ID   DTLA_XENLA              Reviewed;         710 AA.
AC   Q4V837;
DT   10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2005, sequence version 1.
DT   03-AUG-2022, entry version 83.
DE   RecName: Full=Denticleless protein homolog A;
GN   Name=dtl-a; Synonyms=cdt2-a;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION.
RX   PubMed=19595719; DOI=10.1016/j.molcel.2009.05.012;
RA   Havens C.G., Walter J.C.;
RT   "Docking of a specialized PIP Box onto chromatin-bound PCNA creates a
RT   degron for the ubiquitin ligase CRL4Cdt2.";
RL   Mol. Cell 35:93-104(2009).
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. May play a role
CC       in the regulation of the circadian clock (By similarity)
CC       (PubMed:19595719). {ECO:0000250|UniProtKB:Q9NZJ0,
CC       ECO:0000269|PubMed:19595719}.
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|UniProtKB:Q6P1W0}.
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; BC097560; AAH97560.1; -; mRNA.
DR   RefSeq; NP_001090030.1; NM_001096561.1.
DR   AlphaFoldDB; Q4V837; -.
DR   SMR; Q4V837; -.
DR   ELM; Q4V837; -.
DR   DNASU; 735103; -.
DR   GeneID; 735103; -.
DR   CTD; 735103; -.
DR   Xenbase; XB-GENE-6254292; dtl.S.
DR   UniPathway; UPA00143; -.
DR   Proteomes; UP000186698; Genome assembly.
DR   Bgee; 735103; Expressed in blastula and 12 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: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; ISS:UniProtKB.
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..710
FT                   /note="Denticleless protein homolog A"
FT                   /id="PRO_0000396625"
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..398
FT                   /note="WD 7"
FT   REGION          428..534
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          652..698
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        428..459
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        484..534
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        652..686
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   710 AA;  78275 MW;  FAC8E0C7D44FC30E CRC64;
     MLFRSVMNKP RLGYGQKGAP FTYPLQSLLQ CYQCVKQDEH ISYGELGMPV PPFGCAFSTV
     PDMSHVLAVA NEEGIVRLYD TECRDMQRLL MKEFMAHTNA VFDIAWVPGE HKLVTASGDQ
     TAKLWDVMAG ELIGECRGHQ CSLKSVSFSK FERAVFSTGG RDGNIMMWDT RCSKKDGFYR
     QVNQITGAHN AIDKQTPSKM KKRKPSIRGL APSVDSQQSV TVVIFQDEYT IISAGAVDGV
     VKIWDLRKNY SAYRQDPVPV KHFPYPGNST RKLGYSSLVL DPTGTNLFAS CTDDNVYMFN
     ATGLKTDPVS IFRGHQNSTF YIKASVSPDG QFLLSGSSDH SAYIWQVSDP MAAPVTLMGH
     CQEVTSVAWC QSDFTKIATC SDDNTVRVWR LKRSCEDSSE SDKRDSVGWA CKKKFEPSSM
     AANLCTPGKP SVMSSSSLTS SPTPASCAPS NTGDLPMPSS TPISALLPDP KLQTPKRINN
     GGLGVSPKQM SSSKMSIKDW VTRTPKSSTR TDTKTPSPRK AFTPVEQYPS VSSARVQLPY
     EKRAKRRLET SSEYAEHVCP DNCNCVRELE PGLKKAKLDV CFIDKERDSS DDKCLRLSDL
     SKGFDQELSP SPSTSLHMNA TENLLQLGPL SELKSVLLDK ENSSPEKNWL SALGHKFKSS
     PQNKASGSPS SRTSTTKKQQ PRNAPNSPVS VPTPPGSMRK ICTYFFKKSE