ID WDR59_CHICK Reviewed; 973 AA.
AC Q5ZLG9;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 27-MAR-2024, entry version 114.
DE RecName: Full=GATOR2 complex protein WDR59 {ECO:0000305};
GN Name=WDR59 {ECO:0000250|UniProtKB:Q6PJI9};
GN ORFNames=RCJMB04_6d21 {ECO:0000312|EMBL:CAG31424.1};
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=CB; TISSUE=Bursa of Fabricius;
RX PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6;
RA Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P.,
RA Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P.,
RA Hayashizaki Y., Buerstedde J.-M.;
RT "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene
RT function analysis.";
RL Genome Biol. 6:R6.1-R6.9(2005).
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. The GATOR2 complex indirectly activates mTORC1 through the
CC inhibition of the GATOR1 subcomplex. GATOR2 probably acts as an E3
CC ubiquitin-protein ligase toward GATOR1. 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 In the absence of amino acids, GATOR2 is inhibited, activating the
CC GATOR1 complex. {ECO:0000250|UniProtKB:Q6PJI9}.
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. In the presence of abundant
CC amino acids, GATOR2 is released from CASTOR1 and SESN2 and activated.
CC {ECO:0000250|UniProtKB:Q6PJI9}.
CC -!- SUBUNIT: Component of the GATOR2 subcomplex, composed of MIOS, SEC13,
CC SEH1L, WDR24 and WDR59. The GATOR2 complex interacts with CASTOR1 and
CC CASTOR2; 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). Interacts with
CC DDB1-CUL4A/B E3 ligase complexes (By similarity).
CC {ECO:0000250|UniProtKB:Q6PJI9, ECO:0000250|UniProtKB:Q8C0M0}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q6PJI9}.
CC -!- SIMILARITY: Belongs to the WD repeat WDR59 family. {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; AJ719765; CAG31424.1; -; mRNA.
DR RefSeq; NP_001012794.1; NM_001012776.1.
DR AlphaFoldDB; Q5ZLG9; -.
DR SMR; Q5ZLG9; -.
DR STRING; 9031.ENSGALP00000004419; -.
DR PaxDb; 9031-ENSGALP00000004419; -.
DR GeneID; 415688; -.
DR KEGG; gga:415688; -.
DR CTD; 79726; -.
DR VEuPathDB; HostDB:geneid_415688; -.
DR eggNOG; KOG0264; Eukaryota.
DR eggNOG; KOG0309; Eukaryota.
DR HOGENOM; CLU_009370_0_0_1; -.
DR InParanoid; Q5ZLG9; -.
DR PhylomeDB; Q5ZLG9; -.
DR TreeFam; TF314695; -.
DR Reactome; R-GGA-9639288; Amino acids regulate mTORC1.
DR PRO; PR:Q5ZLG9; -.
DR Proteomes; UP000000539; Chromosome 11.
DR Bgee; ENSGALG00000002798; Expressed in testis and 13 other cell types or tissues.
DR GO; GO:0061700; C:GATOR2 complex; ISS:UniProtKB.
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: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; IBA:GO_Central.
DR GO; GO:0031669; P:cellular response to nutrient levels; ISS:UniProtKB.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; ISS:UniProtKB.
DR CDD; cd16692; mRING-H2-C3H3C2_WDR59; 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; 4.
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.
PE 2: Evidence at transcript level;
KW Lysosome; Membrane; Metal-binding; Reference proteome; Repeat; WD repeat;
KW Zinc; Zinc-finger.
FT CHAIN 1..973
FT /note="GATOR2 complex protein WDR59"
FT /id="PRO_0000280723"
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 280..324
FT /note="WD 6"
FT DOMAIN 393..494
FT /note="RWD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00179"
FT ZN_FING 900..920
FT /note="C4-type"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT ZN_FING 921..970
FT /note="RING-type; atypical"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT REGION 346..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 901
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 904
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 913
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 916
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 926
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 937
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 942
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 945
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 948
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 959
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 963
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 965
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
FT BINDING 967
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6PJI9"
SQ SEQUENCE 973 AA; 109882 MW; 52722760595953E0 CRC64;
MAARWSSENV VVEFRDAQAT AMSVDCLGQH AVLSGRRFLY IVNLDAPNEG HRKISRQSKW
DIGAVQWNPH DSYAYYFAAS SNQRVDLYKW KEGNGEVCTS LQGHTRVISD LDWSVFEPDL
LVTSSVDTYI YIWDIKDTRK PTVSLSAVAG ASQVKWNKKN ANCLATSHDG DVRIWDKRKP
STAVEYLAAH LSKIHGLDWH PDNEYTLATS SQDNSVRFWD YRQPRKYLNI LPCQVPVWKA
RYTPFSNGLV TVMVPQLRRE NSLLLWNVFD LNTPVHTFVG HDDVVLEFQW RKQKEGSKDY
QLVTWSRDQT LRMWRIDSQL QRLCANDILD GVDDLIDGIS LLPEPDKALQ PQDSEPQHSS
GHGDEEALKE DFLNDLLVGK KTDQLGLPQT LQQEFSLINV QIRNVNVEMD AVNRSCTVSV
HCGNHRVRML VMFPVQYPNN AAPSFQFINP TSITASMKAK LLKILKDTSL QKVKRNQSCL
EPCLRQLVSW LESVVNQEDS TSSNPYALPN SVTTPLPTFA RVSNAYGSYQ DSNIPFPRTS
GARFCGAGYL VYFTRPMTMH RAVSPTEPTP RSLSALSAYH SGLITPMKIR TETPGNLRLY
SGSPTRSEKE QVSISSFYYK ERKSRRWKSK REGTDANNRP IKAAGKVIIQ DISCLLPVHK
LLGELYILNV NNIQETCQKN AASAMAVGRR DLVQVWSLAM VATDLCLGPK SDPDLEIPWA
QHPFGRQLLE SLLAHYSQLH DVQTLAMLCS VFEAQSRLQG CPNSYGPFPQ RASNLASHSR
YPSFTSSGSC SSMSDPGLGT GGWSIANKDT EQTSTPWCES SPDEFRYSNL MYPDHREREK
DQHEKNKRLL DPANTQQFDD FKKCYGEILY RWGLREKRAE VLKFVSSPPD PHKGIEFGVY
CSHCRSEARG TQCAICKGFT FQCAICHVAV RGSSNFCLTC GHGGHTSHMM EWFRTQEVCP
TGCGCHCLLE STF
//
