| Gene Symbol | DTL |
|---|---|
| Entrez Gene | 51514 |
| Alt Symbol | CDT2, DCAF2, L2DTL, RAMP |
| Species | Human |
| Gene Type | protein-coding |
| Description | denticleless E3 ubiquitin protein ligase homolog (Drosophila) |
| Other Description | DDB1 and CUL4 associated factor 2|DDB1- and CUL4-associated factor 2|RA regulated nuclear matrix associated protein|RA-regulated nuclear matrix-associated protein|denticleless protein homolog|lethal(2) denticleless protein homolog|retinoic acid-regulated nuclear matrix-associated protein |
| Swissprots | Q9NWM5 Q9NW34 Q9NW03 Q96SN0 Q9NZJ0 D3DT98 A8K8H8 Q5VT77 |
| Accessions | EAW93395 EAW93396 EAW93397 EAW93398 Q9NZJ0 AF195765 AAF35182 AF345896 AAK54706 AI800751 AK000742 BAA91355 AK001206 BAA91552 AK001261 BAA91586 AK027651 BAB55267 AK292343 BAF85032 AK299649 BAG61569 AK303346 BAG64408 BC033297 AAH33297 BC033540 AAH33540 BF508267 DB070033 DQ641253 ABG23317 JF432257 ADZ15474 XM_011509614 XP_011507916 NM_001286229 NP_001273158 NM_001286230 NP_001273159 NM_016448 NP_057532 |
| 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) and SETD8. 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. SETD8 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( |
| Subcellular Location | Nucleus. 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. |
| 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. {ECO:0000269|PubMed:11278750, ECO:0000269|PubMed:17106265}. |