DegronMD - O60885(BRD4)

FUNCTION: Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure (PubMed:23589332, PubMed:23317504, PubMed:22334664). During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters. Also recruits P-TEFb complex to distal enhancers, so called anti-pause enhancers in collaboration with JMJD6. BRD4 and JMJD6 are required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II (PubMed:23589332, PubMed:19596240, PubMed:16109377, PubMed:16109376, PubMed:24360279). Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II (PubMed:23086925). According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II; these data however need additional evidences in vivo (PubMed:22509028). In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B (PubMed:19103749). Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters (PubMed:23317504). {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:19596240, ECO:0000269|PubMed:22334664, ECO:0000269|PubMed:22509028, ECO:0000269|PubMed:23086925, ECO:0000269|PubMed:23317504, ECO:0000269|PubMed:23589332, ECO:0000269|PubMed:24360279}.; FUNCTION: [Isoform B]: Acts as a chromatin insulator in the DNA damage response pathway. Inhibits DNA damage response signaling by recruiting the condensin-2 complex to acetylated histones, leading to chromatin structure remodeling, insulating the region from DNA damage response by limiting spreading of histone H2AX/H2A.x phosphorylation. {ECO:0000269|PubMed:23728299}. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

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

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.D301N	TCGA-56-7582	LUSC	TCGA	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation rewiring degron network	0.1944
p.D301N	DO26976	LUSC	ICGC	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation rewiring degron network	0.1944
p.P1210L	TCGA-A6-6781	COAD	TCGA	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.6471
p.P1210L	TCGA-GN-A266	SKCM	TCGA	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.6471
p.P1210L	DO8447	COAD	ICGC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.6471
p.P1210L	DO37432	SKCM	ICGC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.6471
p.R1229H	TCGA-AA-3949	COAD	TCGA	AKSSS	DEG_SPOP_SBC_1	1217:1221	Mutation rewiring degron network	0.1111
p.R1229H	DO7798	COAD	ICGC	AKSSS	DEG_SPOP_SBC_1	1217:1221	Mutation rewiring degron network	0.1111
p.D491N	TCGA-B5-A11H	UCEC	TCGA	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation rewiring degron network	0.1944
p.D491N	DO42825	UCEC	ICGC	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation rewiring degron network	0.1944
p.P1213H	TCGA-BF-A1Q0	SKCM	TCGA	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.7694
p.P1213H	DO47374	SKCM	ICGC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.7694
p.T296P	TCGA-BH-A0B8	BRCA	TCGA	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation altering degron motif	0.8142
p.T296P	DO230845	AML	ICGC	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation altering degron motif	0.8142
p.T296P	DO5486	BRCA	ICGC	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation altering degron motif	0.8142
p.I233N	TCGA-CZ-5453	KIRC	TCGA	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation altering degron motif	0.728
p.I233N	DO18016	KIRC	ICGC	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation altering degron motif	0.728
p.R1228C	TCGA-D9-A6EC	SKCM	TCGA	AKSSS	DEG_SPOP_SBC_1	1217:1221	Mutation rewiring degron network	0.1389
p.R1228C	DO50291	SKCM	ICGC	AKSSS	DEG_SPOP_SBC_1	1217:1221	Mutation rewiring degron network	0.1389
p.P483T	TCGA-DX-A6YT	SARC	TCGA	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation altering degron motif	0.5919
p.P483T	DO220007	SARC	ICGC	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation altering degron motif	0.5919
p.S1215F	TCGA-EE-A2MU	SKCM	TCGA	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.6871
p.S1215F	DO37436	SKCM	ICGC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.6871
p.P226L	TCGA-GF-A3OT	SKCM	TCGA	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation rewiring degron network	0.1389
p.P226L	DO47288	SKCM	ICGC	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation rewiring degron network	0.1389
p.V234I	TCGA-L5-A4OI	ESCA	TCGA	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation altering degron motif	0.5965
p.E1225K	TCGA-Q1-A73O	CESC	TCGA	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation rewiring degron network	0.0833
p.E1225K	TCGA-Q1-A73O	CESC	TCGA	AKSSS	DEG_SPOP_SBC_1	1217:1221	Mutation rewiring degron network	0.2222
p.E1225K	DO51612	CESC	ICGC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation rewiring degron network	0.0833
p.E1225K	DO51612	CESC	ICGC	AKSSS	DEG_SPOP_SBC_1	1217:1221	Mutation rewiring degron network	0.2222
p.E1225K	DO231481	THCA	ICGC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation rewiring degron network	0.0833
p.E1225K	DO231481	THCA	ICGC	AKSSS	DEG_SPOP_SBC_1	1217:1221	Mutation rewiring degron network	0.2222
p.E1225K	DO234131	THCA	ICGC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation rewiring degron network	0.0833
p.E1225K	DO234131	THCA	ICGC	AKSSS	DEG_SPOP_SBC_1	1217:1221	Mutation rewiring degron network	0.2222
p.S488G	TCGA-QG-A5Z2	COAD	TCGA	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation blocking phosphorylation signal	0.7222
p.S488G	DO44096	COAD	ICGC	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation blocking phosphorylation signal	0.7222
p.H223P	DO48400	BLCA	ICGC	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation rewiring degron network	0.0556
p.S492N	DO227987	COCA	ICGC	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation blocking phosphorylation signal	0.6111
p.P297T	DO233245	GACA	ICGC	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation rewiring degron network	0.3056
p.T1216K	DO228974	LICA	ICGC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.7306
p.H223Q	DO228974	LICA	ICGC	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation rewiring degron network	0.0556
p.A481D	DO228971	LICA	ICGC	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation rewiring degron network	0.3056
p.A481D	DO229015	LICA	ICGC	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation rewiring degron network	0.3056
p.P226T	DO229019	LICA	ICGC	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation rewiring degron network	0.1389
p.S490R	DO229026	LICA	ICGC	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation rewiring degron network	0.2222
p.S490R	DO229036	LICA	ICGC	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation rewiring degron network	0.2222
p.H1209N	DO229035	LICA	ICGC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation rewiring degron network	0.3056
p.H1209N	DO229035	LICA	ICGC	AKSSS	DEG_SPOP_SBC_1	1217:1221	Mutation rewiring degron network	0.1111
p.D301E	DO229045	LICA	ICGC	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation rewiring degron network	0.1944
p.I300T	DO23296	LINC	ICGC	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation rewiring degron network	0.2222
p.S1214F	DO220851	MELA	ICGC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.6871
p.S485F	DO220900	MELA	ICGC	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation altering degron motif	0.7982
p.W1202C	DO50684	ORCA	ICGC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation rewiring degron network	0.1111
p.H223Y	DO46394	OV	ICGC	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation rewiring degron network	0.0556
p.T295P	DO38376	STAD	ICGC	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation altering degron motif	0.7031
p.T295P	ACH-000943	Colon/Colorectal Cancer	CCLE	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation altering degron motif	0.7031
p.V480L	DO229208	THCA	ICGC	PPSSS	DEG_SPOP_SBC_1	482:486	Mutation rewiring degron network	0.2778
p.V228I	DO229542	UTCA	ICGC	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation rewiring degron network	0.1944
p.K285N	SIDM00630	Breast Carcinoma	GDSC	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation substituting flanking lysine	0.25
p.K285N	ACH-000876	Breast Cancer	CCLE	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation substituting flanking lysine	0.25
p.A1203T	SIDM00216	Colorectal Carcinoma	GDSC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation rewiring degron network	0.1389
p.A1203T	ACH-000989	Colon/Colorectal Cancer	CCLE	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation rewiring degron network	0.1389
p.A1203T	SNU-175	large intestine	COSMIC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation rewiring degron network	0.1389
p.A292T	SIDM00660	Colorectal Carcinoma	GDSC	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation altering degron motif	0.7139
p.A292T	ACH-000985	Colon/Colorectal Cancer	CCLE	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation altering degron motif	0.7139
p.A292T	LS-411N	large intestine	COSMIC	ADTTT	DEG_SPOP_SBC_1	292:296	Mutation altering degron motif	0.7139
p.Q245R	SIDM01617	Endometrial Carcinoma	GDSC	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation rewiring degron network	0.1944
p.Q245R	ACH-000994	Endometrial/Uterine Cancer	CCLE	IVQTPVMT	DEG_SCF_FBW7_1	233:240	Mutation rewiring degron network	0.1944
p.T1212P	ACH-000833	Sarcoma	CCLE	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.7031
p.T1212P	SJRH30	soft tissue	COSMIC	PTTPSST	DEG_SCF_FBW7_1	1210:1216	Mutation altering degron motif	0.7031

Kaplan plot for BRD4 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

BRD4

UniProt ID: O60885

Entrez ID: 23476

Protein name: Bromodomain-containing protein 4 (Protein HUNK1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for BRD4 in