DTL — Denticleless E3 ubiquitin protein ligase homolog
DTL belongs to a gene co-expression module in 2 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
DTL's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD8⁺ T cells | Replication Stress Checkpoint Cell cycle | ATAD5, BRCA1, CCNE2, CHEK1, EXO1, FAM111B, IFI27L1, MCM10 +1 more | View in SCUBA |
| Hematopoietic progenitor cells | Replication Origin Licensing Cell cycle | BRCA1, CDC6, CLSPN, FAM111B, MCM10, ORC6, WDR76, XRCC2 |
About the gene
| Synonyms | CDT2, DCAF2, L2DTL, RAMP |
|---|---|
| Chromosome | 1: 212035553-212107400 |
| Predicted location | Intracellular |
| Essential gene | Yes |
| Protein class | Essential proteins, Predicted intracellular proteins |
| Biological process | Biological rhythms, DNA damage, DNA replication, Ubl conjugation pathway |
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. 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.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.