DTL
entrez
51514
canonical
uniprot
Q9NZJ0
canonical
ensembl
ENSG00000143476
resolver
ensp
ENSP00000355958
resolver
ensp
ENSP00000443870
resolver
enst
ENST00000542077
resolver
genesymbol
DTL
resolver
genesymbol_syn
CDT2
resolver
genesymbol_syn
CDW1
resolver
genesymbol_syn
DCAF2
resolver
genesymbol_syn
L2DTL
resolver
genesymbol_syn
RAMP
resolver
hgnc
HGNC:30288
resolver
uniprot
A8K8H8
resolver
uniprot
B4E0E6
resolver
uniprot
D3DT98
resolver
uniprot
F5GZ90
resolver
uniprot
Q5VT77
resolver
uniprot
Q96SN0
resolver
uniprot
Q9NW03
resolver
uniprot
Q9NW34
resolver
uniprot
Q9NWM5
resolver
uniprot_entry
B4E0E6_HUMAN
resolver
uniprot_entry
DTL_HUMAN
resolver
uniprot_entry
F5GZ90_HUMAN
resolver
uniprot_sec
A8K8H8
resolver
uniprot_sec
D3DT98
resolver
uniprot_sec
Q5VT77
resolver
uniprot_sec
Q96SN0
resolver
uniprot_sec
Q9NW03
resolver
uniprot_sec
Q9NW34
resolver
uniprot_sec
Q9NWM5
resolver
amino_acid_sequence
MLFNSVLRQPQLGVLRNGWSSQYPLQSLLTGYQCSGNDEHTSYGETGVPVPPFGCTFSSAPNMEHVLAVANEEGFVRLYNTESQSFRKKCFKEWMAHWNAVFDLAWVPGELKLVTAAGDQTAKFWDVKAGELIGTCKGHQCSLKSVAFSKFEKAVFCTGGRDGNIMVWDTRCNKKDGFYRQVNQISGAHNTSDKQTPSKPKKKQNSKGLAPSVDFQQSVTVVLFQDENTLVSAGAVDGIIKVWDLRKNYTAYRQEPIASKSFLYPGSSTRKLGYSSLILDSTGSTLFANCTDDNIYMFNMTGLKTSPVAIFNGHQNSTFYVKSSLSPDDQFLVSGSSDEAAYIWKVSTPWQPPTVLLGHSQEVTSVCWCPSDFTKIATCSDDNTLKIWRLNRGLEEKPGGDKLSTVGWASQKKKESRPGLVTVTSSQSTPAKAPRAKCNPSNSSPSSAACAPSCAGDLPLPSNTPTFSIKTSPAKARSPINRRGSVSSVSPKPPSSFKMSIRNWVTRTPSSSPPITPPASETKIMSPRKALIPVSQKSSQAEACSESRNRVKRRLDSSCLESVKQKCVKSCNCVTELDGQVENLHLDLCCLAGNQEDLSKDSLGPTKSSKIEGAGTSISEPPSPISPYASESCGTLPLPLRPCGEGSEMVGKENSSPENKNWLLAMAAKRKAENPSPRSPSSQTPNSRRQSGKKLPSPVTITPSSMRKICTYFHRKSQEDFCGPEHSTEL
uniprot
proteins
function
FUNCTION: Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A and SDE2 (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613, PubMed:27906959). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration (PubMed:23478445). Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). {ECO:0000269|PubMed:16861906, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17085480, ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:18794348, ECO:0000269|PubMed:19332548, ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:23677613, ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:27906959}.
uniprot
proteins
mass_dalton
79468
uniprot
proteins
mutagenesis
MUTAGEN 246; /note="R->A: Blocks association with DDB1 and ubiquitination by DCX(DTL). No effect on ubiquitination by SCF(FBXO11)."; /evidence="ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:23478445"; MUTAGEN 457; /note="D->A: Increases protein stability, but no effect on interaction with FBXO11 and polyubiquitination. Delays cell migration."; /evidence="ECO:0000269|PubMed:23478445"; MUTAGEN 462; /note="S->A: Blocks interaction with FBXO11 and ubiquitination, increasing protein stability. Delays cell migration."; /evidence="ECO:0000269|PubMed:23478445"; MUTAGEN 463; /note="N->A: No effect on interaction with FBXO11. Increases protein stability."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 464; /note="T->A: Blocks interaction with FBXO11 and increases protein stability. Not phosphorylated by CDK1 or CDK2."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 464; /note="T->D: Blocks interaction with FBXO11."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 465; /note="P->A: Inhibits phosphorylation on T-464. No effect on interaction with FBXO11."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 466; /note="T->A: No effect on interaction with FBXO11."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 466; /note="T->D: No effect on interaction with FBXO11."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 467; /note="F->A: No effect on interaction with FBXO11."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 468; /note="S->A: No effect on interaction with FBXO11."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 468; /note="S->D: No effect on interaction with FBXO11."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 471; /note="T->A: No effect on interaction with FBXO11."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 471; /note="T->D: No effect on interaction with FBXO11."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 472; /note="S->A: No effect on interaction with FBXO11."; /evidence="ECO:0000269|PubMed:23478441"; MUTAGEN 472; /note="S->D: No effect on interaction with FBXO11."; /evidence="ECO:0000269|PubMed:23478441
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination.
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C). Autoubiquitinated through 'Lys-48'-polyubiquitin chains in a PCNA-independent reaction, allowing proteasomal turnover. Polyubiquitinated by SCF(FBXO11) when not phosphorylated, leading to its degradation. A tight regulation of the polyubiquitination by SCF(FBXO11) is involved in the control of different processes such as TGF-beta signaling, cell cycle progression and exit. {ECO:0000269|PubMed:17106265, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445}.; PTM: Phosphorylated at Thr-464 by CDK1/Cyclin-B and CDK2/Cyclin-A but not by CDK2/Cyclin-E, MAPK1 or PLK1. Phosphorylation at Thr-464 inhibits the interaction with FBXO11 and decreases upon cell cycle exit induced by TGF-beta or serum starvation. {ECO:0000269|PubMed:23478441}.
uniprot
proteins
protein_family
WD repeat cdt2 family
uniprot
proteins
pubmed
11278750
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
16861906
uniprot
proteins
pubmed
16949367
uniprot
proteins
pubmed
16964240
uniprot
proteins
pubmed
17041588
uniprot
proteins
pubmed
17085480
uniprot
proteins
pubmed
17106265
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18703516
uniprot
proteins
pubmed
18794347
uniprot
proteins
pubmed
18794348
uniprot
proteins
pubmed
19332548
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20129063
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23213251
uniprot
proteins
pubmed
23478441
uniprot
proteins
pubmed
23478445
uniprot
proteins
pubmed
23677613
uniprot
proteins
pubmed
23892434
uniprot
proteins
pubmed
26431207
uniprot
proteins
pubmed
27906959
uniprot
proteins
sequence_length
730
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26431207}. Nucleus membrane; Peripheral membrane protein; Nucleoplasmic side. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Chromosome. Note=Nuclear matrix-associated protein. Translocates from the interphase nucleus to the metaphase cytoplasm during mitosis.
uniprot
proteins