DTL

Gene Information

Official Symbol: DTL
Official Name: denticleless E3 ubiquitin protein ligase homolog
Aliases and Previous Symbols: N/A
Entrez ID: 51514
UniProt: Q9NZJ0
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: N/A
UniProt Summary: 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), FBXO18/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). {ECO:0000269|PubMed:16861906, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17085480, ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:18794348, ECO:0000269|PubMed:19332548, ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:23677613, ECO:0000269|PubMed:27906959}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
Atovaquone 15μM R08 exp451	-1.99
Nocodazole 0.1μM R03 exp94	-1.86
Vinblastine 0.2μM R03 exp108	-1.73
CCCP 1μM R00 exp11	1.71
VER-155008 3.9μM R06 exp301	1.75
DABN 2μM R00 exp16	1.76
Nicotinamide Riboside 100μM R03 exp139	1.85
Tunicamycin 0.04μM R07 exp418	1.86
A-769662 20μM R07 exp331	1.88
Cycloheximide 0.02μM R00 exp14	1.9
Radicicol 0.16μM R05 exp242	1.95
5-Fluorouracil 2μM R00 exp1	1.98
Betulinic acid 10 to 15μM on day4 R05 exp222	2.02
UM0131023 0.05μM R05 exp248	2.07
Parthenolide 2.5μM R05 exp238	2.18
Metformin 100 to 150μM on day4 R04 exp170	2.23
EPZ-5676 30μM R05 exp233	2.41
Vinblastine 0.002μM R01 exp60	2.49
UM0011500 5μM R05 exp245	2.52
Cycloheximide 0.2μM R00 exp15	2.68
CB-839 10μM R05 exp224	2.69
UM0011500 10μM R05 exp246	2.78

Gene	Correlation
TBC1D3H	0.614
PSMC1	0.576
TBC1D3C	0.576
TBC1D3G	0.571
PSMA6	0.567
SEC13	0.567
CBWD3	0.562
COPG1	0.56
PAN3	0.549
TCEB3C	0.548
SSH2	0.546
SUPT6H	0.546
C14orf93	0.545
NUPL1	0.542
SF3A3	0.542
CBWD5	0.538
VASN	0.538
TBC1D3F	0.538
TBC1D3E	0.535
TBC1D3I	0.535
TBC1D3K	0.534
TBC1D3L	0.534
TCEB3CL	0.534
ORC6	0.532
CBWD6	0.531
ZNF106	0.53
TCEB3CL2	0.527
RPL35	0.525
C1QTNF9B	0.522
NUP160	0.522
RPS2	0.519
TICRR	0.518
TYMS	0.518
TBC1D3	0.518
AAMP	0.517
WDR87	0.516
RPS12	0.516
PSMB1	0.515
CHD4	0.513
MYO1H	0.511
NPIPB5	0.508
PSMB4	0.506
CCNA2	0.506
TWISTNB	0.505
AHCTF1	0.505
DDTL	0.504
SUPT5H	0.503
CDC73	0.503
MT1E	0.502
RANBP2	0.501
PSMB2	0.5
NARFL	0.5
SNRPA1	0.498
AQR	0.497
NUP153	0.496
NOL10	0.496
ZNF655	0.496
PSMD2	0.496
ACSF2	0.495
SH3BP1	0.495
TFIP11	0.494
KPNB1	0.492
RRN3	0.492
AKIRIN2	0.491
KCTD17	0.49
PRPF8	0.49
ZFAND5	0.489
UTP3	0.488
PSMC2	0.488
RBM39	0.487
CLN6	0.486
CLASP1	0.486
CEP192	0.485
RRP7A	0.484
RAD51	0.482
CDC6	0.481
MADCAM1	0.48
RPL14	0.48
NDC80	0.479
COPZ1	0.478
EXOSC3	0.476
SYT9	0.476
MED17	0.476
POLR2J3	0.475
HIST1H2BE	0.475
DDX56	0.474
PSMC3	0.474
COPB2	0.474
SNIP1	0.474
PSMC6	0.473
PSMD11	0.473
SLC4A1	0.473
RPL6	0.473
PSMD14	0.473
PSMD1	0.47
POLE	0.47
SLC6A17	0.47
FAM160A1	0.47
PLK1	0.469
EXOSC9	0.469
GOLGA8J	0.469
CDCA3	0.468
RPA2	0.468
COPB1	0.467
MFSD12	0.467
PSMD3	0.466
PLA2G4F	0.465
UQCRH	0.463
GOSR2	0.462
ANKLE2	0.462
ZNF830	0.462
XYLT2	0.462
WDR43	0.462
NOP16	0.462
ORC1	0.462
RBBP5	0.462
CCDC64B	0.461
SMG7	0.461
CRNKL1	0.46
S1PR4	0.46
LRR1	0.46
GAR1	0.459
VPS54	0.459
ATP6V1C1	0.456
TSG101	0.456
PLEKHA4	0.455
PSMC4	0.455
DISP2	0.455
NAPA	0.454
AATF	0.454
ZNF574	0.454
SULT2B1	0.453
CTR9	0.453
TIMELESS	0.453
MSH5	0.453
ANKLE1	0.452
RRP15	0.452
FBXW9	0.451
UTP20	0.45
RPS28	0.449
TAGLN	0.449
RPSA	0.449
SRGAP2C	0.449
AAAS	0.448
RPS3	0.448
TERF1	0.448
PSMA7	0.448
EIF4A3	0.447
DOCK6	0.447
PSMD8	0.447
CHAF1A	0.446
COPE	0.446
GOLGA6L3	0.446
GOLGA6A	0.446
VPS28	0.445
PCF11	0.445
POLA2	0.445
SF3A2	0.445
POLR1A	0.445
PAN2	0.445
DNTTIP2	0.444
NUP85	0.443
MED12	0.443
DHX38	0.442
PDE4DIP	0.442
POLR2A	0.441
TUBA8	0.441
HAP1	0.44
RAD21	0.44
GID4	0.439
ABT1	0.439
RPS3A	0.439
MAT2A	0.439
COL2A1	0.437
CTAGE4	0.437
CHMP2A	0.437
MED14	0.437
GBF1	0.435
RPS19BP1	0.435
MCOLN1	0.435
SMG1	0.435
EBNA1BP2	0.435
IK	0.434
NUP43	0.434
RPL9	0.434
PSMC5	0.433
NOL12	0.433
C2orf27B	0.431
WDR75	0.431
COPA	0.431
NFATC4	0.431
PAF1	0.431
ATP6AP1	0.428
ATXN1	0.428
RRP1	0.427
POLR2D	0.427
RNF113A	0.427
RFXANK	0.426
PRPF3	0.425
ATP13A1	0.425
PPM1D	0.425
CDT1	0.425
SCAF1	0.425
CHMP4B	0.424
LOC643669	0.424
SF3A1	0.424
MMS22L	0.424
TOP1MT	0.423
OR10G3	0.422
TSPY8	0.421
USP36	0.421
UBL5	0.421
CDH24	0.42
PSMD7	0.42
DDT	0.42
CACTIN	0.419
ITGA2B	0.418
GOLGA6L1	0.418
RPL7L1	0.417
NUP133	0.417
SLC38A7	0.416
RPL26	0.416
HIVEP3	0.416
KIF3C	0.415
TSPY1	0.415
TERF2	0.414
GOLGA6L4	0.414
INTS5	0.413
SAP30BP	0.413
OGFR	0.412
FCN2	0.412
TIPIN	0.412
MCM10	0.412
NBPF10	0.412
GPRIN2	0.411
GLTSCR2	0.411
POLR2F	0.411
TRAIP	0.41
SNX15	0.41
DIDO1	0.409
UPF1	0.408
GOLGA8K	0.408
IGFN1	0.408
NBPF16	0.408
NUFIP2	0.408
NUP205	0.408
PHF2	0.407
HMGCR	0.407
PARP3	0.406
MYT1L	0.406
ATP6V1A	0.406
LRRC56	0.405
COX7A2L	0.405
MYLK3	0.405
ARHGEF35	0.404
PSMB3	0.404
CIAPIN1	0.404
RPS9	0.404
NUMA1	0.404
CDC45	0.403
PIGS	0.403
BRD2	0.403
CCDC116	0.403
RPL8	0.402
PBXIP1	0.402
RPS19	0.402
ADD2	0.402
POLD1	0.401
CGB2	0.401
GOLGA6L6	0.401
CNOT1	0.401
HGC6.3	0.401
EXOSC5	0.401
SFPQ	0.401
GPT	0.4
TRIM52	0.4
UBAP1	0.4
ADRA1D	0.4

Global Fraction of Cell Lines Where Essential: 733/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	1/1
909776.0	1/1
bile duct	28/28
blood	28/28
bone	26/26
breast	32/33
central nervous system	56/56
cervix	4/4
colorectal	17/17
esophagus	13/13
fibroblast	1/1
gastric	16/16
kidney	21/21
liver	19/20
lung	74/75
lymphocyte	16/16
ovary	26/26
pancreas	24/24
peripheral nervous system	16/16
plasma cell	15/15
prostate	1/1
skin	24/24
soft tissue	8/9
thyroid	2/2
upper aerodigestive	21/22
urinary tract	29/29
uterus	5/5

Essentiality in NALM6

Essentiality Rank: 746
Expression level (log2 read counts): 6.89

Expression Distribution

Cul4B-RING E3 ubiquitin ligase complex
Cul4A-RING E3 ubiquitin ligase complex
signal transduction involved in G2 DNA damage checkpoint
Cul4-RING E3 ubiquitin ligase complex
positive regulation of G2/M transition of mitotic cell cycle
G2 DNA damage checkpoint
positive regulation of cell cycle G2/M phase transition
DNA damage response, detection of DNA damage
translesion synthesis
DNA synthesis involved in DNA repair
postreplication repair
protein monoubiquitination
signal transduction involved in DNA damage checkpoint
signal transduction involved in DNA integrity checkpoint
signal transduction involved in cell cycle checkpoint
positive regulation of mitotic cell cycle phase transition
positive regulation of cell cycle phase transition
negative regulation of cell cycle G2/M phase transition
signal transduction in response to DNA damage
DNA biosynthetic process
chromosome
DNA damage checkpoint
response to UV
DNA integrity checkpoint
positive regulation of mitotic cell cycle
cell cycle checkpoint
regulation of G2/M transition of mitotic cell cycle
regulation of cell cycle G2/M phase transition
DNA replication
positive regulation of protein catabolic process
negative regulation of cell cycle phase transition
nuclear membrane
ubiquitin-protein transferase activity
rhythmic process
positive regulation of cell cycle process
protein polyubiquitination
response to light stimulus
negative regulation of cell cycle process
post-translational protein modification
positive regulation of cell cycle