WDR59_MOUSE
ID WDR59_MOUSE Reviewed; 992 AA.
AC Q8C0M0; Q3TC49; Q3UWJ3; Q69Z65; Q6NZK7; Q8BLZ2; Q8BWK9;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=GATOR complex protein WDR59 {ECO:0000305};
DE AltName: Full=CUL4- and DDB1-associated WDR protein 12;
DE AltName: Full=WD repeat-containing protein 59 {ECO:0000312|MGI:MGI:2442115};
GN Name=Wdr59 {ECO:0000312|MGI:MGI:2442115};
GN Synonyms=Cdw12 {ECO:0000312|EMBL:ABK41112.1},
GN Kiaa1923 {ECO:0000312|EMBL:BAD32579.1};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH CUL4.
RX PubMed=17041588; DOI=10.1038/ncb1490;
RA Higa L.A., Wu M., Ye T., Kobayashi R., Sun H., Zhang H.;
RT "CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins
RT and regulates histone methylation.";
RL Nat. Cell Biol. 8:1277-1283(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Fetal brain;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Aorta, Head, Heart, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-839 AND SER-840, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Pancreas, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: As a component of the GATOR subcomplex GATOR2, functions
CC within the amino acid-sensing branch of the TORC1 signaling pathway.
CC Indirectly activates mTORC1 and the TORC1 signaling pathway through the
CC inhibition of the GATOR1 subcomplex. It is negatively regulated by the
CC upstream amino acid sensors SESN2 and CASTOR1.
CC {ECO:0000250|UniProtKB:Q6PJI9}.
CC -!- SUBUNIT: Interacts with DDB1-CUL4A/B E3 ligase complexes (By
CC similarity). Within the GATOR complex, component of the GATOR2
CC subcomplex, made of MIOS, SEC13, SEH1L, WDR24 and WDR59. The GATOR
CC complex strongly interacts with RRAGA/RRAGC and RRAGB/RRAGC
CC heterodimers (By similarity). The GATOR2 complex interacts with CASTOR2
CC and CASTOR1; the interaction is negatively regulated by arginine. The
CC GATOR2 complex interacts with SESN1, SESN2 and SESN3; the interaction
CC is negatively regulated by amino acids (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q6PJI9}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q6PJI9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8C0M0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C0M0-2; Sequence=VSP_023886;
CC Name=3;
CC IsoId=Q8C0M0-3; Sequence=VSP_023885, VSP_023886;
CC -!- SIMILARITY: Belongs to the WD repeat WDR59 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC30708.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD32579.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE42108.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; EF011622; ABK41112.1; -; mRNA.
DR EMBL; AK173301; BAD32579.1; ALT_INIT; mRNA.
DR EMBL; AK030644; BAC27062.1; -; mRNA.
DR EMBL; AK040807; BAC30708.1; ALT_INIT; mRNA.
DR EMBL; AK052262; BAC34902.1; -; mRNA.
DR EMBL; AK136303; BAE22922.1; -; mRNA.
DR EMBL; AK170910; BAE42108.1; ALT_SEQ; mRNA.
DR EMBL; BC066082; AAH66082.1; -; mRNA.
DR CCDS; CCDS52672.1; -. [Q8C0M0-3]
DR CCDS; CCDS85613.1; -. [Q8C0M0-2]
DR RefSeq; NP_001164213.1; NM_001170742.1. [Q8C0M0-2]
DR RefSeq; NP_001164214.1; NM_001170743.1. [Q8C0M0-3]
DR RefSeq; NP_795897.2; NM_176923.4.
DR AlphaFoldDB; Q8C0M0; -.
DR SMR; Q8C0M0; -.
DR BioGRID; 235303; 7.
DR STRING; 10090.ENSMUSP00000043671; -.
DR iPTMnet; Q8C0M0; -.
DR PhosphoSitePlus; Q8C0M0; -.
DR EPD; Q8C0M0; -.
DR jPOST; Q8C0M0; -.
DR MaxQB; Q8C0M0; -.
DR PaxDb; Q8C0M0; -.
DR PeptideAtlas; Q8C0M0; -.
DR PRIDE; Q8C0M0; -.
DR ProteomicsDB; 275203; -. [Q8C0M0-1]
DR ProteomicsDB; 275204; -. [Q8C0M0-2]
DR ProteomicsDB; 275205; -. [Q8C0M0-3]
DR Antibodypedia; 48159; 50 antibodies from 16 providers.
DR DNASU; 319481; -.
DR Ensembl; ENSMUST00000034437; ENSMUSP00000034437; ENSMUSG00000031959. [Q8C0M0-3]
DR Ensembl; ENSMUST00000038193; ENSMUSP00000043671; ENSMUSG00000031959. [Q8C0M0-2]
DR GeneID; 319481; -.
DR KEGG; mmu:319481; -.
DR UCSC; uc009nmi.2; mouse. [Q8C0M0-3]
DR UCSC; uc009nmj.2; mouse. [Q8C0M0-2]
DR CTD; 79726; -.
DR MGI; MGI:2442115; Wdr59.
DR VEuPathDB; HostDB:ENSMUSG00000031959; -.
DR eggNOG; KOG0302; Eukaryota.
DR eggNOG; KOG0309; Eukaryota.
DR GeneTree; ENSGT00940000157600; -.
DR InParanoid; Q8C0M0; -.
DR OMA; HDACIPF; -.
DR PhylomeDB; Q8C0M0; -.
DR TreeFam; TF314695; -.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 319481; 9 hits in 73 CRISPR screens.
DR ChiTaRS; Wdr59; mouse.
DR PRO; PR:Q8C0M0; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8C0M0; protein.
DR Bgee; ENSMUSG00000031959; Expressed in embryonic brain and 96 other tissues.
DR ExpressionAtlas; Q8C0M0; baseline and differential.
DR Genevisible; Q8C0M0; MM.
DR GO; GO:0061700; C:GATOR2 complex; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; ISS: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:0035591; F:signaling adaptor activity; IBA:GO_Central.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISO:MGI.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISO:MGI.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IBA:GO_Central.
DR CDD; cd16692; mRING-H2-C3H3C2_WDR59; 1.
DR Gene3D; 2.130.10.10; -; 2.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR006575; RWD-domain.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
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; IPR039456; WDR59_mRING-H2-C3H3C2.
DR Pfam; PF00400; WD40; 3.
DR SMART; SM00591; RWD; 1.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF54495; SSF54495; 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.
PE 1: Evidence at protein level;
KW Alternative splicing; Lysosome; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; WD repeat.
FT CHAIN 1..992
FT /note="GATOR complex protein WDR59"
FT /id="PRO_0000280722"
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 660..706
FT /note="WD 8"
FT REGION 343..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 849..870
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 348..373
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 849..869
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 564
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT MOD_RES 839
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 840
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 848
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT VAR_SEQ 622
FT /note="R -> RMSPRSARRRWSIQAINDFP (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15368895"
FT /id="VSP_023885"
FT VAR_SEQ 733..750
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15368895,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_023886"
FT CONFLICT 154
FT /note="V -> A (in Ref. 3; BAC27062)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="D -> G (in Ref. 3; BAC27062)"
FT /evidence="ECO:0000305"
FT CONFLICT 499
FT /note="D -> E (in Ref. 3; BAE22922)"
FT /evidence="ECO:0000305"
FT CONFLICT 825
FT /note="Missing (in Ref. 3; BAC27062)"
FT /evidence="ECO:0000305"
FT CONFLICT 961
FT /note="H -> L (in Ref. 3; BAC34902)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 992 AA; 111726 MW; FA85E469CE518AFA CRC64;
MAARWSSENV VVEFRDSQAT AMSVDCLGQH AVLSGRRFLY IVNLDAPFEG HRKISRQSKW
DIGAVQWNPH DSFAHYFAAS SNQRVDLYKW KDGSGEVGTT LQGHTRVISD LDWAVFEPDL
LVTSSVDTYI YIWDIKDTRK PTVALSAVAG ASQVKWNKKN ANYLATSHDG DVRIWDKRKP
STAVEYLAAH LSKIHGLDWH PDSEHIFATS SQDNSVKFWD YRQPRKYLNI LPCQVPVWKA
RYTPFSNGLV TVMVPQLRRE NSLLLWNASD LNAPVHTFVG HDDVVLEFQW RRQKEGSKDY
QLVTWSRDQT LRMWRVDYQM QRLCANDILD GVDEFIESIS LLPEPEKTPH PQDIDHQPSL
SHGEEDAIKE DPPSSLLEEK RSDQLGLPQT LQQEFSLINV QIRNVNVEMD AADRSCTVSV
HCSNHRVKML VTFPAQYPNN AAPSFQFINP TTITSAVKAK LLKILKDTSL QKVKRNQSCL
EPCLRQLVSC LESFVNQEDS ASSNPFALQN SVTPPLPTFA RVTTAYGSYQ DANIPFPRTS
GARFCGAGYL VYFTRPMTMH RAVSPTEPTP RSLSALSAYH TGLIAPMKIR TEAPGNLRLY
SGSPTRSEKE QVSISSFYYK ERKSRRWKSK REGSDSGNRP IKAAGKVIIQ DVSCLLPVHK
SLGELYILNV NDTQETCQKN ATSAMLVGRK DLVQVWSLAT VATDLCLGPK SDPDLETPWA
RHPFGRQLLE SLWGDRESTR VCGPPLSGAR LAHYCQLRDV QTLAMLCSVF EAQSRPQGLP
NPFGPFPNRS SNLVVSHSRY PSFTSSGSCS SMSDPGFNTG GWNIAGRETE HISSPWGESS
PEELRFGSLT YSDPRERERD QHDKNKRLLD PANTQQFDDF KKCYGEILYR WGLREKRAEV
LKFVSCPPDP HKGIEFGVYC SHCRSEVRGT QCAICKGFTF QCAICHVAVR GSSNFCLTCG
HGGHTSHMME WFRTQEVCPT GCGCHCLLES TF
