ID:DTL_HUMAN DESCRIPTION: RecName: Full=Denticleless protein homolog; AltName: Full=DDB1- and CUL4-associated factor 2; AltName: Full=Lethal(2) denticleless protein homolog; AltName: Full=Retinoic acid-regulated nuclear matrix-associated protein; 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 and CDKN1A/p21(CIP1). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication. CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing. 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. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Component of the DCX(DTL) E3 ubiquitin ligase complex, at least composed of CUL4 (CUL4A or CUL4B), DDB1, DTL/CDT2 and RBX1. Interacts with CDKN1A and CDT1. INTERACTION: Q16531:DDB1; NbExp=3; IntAct=EBI-1176075, EBI-350322; SUBCELLULAR LOCATION: Nucleus. Nucleus membrane; Peripheral membrane protein; Nucleoplasmic side. Cytoplasm, cytoskeleton, centrosome. Note=Nuclear matrix-associated protein. Translocates from the interphase nucleus to the metaphase cytoplasm during mitosis. TISSUE SPECIFICITY: Expressed in placenta and testis, very low expression seen in skeletal muscle. Detected in all hematopoietic tissues examined, with highest expression in thymus and bone marrow. A low level detected in the spleen and lymph node, and barely detectable level in the peripheral leukocytes. RA treatment down-regulated the expression in NT2 cell. DEVELOPMENTAL STAGE: Expressed in all fetal tissues examined, included brain, lung, liver, and kidney. PTM: Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C). PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. SIMILARITY: Belongs to the WD repeat cdt2 family. SIMILARITY: Contains 7 WD repeats. SEQUENCE CAUTION: Sequence=BAA91552.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAA91586.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): DTL CDC HuGE Published Literature: DTL Positive Disease Associations: Stroke Related Studies:
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9NZJ0
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.