cells to promote cell growth
CC and maintain the oocyte fate (PubMed:27166823, PubMed:21521741,
CC PubMed:23723238). GATOR1 and GATOR2 act at different stages of
CC oogenesis to regulate TORC1 in order to control meiotic entry and
CC promote oocyte growth and development (PubMed:21521741,
CC PubMed:25512509, PubMed:14973288, PubMed:23723238). After exactly four
CC mitotic cyst divisions, the GATOR1 complex members (Iml1, Nprl2 and
CC Nprl3) down-regulate TORC1 to slow cellular metabolism and promote the
CC mitotic/meiotic transition (PubMed:25512509). At later stages of
CC oogenesis, the mio and Nup44A components of the GATOR2 complex inhibit
CC GATOR1 and thus activate TORC1 to promote meiotic progression, and
CC drive oocyte growth and development (PubMed:21521741, PubMed:25512509).
CC In addition to its role in the regulation of the TORC1 complex,
CC functions independently of TORC1 to prevent the inappropriate
CC accumulation of autolysosomes in germline tissues (PubMed:27166823).
CC {ECO:0000269|PubMed:14973288, ECO:0000269|PubMed:21521741,
CC ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25512509,
CC ECO:0000269|PubMed:27166823}.
CC -!- SUBUNIT: Component of the GATOR complex consisting of mio, Nup44A/Seh1,
CC Im11, Nplr3, Nplr2, Wdr24, Wdr59 and Sec13 (PubMed:27166823). Within
CC the GATOR complex, probable component of the GATOR2 subcomplex which is
CC likely composed of mio, Nup44A/Seh1, Wdr24, Wdr59 and Sec13
CC (PubMed:27166823). Interacts with Wdr24 (PubMed:27166823). Interacts
CC with nucleoporin Nup44A/Seh1 (PubMed:21521741).
CC {ECO:0000269|PubMed:21521741, ECO:0000269|PubMed:27166823}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14973288}. Lysosome
CC {ECO:0000269|PubMed:25512509}. Note=Accumulates in pro-oocyte nuclei in
CC early prophase of meiosis I (PubMed:14973288). In egg chambers,
CC detected in lysosomes and autolysosomes of both fed and starved females
CC (PubMed:25512509). {ECO:0000269|PubMed:14973288,
CC ECO:0000269|PubMed:25512509}.
CC -!- TISSUE SPECIFICITY: Present in the oocyte.
CC {ECO:0000269|PubMed:14973288}.
CC -!- DISRUPTION PHENOTYPE: Egg chambers contain 16 polyploid nurse cells
CC because the oocyte enters the endocycle and develops as a polyploid
CC nurse cell. {ECO:0000269|PubMed:14973288}.
CC -!- SIMILARITY: Belongs to the WD repeat mio family. {ECO:0000305}.
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DR EMBL; AE014134; AAF51288.2; -; Genomic_DNA.
DR EMBL; AY061485; AAL29033.1; -; mRNA.
DR RefSeq; NP_608656.1; NM_134812.3.
DR AlphaFoldDB; Q9VQ89; -.
DR SMR; Q9VQ89; -.
DR BioGRID; 59628; 10.
DR IntAct; Q9VQ89; 1.
DR STRING; 7227.FBpp0077507; -.
DR PaxDb; Q9VQ89; -.
DR PRIDE; Q9VQ89; -.
DR EnsemblMetazoa; FBtr0077835; FBpp0077507; FBgn0031399.
DR GeneID; 33399; -.
DR KEGG; dme:Dmel_CG7074; -.
DR CTD; 33399; -.
DR FlyBase; FBgn0031399; mio.
DR VEuPathDB; VectorBase:FBgn0031399; -.
DR eggNOG; KOG1008; Eukaryota.
DR GeneTree; ENSGT00390000015038; -.
DR HOGENOM; CLU_005843_1_0_1; -.
DR InParanoid; Q9VQ89; -.
DR OMA; QSHNSTC; -.
DR OrthoDB; 890767at2759; -.
DR PhylomeDB; Q9VQ89; -.
DR BioGRID-ORCS; 33399; 0 hits in 1 CRISPR screen.
DR ChiTaRS; Mondo; fly.
DR GenomeRNAi; 33399; -.
DR PRO; PR:Q9VQ89; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0031399; Expressed in adult Malpighian tubule (Drosophila) and 24 other tissues.
DR Genevisible; Q9VQ89; DM.
DR GO; GO:0044754; C:autolysosome; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0001674; C:female germ cell nucleus; IDA:UniProtKB.
DR GO; GO:0061700; C:GATOR2 complex; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0032991; C:protein-containing complex; IPI:FlyBase.
DR GO; GO:0035859; C:Seh1-associated complex; IDA:FlyBase.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IMP:FlyBase.
DR GO; GO:0007293; P:germarium-derived egg chamber formation; IMP:FlyBase.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:FlyBase.
DR GO; GO:0009994; P:oocyte differentiation; IMP:UniProtKB.
DR GO; GO:0030716; P:oocyte fate determination; IMP:FlyBase.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0045793; P:positive regulation of cell size; IMP:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IMP:FlyBase.
DR GO; GO:0040020; P:regulation of meiotic nuclear division; IMP:FlyBase.
DR CDD; cd16691; mRING-H2-C3H3C2_Mio; 1.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR037593; MIOS/Sea4.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR031488; Zn_ribbon_mio.
DR PANTHER; PTHR16453; PTHR16453; 1.
DR Pfam; PF00400; WD40; 1.
DR Pfam; PF17034; zinc_ribbon_16; 1.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Developmental protein; Differentiation;
KW Lysosome; Meiosis; Mitosis; Nucleus; Oogenesis; Reference proteome; Repeat;
KW WD repeat.
FT CHAIN 1..867
FT /note="GATOR complex protein MIOS"
FT /id="PRO_0000329410"
FT REPEAT 51..86
FT /note="WD 1"
FT REPEAT 100..144
FT /note="WD 2"
FT REPEAT 149..188
FT /note="WD 3"
FT REPEAT 190..228
FT /note="WD 4"
FT REPEAT 231..272
FT /note="WD 5"
FT REGION 350..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 817..867
FT /note="Missing: Significant decrease in TORC1 activity in
FT adult ovaries indicated by reduced phosphorylation of
FT S6K/p70S6K and the accumulation of autolysosomes. Female
FT germline clones are smaller compared to wild-type cells. In
FT contrast, somatic tissues do not display a significant
FT decrease in TORC1 activity and there is only a negligible
FT decrease in cell size. RNAi-mediated knockdown of Nprl1 or
FT Nprl3 rescues the ovarian defects in mutants, but not the
FT accumulation of lysosomes."
FT /evidence="ECO:0000269|PubMed:25512509,
FT ECO:0000269|PubMed:27166823"
SQ SEQUENCE 867 AA; 98602 MW; 76AED774B9C34E4D CRC64;
MSGNTHGLSW FPHFPDKFVS WGQEIHLYEV RRKDDHSQKS RLPYISVNYL ANESRYQYAR
CVAASYHSDQ PIIAVGLADG KVGICNFRDT YDSSWEYTPR QQRMCTCLAW NELDANILAI
GHDRHRNDTC ITIWDIERGV PKETANFFGV GESANSICWD RNHRTVIAGM SQKMIKLFDL
RQSNATCQSI QTKTVQGLSV SPNGNYLCSY VDSVITLWDP RNIKSPLRQI QSSKNHLQIA
WCPTRTSLLS SLQRDSSYIT LYDIRSVDTD NSGEIYHVKR QISPFPARYQ HSGKFSFVNC
LSWHSRDFER ALLLADALNI LDFRLPATLH TAHSNRRKLP LLMQRPLYTP ASPTSTAATP
TQQQPTSSCS TNSGSSLDFS TPGGSPFNVD LLKPELFELD LVDETRQRAL EDYGIKPDNK
RFGELHLTPY LRNVWSTLNN VYSEDRLTGL KATLGINLGH TSEALMASSR IESQVLQWPE
GINNSNKLIC YRSEQRDLAL QLCGWAFEQE LDRFIDQLYA NKEYSRAAMI CVFHLKIFHA
CNILSSAADN MRDPSMYRIT VIALSSFNAD RCSSTWRNQR SSANMQIHDP HLRAVFSFLT
MEKDNFDAVL KEEGVSLSDR MAFACKYLSE TKLADYVAQQ IQAAIDGGDL NGLLLTGESQ
DGIDILQSYM DTSFDVQTVA LVAINYFRQE LFEDKRIQYW IASYLDHLNS WGLWEKRAEL
DIKIESIRPS SRSSRTVFLS CNFCGKSVSN ALLDEPRPRS TTTSTNRLSS CPSCRKPLPR
CSLCLMHMGT MVNMSNGETP TTTPDVPGWQ TKPFSKWFSW CQTCRHGGHT EHIMQWFKQN
SECPVSSCNC RCFDMDGTKP NTLRDIS
