WDR24_HUMAN
ID WDR24_HUMAN Reviewed; 790 AA.
AC Q96S15; A2IDB8; D3DU59; Q96GC7; Q9H0B7;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=GATOR complex protein WDR24 {ECO:0000305};
DE AltName: Full=WD repeat-containing protein 24 {ECO:0000312|HGNC:HGNC:20852};
GN Name=WDR24 {ECO:0000312|HGNC:HGNC:20852};
GN Synonyms=C16orf21 {ECO:0000312|HGNC:HGNC:20852};
GN ORFNames=JFP7 {ECO:0000312|EMBL:AAK61244.1};
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 [GENOMIC DNA].
RX PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C.,
RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.;
RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of
RT the short arm of human chromosome 16.";
RL Hum. Mol. Genet. 10:339-352(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Lung;
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-594, AND IDENTIFICATION BY
RP 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-470; SER-496 AND THR-581, 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 [8]
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 [9]
RP 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 [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-470 AND SER-496, AND
RP IDENTIFICATION BY 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 [12]
RP 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 [13]
RP FUNCTION.
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 [14]
RP FUNCTION, AND INTERACTION WITH SESN2.
RX PubMed=26449471; DOI=10.1126/science.aab2674;
RA Wolfson R.L., Chantranupong L., Saxton R.A., Shen K., Scaria S.M.,
RA Cantor J.R., Sabatini D.M.;
RT "Sestrin2 is a leucine sensor for the mTORC1 pathway.";
RL Science 351:43-48(2016).
RN [15]
RP FUNCTION, AND INTERACTION WITH SESN2.
RX PubMed=26586190; DOI=10.1126/science.aad2087;
RA Saxton R.A., Knockenhauer K.E., Wolfson R.L., Chantranupong L.,
RA Pacold M.E., Wang T., Schwartz T.U., Sabatini D.M.;
RT "Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway.";
RL Science 351:53-58(2016).
RN [16]
RP FUNCTION.
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).
RN [17]
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).
CC -!- FUNCTION: As a component of the GATOR subcomplex GATOR2, functions
CC within the amino acid-sensing branch of the TORC1 signaling pathway
CC (PubMed:23723238, PubMed:27166823). Indirectly activates mTORC1 and the
CC TORC1 signaling pathway through the inhibition of the GATOR1 subcomplex
CC (PubMed:23723238). It is negatively regulated by the upstream amino
CC acid sensors SESN2 and CASTOR1 (PubMed:26449471, PubMed:26586190,
CC PubMed:27487210). In addition to its role in regulation of the TORC1
CC complex, promotes the acidification of lysosomes and facilitates
CC autophagic flux (PubMed:27166823). {ECO:0000269|PubMed:23723238,
CC ECO:0000269|PubMed:26449471, ECO:0000269|PubMed:26586190,
CC ECO:0000269|PubMed:27166823, ECO:0000269|PubMed:27487210}.
CC -!- SUBUNIT: Within the GATOR complex, component of the GATOR2 subcomplex,
CC made of MIOS, SEC13, SEH1L, WDR24 and WDR59. The GATOR complex strongly
CC interacts with RRAGA/RRAGC and RRAGB/RRAGC heterodimers
CC (PubMed:23723238). The GATOR2 complex interacts with CASTOR2 and
CC CASTOR1; 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, PubMed:26449471, PubMed:26586190).
CC {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25263562,
CC ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:26449471,
CC ECO:0000269|PubMed:26586190, ECO:0000269|PubMed:26972053}.
CC -!- INTERACTION:
CC Q96S15; Q92624: APPBP2; NbExp=4; IntAct=EBI-746424, EBI-743771;
CC Q96S15; Q9NXC5: MIOS; NbExp=15; IntAct=EBI-746424, EBI-2515122;
CC Q96S15; P58004: SESN2; NbExp=17; IntAct=EBI-746424, EBI-3939642;
CC Q96S15; P58005: SESN3; NbExp=3; IntAct=EBI-746424, EBI-16179942;
CC Q96S15; Q5T011: SZT2; NbExp=5; IntAct=EBI-746424, EBI-10749411;
CC Q96S15; Q6PJI9: WDR59; NbExp=8; IntAct=EBI-746424, EBI-2515073;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:28199306}.
CC -!- SIMILARITY: Belongs to the WD repeat WDR24 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK61244.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AE006464; AAK61244.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL136863; CAB66797.1; -; mRNA.
DR EMBL; Z92544; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85752.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85753.1; -; Genomic_DNA.
DR EMBL; BC008025; AAH08025.1; -; mRNA.
DR EMBL; BC009761; AAH09761.2; -; mRNA.
DR CCDS; CCDS10420.1; -.
DR RefSeq; NP_115635.1; NM_032259.3.
DR AlphaFoldDB; Q96S15; -.
DR SMR; Q96S15; -.
DR BioGRID; 123953; 37.
DR ComplexPortal; CPX-6227; GATOR2 complex.
DR CORUM; Q96S15; -.
DR DIP; DIP-53812N; -.
DR IntAct; Q96S15; 22.
DR MINT; Q96S15; -.
DR STRING; 9606.ENSP00000293883; -.
DR iPTMnet; Q96S15; -.
DR PhosphoSitePlus; Q96S15; -.
DR SwissPalm; Q96S15; -.
DR BioMuta; WDR24; -.
DR DMDM; 74762692; -.
DR EPD; Q96S15; -.
DR jPOST; Q96S15; -.
DR MassIVE; Q96S15; -.
DR MaxQB; Q96S15; -.
DR PaxDb; Q96S15; -.
DR PeptideAtlas; Q96S15; -.
DR PRIDE; Q96S15; -.
DR Antibodypedia; 42379; 47 antibodies from 18 providers.
DR DNASU; 84219; -.
DR Ensembl; ENST00000293883.9; ENSP00000293883.4; ENSG00000127580.17.
DR GeneID; 84219; -.
DR KEGG; hsa:84219; -.
DR MANE-Select; ENST00000293883.9; ENSP00000293883.4; NM_032259.4; NP_115635.1.
DR UCSC; uc002ciz.2; human.
DR CTD; 84219; -.
DR GeneCards; WDR24; -.
DR HGNC; HGNC:20852; WDR24.
DR HPA; ENSG00000127580; Low tissue specificity.
DR neXtProt; NX_Q96S15; -.
DR OpenTargets; ENSG00000127580; -.
DR PharmGKB; PA134918496; -.
DR VEuPathDB; HostDB:ENSG00000127580; -.
DR eggNOG; KOG0269; Eukaryota.
DR GeneTree; ENSGT00940000159396; -.
DR HOGENOM; CLU_010233_0_0_1; -.
DR InParanoid; Q96S15; -.
DR OMA; QDGTMKC; -.
DR OrthoDB; 590848at2759; -.
DR PhylomeDB; Q96S15; -.
DR TreeFam; TF314190; -.
DR PathwayCommons; Q96S15; -.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SignaLink; Q96S15; -.
DR SIGNOR; Q96S15; -.
DR BioGRID-ORCS; 84219; 472 hits in 1092 CRISPR screens.
DR GeneWiki; WDR24; -.
DR GenomeRNAi; 84219; -.
DR Pharos; Q96S15; Tdark.
DR PRO; PR:Q96S15; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q96S15; protein.
DR Bgee; ENSG00000127580; Expressed in right uterine tube and 99 other tissues.
DR ExpressionAtlas; Q96S15; baseline and differential.
DR Genevisible; Q96S15; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0061700; C:GATOR2 complex; IDA:SGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005774; C:vacuolar membrane; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IC:ComplexPortal.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IBA:GO_Central.
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 GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
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; 1.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 3.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 2.
PE 1: Evidence at protein level;
KW Autophagy; Lysosome; Membrane; Phosphoprotein; Reference proteome; Repeat;
KW WD repeat.
FT CHAIN 1..790
FT /note="GATOR complex protein WDR24"
FT /id="PRO_0000051375"
FT REPEAT 72..112
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 118..158
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 161..201
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 205..245
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 249..291
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 295..338
FT /note="WD 6"
FT /evidence="ECO:0000255"
FT MOD_RES 470
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 581
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 594
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 598
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFJ9"
SQ SEQUENCE 790 AA; 88207 MW; 6C109240F6251898 CRC64;
MEKMSRVTTA LGGSVLTGRT MHCHLDAPAN AISVCRDAAQ VVVAGRSIFK IYAIEEEQFV
EKLNLRVGRK PSLNLSCADV VWHQMDENLL ATAATNGVVV TWNLGRPSRN KQDQLFTEHK
RTVNKVCFHP TEAHVLLSGS QDGFMKCFDL RRKDSVSTFS GQSESVRDVQ FSIRDYFTFA
STFENGNVQL WDIRRPDRCE RMFTAHNGPV FCCDWHPEDR GWLATGGRDK MVKVWDMTTH
RAKEMHCVQT IASVARVKWR PECRHHLATC SMMVDHNIYV WDVRRPFVPA AMFEEHRDVT
TGIAWRHPHD PSFLLSGSKD SSLCQHLFRD ASQPVERANP EGLCYGLFGD LAFAAKESLV
AAESGRKPYT GDRRHPIFFK RKLDPAEPFA GLASSALSVF ETEPGGGGMR WFVDTAERYA
LAGRPLAELC DHNAKVAREL GRNQVAQTWT MLRIIYCSPG LVPTANLNHS VGKGGSCGLP
LMNSFNLKDM APGLGSETRL DRSKGDARSD TVLLDSSATL ITNEDNEETE GSDVPADYLL
GDVEGEEDEL YLLDPEHAHP EDPECVLPQE AFPLRHEIVD TPPGPEHLQD KADSPHVSGS
EADVASLAPV DSSFSLLSVS HALYDSRLPP DFFGVLVRDM LHFYAEQGDV QMAVSVLIVL
GERVRKDIDE QTQEHWYTSY IDLLQRFRLW NVSNEVVKLS TSRAVSCLNQ ASTTLHVNCS
HCKRPMSSRG WVCDRCHRCA SMCAVCHHVV KGLFVWCQGC SHGGHLQHIM KWLEGSSHCP
AGCGHLCEYS
