L2DTL_DROME
ID L2DTL_DROME Reviewed; 769 AA.
AC Q24371; Q9W1K9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Protein lethal(2)denticleless;
DE AltName: Full=Protein DTL83;
GN Name=l(2)dtl; Synonyms=DTL83; ORFNames=CG11295;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
RC STRAIN=Oregon-R;
RX PubMed=8666267; DOI=10.1016/0378-1119(95)00885-3;
RA Kurzik-Dumke U., Neubauer M., Debes A.;
RT "Identification of a novel Drosophila melanogaster heat-shock gene,
RT lethal(2)denticleless [l(2)dtl], coding for an 83-kDa protein.";
RL Gene 171:163-170(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
RC STRAIN=Oregon-2;
RA Gunacker S., Neubhuer M., Kurzik-Dumke U.;
RT "Sequence of a 10291 nt genomic region of Drosophila melanogaster
RT harbouring the genes l(2)tid, l(2)not, l(2)rot, and l(2)dtl.";
RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-655, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=17372656; DOI=10.1039/b617545g;
RA Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A.,
RA Eng J.K., Aebersold R., Tao W.A.;
RT "An integrated chemical, mass spectrometric and computational strategy for
RT (quantitative) phosphoproteomics: application to Drosophila melanogaster
RT Kc167 cells.";
RL Mol. Biosyst. 3:275-286(2007).
RN [7]
RP FUNCTION.
RX PubMed=19081076; DOI=10.1016/j.devcel.2008.10.003;
RA Shibutani S.T., de la Cruz A.F., Tran V., Turbyfill W.J. III, Reis T.,
RA Edgar B.A., Duronio R.J.;
RT "Intrinsic negative cell cycle regulation provided by PIP box- and
RT Cul4Cdt2-mediated destruction of E2f1 during S phase.";
RL Dev. Cell 15:890-900(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-201; SER-204; THR-456;
RP SER-459; SER-524; SER-679; SER-691 AND SER-711, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
CC -!- FUNCTION: Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3
CC ubiquitin-protein ligase complex required for cell cycle control. The
CC DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the
CC polyubiquitination and subsequent degradation of E2f during S phase.
CC E2f degradation is necessary to ensure proper development. Substrates
CC require their interaction with PCNA for their polyubiquitination:
CC substrates interact with PCNA via their PIP-box, leading to recruit the
CC DCX(DTL) complex. {ECO:0000269|PubMed:19081076}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the DCX(DTL) E3 ubiquitin ligase complex, at
CC least composed of Cul-4, pic/DDB1, l(2)dtl/CDT2 and Roc1a.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q24371-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q24371-2; Sequence=VSP_015188;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed during embryogenesis with no
CC sign of tissue specificity in expression up to stage 17.
CC -!- DEVELOPMENTAL STAGE: Detected at all developmental stages. The
CC extremely high level of transcription detected in the early embryo and
CC in adults is caused by maternal message.
CC -!- INDUCTION: By heat shock.
CC -!- SIMILARITY: Belongs to the WD repeat cdt2 family. {ECO:0000305}.
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DR EMBL; X83414; CAA58441.1; -; Genomic_DNA.
DR EMBL; X98094; CAA66723.1; -; Genomic_DNA.
DR EMBL; AE013599; AAF47049.1; -; Genomic_DNA.
DR EMBL; AY121647; AAM51974.1; -; mRNA.
DR PIR; S51748; S51748.
DR RefSeq; NP_524871.1; NM_080132.3. [Q24371-1]
DR AlphaFoldDB; Q24371; -.
DR SMR; Q24371; -.
DR BioGRID; 70176; 4.
DR STRING; 7227.FBpp0071994; -.
DR iPTMnet; Q24371; -.
DR PaxDb; Q24371; -.
DR DNASU; 46326; -.
DR EnsemblMetazoa; FBtr0072085; FBpp0071994; FBgn0013548. [Q24371-1]
DR GeneID; 46326; -.
DR KEGG; dme:Dmel_CG11295; -.
DR UCSC; CG11295-RA; d. melanogaster. [Q24371-1]
DR FlyBase; FBgn0013548; l(2)dtl.
DR VEuPathDB; VectorBase:FBgn0013548; -.
DR eggNOG; KOG0321; Eukaryota.
DR GeneTree; ENSGT00530000064210; -.
DR HOGENOM; CLU_023407_1_0_1; -.
DR InParanoid; Q24371; -.
DR OMA; ANCMDNT; -.
DR PhylomeDB; Q24371; -.
DR Reactome; R-DME-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-DME-8951664; Neddylation.
DR SignaLink; Q24371; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 46326; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 46326; -.
DR PRO; PR:Q24371; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0013548; Expressed in secondary oocyte and 18 other tissues.
DR Genevisible; Q24371; DM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
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 Pfam; PF00400; WD40; 5.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 5.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cytoplasm; Phosphoprotein;
KW Reference proteome; Repeat; Stress response; Ubl conjugation pathway;
KW WD repeat.
FT CHAIN 1..769
FT /note="Protein lethal(2)denticleless"
FT /id="PRO_0000051057"
FT REPEAT 99..129
FT /note="WD 1"
FT REPEAT 143..174
FT /note="WD 2"
FT REPEAT 194..249
FT /note="WD 3"
FT REPEAT 264..303
FT /note="WD 4"
FT REPEAT 320..349
FT /note="WD 5"
FT REPEAT 362..393
FT /note="WD 6"
FT REGION 196..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 448..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..562
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 655..769
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 198..221
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 507..522
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 523..537
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 544..562
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 685..743
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 201
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 204
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 456
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 459
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 524
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17372656"
FT MOD_RES 679
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 711
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT VAR_SEQ 1..28
FT /note="MNIYNKLRAREHGYGNERTYDFALRRLS -> MATAMRGPTTSPCAAFP
FT (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_015188"
FT CONFLICT 309
FT /note="Q -> P (in Ref. 1; CAA58441 and 2; CAA66723)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 769 AA; 84118 MW; D5F54EC8C2134893 CRC64;
MNIYNKLRAR EHGYGNERTY DFALRRLSVA KEDSWRGIAP ANYCPDFNPE PPIFSAKFAN
CDGYRHILAI ANEDGKITLQ DTTQRNHQPE EQSLVGPQCH FNAVFDLEWA PGQMRFVSAS
GDHTARLWEV AGSGIRGLNS YVGHTRSVKS AAFKRTDPAV FATGGRDGAI LIWDIRANLN
MDLTSRVDNC IYSGHTGGPG TPVSQRKQRT RTPKMAGGTT SSSITGLAFQ DNDTLISCGA
GDGVIKVWDL RRNYTAYKKE PLPRHKLPYA GSSTFRGFTN LIVDASGTRL YANCMDNTIY
CYNLASYSQR PLACYKGLLN STFYIKSCLS PDGKYLLSGS SDERAYIWNL DHAEEPLVAL
AGHTVEVTCV AWGSSHDCPI VTCSDDARHK IWRIGPDLDG LSEAERAEKY RGTASYVREF
GKKAFGPSSG NHKYNLRDLE STPRSLKRLM DQNERTPGSV EKTTTKRSFL EMLGVAGQET
EATEQPQKRA KPLESRGRRL FGPSSQETAC RHIQLQSINE EDASPSKRQK ENSAAEDVSP
LHKLLSTPSH SPLSENVNHV YTSPPTTSAA AAAVAADALN PPPISAAIYS PTSNLPNYVL
DGEAPHLGIM SPKRKAKEKV DWLTNIRKQK LMSGRAHVTL SEKISEEQQA DVLASPRLQS
LRQSECSPRI HASPRRRISH TDGGGGTPAG SSSHSHSQSQ PKTPTSSRRN SETTLLRFFS
IQRSSSVPAE ETTTTNAAPS SSDPHPPAVT APAATPLSMR TPTTAVGSD
