DegronMD - Q9NZJ0(DTL)

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). {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:26431207, ECO:0000269|PubMed:27906959}. View more >>

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GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.L460V	TCGA-62-A471	LUAD	TCGA	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.3056
p.E648Q	TCGA-AJ-A3QS	UCEC	TCGA	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation rewiring degron network	0.25
p.R417K	TCGA-AP-A0LM	UCEC	TCGA	SRPGLVTVT	DEG_APCC_DBOX_1	416:424	Mutation altering degron motif	0.7237
p.R528I	TCGA-B5-A0JY	UCEC	TCGA	PRKALIPVS	DEG_APCC_DBOX_1	527:535	Mutation altering degron motif	0.8102
p.G208V	TCGA-B8-A54J	KIRC	TCGA	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation rewiring degron network	0.3056
p.P527L	TCGA-BR-4184	STAD	TCGA	PRKALIPVS	DEG_APCC_DBOX_1	527:535	Mutation altering degron motif	0.6471
p.P527L	TCGA-OD-A75X	SKCM	TCGA	PRKALIPVS	DEG_APCC_DBOX_1	527:535	Mutation altering degron motif	0.6471
p.P533H	TCGA-BS-A0UL	UCEC	TCGA	PRKALIPVS	DEG_APCC_DBOX_1	527:535	Mutation altering degron motif	0.6583
p.S520L	TCGA-D1-A0ZO	UCEC	TCGA	PPITPPAS	DEG_SCF_FBW7_1	513:520	Mutation altering degron motif	0.8778
p.S520L	TCGA-KQ-A41R	BLCA	TCGA	PPITPPAS	DEG_SCF_FBW7_1	513:520	Mutation altering degron motif	0.8778
p.L223I	TCGA-D3-A3C8	SKCM	TCGA	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation rewiring degron network	0.2778
p.P517L	TCGA-D3-A5GS	SKCM	TCGA	PPITPPAS	DEG_SCF_FBW7_1	513:520	Mutation altering degron motif	0.7582
p.R507Q	TCGA-E6-A1LX	UCEC	TCGA	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation altering degron motif	0.6218
p.G651D	TCGA-G4-6304	COAD	TCGA	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation altering degron motif	0.6087
p.F497L	TCGA-LT-A5Z6	BLCA	TCGA	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation rewiring degron network	0.1111
p.P527S	TCGA-OD-A75X	SKCM	TCGA	PRKALIPVS	DEG_APCC_DBOX_1	527:535	Mutation altering degron motif	0.5641
p.K202E	TCGA-VQ-A8P2	STAD	TCGA	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation substituting flanking lysine	0.25
p.P465L	TCGA-YG-AA3N	SKCM	TCGA	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation altering degron motif	0.7582
p.S510P	TCGA-ZB-A966	THYM	TCGA	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation altering degron motif	0.6752
p.F455L	DO44029	BLCA	ICGC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.1667
p.S478L	DO223592	BLCA	ICGC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation blocking phosphorylation signal	0.5
p.S478L	DO41927	UCEC	ICGC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation blocking phosphorylation signal	0.5
p.R508I	DO224590	BRCA	ICGC	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation altering degron motif	0.8102
p.R508I	DO1018	BRCA	ICGC	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation altering degron motif	0.8102
p.G650E	DO1076	BRCA	ICGC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation rewiring degron network	0.3056
p.S219F	DO1128	BRCA	ICGC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation altering degron motif	0.7982
p.R228Q	DO6048	BRCA	ICGC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation rewiring degron network	0.1389
p.R508K	DO49916	CESC	ICGC	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation altering degron motif	0.7237
p.R506K	DO49918	CESC	ICGC	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation altering degron motif	0.7237
p.K652T	DO229010	COCA	ICGC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation altering degron motif	0.7306
p.K652T	DO229013	COCA	ICGC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation altering degron motif	0.7306
p.K652T	DO229016	COCA	ICGC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation altering degron motif	0.7306
p.K652T	DO229003	COCA	ICGC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation altering degron motif	0.7306
p.K652T	DO229005	COCA	ICGC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation altering degron motif	0.7306
p.R211Q	DO50449	ESAD	ICGC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation altering degron motif	0.7329
p.T474P	DO228297	LICA	ICGC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.1667
p.S225N	DO228827	LICA	ICGC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation rewiring degron network	0.2222
p.S662I	DO228948	LICA	ICGC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation rewiring degron network	0.1389
p.A209S	DO228976	LICA	ICGC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation altering degron motif	0.7588
p.R204L	DO229029	LICA	ICGC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation rewiring degron network	0.1944
p.A409S	DO229026	LICA	ICGC	SRPGLVTVT	DEG_APCC_DBOX_1	416:424	Mutation rewiring degron network	0.1389
p.V521L	DO229037	LICA	ICGC	PRKALIPVS	DEG_APCC_DBOX_1	527:535	Mutation rewiring degron network	0.1667
p.V521L	DO229037	LICA	ICGC	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation rewiring degron network	0.0833
p.V521L	DO229037	LICA	ICGC	PPITPPAS	DEG_SCF_FBW7_1	513:520	Mutation rewiring degron network	0.3056
p.L418V	DO45347	LUAD	ICGC	SRPGLVTVT	DEG_APCC_DBOX_1	416:424	Mutation altering degron motif	0.6765
p.R512S	DO27240	LUSC	ICGC	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation altering degron motif	0.7427
p.N644K	DO232846	NACA	ICGC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation rewiring degron network	0.1389
p.P643T	DO233293	NACA	ICGC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation rewiring degron network	0.1111
p.H543R	DO36556	READ	ICGC	PRKALIPVS	DEG_APCC_DBOX_1	527:535	Mutation rewiring degron network	0.1111
p.P475L	DO47706	SKCM	ICGC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation substituting flanking lysine	0.25
p.P451L	DO37936	SKCM	ICGC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.0556
p.P223S	DO51268	SKCM	ICGC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation rewiring degron network	0.2778
p.P423L	DO51298	SKCM	ICGC	SRPGLVTVT	DEG_APCC_DBOX_1	416:424	Mutation altering degron motif	0.7582
p.G650R	DO38427	STAD	ICGC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation rewiring degron network	0.3056
p.K510R	DO47789	STAD	ICGC	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation altering degron motif	0.7237
p.P656L	DO40978	UCEC	ICGC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation blocking phosphorylation signal	0.75
p.R465Q	DO41020	UCEC	ICGC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation altering degron motif	0.7329
p.A216S	DO42472	UCEC	ICGC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation altering degron motif	0.7588
p.R477Q	SIDM00322	Esophageal Squamous Cell Carcinoma	GDSC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.0833
p.R477Q	ACH-000561	Esophageal Cancer	CCLE	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.0833
p.R477Q	T-T	oesophagus	COSMIC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.0833
p.A665V	SIDM00572	Gastric Carcinoma	GDSC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation rewiring degron network	0.0556
p.A665V	ACH-000911	Gastric Cancer	CCLE	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation rewiring degron network	0.0556
p.A665V	NUGC-3	stomach	COSMIC	GKENS	DEG_APCC_KENBOX_2	651:655	Mutation rewiring degron network	0.0556
p.A474S	SIDM01251	T-Cell Non-Hodgkin's Lymphoma	GDSC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.1667
p.A474S	ACH-000509	Lymphoma	CCLE	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.1667
p.A474S	ACH-002240	Lymphoma	CCLE	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.1667
p.A474S	H9	haematopoietic and lymphoid tissue	COSMIC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.1667
p.Q540P	SIDM00047	Non-Small Cell Lung Carcinoma	GDSC	PRKALIPVS	DEG_APCC_DBOX_1	527:535	Mutation rewiring degron network	0.1944
p.Q540P	ACH-002102	Lung Cancer	CCLE	PRKALIPVS	DEG_APCC_DBOX_1	527:535	Mutation rewiring degron network	0.1944
p.Q540P	EMC-BAC-2	lung	COSMIC	PRKALIPVS	DEG_APCC_DBOX_1	527:535	Mutation rewiring degron network	0.1944
p.T424M	SIDM00114	Non-Small Cell Lung Carcinoma	GDSC	SRPGLVTVT	DEG_APCC_DBOX_1	416:424	Mutation altering degron motif	0.7423
p.T424M	SIDM00048	Non-Small Cell Lung Carcinoma	GDSC	SRPGLVTVT	DEG_APCC_DBOX_1	416:424	Mutation altering degron motif	0.7423
p.T424M	SIDM00032	Bladder Carcinoma	GDSC	SRPGLVTVT	DEG_APCC_DBOX_1	416:424	Mutation altering degron motif	0.7423
p.T424M	SIDM00907	Burkitt's Lymphoma	GDSC	SRPGLVTVT	DEG_APCC_DBOX_1	416:424	Mutation altering degron motif	0.7423
p.K201N	SIDM00837	Colorectal Carcinoma	GDSC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation substituting flanking lysine	0.2222
p.K201N	ACH-000958	Colon/Colorectal Cancer	CCLE	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation substituting flanking lysine	0.2222
p.L460F	SIDM01128	Small Cell Lung Carcinoma	GDSC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.3056
p.L460F	ACH-000767	Lung Cancer	CCLE	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.3056
p.L460F	NCI-H526	lung	COSMIC	PSNTPTFS	DEG_SCF_FBW7_1	461:468	Mutation rewiring degron network	0.3056
p.D226Y	ACH-000998	Colon/Colorectal Cancer	CCLE	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation rewiring degron network	0.1944
p.D226Y	CW-2	large intestine	COSMIC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation rewiring degron network	0.1944
p.S217F	Mewo	skin	COSMIC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation altering degron motif	0.7982
p.A432S	H9	haematopoietic and lymphoid tissue	COSMIC	SRPGLVTVT	DEG_APCC_DBOX_1	416:424	Mutation blocking ubiquitination signal	0.5556
p.K522Q	Hep_3B2_1-7	NS	COSMIC	PRKALIPVS	DEG_APCC_DBOX_1	527:535	Mutation rewiring degron network	0.1944
p.K522Q	Hep_3B2_1-7	NS	COSMIC	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation rewiring degron network	0.0556
p.K522Q	Hep_3B2_1-7	NS	COSMIC	PPITPPAS	DEG_SCF_FBW7_1	513:520	Mutation rewiring degron network	0.2778
p.Q498P	EMC-BAC-2	lung	COSMIC	VTRTPSSS	DEG_SCF_FBW7_1	505:512	Mutation blocking ubiquitination signal	0.5833
p.L230F	CP66-MEL	skin	COSMIC	LAPSVDFQQSVTV	DEG_ODPH_VHL_1	209:221	Mutation rewiring degron network	0.0833
p.L418F	NCI-H526	lung	COSMIC	SRPGLVTVT	DEG_APCC_DBOX_1	416:424	Mutation altering degron motif	0.6981

Kaplan plot for DTL in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

DTL

UniProt ID: Q9NZJ0

Entrez ID: 51514

Protein name: Denticleless protein homolog (DDB1- and CUL4-associated factor 2) (Lethal(2) denticleless protein homolog) (Retinoic acid-regulated nuclear matrix-associated protein)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for DTL in