DTL_DANRE
ID DTL_DANRE Reviewed; 647 AA.
AC Q5RHI5; Q7ZU24; Q8JHI4;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Denticleless protein homolog;
GN Name=dtl; Synonyms=cdt2; ORFNames=si:dkey-18c8.4;
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 TISSUE=Embryo;
RX PubMed=12006978; DOI=10.1038/ng896;
RA Golling G., Amsterdam A., Sun Z., Antonelli M., Maldonado E., Chen W.,
RA Burgess S., Haldi M., Artzt K., Farrington S., Lin S.-Y., Nissen R.M.,
RA Hopkins N.;
RT "Insertional mutagenesis in zebrafish rapidly identifies genes essential
RT for early vertebrate development.";
RL Nat. Genet. 31:135-140(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=17085480; DOI=10.1101/gad.1482106;
RA Sansam C.L., Shepard J.L., Lai K., Ianari A., Danielian P.S., Amsterdam A.,
RA Hopkins N., Lees J.A.;
RT "DTL/CDT2 is essential for both CDT1 regulation and the early G2/M
RT checkpoint.";
RL Genes Dev. 20:3117-3129(2006).
CC -!- FUNCTION: Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3
CC ubiquitin-protein ligase complex required for cell cycle control, DNA
CC damage response and translesion DNA synthesis. The DCX(DTL) complex,
CC also named CRL4(CDT2) complex, mediates the polyubiquitination and
CC subsequent degradation of CDT1, CDKN1A/p21(CIP1), KMT5A and SDE2. CDT1
CC degradation in response to DNA damage is necessary to ensure proper
CC cell cycle regulation of DNA replication. CDKN1A/p21(CIP1) degradation
CC during S phase or following UV irradiation is essential to control
CC replication licensing. KMT5A degradation is also important for a proper
CC regulation of mechanisms such as TGF-beta signaling, cell cycle
CC progression, DNA repair and cell migration. Most substrates require
CC their interaction with PCNA for their polyubiquitination: substrates
CC interact with PCNA via their PIP-box, and those containing the 'K+4'
CC motif in the PIP box, recruit the DCX(DTL) complex, leading to their
CC degradation. In undamaged proliferating cells, the DCX(DTL) complex
CC also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being
CC involved in PCNA-dependent translesion DNA synthesis (By similarity).
CC May play a role in the regulation of the circadian clock (By
CC similarity). {ECO:0000250|UniProtKB:Q9NZJ0}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the DCX(DTL) E3 ubiquitin ligase complex, at
CC least composed of cul4 (cul4a or cul4b), ddb1, dtl/cdt2 and rbx1.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9NZJ0}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250}. Chromosome {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: General developmental defects, including
CC apoptosis in the central nervous system and a dorsally curved tail,
CC which appear by 28 hpf. Effects are due to general cell cycle defects,
CC including defects in the G2/M checkpoint.
CC {ECO:0000269|PubMed:17085480}.
CC -!- SIMILARITY: Belongs to the WD repeat cdt2 family. {ECO:0000305}.
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DR EMBL; AF506212; AAM34656.1; -; mRNA.
DR EMBL; BX511163; CAI20732.1; -; Genomic_DNA.
DR EMBL; BX510324; CAI20732.1; JOINED; Genomic_DNA.
DR EMBL; BX510324; CAI20792.1; -; Genomic_DNA.
DR EMBL; BX511163; CAI20792.1; JOINED; Genomic_DNA.
DR EMBL; BC045316; AAH45316.1; -; mRNA.
DR RefSeq; NP_775348.1; NM_173241.1.
DR AlphaFoldDB; Q5RHI5; -.
DR SMR; Q5RHI5; -.
DR STRING; 7955.ENSDARP00000033992; -.
DR PaxDb; Q5RHI5; -.
DR Ensembl; ENSDART00000034098; ENSDARP00000033992; ENSDARG00000023002.
DR GeneID; 192314; -.
DR KEGG; dre:192314; -.
DR CTD; 51514; -.
DR ZFIN; ZDB-GENE-020419-34; dtl.
DR eggNOG; KOG0321; Eukaryota.
DR GeneTree; ENSGT00530000064210; -.
DR HOGENOM; CLU_023407_0_0_1; -.
DR InParanoid; Q5RHI5; -.
DR OMA; VSMRKIC; -.
DR OrthoDB; 1288134at2759; -.
DR PhylomeDB; Q5RHI5; -.
DR TreeFam; TF324483; -.
DR Reactome; R-DRE-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-DRE-8951664; Neddylation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q5RHI5; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 20.
DR Bgee; ENSDARG00000023002; Expressed in cleaving embryo and 43 other tissues.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0031465; C:Cul4B-RING E3 ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0006513; P:protein monoubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0009411; P:response to UV; ISS:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0019985; P:translesion synthesis; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
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; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 5.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 2: Evidence at transcript level;
KW Biological rhythms; Chromosome; Cytoplasm; Cytoskeleton; DNA damage;
KW DNA replication; Nucleus; Reference proteome; Repeat;
KW Ubl conjugation pathway; WD repeat.
FT CHAIN 1..647
FT /note="Denticleless protein homolog"
FT /id="PRO_0000396624"
FT REPEAT 48..88
FT /note="WD 1"
FT REPEAT 95..134
FT /note="WD 2"
FT REPEAT 137..177
FT /note="WD 3"
FT REPEAT 209..248
FT /note="WD 4"
FT REPEAT 264..303
FT /note="WD 5"
FT REPEAT 308..349
FT /note="WD 6"
FT REPEAT 353..393
FT /note="WD 7"
FT REGION 410..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..647
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 167..170
FT /note="DDB1-binding motif"
FT /evidence="ECO:0000250"
FT MOTIF 238..241
FT /note="DDB1-binding motif"
FT /evidence="ECO:0000250"
FT COMPBIAS 410..444
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 452..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 539..570
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 571..608
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 32
FT /note="G -> C (in Ref. 1; AAM34656)"
FT /evidence="ECO:0000305"
FT CONFLICT 136
FT /note="K -> E (in Ref. 3; AAH45316)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="A -> V (in Ref. 3; AAH45316)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="V -> I (in Ref. 1; AAM34656)"
FT /evidence="ECO:0000305"
FT CONFLICT 311
FT /note="N -> S (in Ref. 1; AAM34656)"
FT /evidence="ECO:0000305"
FT CONFLICT 340
FT /note="K -> R (in Ref. 1; AAM34656)"
FT /evidence="ECO:0000305"
FT CONFLICT 503
FT /note="H -> R (in Ref. 1; AAM34656)"
FT /evidence="ECO:0000305"
FT CONFLICT 557
FT /note="L -> Q (in Ref. 1; AAM34656)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 647 AA; 70769 MW; 33A45A01E42621DC CRC64;
MTLFHHVVDR GAKKRGRNGE QRLFPLSSLL DGYECARRDE HISYGASAAA VPPFGCTFSS
AHGQQNCLAV ANEEGFVTIF NTGEKQSSVL KEWQAHDNAV FDIAWVPGTN CLVTASGDQT
ARLWDVITGD LLGTFKGHQC SLKSVAFYKQ EKAVFSTGGR DGNIMIWDTR CSKKDGFYRQ
VKQISGAHMK PERFTPQTKK RRGMAPPVDS QQGVTVVLFC DETKLISSGA VDGIIKMWDL
RRNYTAYHQN PLPLQAYPYP GSCTRKLGYS GLSLDYTGSR LFSNCTDDNI YMFNISGLKT
TPVAVFSGHS NSSFYVKSTV SPDDQFLASG SSDHNVYIWK ISDPKQAPMM LQGHSQEVTS
VAWCPTDFTK IASCSDDNTV RIWRLNRKPE GENSTIQDGN LVGWTIRKVQ SPNRTPGHHS
PVELTPSKNP GSVRSVSLAS PQPATCAPTG AALPLPSNTS SAPPAKLTSP KMPSSLQQWI
SRSSKSPVRK ALTPVLQGLS FEHRVKRRLE TGDSASSGLG EEIDGVSELY PNVKRSRSSV
STLKKEDSFG LESEKRLGSD GAEASGKENS SPRRTDWLSV ISQKFKGSAQ PKSPSSGSSQ
QDTRTLESPA AVSPRPMKVF SPPTNKKASP SKPMKKISSY FMKRTQD
