DTL_XENTR
ID DTL_XENTR Reviewed; 713 AA.
AC Q6P1W0;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Denticleless protein homolog;
GN Name=dtl; Synonyms=cdt2, l2dtl; ORFNames=TEgg011o17.1;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Egg;
RG Sanger Xenopus tropicalis EST/cDNA project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, INTERACTION WITH DDB1, AND IDENTIFICATION IN A COMPLEX WITH DDB1
RP AND CUL4B.
RX PubMed=16949367; DOI=10.1016/j.molcel.2006.08.010;
RA Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C.;
RT "A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is
RT required for S phase destruction of the replication factor Cdt1.";
RL Mol. Cell 23:709-721(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 (PubMed:16949367).
CC May play a role in the regulation of the circadian clock (By
CC similarity). {ECO:0000250|UniProtKB:Q9NZJ0,
CC ECO:0000269|PubMed:16949367}.
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:0000269|PubMed:16949367}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9NZJ0}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250}. Chromosome {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the WD repeat cdt2 family. {ECO:0000305}.
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DR EMBL; CR848464; CAJ81765.1; -; mRNA.
DR EMBL; BC064851; AAH64851.1; -; mRNA.
DR RefSeq; NP_989402.1; NM_204071.1.
DR AlphaFoldDB; Q6P1W0; -.
DR SMR; Q6P1W0; -.
DR STRING; 8364.ENSXETP00000028254; -.
DR PaxDb; Q6P1W0; -.
DR DNASU; 395039; -.
DR Ensembl; ENSXETT00000031497; ENSXETP00000031497; ENSXETG00000014394.
DR GeneID; 395039; -.
DR KEGG; xtr:395039; -.
DR CTD; 51514; -.
DR Xenbase; XB-GENE-985623; dtl.
DR eggNOG; KOG0321; Eukaryota.
DR HOGENOM; CLU_023407_0_0_1; -.
DR InParanoid; Q6P1W0; -.
DR OMA; SMAANLC; -.
DR OrthoDB; 1288134at2759; -.
DR PhylomeDB; Q6P1W0; -.
DR TreeFam; TF324483; -.
DR Reactome; R-XTR-8951664; Neddylation.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000008143; Chromosome 5.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000014394; Expressed in 4-cell stage embryo and 8 other tissues.
DR ExpressionAtlas; Q6P1W0; baseline.
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; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; IMP:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; 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; 7.
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 1: Evidence at protein 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..713
FT /note="Denticleless protein homolog"
FT /id="PRO_0000274870"
FT REPEAT 47..89
FT /note="WD 1"
FT REPEAT 96..135
FT /note="WD 2"
FT REPEAT 138..178
FT /note="WD 3"
FT REPEAT 215..254
FT /note="WD 4"
FT REPEAT 270..309
FT /note="WD 5"
FT REPEAT 314..355
FT /note="WD 6"
FT REPEAT 359..399
FT /note="WD 7"
FT REGION 474..544
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 604..623
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 635..700
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 168..171
FT /note="DDB1-binding motif"
FT /evidence="ECO:0000250"
FT MOTIF 197..204
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 244..247
FT /note="DDB1-binding motif"
FT /evidence="ECO:0000250"
FT COMPBIAS 479..516
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 608..623
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 663..700
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 713 AA; 78193 MW; 8604AFEDBB987E19 CRC64;
MLFRSVVNKP RLGCRQRGVP FTHPLQSLLQ CYQCAKHDEH TSYGELGAAV PPFGCAFSTV
PDMSHVLAVA NEEGIVRLYD TECRDVQRLV VKEFMAHTNA VFDIAWVPGE HKLVTASGDQ
TAKLWDVKAG DLIGECKGHQ CSLKSVAFSK FEKAVFSTGG RDGNIMVWDT RCNKKDGFYR
QVNQITGAHN ALDKQTPSKV KKRKPYVRGL APSVDSQQSV TVVIFQDEHT IISAGAVDGI
VKVWDLRKNY SAYRQDPVPA KLFPYPGNST RKLGYSNLVL DPTGTNLFAS CTDDNVYMFN
ATGLKTEPVS VFGGHQNSTF YIKTSVSPDG QFLLSGSSDH SAYIWQVSDP KVPPVTLTGH
CQEVTSVAWC QSDFTKIATC SDDNTVRVWR LKRSSEDSAQ SDKTETVGWA CQKKCVPPSM
AANLCTPGKP SMIPSSSLMS SPTPATCAPS YTGDLPMPSS TPVSALLPIP KLQTPQRLNG
EGLGASPKQT SSSKISIKDW ITRTPKSSTR ADTKTPSPRK AFTPVEQYPS VSSTRVQMPY
EKRAKRRLET SSEDVEHVCL DHCNCVMELE PGLKKAKLDL CSFSEKERDG SDDKCLRLSD
LSRGFDQEFS PGPSTSFLIN GTVNPPLSPL SELKSDLRDK ENSSPEKNWL SALGHKFKSD
KSSPQNKAAS SPSSRNSTSK KHPTRNAPNS PVSVPTTPGS MRKICTYFFK KSE
