DegronMD - Q9BYW2(SETD2)

FUNCTION: Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (PubMed:19332550). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002). Acts as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (PubMed:21792193). Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565, PubMed:28753426). Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (PubMed:28753426). {ECO:0000250|UniProtKB:E9Q5F9, ECO:0000269|PubMed:16118227, ECO:0000269|PubMed:19141475, ECO:0000269|PubMed:21526191, ECO:0000269|PubMed:21792193, ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:23325844, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24843002, ECO:0000269|PubMed:27317772, ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426}.; FUNCTION: (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. {ECO:0000269|PubMed:11461154}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S2470I	TCGA-12-0707	GBM	TCGA	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation rewiring degron network	0.1667
p.S2470I	DO12634	GBM	ICGC	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation rewiring degron network	0.1667
p.E2472K	TCGA-AA-3984	COAD	TCGA	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation rewiring degron network	0.1111
p.E2472K	DO9002	COAD	ICGC	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation rewiring degron network	0.1111
p.S2452L	TCGA-AD-6548	COAD	TCGA	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation rewiring degron network	0.1111
p.S2452L	TCGA-B5-A11E	UCEC	TCGA	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation rewiring degron network	0.1111
p.S2452L	DO9586	COAD	ICGC	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation rewiring degron network	0.1111
p.S2452L	DO41644	UCEC	ICGC	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation rewiring degron network	0.1111
p.A2460V	TCGA-AM-5821	COAD	TCGA	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation altering degron motif	0.5825
p.A2460V	DO8240	COAD	ICGC	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation altering degron motif	0.5825
p.S1849L	TCGA-B5-A0JY	UCEC	TCGA	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation blocking phosphorylation signal	0.6389
p.S1849L	TCGA-VQ-A8P2	STAD	TCGA	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation blocking phosphorylation signal	0.6389
p.S1849L	DO234255	ESAD	ICGC	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation blocking phosphorylation signal	0.6389
p.S1849L	DO51761	STAD	ICGC	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation blocking phosphorylation signal	0.6389
p.S1849L	DO43041	UCEC	ICGC	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation blocking phosphorylation signal	0.6389
p.S1849L	ACH-000686	Liver Cancer	CCLE	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation blocking phosphorylation signal	0.6389
p.D1869V	TCGA-BP-4963	KIRC	TCGA	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation rewiring degron network	0.1111
p.D1869V	DO20653	KIRC	ICGC	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation rewiring degron network	0.1111
p.S2463Y	TCGA-CA-6717	COAD	TCGA	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation altering degron motif	0.712
p.S2463Y	DO8264	COAD	ICGC	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation altering degron motif	0.712
p.R1850C	TCGA-E1-A7YK	LGG	TCGA	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation rewiring degron network	0.2222
p.R1850C	DO219793	LGG	ICGC	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation rewiring degron network	0.2222
p.K759E	TCGA-EE-A3AC	SKCM	TCGA	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.3056
p.K759E	DO37631	SKCM	ICGC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.3056
p.S130Y	TCGA-EI-6881	READ	TCGA	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation blocking phosphorylation signal	0.6389
p.S130Y	DO37098	READ	ICGC	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation blocking phosphorylation signal	0.6389
p.D1175Y	TCGA-EO-A22R	UCEC	TCGA	VDSTS	DEG_SPOP_SBC_1	1168:1172	Mutation rewiring degron network	0.25
p.D1175Y	DO42713	UCEC	ICGC	VDSTS	DEG_SPOP_SBC_1	1168:1172	Mutation rewiring degron network	0.25
p.Q1164H	TCGA-EY-A1GU	UCEC	TCGA	VDSTS	DEG_SPOP_SBC_1	1168:1172	Mutation rewiring degron network	0.2222
p.Q1164H	DO41518	UCEC	ICGC	VDSTS	DEG_SPOP_SBC_1	1168:1172	Mutation rewiring degron network	0.2222
p.N1847S	TCGA-NC-A5HM	LUSC	TCGA	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation rewiring degron network	0.1389
p.N1847S	DO219195	LUSC	ICGC	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation rewiring degron network	0.1389
p.S1865I	DO222479	BTCA	ICGC	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation rewiring degron network	0.2222
p.G1182D	DO222765	COCA	ICGC	VDSTS	DEG_SPOP_SBC_1	1168:1172	Mutation rewiring degron network	0.0556
p.P1860S	DO233686	GACA	ICGC	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation altering degron motif	0.5641
p.P2160T	DO228976	LICA	ICGC	PPGY	ITCH	2168:2171	Mutation rewiring degron network	0.1111
p.P1180T	DO228976	LICA	ICGC	VDSTS	DEG_SPOP_SBC_1	1168:1172	Mutation rewiring degron network	0.1111
p.A170E	DO228985	LICA	ICGC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation rewiring degron network	0.1111
p.H147N	DO229025	LICA	ICGC	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation rewiring degron network	0.2222
p.A2165D	DO229031	LICA	ICGC	PPGY	ITCH	2168:2171	Mutation rewiring degron network	0.25
p.T749K	DO229038	LICA	ICGC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation blocking phosphorylation signal	0.6667
p.T181K	DO229038	LICA	ICGC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation altering degron motif	0.7306
p.D1871E	DO229045	LICA	ICGC	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation rewiring degron network	0.0556
p.P1158T	DO229045	LICA	ICGC	VDSTS	DEG_SPOP_SBC_1	1168:1172	Mutation rewiring degron network	0.0556
p.M761I	DO23336	LINC	ICGC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.25
p.M761I	SIDM00057	Neuroblastoma	GDSC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.25
p.M761I	SIDM00552	Rhabdomyosarcoma	GDSC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.25
p.M761I	SIDM01026	Esophageal Squamous Cell Carcinoma	GDSC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.25
p.M761I	SIDM00360	Other Solid Cancers	GDSC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.25
p.M761I	KYSE-510	oesophagus	COSMIC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.25
p.M761I	KYM-1	soft tissue	COSMIC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.25
p.M761I	QGP-1	pancreas	COSMIC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.25
p.P132S	DO220873	MELA	ICGC	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation rewiring degron network	0.25
p.P190S	DO220891	MELA	ICGC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation rewiring degron network	0.1111
p.P2160L	DO220906	MELA	ICGC	PPGY	ITCH	2168:2171	Mutation rewiring degron network	0.1111
p.P187S	DO222635	MELA	ICGC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation rewiring degron network	0.1944
p.K141R	DO32980	PACA	ICGC	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation altering degron motif	0.6126
p.E138D	DO229491	SKCA	ICGC	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation altering degron motif	0.5647
p.Q757H	SIDM02021	Esophageal Carcinoma	GDSC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation altering degron motif	0.647
p.V768L	SIDM00759	Non-Small Cell Lung Carcinoma	GDSC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.0556
p.V768L	SIDM00650	Small Cell Lung Carcinoma	GDSC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.0556
p.V768L	SIDM00954	Breast Carcinoma	GDSC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.0556
p.V768L	SIDM01681	Non-Cancerous	GDSC	VSPHQD	LIG_APCC_ABBA_1	753:758	Mutation rewiring degron network	0.0556
p.P1858H	SIDM00577	Neuroblastoma	GDSC	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation altering degron motif	0.7694
p.P1858H	ACH-001603	Neuroblastoma	CCLE	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation altering degron motif	0.7694
p.P1858H	NH-12	autonomic ganglia	COSMIC	PLNTPDPS	DEG_SCF_FBW7_1	1854:1861	Mutation altering degron motif	0.7694
p.K145N	SIDM01171	Glioblastoma	GDSC	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation rewiring degron network	0.2778
p.K145N	ACH-000571	Brain Cancer	CCLE	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation rewiring degron network	0.2778
p.K145N	T98G	central nervous system	COSMIC	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation rewiring degron network	0.2778
p.G140D	SIDM00683	Prostate Carcinoma	GDSC	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation altering degron motif	0.6087
p.G140D	ACH-000977	lymph node	CCLE	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation altering degron motif	0.6087
p.G140D	LNCaP-Clone-FGC	prostate	COSMIC	SRVELGKIH	DEG_APCC_DBOX_1	135:143	Mutation altering degron motif	0.6087
p.T182A	SIDM00221	Melanoma	GDSC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation altering degron motif	0.7139
p.P186L	SIDM00670	Pancreatic Carcinoma	GDSC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation rewiring degron network	0.2222
p.P186L	SIDM00309	Mesothelioma	GDSC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation rewiring degron network	0.2222
p.P186L	SIDM01072	Squamous Cell Lung Carcinoma	GDSC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation rewiring degron network	0.2222
p.S180A	SIDM00154	Mesothelioma	GDSC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation altering degron motif	0.7588
p.S180A	ACH-002130	Lung Cancer	CCLE	AESTT	DEG_SPOP_SBC_1	178:182	Mutation altering degron motif	0.7588
p.S180A	H2795	pleura	COSMIC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation altering degron motif	0.7588
p.K2453N	SIDM00534	Colorectal Carcinoma	GDSC	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation substituting flanking lysine	0.25
p.K2453N	ACH-000986	Colon/Colorectal Cancer	CCLE	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation substituting flanking lysine	0.25
p.K2453N	HT-115	large intestine	COSMIC	ADTSS	DEG_SPOP_SBC_1	2460:2464	Mutation substituting flanking lysine	0.25
p.K170Q	HCC2998	large intestine	COSMIC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation rewiring degron network	0.1111
p.R175C	LOXIMVI	skin	COSMIC	AESTT	DEG_SPOP_SBC_1	178:182	Mutation rewiring degron network	0.25

Kaplan plot for SETD2 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

SETD2

UniProt ID: Q9BYW2

Entrez ID: 29072

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for SETD2 in