ID WDR24_DANRE Reviewed; 779 AA.
AC Q7ZVL2;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 27-MAR-2024, entry version 112.
DE RecName: Full=GATOR2 complex protein WDR24 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q96S15};
GN Name=wdr24 {ECO:0000250|UniProtKB:Q96S15};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB; TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalytic component of the GATOR2 complex, a multiprotein
CC complex that acts as an activator of the amino acid-sensing branch of
CC the mTORC1 signaling pathway. The GATOR2 complex indirectly activates
CC mTORC1 through the inhibition of the GATOR1 subcomplex. GATOR2 probably
CC acts as an E3 ubiquitin-protein ligase toward GATOR1. In the presence
CC of abundant amino acids, the GATOR2 complex mediates ubiquitination of
CC the NPRL2 core component of the GATOR1 complex, leading to GATOR1
CC inactivation. In the absence of amino acids, GATOR2 is inhibited,
CC activating the GATOR1 complex. In addition to its role in regulation of
CC the mTORC1 complex, promotes the acidification of lysosomes and
CC facilitates autophagic flux. Within the GATOR2 complex, WDR24
CC constitutes the catalytic subunit that mediates 'Lys-6'-linked
CC ubiquitination of NPRL2. {ECO:0000250|UniProtKB:Q96S15}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q96S15};
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:Q96S15}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q96S15}.
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. {ECO:0000250|UniProtKB:Q96S15}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q96S15}.
CC -!- SIMILARITY: Belongs to the WD repeat WDR24 family. {ECO:0000305}.
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DR EMBL; BC045501; AAH45501.1; -; mRNA.
DR RefSeq; NP_998228.1; NM_213063.1.
DR AlphaFoldDB; Q7ZVL2; -.
DR SMR; Q7ZVL2; -.
DR STRING; 7955.ENSDARP00000008451; -.
DR PaxDb; 7955-ENSDARP00000008451; -.
DR GeneID; 406336; -.
DR KEGG; dre:406336; -.
DR AGR; ZFIN:ZDB-GENE-040426-2012; -.
DR CTD; 84219; -.
DR ZFIN; ZDB-GENE-040426-2012; wdr24.
DR eggNOG; KOG0269; Eukaryota.
DR InParanoid; Q7ZVL2; -.
DR OrthoDB; 119005at2759; -.
DR PhylomeDB; Q7ZVL2; -.
DR Reactome; R-DRE-9639288; Amino acids regulate mTORC1.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q7ZVL2; -.
DR Proteomes; UP000000437; Chromosome 24.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0061700; C:GATOR2 complex; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005774; C:vacuolar membrane; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
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:0016239; P:positive regulation of macroautophagy; IBA:GO_Central.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; ISS:UniProtKB.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; ISS:UniProtKB.
DR CDD; cd16693; mRING-H2-C3H3C2_WDR24; 1.
DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
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; IPR037590; WDR24.
DR PANTHER; PTHR46200; GATOR COMPLEX PROTEIN WDR24; 1.
DR PANTHER; PTHR46200:SF1; GATOR COMPLEX PROTEIN WDR24; 1.
DR Pfam; PF00400; WD40; 3.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; WD40 repeat-like; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 3.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 2: Evidence at transcript level;
KW Autophagy; Lysosome; Membrane; Metal-binding; Reference proteome; Repeat;
KW Transferase; Ubl conjugation pathway; WD repeat; Zinc; Zinc-finger.
FT CHAIN 1..779
FT /note="GATOR2 complex protein WDR24"
FT /id="PRO_0000051378"
FT REPEAT 66..106
FT /note="WD 1"
FT REPEAT 112..152
FT /note="WD 2"
FT REPEAT 155..195
FT /note="WD 3"
FT REPEAT 199..239
FT /note="WD 4"
FT REPEAT 243..285
FT /note="WD 5"
FT REPEAT 289..332
FT /note="WD 6"
FT ZN_FING 707..729
FT /note="C4-type"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT ZN_FING 730..779
FT /note="RING-type; atypical"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT REGION 506..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 570..590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 708
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 711
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 722
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 725
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 732
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 735
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 746
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 749
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 751
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 754
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 757
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 768
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 772
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 774
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
FT BINDING 776
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q96S15"
SQ SEQUENCE 779 AA; 88855 MW; B9080162017638D8 CRC64;
MEKMTRVSTI NGRTMFCHLD APANAISVCR DATQVVVAGR NIFKIYGLEE DGFVERLNLR
VGRKPSLNFS CADVMWHQME ENLLATAATN GAVVTWNLSR PCRNKQEQLF TEHKRTVNKV
CFHPTEVNML LSGSQDGFMK CFDLRKKESV STFSGQSESV RDVQFSMKDY FTFAASFENG
NVQLWDIRRP DRYERMFTAH TGPVFCCDWH PEDRGWLATG GRDKMVKVWD MSTNRVKEIY
CVQTFASVAR VKWRPERRYH LATCSMMVDH NIYVWDVRRP FIPFATFEEH KDVTTGIVWR
HQHDPYFLLS GSKDSTLYQH MFKDASRPVD RANPEGLCFG LFGDLAFAAK ESLMSAPASA
GDVGRKTYPG GDRRYPIFFF KKPDVTEQFA QVSSALSVFE SEADSSAGMD WFINTAQSYL
LSGKPFAELC EHNAHVAKSL NRPQESTTWT MLRIMFSEPA NPSLSTNHNL NKSGNLPLVN
SFSMKEMSGA LNERNKENRQ DNIHSLETNL NNNDENEETE GSEGQAEYLF VDDELDDDEL
YSMEHDNQPA EESEYLLPQE AFPLRHEIMD HPSAPEPLQE KQESPHVSGS EAESMCLTPM
ESFSLISVSQ QLFSPHLPPK FFCPIVKEML CYYAEQGDVQ MAVSVLIVLG DRIRKEIDEL
MQEHWYMSYI DLLQRFELWN VSNEVIKLST CGAIMCLNQA STTLHINCSN CKRPMSNKGW
ICDRCHQCAS VCAVCHHVVK GLFVWCQGCS HGGHLEHVME WLKQSKHCPA GCGHLCEYT
//
