ID WDR59_HUMAN Reviewed; 974 AA. AC Q6PJI9; B3KRC3; Q71RE7; Q96PW5; Q9BSW6; Q9HA43; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-2007, sequence version 2. DT 27-MAR-2024, entry version 169. DE RecName: Full=GATOR2 complex protein WDR59 {ECO:0000305}; DE AltName: Full=WD repeat-containing protein 59 {ECO:0000312|HGNC:HGNC:25706}; GN Name=WDR59 {ECO:0000303|PubMed:35831510, ECO:0000303|PubMed:36528027, GN ECO:0000312|HGNC:HGNC:25706}; GN Synonyms=KIAA1923 {ECO:0000303|PubMed:11572484}; GN ORFNames=FP977 {ECO:0000312|EMBL:AAQ15226.1}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). RC TISSUE=Mammary gland; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 170-974 (ISOFORM 1). RC TISSUE=Lung, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 143-974 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=11572484; DOI=10.1093/dnares/8.4.179; RA Nagase T., Kikuno R., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XXI. The RT complete sequences of 60 new cDNA clones from brain which code for large RT proteins."; RL DNA Res. 8:179-187(2001). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-821 AND SER-822, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-564; SER-822 AND SER-830, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [10] RP INTERACTION WITH SESN1; SESN2 AND SESN3. RX PubMed=25263562; DOI=10.1016/j.celrep.2014.09.014; RA Chantranupong L., Wolfson R.L., Orozco J.M., Saxton R.A., Scaria S.M., RA Bar-Peled L., Spooner E., Isasa M., Gygi S.P., Sabatini D.M.; RT "The Sestrins interact with GATOR2 to negatively regulate the amino-acid- RT sensing pathway upstream of mTORC1."; RL Cell Rep. 9:1-8(2014). RN [11] RP FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH SESN2. RX PubMed=25457612; DOI=10.1016/j.celrep.2014.10.019; RA Parmigiani A., Nourbakhsh A., Ding B., Wang W., Kim Y.C., Akopiants K., RA Guan K.L., Karin M., Budanov A.V.; RT "Sestrins inhibit mTORC1 kinase activation through the GATOR complex."; RL Cell Rep. 9:1281-1291(2014). RN [12] RP FUNCTION, IDENTIFICATION IN GATOR COMPLEX, AND SUBUNIT. 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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-564, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP ACTIVITY REGULATION, AND INTERACTION WITH CASTOR2 AND CASTOR1. RX PubMed=26972053; DOI=10.1016/j.cell.2016.02.035; RA Chantranupong L., Scaria S.M., Saxton R.A., Gygi M.P., Shen K., Wyant G.A., RA Wang T., Harper J.W., Gygi S.P., Sabatini D.M.; RT "The CASTOR proteins are arginine sensors for the mTORC1 pathway."; RL Cell 165:153-164(2016). RN [15] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=27487210; DOI=10.1038/nature19079; RA Saxton R.A., Chantranupong L., Knockenhauer K.E., Schwartz T.U., RA Sabatini D.M.; RT "Mechanism of arginine sensing by CASTOR1 upstream of mTORC1."; RL Nature 536:229-233(2016). RN [16] RP SUBCELLULAR LOCATION. RX PubMed=28199306; DOI=10.1038/nature21423; RA Wolfson R.L., Chantranupong L., Wyant G.A., Gu X., Orozco J.M., Shen K., RA Condon K.J., Petri S., Kedir J., Scaria S.M., Abu-Remaileh M., RA Frankel W.N., Sabatini D.M.; RT "KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to RT regulate mTORC1."; RL Nature 543:438-442(2017). RN [17] RP FUNCTION, IDENTIFICATION IN GATOR2 COMPLEX, AND MUTAGENESIS OF RP 924-CYS--CYS-927. RX PubMed=36528027; DOI=10.1016/j.molcel.2022.11.021; RA Jiang C., Dai X., He S., Zhou H., Fang L., Guo J., Liu S., Zhang T., RA Pan W., Yu H., Fu T., Li D., Inuzuka H., Wang P., Xiao J., Wei W.; RT "Ring domains are essential for GATOR2-dependent mTORC1 activation."; RL Mol. Cell 83:74-89(2023). RN [18] RP FUNCTION. RX PubMed=36577058; DOI=10.1073/pnas.2212330120; RA Zhang Y., Ting C.Y., Yang S., Reich J., Fru K., Lilly M.A.; RT "Wdr59 promotes or inhibits TORC1 activity depending on cellular context."; RL Proc. Natl. Acad. Sci. U.S.A. 120:e2212330120-e2212330120(2023). RN [19] {ECO:0007744|PDB:7UHY} RP STRUCTURE BY ELECTRON MICROSCOPY (3.66 ANGSTROMS) IN COMPLEX WITH ZINC; RP WDR24; SEC13; MIOS AND SEH1L, FUNCTION, IDENTIFICATION IN GATOR2 COMPLEX, RP AND MUTAGENESIS OF LEU-698 AND 728-LEU--LEU-732. RX PubMed=35831510; DOI=10.1038/s41586-022-04939-z; RA Valenstein M.L., Rogala K.B., Lalgudi P.V., Brignole E.J., Gu X., RA Saxton R.A., Chantranupong L., Kolibius J., Quast J.P., Sabatini D.M.; RT "Structure of the nutrient-sensing hub GATOR2."; RL Nature 607:610-616(2022). CC -!- FUNCTION: As a component of the GATOR2 complex, functions as an CC activator of the amino acid-sensing branch of the mTORC1 signaling CC pathway (PubMed:25457612, PubMed:23723238, PubMed:27487210, CC PubMed:36528027, PubMed:36577058, PubMed:35831510). The GATOR2 complex CC indirectly activates mTORC1 through the inhibition of the GATOR1 CC subcomplex (PubMed:23723238, PubMed:27487210, PubMed:36528027, CC PubMed:35831510). GATOR2 probably acts as an E3 ubiquitin-protein CC ligase toward GATOR1 (PubMed:36528027). In the presence of abundant CC amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 CC core component of the GATOR1 complex, leading to GATOR1 inactivation CC (PubMed:36528027). In the absence of amino acids, GATOR2 is inhibited, CC activating the GATOR1 complex (PubMed:25457612, PubMed:27487210). CC {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25457612, CC ECO:0000269|PubMed:27487210, ECO:0000269|PubMed:35831510, CC ECO:0000269|PubMed:36528027, ECO:0000269|PubMed:36577058}. CC -!- ACTIVITY REGULATION: The GATOR2 complex is negatively regulated by the CC upstream amino acid sensors CASTOR1 and SESN2, which sequester the CC GATOR2 complex in absence of amino acids (PubMed:26972053, CC PubMed:25457612, PubMed:27487210). In the presence of abundant amino CC acids, GATOR2 is released from CASTOR1 and SESN2 and activated CC (PubMed:26972053, PubMed:25457612, PubMed:27487210). CC {ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:26972053, CC ECO:0000269|PubMed:27487210}. CC -!- SUBUNIT: Component of the GATOR2 subcomplex, composed of MIOS, SEC13, CC SEH1L, WDR24 and WDR59 (PubMed:23723238, PubMed:36528027, CC PubMed:35831510). The GATOR2 complex interacts with CASTOR1 and CC CASTOR2; the interaction is negatively regulated by arginine CC (PubMed:26972053). The GATOR2 complex interacts with SESN1, SESN2 and CC SESN3; the interaction is negatively regulated by amino acids CC (PubMed:25263562, PubMed:25457612). Interacts with DDB1-CUL4A/B E3 CC ligase complexes (By similarity). {ECO:0000250|UniProtKB:Q8C0M0, CC ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25263562, CC ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:26972053, CC ECO:0000269|PubMed:35831510, ECO:0000269|PubMed:36528027}. CC -!- INTERACTION: CC Q6PJI9; Q8WTX7: CASTOR1; NbExp=6; IntAct=EBI-2515073, EBI-10276168; CC Q6PJI9; A6NHX0: CASTOR2; NbExp=6; IntAct=EBI-2515073, EBI-11102839; CC Q6PJI9; Q96S15: WDR24; NbExp=8; IntAct=EBI-2515073, EBI-746424; CC Q6PJI9; P62258: YWHAE; NbExp=2; IntAct=EBI-2515073, EBI-356498; CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:28199306}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q6PJI9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6PJI9-2; Sequence=VSP_023884; CC Name=3; CC IsoId=Q6PJI9-3; Sequence=VSP_023882; CC Name=4; CC IsoId=Q6PJI9-4; Sequence=VSP_023881, VSP_023883; CC -!- SIMILARITY: Belongs to the WD repeat WDR59 family. {ECO:0000305}. CC -!- CAUTION: The E3 ubiquitin-protein ligase activity of the GATOR2 complex CC is subject to discussion (PubMed:35831510, PubMed:36528027). According CC to a report, the GATOR2 complex does not catalyze ubiquitination of the CC GATOR1 complex (PubMed:35831510). In contrast, another publication CC showed that the GATOR2 complex mediates ubiquitination of the NPRL2 CC core component of the GATOR1 complex, leading to GATOR1 inactivation CC (PubMed:36528027). {ECO:0000269|PubMed:35831510, CC ECO:0000269|PubMed:36528027}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB67816.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK022332; BAB14015.1; -; mRNA. DR EMBL; AK091316; BAG52335.1; -; mRNA. DR EMBL; AF370390; AAQ15226.1; -; mRNA. DR EMBL; BC004519; AAH04519.1; -; mRNA. DR EMBL; BC014887; AAH14887.2; -; mRNA. DR EMBL; AB067510; BAB67816.1; ALT_FRAME; mRNA. DR CCDS; CCDS32488.1; -. [Q6PJI9-1] DR CCDS; CCDS82011.1; -. [Q6PJI9-2] DR RefSeq; NP_001311100.1; NM_001324171.1. [Q6PJI9-2] DR RefSeq; NP_085058.3; NM_030581.3. [Q6PJI9-1] DR PDB; 7UHY; EM; 3.66 A; D=1-974. DR PDBsum; 7UHY; -. DR AlphaFoldDB; Q6PJI9; -. DR EMDB; EMD-26519; -. DR SMR; Q6PJI9; -. DR BioGRID; 122841; 127. DR ComplexPortal; CPX-6227; GATOR2 complex. DR CORUM; Q6PJI9; -. DR IntAct; Q6PJI9; 47. DR MINT; Q6PJI9; -. DR STRING; 9606.ENSP00000262144; -. DR iPTMnet; Q6PJI9; -. DR PhosphoSitePlus; Q6PJI9; -. DR BioMuta; WDR59; -. DR DMDM; 134035358; -. DR EPD; Q6PJI9; -. DR jPOST; Q6PJI9; -. DR MassIVE; Q6PJI9; -. DR MaxQB; Q6PJI9; -. DR PaxDb; 9606-ENSP00000262144; -. DR PeptideAtlas; Q6PJI9; -. DR ProteomicsDB; 67210; -. [Q6PJI9-1] DR ProteomicsDB; 67211; -. [Q6PJI9-2] DR ProteomicsDB; 67212; -. [Q6PJI9-3] DR ProteomicsDB; 67213; -. [Q6PJI9-4] DR Pumba; Q6PJI9; -. DR Antibodypedia; 48159; 55 antibodies from 16 providers. DR DNASU; 79726; -. DR Ensembl; ENST00000262144.11; ENSP00000262144.6; ENSG00000103091.15. [Q6PJI9-1] DR Ensembl; ENST00000616369.4; ENSP00000482446.1; ENSG00000103091.15. [Q6PJI9-2] DR GeneID; 79726; -. DR KEGG; hsa:79726; -. DR MANE-Select; ENST00000262144.11; ENSP00000262144.6; NM_030581.4; NP_085058.3. DR UCSC; uc002fdh.2; human. [Q6PJI9-1] DR AGR; HGNC:25706; -. DR CTD; 79726; -. DR DisGeNET; 79726; -. DR GeneCards; WDR59; -. DR HGNC; HGNC:25706; WDR59. DR HPA; ENSG00000103091; Low tissue specificity. DR MIM; 617418; gene. DR neXtProt; NX_Q6PJI9; -. DR OpenTargets; ENSG00000103091; -. DR PharmGKB; PA142670593; -. DR VEuPathDB; HostDB:ENSG00000103091; -. DR eggNOG; KOG0264; Eukaryota. DR eggNOG; KOG0309; Eukaryota. DR GeneTree; ENSGT00940000157600; -. DR HOGENOM; CLU_009370_0_0_1; -. DR InParanoid; Q6PJI9; -. DR OMA; HRRETCL; -. DR OrthoDB; 23438at2759; -. DR PhylomeDB; Q6PJI9; -. DR TreeFam; TF314695; -. DR PathwayCommons; Q6PJI9; -. DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1. DR SignaLink; Q6PJI9; -. DR SIGNOR; Q6PJI9; -. DR BioGRID-ORCS; 79726; 131 hits in 1170 CRISPR screens. DR ChiTaRS; WDR59; human. DR GenomeRNAi; 79726; -. DR Pharos; Q6PJI9; Tdark. DR PRO; PR:Q6PJI9; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q6PJI9; Protein. DR Bgee; ENSG00000103091; Expressed in right lobe of thyroid gland and 196 other cell types or tissues. DR ExpressionAtlas; Q6PJI9; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0061700; C:GATOR2 complex; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0035859; C:Seh1-associated complex; IBA:GO_Central. DR GO; GO:0005774; C:vacuolar membrane; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. 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:0031669; P:cellular response to nutrient levels; IDA:UniProtKB. DR GO; GO:1904262; P:negative regulation of TORC1 signaling; NAS:ComplexPortal. DR GO; GO:0032008; P:positive regulation of TOR signaling; IMP:SGD. DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IDA:UniProtKB. DR CDD; cd16692; mRING-H2-C3H3C2_WDR59; 1. DR Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 2. DR InterPro; IPR006575; RWD_dom. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR InterPro; IPR049567; WDR59-like. DR InterPro; IPR039456; WDR59_mRING-H2-C3H3C2. DR InterPro; IPR049566; WDR59_RTC1-like_RING_Znf. DR PANTHER; PTHR46170; GATOR COMPLEX PROTEIN WDR59; 1. DR PANTHER; PTHR46170:SF1; GATOR COMPLEX PROTEIN WDR59; 1. DR Pfam; PF00400; WD40; 2. DR Pfam; PF17120; zf-RING_16; 1. DR SMART; SM00591; RWD; 1. DR SMART; SM00320; WD40; 5. DR SUPFAM; SSF54495; UBC-like; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS50908; RWD; 1. DR PROSITE; PS00678; WD_REPEATS_1; 1. DR PROSITE; PS50082; WD_REPEATS_2; 2. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR Genevisible; Q6PJI9; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Lysosome; Membrane; Metal-binding; KW Phosphoprotein; Reference proteome; Repeat; WD repeat; Zinc; Zinc-finger. FT CHAIN 1..974 FT /note="GATOR2 complex protein WDR59" FT /id="PRO_0000280721" FT REPEAT 57..98 FT /note="WD 1" FT REPEAT 103..143 FT /note="WD 2" FT REPEAT 146..185 FT /note="WD 3" FT REPEAT 189..229 FT /note="WD 4" FT REPEAT 232..276 FT /note="WD 5" FT REPEAT 278..318 FT /note="WD 6" FT REPEAT 319..362 FT /note="WD 7" FT DOMAIN 393..494 FT /note="RWD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00179" FT REPEAT 668..706 FT /note="WD 8" FT ZN_FING 901..920 FT /note="C4-type" FT /evidence="ECO:0000305|PubMed:35831510" FT ZN_FING 921..973 FT /note="RING-type; atypical" FT /evidence="ECO:0000305|PubMed:35831510" FT REGION 350..374 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 831..852 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 831..851 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 902 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 905 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 914 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 917 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 927 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 938 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 943 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 946 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 949 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 960 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 964 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 966 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT BINDING 968 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:35831510, FT ECO:0007744|PDB:7UHY" FT MOD_RES 564 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 821 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 822 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 830 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..556 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_023881" FT VAR_SEQ 1..408 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15498874" FT /id="VSP_023882" FT VAR_SEQ 557..571 FT /note="MTMHRAVSPTEPTPR -> MTGLQPVWIIIIFNYR (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_023883" FT VAR_SEQ 572..974 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023884" FT VARIANT 201 FT /note="P -> T (in dbSNP:rs11557260)" FT /id="VAR_053436" FT MUTAGEN 698 FT /note="L->E: Abolished interaction with WDR24 and assembly FT of the GATOR2 complex; when associated with 728-E--E-732." FT /evidence="ECO:0000269|PubMed:35831510" FT MUTAGEN 728..732 FT /note="LLESL->ELESE: Abolished interaction with WDR24 and FT assembly of the GATOR2 complex; when associated with FT E-698." FT /evidence="ECO:0000269|PubMed:35831510" FT MUTAGEN 924..927 FT /note="CAIC->AAIA: Impaired amino-acid-mediated mTORC1 FT activation." FT /evidence="ECO:0000269|PubMed:36528027" FT CONFLICT 441 FT /note="A -> S (in Ref. 4; BAB67816)" FT /evidence="ECO:0000305" SQ SEQUENCE 974 AA; 109793 MW; 72F651A38EA51CBA CRC64; MAARWSSENV VVEFRDSQAT AMSVDCLGQH AVLSGRRFLY IVNLDAPFEG HRKISRQSKW DIGAVQWNPH DSFAHYFAAS SNQRVDLYKW KDGSGEVGTT LQGHTRVISD LDWAVFEPDL LVTSSVDTYI YIWDIKDTRK PTVALSAVAG ASQVKWNKKN ANCLATSHDG DVRIWDKRKP STAVEYLAAH LSKIHGLDWH PDSEHILATS SQDNSVKFWD YRQPRKYLNI LPCQVPVWKA RYTPFSNGLV TVMVPQLRRE NSLLLWNVFD LNTPVHTFVG HDDVVLEFQW RKQKEGSKDY QLVTWSRDQT LRMWRVDSQM QRLCANDILD GVDEFIESIS LLPEPEKTLH TEDTDHQHTA SHGEEEALKE DPPRNLLEER KSDQLGLPQT LQQEFSLINV QIRNVNVEMD AADRSCTVSV HCSNHRVKML VKFPAQYPNN AAPSFQFINP TTITSTMKAK LLKILKDTAL QKVKRGQSCL EPCLRQLVSC LESFVNQEDS ASSNPFALPN SVTPPLPTFA RVTTAYGSYQ DANIPFPRTS GARFCGAGYL VYFTRPMTMH RAVSPTEPTP RSLSALSAYH TGLIAPMKIR TEAPGNLRLY SGSPTRSEKE QVSISSFYYK ERKSRRWKSK REGSDSGNRQ IKAAGKVIIQ DIACLLPVHK SLGELYILNV NDIQETCQKN AASALLVGRK DLVQVWSLAT VATDLCLGPK SDPDLETPWA RHPFGRQLLE SLLAHYCRLR DVQTLAMLCS VFEAQSRPQG LPNPFGPFPN RSSNLVVSHS RYPSFTSSGS CSSMSDPGLN TGGWNIAGRE AEHLSSPWGE SSPEELRFGS LTYSDPRERE RDQHDKNKRL LDPANTQQFD DFKKCYGEIL YRWGLREKRA EVLKFVSCPP DPHKGIEFGV YCSHCRSEVR GTQCAICKGF TFQCAICHVA VRGSSNFCLT CGHGGHTSHM MEWFRTQEVC PTGCGCHCLL ESTF //