DegronMD - Q15047(SETDB1)

FUNCTION: Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation (PubMed:12869583). Required for HUSH-mediated heterochromatin formation and gene silencing. Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation (PubMed:27732843, PubMed:14536086). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 (PubMed:14536086,). SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:O88974, ECO:0000269|PubMed:12869583, ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:27732843}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P285Q	TCGA-09-2044	OV	TCGA	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation rewiring degron network	0.1111
p.P285Q	TCGA-09-2044	OV	TCGA	RFLIFFD	LIG_APCC_ABBAyCdc20_2	292:298	Mutation rewiring degron network	0.1389
p.P285Q	DO28923	OV	ICGC	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation rewiring degron network	0.1111
p.P285Q	DO28923	OV	ICGC	RFLIFFD	LIG_APCC_ABBAyCdc20_2	292:298	Mutation rewiring degron network	0.1389
p.Q307L	TCGA-86-6562	LUAD	TCGA	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation rewiring degron network	0.0833
p.Q307L	TCGA-86-6562	LUAD	TCGA	RFLIFFD	LIG_APCC_ABBAyCdc20_2	292:298	Mutation rewiring degron network	0.0833
p.Q307L	DO24013	LUAD	ICGC	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation rewiring degron network	0.0833
p.Q307L	DO24013	LUAD	ICGC	RFLIFFD	LIG_APCC_ABBAyCdc20_2	292:298	Mutation rewiring degron network	0.0833
p.D298Y	TCGA-A1-A0SO	BRCA	TCGA	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation altering degron motif	0.7325
p.D298Y	TCGA-A1-A0SO	BRCA	TCGA	RFLIFFD	LIG_APCC_ABBAyCdc20_2	292:298	Mutation altering degron motif	0.7325
p.V132G	TCGA-A5-A0G2	UCEC	TCGA	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation rewiring degron network	0.2222
p.V132G	DO41235	UCEC	ICGC	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation rewiring degron network	0.2222
p.T943I	TCGA-A6-2684	COAD	TCGA	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.1944
p.T943I	DO10236	COAD	ICGC	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.1944
p.K290T	TCGA-BR-8680	STAD	TCGA	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation substituting flanking lysine	0.3611
p.K290T	DO47769	STAD	ICGC	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation substituting flanking lysine	0.3611
p.D299Y	TCGA-D6-A4ZB	HNSC	TCGA	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation rewiring degron network	0.3056
p.D299Y	TCGA-D6-A4ZB	HNSC	TCGA	RFLIFFD	LIG_APCC_ABBAyCdc20_2	292:298	Mutation rewiring degron network	0.3056
p.D299Y	DO44446	HNSC	ICGC	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation rewiring degron network	0.3056
p.D299Y	DO44446	HNSC	ICGC	RFLIFFD	LIG_APCC_ABBAyCdc20_2	292:298	Mutation rewiring degron network	0.3056
p.R151C	TCGA-DF-A2KZ	UCEC	TCGA	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation rewiring degron network	0.0833
p.R151C	TCGA-EE-A2MJ	SKCM	TCGA	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation rewiring degron network	0.0833
p.R151C	DO38099	SKCM	ICGC	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation rewiring degron network	0.0833
p.R151C	DO52409	UCEC	ICGC	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation rewiring degron network	0.0833
p.L294I	TCGA-EO-A22U	UCEC	TCGA	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation altering degron motif	0.6063
p.L294I	TCGA-EO-A22U	UCEC	TCGA	RFLIFFD	LIG_APCC_ABBAyCdc20_2	292:298	Mutation altering degron motif	0.6063
p.S940F	TCGA-MN-A4N4	LUAD	TCGA	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.2778
p.S940F	DO26250	LUAD	ICGC	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.2778
p.R932Q	TCGA-N5-A4RO	UCS	TCGA	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.2778
p.Y304C	TCGA-R8-A6MO	LGG	TCGA	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation rewiring degron network	0.1667
p.Y304C	TCGA-R8-A6MO	LGG	TCGA	RFLIFFD	LIG_APCC_ABBAyCdc20_2	292:298	Mutation rewiring degron network	0.1667
p.Y304C	DO48508	LGG	ICGC	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation rewiring degron network	0.1667
p.Y304C	DO48508	LGG	ICGC	RFLIFFD	LIG_APCC_ABBAyCdc20_2	292:298	Mutation rewiring degron network	0.1667
p.G933S	TCGA-W3-AA1R	SKCM	TCGA	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.3056
p.G933S	DO51275	SKCM	ICGC	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.3056
p.D131G	DO224763	BRCA	ICGC	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation rewiring degron network	0.1944
p.R932W	DO222769	COCA	ICGC	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.2778
p.R928Q	DO233617	GACA	ICGC	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.1667
p.S142I	DO228952	LICA	ICGC	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation altering degron motif	0.7341
p.S134I	DO228976	LICA	ICGC	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation blocking phosphorylation signal	0.7222
p.V305F	DO228985	LICA	ICGC	FLIFFD	LIG_APCC_ABBA_1	293:298	Mutation rewiring degron network	0.1389
p.V305F	DO228985	LICA	ICGC	RFLIFFD	LIG_APCC_ABBAyCdc20_2	292:298	Mutation rewiring degron network	0.1389
p.Q930H	DO229045	LICA	ICGC	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.2222
p.Q930H	SIDM00958	Chronic Myelogenous Leukemia	GDSC	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.2222
p.Q930H	ACH-000920	Leukemia	CCLE	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.2222
p.Q930H	CML-T1	haematopoietic and lymphoid tissue	COSMIC	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.2222
p.T927P	DO45049	LINC	ICGC	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.1389
p.H948R	SIDM00845	Burkitt's Lymphoma	GDSC	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation rewiring degron network	0.0556
p.N937D	SIDM01263	T-Lymphoblastic Leukemia	GDSC	QKENG	DEG_APCC_KENBOX_2	934:938	Mutation altering degron motif	0.6932
p.I135V	SIDM01033	Bladder Carcinoma	GDSC	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation rewiring degron network	0.3056
p.I135V	ACH-000486	Bladder Cancer	CCLE	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation rewiring degron network	0.3056
p.I135V	KU-19-19	urinary tract	COSMIC	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation rewiring degron network	0.3056
p.L150I	OPM-2	haematopoietic and lymphoid tissue	COSMIC	DSGDAGS	DEG_SCF_TRCP1_1	136:142	Mutation rewiring degron network	0.1111

Kaplan plot for SETDB1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

SETDB1

UniProt ID: Q15047

Entrez ID: 9869

Protein name: Histone-lysine N-methyltransferase SETDB1 (EC 2.1.1.366) (ERG-associated protein with SET domain) (ESET) (Histone H3-K9 methyltransferase 4) (H3-K9-HMTase 4) (Lysine N-methyltransferase 1E) (SET domain bifurcated 1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for SETDB1 in