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Identification
HMDB Protein ID HMDBP14567
Secondary Accession Numbers None
Name Denticleless protein homolog
Synonyms
  1. DDB1- and CUL4-associated factor 2
  2. Lethal(2) denticleless protein homolog
  3. Retinoic acid-regulated nuclear matrix-associated protein
Gene Name DTL
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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).
Pathways
  • protein ubiquitination
Reactions Not Available
GO Classification
Biological Process
positive regulation of protein catabolic process
protein polyubiquitination
DNA replication
ubiquitin-dependent protein catabolic process
protein monoubiquitination
response to DNA damage stimulus
post-translational protein modification
positive regulation of G2/M transition of mitotic cell cycle
response to UV
translesion synthesis
signal transduction involved in G2 DNA damage checkpoint
DNA damage response, detection of DNA damage
rhythmic process
regulation of cell cycle
Cellular Component
cytosol
centrosome
chromosome
nucleolus
nucleus
Cul4A-RING E3 ubiquitin ligase complex
Cul4B-RING E3 ubiquitin ligase complex
nucleoplasm
Cul4-RING E3 ubiquitin ligase complex
nuclear membrane
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 730
Molecular Weight 79467.075
Theoretical pI 8.861
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9NZJ0
UniProtKB/Swiss-Prot Entry Name DTL_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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