Tchem SMARCA4 Transcription activator BRG1

Protein Summary

Description

Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating the calcium-dependent release of a repressor complex and the recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by SMARCA4-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves the release of HDAC1 and recruitment of CREBBP. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development, a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. SMARCA4/BAF190A may promote neural stem cell self-renewal/proliferation by enhancing Notch-dependent proliferative signals, while concurrently making the neural stem cell insensitive to SHH-dependent differentiating cues (By similarity). Acts as a corepressor of ZEB1 to regulate E-cadherin transcription and is required for induction of epithelial-mesenchymal transition (EMT) by ZEB1. Binds via DLX1 to enhancers located in the intergenic region between DLX5 and DLX6 and this binding is stabilized by the long non-coding RNA (lncRNA) Evf2 (By similarity). Binds to RNA in a promiscuous manner (By similarity). Binding to RNAs including lncRNA Evf2 leads to inhibition of SMARCA4 ATPase and chromatin remodeling activities (By similarity). The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

Uniprot Accession IDs

• P51532
• B1A8Z4
• B1A8Z5
• B1A8Z6
• B1A8Z7
• E9PBR8
• O95052
• Q9HBD3

Gene Name

• SMARCA4

Ensembl ID

• ENST00000344626
• ENSP00000343896
• ENSG00000127616
• ENST00000429416
• ENSP00000395654
• ENST00000444061
• ENSP00000392837
• ENST00000541122
• ENSP00000445036
• ENST00000589677
• ENSP00000464778
• ENST00000590574
• ENSP00000466963
• ENST00000643296
• ENSP00000496635
• ENST00000644737
• ENSP00000495548
• ENST00000645460
• ENSP00000494463
• ENST00000646484
• ENSP00000495536
• ENST00000646510
• ENSP00000494772
• ENST00000647230
• ENSP00000494676

Symbol

• BAF190A
• BRG1
• SNF2B
• SNF2L4
• BRG1
• CSS4
• SNF2
• SWI2
• MRD16
• RTPS2
• BAF190
• SNF2L4
• SNF2LB
• hSNF2b
• BAF190A

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
molecular function	1
protein complex	1
protein domain	1

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Helicase / Dna Helicase / Transcription Activator Brg1

Protein / Nucleic Acid Binding / Dna Binding Protein / Dna Helicase / Transcription Activator Brg1

DTO Classes

Protein / Epigenetic Regulator / Reader / Bromodomain / Transcription Activator Brg1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1135.71   (req: < 5)

Gene RIFs: 359   (req: <= 3)

Antibodies: 444   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1135.71   (req: >= 5)

Gene RIFs: 359   (req: > 3)

Antibodies: 444   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 35

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 15

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0