Overview
| Uniprot ID | Q9NZJ0 |
|---|
| Protein Name | Denticleless protein homolog |
|---|
| Gene Name | DTL |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 432 |
SSQSTPAKAPRAKCN |
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)
Protein Sequence
10
MLFNSVLRQP
20
QLGVLRNGWS
30
SQYPLQSLLT
40
GYQCSGNDEH
50
TSYGETGVPV
60
PPFGCTFSSA
70
PNMEHVLAVA
80
NEEGFVRLYN
90
TESQSFRKKC
100
FKEWMAHWNA
110
VFDLAWVPGE
120
LKLVTAAGDQ
130
TAKFWDVKAG
140
ELIGTCKGHQ
150
CSLKSVAFSK
160
FEKAVFCTGG
170
RDGNIMVWDT
180
RCNKKDGFYR
190
QVNQISGAHN
200
TSDKQTPSKP
210
KKKQNSKGLA
220
PSVDFQQSVT
230
VVLFQDENTL
240
VSAGAVDGII
250
KVWDLRKNYT
260
AYRQEPIASK
270
SFLYPGSSTR
280
KLGYSSLILD
290
STGSTLFANC
300
TDDNIYMFNM
310
TGLKTSPVAI
320
FNGHQNSTFY
330
VKSSLSPDDQ
340
FLVSGSSDEA
350
AYIWKVSTPW
360
QPPTVLLGHS
370
QEVTSVCWCP
380
SDFTKIATCS
390
DDNTLKIWRL
400
NRGLEEKPGG
410
DKLSTVGWAS
420
QKKKESRPGL
430
VTVTSSQSTP
440
AKAPRAKCNP
450
SNSSPSSAAC
460
APSCAGDLPL
470
PSNTPTFSIK
480
TSPAKARSPI
490
NRRGSVSSVS
500
PKPPSSFKMS
510
IRNWVTRTPS
520
SSPPITPPAS
530
ETKIMSPRKA
540
LIPVSQKSSQ
550
AEACSESRNR
560
VKRRLDSSCL
570
ESVKQKCVKS
580
CNCVTELDGQ
590
VENLHLDLCC
600
LAGNQEDLSK
610
DSLGPTKSSK
620
IEGAGTSISE
630
PPSPISPYAS
640
ESCGTLPLPL
650
RPCGEGSEMV
660
GKENSSPENK
670
NWLLAMAAKR
680
KAENPSPRSP
690
SSQTPNSRRQ
700
SGKKLPSPVT
710
ITPSSMRKIC
720
TYFHRKSQED
730
FCGPEHSTEL
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005813 |
centrosome |
| Cellular Component |
GO:0005694 |
chromosome |
| Cellular Component |
GO:0080008 |
Cul4-RING E3 ubiquitin ligase complex |
| Cellular Component |
GO:0031464 |
Cul4A-RING E3 ubiquitin ligase complex |
| Cellular Component |
GO:0031465 |
Cul4B-RING E3 ubiquitin ligase complex |
| Cellular Component |
GO:0031965 |
nuclear membrane |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0030674 |
protein-macromolecule adaptor activity |
| Biological Process |
GO:0006974 |
DNA damage response |
| Biological Process |
GO:0007095 |
mitotic G2 DNA damage checkpoint signaling |
| Biological Process |
GO:0010971 |
positive regulation of G2/M transition of mitotic cell cycle |
| Biological Process |
GO:0045732 |
positive regulation of protein catabolic process |
| Biological Process |
GO:0043161 |
proteasome-mediated ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0006513 |
protein monoubiquitination |
| Biological Process |
GO:0000209 |
protein polyubiquitination |
| Biological Process |
GO:0051726 |
regulation of cell cycle |
| Biological Process |
GO:1901987 |
regulation of cell cycle phase transition |
| Biological Process |
GO:0030174 |
regulation of DNA-templated DNA replication initiation |
| Biological Process |
GO:0009411 |
response to UV |
| Biological Process |
GO:0048511 |
rhythmic process |
| Biological Process |
GO:0019985 |
translesion synthesis |
| Biological Process |
GO:0006511 |
ubiquitin-dependent protein catabolic process |
Reference
PMID: N/A