GLD1_CAEEL
ID GLD1_CAEEL Reviewed; 463 AA.
AC Q17339; O02540;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Female germline-specific tumor suppressor gld-1;
DE AltName: Full=Defective in germ line development protein 1;
GN Name=gld-1; ORFNames=T23G11.3;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=Bristol N2;
RX PubMed=7601353; DOI=10.1101/gad.9.12.1491;
RA Jones A.R., Schedl T.;
RT "Mutations in gld-1, a female germ cell-specific tumor suppressor gene in
RT Caenorhabditis elegans, affect a conserved domain also found in Src-
RT associated protein Sam68.";
RL Genes Dev. 9:1491-1504(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP CHARACTERIZATION.
RX PubMed=11562350; DOI=10.1101/gad.915901;
RA Lee M.-H., Schedl T.;
RT "Identification of in vivo mRNA targets of GLD-1, a maxi-KH motif
RT containing protein required for C. elegans germ cell development.";
RL Genes Dev. 15:2408-2420(2001).
RN [4]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=19758560; DOI=10.1016/j.devcel.2009.08.003;
RA Biedermann B., Wright J., Senften M., Kalchhauser I., Sarathy G., Lee M.H.,
RA Ciosk R.;
RT "Translational repression of cyclin E prevents precocious mitosis and
RT embryonic gene activation during C. elegans meiosis.";
RL Dev. Cell 17:355-364(2009).
RN [5]
RP FUNCTION, PHOSPHORYLATION, AND MUTAGENESIS OF SER-22; SER-39 AND THR-348.
RX PubMed=21455289; DOI=10.1371/journal.pgen.1001348;
RA Jeong J., Verheyden J.M., Kimble J.;
RT "Cyclin E and Cdk2 control GLD-1, the mitosis/meiosis decision, and
RT germline stem cells in Caenorhabditis elegans.";
RL PLoS Genet. 7:E1001348-E1001348(2011).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=29168500; DOI=10.1038/nature24620;
RA Bohnert K.A., Kenyon C.;
RT "A lysosomal switch triggers proteostasis renewal in the immortal C.
RT elegans germ lineage.";
RL Nature 551:629-633(2017).
RN [7] {ECO:0007744|PDB:3K6T, ECO:0007744|PDB:3KBL}
RP X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS) OF 144-200, SUBUNIT, DOMAIN, AND
RP MUTAGENESIS OF TYR-149; LEU-150; GLU-156; LEU-160; PHE-163; PRO-164;
RP PHE-167; ASN-169; VAL-170; GLU-177 AND VAL-181.
RX PubMed=20223220; DOI=10.1016/j.str.2009.12.016;
RA Beuck C., Szymczyna B.R., Kerkow D.E., Carmel A.B., Columbus L.,
RA Stanfield R.L., Williamson J.R.;
RT "Structure of the GLD-1 homodimerization domain: insights into STAR
RT protein-mediated translational regulation.";
RL Structure 18:377-389(2010).
RN [8] {ECO:0007744|PDB:4JVY}
RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 144-337 IN COMPLEX WITH RNA,
RP RNA-BINDING, AND DOMAIN.
RX PubMed=23630077; DOI=10.1101/gad.216531.113;
RA Teplova M., Hafner M., Teplov D., Essig K., Tuschl T., Patel D.J.;
RT "Structure-function studies of STAR family Quaking proteins bound to their
RT in vivo RNA target sites.";
RL Genes Dev. 27:928-940(2013).
RN [9] {ECO:0007744|PDB:2MJH}
RP STRUCTURE BY NMR OF 195-336 IN COMPLEX WITH RNA, FUNCTION, RNA-BINDING, AND
RP MUTAGENESIS OF PRO-228; LYS-313; ARG-314; LYS-315 AND LEU-320.
RX PubMed=24838563; DOI=10.1093/nar/gku445;
RA Daubner G.M., Brummer A., Tocchini C., Gerhardy S., Ciosk R., Zavolan M.,
RA Allain F.H.;
RT "Structural and functional implications of the QUA2 domain on RNA
RT recognition by GLD-1.";
RL Nucleic Acids Res. 42:8092-8105(2014).
CC -!- FUNCTION: RNA-binding protein which recognizes the 5'-UACUCAU-3' RNA
CC consensus sequence (PubMed:24838563). Binds sequences in both the
CC 5'coding and the 3'-UTR region of rme-2 mRNA (PubMed:11562350). Binds
CC sequences in the 3'-UTR region of cye-1 mRNA. Binds to cyb-2.1, cyb-2.2
CC and cyb-3 mRNA (PubMed:19758560). Binds sequences in the 3'-UTR region
CC of tra-2 mRNA (PubMed:24838563). Germ line-specific tumor suppressor
CC essential for oogenesis (PubMed:7601353). Controls the spatial pattern
CC of translation of multiple oogenesis specific mRNAs (e.g. yolk receptor
CC rme-2) by repression of translation during early meiotic prophase
CC (leptotene to pachytene) and then derepression of translation during
CC diplotene/ diakinesis, following its degradation. Also functions to
CC promote the male sexual fate in the hermaphrodite germline but not the
CC male germline (PubMed:7601353, PubMed:11562350, PubMed:24838563).
CC Represses translation of the vacuolar ATPase component vha-13 in the
CC distal gonad (PubMed:29168500). Functions redundantly with gld-2 to
CC promote the initiation of meiotic development and/or inhibit stem cell
CC proliferation (PubMed:11562350). By regulating cye-1 expression,
CC prevents entry into mitosis in meiotic germline cells (PubMed:19758560,
CC PubMed:21455289). {ECO:0000269|PubMed:11562350,
CC ECO:0000269|PubMed:19758560, ECO:0000269|PubMed:21455289,
CC ECO:0000269|PubMed:24838563, ECO:0000269|PubMed:29168500,
CC ECO:0000269|PubMed:7601353}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:20223220}.
CC -!- TISSUE SPECIFICITY: Expressed in proximal and distal oocytes in female
CC worms but is eliminated from proximal oocytes following mating.
CC {ECO:0000269|PubMed:29168500}.
CC -!- DOMAIN: The KH domain and the Qua2 region are involved in RNA binding.
CC {ECO:0000269|PubMed:23630077}.
CC -!- PTM: Phosphorylated by cdk-2 which may negatively regulate its
CC expression in distal mitotic germline cells.
CC {ECO:0000269|PubMed:21455289}.
CC -!- PTM: Undergoes proteasomal degradation in proximal oocytes following
CC mating. {ECO:0000269|PubMed:29168500}.
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DR EMBL; U20535; AAC46632.1; -; Genomic_DNA.
DR EMBL; Z81130; CAB03417.1; -; Genomic_DNA.
DR PIR; T25193; T25193.
DR RefSeq; NP_492143.1; NM_059742.6.
DR PDB; 2MJH; NMR; -; A=195-336.
DR PDB; 3K6T; X-ray; 2.04 A; A/B/C/D=144-200.
DR PDB; 3KBL; X-ray; 2.28 A; A/B/C/D=144-200.
DR PDB; 4JVY; X-ray; 2.85 A; A/B=144-337.
DR PDBsum; 2MJH; -.
DR PDBsum; 3K6T; -.
DR PDBsum; 3KBL; -.
DR PDBsum; 4JVY; -.
DR AlphaFoldDB; Q17339; -.
DR BMRB; Q17339; -.
DR SMR; Q17339; -.
DR BioGRID; 37974; 86.
DR DIP; DIP-24870N; -.
DR IntAct; Q17339; 4.
DR STRING; 6239.T23G11.3.2; -.
DR BindingDB; Q17339; -.
DR ChEMBL; CHEMBL1293302; -.
DR DrugCentral; Q17339; -.
DR iPTMnet; Q17339; -.
DR EPD; Q17339; -.
DR PaxDb; Q17339; -.
DR PeptideAtlas; Q17339; -.
DR EnsemblMetazoa; T23G11.3.1; T23G11.3.1; WBGene00001595.
DR GeneID; 172532; -.
DR KEGG; cel:CELE_T23G11.3; -.
DR UCSC; T23G11.3; c. elegans.
DR CTD; 172532; -.
DR WormBase; T23G11.3; CE14096; WBGene00001595; gld-1.
DR eggNOG; KOG1588; Eukaryota.
DR GeneTree; ENSGT00940000167937; -.
DR HOGENOM; CLU_573960_0_0_1; -.
DR InParanoid; Q17339; -.
DR OMA; PNPARVM; -.
DR OrthoDB; 1565749at2759; -.
DR PhylomeDB; Q17339; -.
DR SignaLink; Q17339; -.
DR EvolutionaryTrace; Q17339; -.
DR PRO; PR:Q17339; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00001595; Expressed in adult organism and 24 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005829; C:cytosol; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043186; C:P granule; IDA:WormBase.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:WormBase.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; IDA:WormBase.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0003727; F:single-stranded RNA binding; IDA:WormBase.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:2000623; P:negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IMP:WormBase.
DR GO; GO:0017148; P:negative regulation of translation; IMP:WormBase.
DR GO; GO:0030716; P:oocyte fate determination; IGI:UniProtKB.
DR GO; GO:0048477; P:oogenesis; IEA:UniProtKB-KW.
DR GO; GO:2000196; P:positive regulation of female gonad development; IGI:UniProtKB.
DR GO; GO:0060282; P:positive regulation of oocyte development; IGI:UniProtKB.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IGI:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IGI:UniProtKB.
DR GO; GO:1905936; P:regulation of germ cell proliferation; IGI:UniProtKB.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; IBA:GO_Central.
DR Gene3D; 3.30.1370.10; -; 1.
DR InterPro; IPR045071; BBP-like.
DR InterPro; IPR031119; GLD1-like.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR032377; STAR_dimer.
DR PANTHER; PTHR11208; PTHR11208; 1.
DR PANTHER; PTHR11208:SF125; PTHR11208:SF125; 1.
DR Pfam; PF00013; KH_1; 1.
DR Pfam; PF16544; STAR_dimer; 1.
DR SMART; SM00322; KH; 1.
DR SUPFAM; SSF54791; SSF54791; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Developmental protein; Differentiation; Meiosis; Oogenesis;
KW Phosphoprotein; Reference proteome; RNA-binding; Translation regulation.
FT CHAIN 1..463
FT /note="Female germline-specific tumor suppressor gld-1"
FT /id="PRO_0000050112"
FT DOMAIN 208..260
FT /note="KH"
FT REGION 1..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 135..205
FT /note="Qua1 domain; involved in homodimerization"
FT /evidence="ECO:0000269|PubMed:20223220"
FT REGION 305..336
FT /note="Qua2 domain; involved in RNA binding"
FT /evidence="ECO:0000269|PubMed:23630077"
FT REGION 443..463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..37
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 220
FT /note="Involved in RNA binding"
FT /evidence="ECO:0000269|PubMed:24838563"
FT SITE 228
FT /note="Important for the interaction between KH and Qua2
FT domains"
FT /evidence="ECO:0000269|PubMed:24838563"
FT SITE 243
FT /note="Involved in RNA binding"
FT /evidence="ECO:0000269|PubMed:23630077,
FT ECO:0000269|PubMed:24838563"
FT SITE 247
FT /note="Involved in RNA binding"
FT /evidence="ECO:0000269|PubMed:23630077,
FT ECO:0000269|PubMed:24838563"
FT SITE 253
FT /note="Important for RNA binding"
FT /evidence="ECO:0000269|PubMed:23630077"
FT SITE 313
FT /note="Involved in RNA binding"
FT /evidence="ECO:0000269|PubMed:23630077,
FT ECO:0000269|PubMed:24838563"
FT SITE 316
FT /note="Involved in RNA binding"
FT /evidence="ECO:0000269|PubMed:23630077,
FT ECO:0000269|PubMed:24838563"
FT SITE 320
FT /note="Important for the interaction between KH and Qua2
FT domains"
FT /evidence="ECO:0000269|PubMed:24838563"
FT MUTAGEN 22
FT /note="S->A: May abolish phosphorylation by cdk-2.
FT Increased expression in the gonad mitotic zone and
FT reduction in the size of the mitotic region; when
FT associated with A-39 and A-348."
FT /evidence="ECO:0000269|PubMed:21455289"
FT MUTAGEN 39
FT /note="S->A: May abolish phosphorylation by cdk-2.
FT Increased expression in the gonad mitotic zone and
FT reduction in the size of the mitotic region; when
FT associated with A-22 and A-348."
FT /evidence="ECO:0000269|PubMed:21455289"
FT MUTAGEN 149
FT /note="Y->F: Moderate decrease in monomer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 150
FT /note="L->A: Moderate decrease in monomer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 156
FT /note="E->A: No effect on homodimer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 160
FT /note="L->A: Moderate decrease in homodimer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 163
FT /note="F->A: Moderate decrease in homodimer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 164
FT /note="P->A: No effect on homodimer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 167
FT /note="F->A: Moderate decrease in homodimer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 169
FT /note="N->A: No effect on homodimer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 170
FT /note="V->A: No effect on homodimer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 173
FT /note="L->A: Severe decrease in homodimer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 177
FT /note="E->A: Severe decrease in monomer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 177
FT /note="E->G: Loss of monomer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 181
FT /note="V->A: Moderate decrease in monomer stability."
FT /evidence="ECO:0000269|PubMed:20223220"
FT MUTAGEN 228
FT /note="P->A: 19-fold decrease in RNA binding affinity."
FT /evidence="ECO:0000269|PubMed:24838563"
FT MUTAGEN 228
FT /note="P->S: In rrr1; 89-fold decrease in RNA binding
FT affinity. Small abnormal stacked oocytes and feminization
FT of germline. Overexpression of oma-2 and to a lesser extent
FT of egg-1 in germline."
FT /evidence="ECO:0000269|PubMed:24838563"
FT MUTAGEN 313
FT /note="K->A: 64-fold decrease in RNA binding affinity."
FT /evidence="ECO:0000269|PubMed:24838563"
FT MUTAGEN 313
FT /note="K->R: 11-fold decrease in RNA binding affinity; when
FT associated with K-314."
FT /evidence="ECO:0000269|PubMed:24838563"
FT MUTAGEN 314
FT /note="R->K: 1.2-fold decrease in RNA binding affinity. 11-
FT fold decrease in RNA binding affinity; when associated with
FT R-313. 1.3-fold decrease in RNA binding affinity; when
FT associated with R-315."
FT /evidence="ECO:0000269|PubMed:24838563"
FT MUTAGEN 315
FT /note="K->R: 1.3-fold decrease in RNA binding affinity;
FT when associated with K-314."
FT /evidence="ECO:0000269|PubMed:24838563"
FT MUTAGEN 320
FT /note="L->S: 26-fold decrease in RNA binding affinity."
FT /evidence="ECO:0000269|PubMed:24838563"
FT MUTAGEN 348
FT /note="T->A: May abolish phosphorylation by cdk-2.
FT Increased expression in the gonad mitotic zone and
FT reduction in the size of the mitotic region; when
FT associated with A-22 and A-39."
FT /evidence="ECO:0000269|PubMed:21455289"
FT HELIX 147..160
FT /evidence="ECO:0007829|PDB:3K6T"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:3K6T"
FT HELIX 168..189
FT /evidence="ECO:0007829|PDB:3K6T"
FT STRAND 202..210
FT /evidence="ECO:0007829|PDB:4JVY"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:4JVY"
FT HELIX 221..226
FT /evidence="ECO:0007829|PDB:4JVY"
FT HELIX 228..230
FT /evidence="ECO:0007829|PDB:4JVY"
FT HELIX 231..240
FT /evidence="ECO:0007829|PDB:4JVY"
FT STRAND 243..248
FT /evidence="ECO:0007829|PDB:4JVY"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:2MJH"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:4JVY"
FT HELIX 255..261
FT /evidence="ECO:0007829|PDB:4JVY"
FT HELIX 268..271
FT /evidence="ECO:0007829|PDB:4JVY"
FT STRAND 274..283
FT /evidence="ECO:0007829|PDB:4JVY"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:4JVY"
FT HELIX 287..301
FT /evidence="ECO:0007829|PDB:4JVY"
FT HELIX 311..325
FT /evidence="ECO:0007829|PDB:4JVY"
FT TURN 328..330
FT /evidence="ECO:0007829|PDB:4JVY"
SQ SEQUENCE 463 AA; 50586 MW; DAC4171422D696BF CRC64;
MPSCTTPTYG VSTQLESQSS ESPSRSSVMT PTSLDGDNSP RKRFPIIDNV PADRWPSTRR
DGWSSVRAPP PARLTLSTNN RHIMSPISSA YSQTPNSLLS PAMFNPKSRS IFSPTLPATP
MSYGKSSMDK SLFSPTATEP IEVEATVEYL ADLVKEKKHL TLFPHMFSNV ERLLDDEIGR
VRVALFQTEF PRVELPEPAG DMISITEKIY VPKNEYPDYN FVGRILGPRG MTAKQLEQDT
GCKIMVRGKG SMRDKSKESA HRGKANWEHL EDDLHVLVQC EDTENRVHIK LQAALEQVKK
LLIPAPEGTD ELKRKQLMEL AIINGTYRPM KSPNPARVMT AVPLLSPTPL RSSGPVLMSP
TPGSGLPSTT FGGSILSPTL TASNLLGSNV FDYSLLSPSM FDSFSSLQLA SDLTFPKYPT
TTSFVNSFPG LFTSASSFAN QTNTNVSPSG ASPSASSVNN TSF
