IML1_DROME
ID IML1_DROME Reviewed; 1544 AA.
AC Q9W0E3; E8NH72; Q8IRG9; Q8SY36;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=GATOR complex protein Iml1 {ECO:0000303|PubMed:25512509};
DE AltName: Full=Increased minichromosome loss 1 {ECO:0000303|PubMed:25512509};
GN Name=Iml1 {ECO:0000303|PubMed:25512509, ECO:0000312|FlyBase:FBgn0035227};
GN Synonyms=DEPDC5 {ECO:0000303|PubMed:23723238},
GN SEA1 {ECO:0000312|FlyBase:FBgn0035227};
GN ORFNames=CG12090 {ECO:0000312|FlyBase:FBgn0035227};
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:AAL68237.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 255-1544 (ISOFORM B).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL68237.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAL68237.1};
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] {ECO:0000312|EMBL:ADX35927.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 964-1544 (ISOFORM B).
RC STRAIN=Berkeley {ECO:0000312|EMBL:ADX35927.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:ADX35927.1};
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (FEB-2011) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
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 [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 [7] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27672113; DOI=10.1534/g3.116.035337;
RA Wei Y., Reveal B., Cai W., Lilly M.A.;
RT "The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to
RT Nutrient Stress in Drosophila melanogaster.";
RL G3 (Bethesda) 6:3859-3867(2016).
RN [8] {ECO:0000305}
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: An essential component of the GATOR subcomplex GATOR1 which
CC functions as an inhibitor of the amino acid-sensing branch of the TORC1
CC signaling pathway (PubMed:23723238, PubMed:27672113, PubMed:25512509).
CC The two GATOR subcomplexes, GATOR1 and GATOR2, regulate the TORC1
CC pathway in order to mediate metabolic homeostasis, female gametogenesis
CC and the response to amino acid limitation and complete starvation
CC (PubMed:23723238, PubMed:27672113, PubMed:25512509). The function of
CC GATOR1 in negatively regulating the TORC1 pathway is essential for
CC maintaining baseline levels of TORC1 activity under nutrient rich
CC conditions, and for promoting survival during amino acid or complete
CC starvation by inhibiting TORC1-dependent cell growth and promoting
CC catabolic metabolism and autophagy (PubMed:23723238, PubMed:27672113,
CC PubMed:25512509). 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:27672113,
CC PubMed:25512509). After exactly four mitotic cyst divisions, the GATOR1
CC complex members (Iml1, Nprl2 and Nprl3) down-regulate TORC1 to slow
CC cellular metabolism and promote the mitotic/meiotic transition
CC (PubMed:27672113, PubMed:25512509). At later stages of oogenesis, the
CC mio and Nup44A components of the GATOR2 complex inhibit GATOR1 and thus
CC activate TORC1 to promote meiotic progression, and drive oocyte growth
CC and development (PubMed:27672113, PubMed:25512509).
CC {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25512509,
CC ECO:0000269|PubMed:27672113}.
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 GATOR1 subcomplex which is
CC likely composed of Iml1, Nplr2 and Nplr3 (PubMed:27166823).
CC {ECO:0000269|PubMed:27166823}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A {ECO:0000312|FlyBase:FBgn0035227};
CC IsoId=Q9W0E3-1; Sequence=Displayed;
CC Name=B {ECO:0000312|FlyBase:FBgn0035227};
CC IsoId=Q9W0E3-2; Sequence=VSP_060140, VSP_060141;
CC -!- DISRUPTION PHENOTYPE: Pupal lethal (PubMed:27672113). Under nutrient-
CC replete conditions, larvae display a significant increase in TORC1
CC activity, indicated by increased phosphorylation of S6K/p70S6K
CC (PubMed:27672113). RNAi-mediated knockdown in the female germline
CC results in a large percentage of ovarian cysts delaying mitotic exit
CC (PubMed:25512509, PubMed:27672113). Instead, cysts undergo a fifth
CC mitotic division before meiotic commitment to produce 32-cell cysts
CC with a single oocyte (PubMed:25512509, PubMed:27672113). Double RNAi-
CC mediated knockdown with GATOR1 complex member Nprl2 in the female
CC germline increases the penetrance of ovarian cysts displaying delayed
CC mitotic exit and producing 32-cell cysts (PubMed:27672113,
CC PubMed:25512509). The number of ovarian cysts that delay meiotic
CC commitment and undergo a fifth mitotic division are decreased when
CC females are fed the mTORC1 complex inhibitor rapamycin
CC (PubMed:25512509). {ECO:0000269|PubMed:25512509,
CC ECO:0000269|PubMed:27672113}.
CC -!- SIMILARITY: Belongs to the IML1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL68237.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE014296; AAF47505.2; -; Genomic_DNA.
DR EMBL; AE014296; AAN11485.1; -; Genomic_DNA.
DR EMBL; AY075414; AAL68237.1; ALT_INIT; mRNA.
DR EMBL; BT125948; ADX35927.1; -; mRNA.
DR RefSeq; NP_647618.1; NM_139361.2. [Q9W0E3-2]
DR RefSeq; NP_728621.1; NM_167889.2. [Q9W0E3-1]
DR AlphaFoldDB; Q9W0E3; -.
DR SMR; Q9W0E3; -.
DR IntAct; Q9W0E3; 1.
DR STRING; 7227.FBpp0072587; -.
DR PaxDb; Q9W0E3; -.
DR EnsemblMetazoa; FBtr0072703; FBpp0072587; FBgn0035227. [Q9W0E3-1]
DR EnsemblMetazoa; FBtr0072704; FBpp0072588; FBgn0035227. [Q9W0E3-2]
DR GeneID; 38176; -.
DR KEGG; dme:Dmel_CG12090; -.
DR UCSC; CG12090-RA; d. melanogaster. [Q9W0E3-1]
DR CTD; 38176; -.
DR FlyBase; FBgn0035227; Iml1.
DR VEuPathDB; VectorBase:FBgn0035227; -.
DR eggNOG; KOG3572; Eukaryota.
DR GeneTree; ENSGT00390000016559; -.
DR InParanoid; Q9W0E3; -.
DR OrthoDB; 45642at2759; -.
DR PhylomeDB; Q9W0E3; -.
DR BioGRID-ORCS; 38176; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 38176; -.
DR PRO; PR:Q9W0E3; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0035227; Expressed in insect adult head and 24 other tissues.
DR ExpressionAtlas; Q9W0E3; baseline and differential.
DR Genevisible; Q9W0E3; DM.
DR GO; GO:1990130; C:GATOR1 complex; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0035859; C:Seh1-associated complex; IDA:FlyBase.
DR GO; GO:0005096; F:GTPase activator activity; ISS:FlyBase.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB.
DR GO; GO:0048142; P:germarium-derived cystoblast division; IMP:FlyBase.
DR GO; GO:0051729; P:germline cell cycle switching, mitotic to meiotic cell cycle; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0045792; P:negative regulation of cell size; IMP:UniProtKB.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:FlyBase.
DR GO; GO:0010508; P:positive regulation of autophagy; IBA:GO_Central.
DR InterPro; IPR045838; DEPDC5_CTD.
DR InterPro; IPR027244; IML1.
DR PANTHER; PTHR13179; PTHR13179; 2.
DR Pfam; PF19418; DEPDC5_CTD; 1.
DR Pfam; PF12257; IML1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Meiosis; Mitosis;
KW Reference proteome.
FT CHAIN 1..1544
FT /note="GATOR complex protein Iml1"
FT /id="PRO_0000447024"
FT REGION 615..649
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1037..1072
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 616..645
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1037..1061
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 723..763
FT /note="Missing (in isoform B)"
FT /id="VSP_060140"
FT VAR_SEQ 1021..1072
FT /note="YLASLLQDSPIAHITKRRHSTSIISRPQPNQGLTNSPFRERVGSNRLPEKRP
FT -> QHDTPRITEKHHNQLNSPLQ (in isoform B)"
FT /id="VSP_060141"
FT CONFLICT Q9W0E3-2:980..981
FT /note="QH -> H (in Ref. 4; ADX35927)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1544 AA; 176732 MW; DD95525E5DB137A2 CRC64;
MKLYKLNTHT RGCNKSYDAD LVMNLKDHPN ANVGDVVEIY APDEENGTHL LLQITEFNGS
CGRDVISIES GIANAFKMRP YSNVVMRIVK PADVALDSIE ITFKDQYMGR SEMWRLKTYL
TDTCVYVNKK IDYNDMQIRC QVYEMWSQGE RVASGVITED TKIVFRSSTS MVYLFLQMSS
EMWDFDIHGD LYFEKAVNGF LTELFQKWRK LSCNHEVTIV LFSRTFYAAK SLDEFPEHMR
DCLQQDYKGR FYEDFYRVAI QNERCDDWCT VLGQLRKLFT SYQATVLRYH ERENMKIPPA
TNSSATQGNF LEVLNISLNT FEKHYLDRTF DRTGQLSVVI TPGVGVFSVD RELTNITKQR
IIDNGVGSDL VCVGEQPLHA VPLLKFHNKD TTLTSADDYS LPHWINLSFY STNKKIVYSS
FIPRIKLPLF GSQLTLHDGV GDGEGEENER HFLSCNQSEY KHNSLFDYDA YDEQIFQPLP
AQSTCSLQRV VRAKKTSVPS LETYAYRNND WENLTPTQIP AMRRKMSDPD IHHGTSAMLA
ALQPDTTNLS ESLASEKNSR RTIVSIAPIV RPGRALINPF DPSQVTIKLT SNRRRWTHIF
PKGPTGVLIQ QHHYQAVPAK PTQAGQQRPL QQTQSNNNND QEDYGCENGE QYDRVSSHSL
LNKSDSSQSF VMGDEPIDFF KRRQNSPMNP QPANVPNLTA TQAKSYLWGA TGEQEWTPAI
TTVKHLRPIV EGEHHHLGSL EALRALDPPP DAEAGGGRGK IIIGVDWKSL TIPACLPITT
DYFPDKRSLN NDYVISDYTL LPDDVNHDYA QSRAVYRKPL STEEVCKEIV SQRLAQGFQL
IVVDEKPPTA SGCSSGSAVQ PVKLSRETNK EYLLSIGRIF HKISLSGSVI TVTGYRPRHP
YPPINVDYRY RFHAPQHETY EISGVNFTTE KLENFNWNHM DLYICTRGDV DYPLMESLKY
WRYRMYLLPR ENIVSKIASC QRCDIFPDVT ADNTREQVED FVRLIEAVSK LKRQYARKAR
YLASLLQDSP IAHITKRRHS TSIISRPQPN QGLTNSPFRE RVGSNRLPEK RPSINVRPKL
ENGRIPRIFP ATDAAAAAGV AARDDQDDGF PVDIKFSPNA TLPEIFEAMK HPVNGVGFFS
QTQSLPSCTF VSYDALMWLK TRLNNGRHPL DLLEAMRKER MICHASGDWK KPVVPGFVFY
YVVQQDKNAK DYAPPLDDYS AFVNEWLEIE FQGCSFLWHD EPVTTPVPNF LRDSPAPQSW
TETSSNKRVY RQSHLEIDVN QKSDRMEWGH VKHHTVLQPR FAFEIVVEWV TSSGPIVADL
IGGWMRKANQ FNFLVSVPAD PMAEPFTKKS DPLRGPIFIP LCTTFLPNGA ALFDEFPEES
RSDRMLFFQE AILGKFGFLP CVLEKKYSVG KDLPKEYQYV HCTGNMFALI RCATNNYQVE
SPILKEANVT RCVYGHTNNT NVPKKVGFLW AWNHMIPNKK WKAQTINNSA DGELFQLKML
KDFREFCSNS DQRLSTFWTQ SQELKRRAQK FEFNNNNTEE NKMK
