BRD4 bromodomain containing 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: BRD4provided by HGNC
Official Full Name: bromodomain containing 4provided by HGNC
Primary source: HGNC:HGNC:13575
See related: Ensembl:ENSG00000141867 MIM:608749; Vega:OTTHUMG00000183252
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CAP; MCAP; HUNK1; HUNKI
Summary: The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human RING3 protein, a serine/threonine kinase. Each of these proteins contains two bromodomains, a conserved sequence motif which may be involved in chromatin targeting. This gene has been implicated as the chromosome 19 target of translocation t(15;19)(q13;p13.1), which defines an upper respiratory tract carcinoma in young people. Two alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in placenta (RPKM 10.8), testis (RPKM 9.2) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 19p13.12

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	19	NC_000019.10 (15236836..15332543, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (15348301..15443354, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

miR204 directly binds to UCA1 and the 3'untranslated region of BRD4. Furthermore, UCA1 competed with BRD4 for miR204 binding. miR204 knockdown enhanced BRD4 expression, which can be partially restored by short hairpinUCA1.
Title: Long non‑coding RNA UCA1 promotes papillary thyroid cancer cell proliferation via miR‑204‑mediated BRD4 activation.
High BRD4 expression is associated with preeclampsia.
Title: Bromodomain protein BRD4 is increased in human placentas from women with early-onset preeclampsia.
BRD4 silencing was negatively correlated palomid 529-induced apoptosis in the primary human renal cell carcinoma cells and tumor growth in SCID mice.
Title: Bromodomain-Containing Protein 4 (BRD4) Inhibition Sensitizes Palomid 529-Induced Anti-Renal Cell Carcinoma Cell Activity in Vitro and in Vivo.
Study in melanoma cell and in vivo melanoma models provides evidence for a direct role of BRD4 binding at super-enhancers that drive the expression of PGC-1alphaalpha and SOX10, a transcription factor involved in melanocyte development.
Title: Super-enhancers define a proliferative PGC-1α-expressing melanoma subgroup sensitive to BET inhibition.
miR-608 inhibits hepatocellular carcinoma cell proliferation possibly via targeting BET family protein BRD4.
Title: microRNA-608 inhibits human hepatocellular carcinoma cell proliferation via targeting the BET family protein BRD4.
MS645 blocks BRD4 binding to transcription enhancer/mediator proteins MED1 and YY1 with potency superior to monovalent BET inhibitors, resulting in down-regulation of proinflammatory cytokines and genes for cell-cycle control and DNA damage repair that are largely unaffected by monovalent BrD inhibition.
Title: Spatially constrained tandem bromodomain inhibition bolsters sustained repression of BRD4 transcriptional activity for TNBC cell growth.
Study shows that BRD4 is significantly highly expressed in gastric cancer patients and cell lines and positively regulates the expression of c-MYC through transcription regulation and epigenetic levels. Functionally, these result demonstrate that the knockdown of BRD4 represses the proliferation and induces the apoptosis of gastric cancer cells through repression of c-MYC.
Title: BRD4 promotes gastric cancer progression through the transcriptional and epigenetic regulation of c-MYC.
BRD4 hyperphosphorylation is associated with cellular transformation in NUT midline carcinoma
Title: Uncovering BRD4 hyperphosphorylation associated with cellular transformation in NUT midline carcinoma.
Results suggest structure-based drug design of bromodomain-containing protein 4 (Brd4) inhibitors.
Title: Molecular docking and dynamics simulation study of flavonoids as BET bromodomain inhibitors.
Cells harboring the fusion gene are selectively sensitive to small-molecule inhibition of protein targets induced by, or bound to, PAX3-FOXO1-occupied super enhancers. Furthermore, PAX3-FOXO1 recruits and requires the BET bromodomain protein BRD4 to function at super enhancers, resulting in a complete dependence on BRD4 and a significant susceptibility to BRD inhibition
Title: PAX3-FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability.

Submit: New GeneRIF Correction See all GeneRIFs (168)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 replication is inhibited by BRD4; siRNA-mediated knockdown allows for Tat-induced latency reversal	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	The RxL or KxL motif and the polybasic cluster of HIV-1 Tat and BRD4 exhibit similar importance for P-TEFb activation	PubMed
	tat	The C-terminal 34 residues (1329-1362) of BRD4 are crucial for interaction with P-TEFb. Overexpression of the BRD4 P-TEFb-interacting domain disrupts the interaction between HIV-1 Tat and P-TEFb	PubMed
	tat	CDK9-CycT1-AFF1 is stimulated by HIV-1 Tat and transferred as a single complex unit to BRD4 upon stress-induced disruption of AFF1-containing 7SK snRNP (HEXIM1, MEPCE, LARP7, 7SK RNA, CDK9, CycT1, and AFF1)	PubMed
	tat	Phosphorylation of CDK9 at position Ser175 regulates the competition between HIV-1 Tat and BRD4 for P-TEFb binding	PubMed
	tat	Brd4 inhibits HIV-1 Tat-human super elongation complex (components AFF4, ELL2, CycT1, and CDK9) by competing with HIV-1 Tat for binding to P-TEFb on HIV-1 promoter	PubMed
	tat	JQ1, a small molecule inhibitor of Brd4, directly dissociates Brd4 from HIV-1 promoter and promotes subsequently HIV-1 Tat binding to HIV-1 promoter, resulting in increased phosphorylation of RNA polymerase II and viral transcription	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH69303 (e-PCR)
- UniSTS:73824

MARC_6953-6954:992007586:1 (e-PCR)
- UniSTS:231291

MARC_6953-6954:996689872:1 (e-PCR)
- UniSTS:231291

G19768 (e-PCR)
- UniSTS:29337

A001Y01 (e-PCR)
- UniSTS:29338

RH91446 (e-PCR)
- UniSTS:90352

G20884 (e-PCR)
- UniSTS:81145

A006J46 (e-PCR)
- UniSTS:81146

Homology

Orthologs from Annotation Pipeline: 165 organisms have orthologs with human gene BRD4
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
RNA polymerase II C-terminal domain binding	IDA Inferred from Direct Assay more info	PubMed
RNA polymerase II CTD heptapeptide repeat kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
lysine-acetylated histone binding	IDA Inferred from Direct Assay more info	PubMed
p53 binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
cellular response to DNA damage stimulus	IEA Inferred from Electronic Annotation more info
chromatin organization	IEA Inferred from Electronic Annotation more info
positive regulation of G2/M transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of I-kappaB kinase/NF-kappaB signaling	IDA Inferred from Direct Assay more info	PubMed
positive regulation of histone H3-K36 trimethylation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription elongation from RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription elongation from RNA polymerase II promoter	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
protein phosphorylation	IEA Inferred from Electronic Annotation more info
regulation of inflammatory response	IDA Inferred from Direct Assay more info	PubMed
regulation of phosphorylation of RNA polymerase II C-terminal domain	IDA Inferred from Direct Assay more info	PubMed
regulation of transcription involved in G1/S transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
viral process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
condensed nuclear chromosome	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: bromodomain-containing protein 4

Names: chromosome-associated protein

NP_001317313.1

EC 3.1.1.31

NP_055114.1

EC 3.1.1.31

NP_490597.1

EC 3.1.1.31

XP_011526156.1

EC 3.1.1.31

XP_011526158.1

EC 3.1.1.31

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001330384.1 → NP_001317313.1 bromodomain-containing protein 4 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (short) differs in the 3' UTR and coding region compared to variant long. The resulting isoform (short) is shorter and has a distinct C-terminus compared to isoform long.

Source sequence(s)

AC005776, BC035266

Consensus CDS

CCDS82307.1

UniProtKB/Swiss-Prot

O60885

UniProtKB/TrEMBL

A0A024R7H8

Related

ENSP00000353112.4, ENST00000360016.9

Conserved Domains (3) summary

cd05497
Location:58 → 164

Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...

cd05498
Location:353 → 454

Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...

pfam17035
Location:609 → 673

BET; Bromodomain extra-terminal - transcription regulation
NM_014299.2 → NP_055114.1 bromodomain-containing protein 4 isoform short

See identical proteins and their annotated locations for NP_055114.1

Status: REVIEWED

Description

Transcript Variant: This variant (short) differs in the 3' UTR and coding region compared to variant long. The resulting isoform (short) is shorter and has a distinct C-terminus compared to isoform long.

Source sequence(s)

AC004798, BC035266, Y12059

Consensus CDS

CCDS46004.1

UniProtKB/Swiss-Prot

O60885

Related

ENSP00000360901.3, OTTHUMP00000271251, ENST00000371835.8, OTTHUMT00000465801

Conserved Domains (3) summary

cd05497
Location:58 → 164

Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...

cd05498
Location:353 → 454

Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...

pfam17035
Location:609 → 673

BET; Bromodomain extra-terminal - transcription regulation
NM_058243.2 → NP_490597.1 bromodomain-containing protein 4 isoform long

See identical proteins and their annotated locations for NP_490597.1

Status: REVIEWED

Description

Transcript Variant: This variant (long) encodes the full length isoform.

Source sequence(s)

AF386649, BC035266

Consensus CDS

CCDS12328.1

UniProtKB/Swiss-Prot

O60885

Related

ENSP00000263377.1, OTTHUMP00000271250, ENST00000263377.6, OTTHUMT00000465800

Conserved Domains (6) summary

cd05497
Location:58 → 164

Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...

cd05498
Location:353 → 454

Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...

pfam17035
Location:609 → 673

BET; Bromodomain extra-terminal - transcription regulation

pfam17105
Location:1321 → 1362

BRD4_CDT; C-terminal domain of bromodomain protein 4

cl25742
Location:1230 → 1271

ERM; Ezrin/radixin/moesin family

cl27169
Location:809 → 922

ZipA; ZipA C-terminal domain. ZipA, a membrane-anchored protein, is one of at least nine essential gene products necessary for assembly of the septal ring which mediates cell division in E.coli. ZipA and FtsA directly bind FtsZ, a homolog of eukaryotic ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p12 Primary Assembly

Range

15236836..15332543 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011527854.2 → XP_011526156.1 bromodomain-containing protein 4 isoform X1

See identical proteins and their annotated locations for XP_011526156.1

UniProtKB/Swiss-Prot

O60885

Conserved Domains (6) summary

cd05497
Location:58 → 164

Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...

cd05498
Location:353 → 454

Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...

pfam17035
Location:609 → 673

BET; Bromodomain extra-terminal - transcription regulation

pfam17105
Location:1321 → 1362

BRD4_CDT; C-terminal domain of bromodomain protein 4

cl25742
Location:1230 → 1271

ERM; Ezrin/radixin/moesin family

cl27169
Location:809 → 922

ZipA; ZipA C-terminal domain. ZipA, a membrane-anchored protein, is one of at least nine essential gene products necessary for assembly of the septal ring which mediates cell division in E.coli. ZipA and FtsA directly bind FtsZ, a homolog of eukaryotic ...
XM_011527856.3 → XP_011526158.1 bromodomain-containing protein 4 isoform X2

See identical proteins and their annotated locations for XP_011526158.1

UniProtKB/Swiss-Prot

O60885

Conserved Domains (3) summary

cd05497
Location:58 → 164

Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...

cd05498
Location:353 → 454

Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...

pfam17035
Location:609 → 673

BET; Bromodomain extra-terminal - transcription regulation