RAMP 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. 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. KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration. 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. The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1. Belongs to the WD repeat cdt2 family. 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. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Adaptor/scaffold; Ubiquitin ligase
Chromosomal Location of Human Ortholog: 1|1 H6
Cellular Component:  centrosome; chromosome; Cul4-RING E3 ubiquitin ligase complex; Cul4A-RING E3 ubiquitin ligase complex; Cul4B-RING E3 ubiquitin ligase complex; cytoplasm; cytoskeleton; cytosol; membrane; nucleolus; nucleus
Biological Process:  cellular response to DNA damage stimulus; DNA replication; positive regulation of G2/M transition of mitotic cell cycle; positive regulation of protein catabolic process; protein monoubiquitination; protein polyubiquitination; regulation of cell cycle; response to UV; signal transduction involved in G2 DNA damage checkpoint; translesion synthesis; ubiquitin-dependent protein catabolic process
Reference #:  Q3TLR7 (UniProtKB)
Alt. Names/Synonyms: 2810047L02Rik; 5730564G15Rik; denticleless homolog (Drosophila); Denticleless protein homolog; Dtl; L2dtl; Lethal(2) denticleless protein homolog; Meth A RAMP; Meth A retinoic acid-regulated nuclear matrix-associated protein; Ramp; Retinoic acid-regulated nuclear matrix-associated protein; retinoic-acid regulated nuclear matrix-associated protein
Gene Symbols: Dtl
Molecular weight: 79,131 Da
Basal Isoelectric point: 9.07  Predict pI for various phosphorylation states
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Protein Structure Not Found.

Cross-references to other databases:  STRING  |  BioGPS  |  Pfam  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene