SMARCA4

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]

SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 4

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).

Biological Process chromatin remodelingManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of androgen receptor signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process negative regulation of cell differentiation1 PublicationIC:ComplexPortal
Biological Process negative regulation of cell growthManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process negative regulation of DNA-templated transcriptionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentTAS:BHF-UCL
Biological Process nervous system developmentIEA:UniProtKB-KW
Biological Process neural retina developmentManual Assertion Based On ExperimentIEP:BHF-UCL
Biological Process nucleosome disassemblyManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation by host of viral transcriptionManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of cell differentiation2 PublicationsIC:ComplexPortal
Biological Process positive regulation of cell population proliferation1 PublicationIC:ComplexPortal
Biological Process positive regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of DNA-templated transcriptionManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of double-strand break repair2 PublicationsIC:ComplexPortal
Biological Process positive regulation of glucose mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of miRNA transcriptionManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of myoblast differentiation2 PublicationsIC:ComplexPortal
Biological Process positive regulation of stem cell population maintenance2 PublicationsIC:ComplexPortal
Biological Process positive regulation of T cell differentiation1 PublicationIC:ComplexPortal
Biological Process positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of transcription of nucleolar large rRNA by RNA polymerase IManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of Wnt signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process regulation of G0 to G1 transition1 PublicationIC:ComplexPortal
Biological Process regulation of G1/S transition of mitotic cell cycle1 PublicationIC:ComplexPortal
Biological Process regulation of mitotic metaphase/anaphase transition2 PublicationsIC:ComplexPortal
Biological Process regulation of nucleotide-excision repair1 PublicationIC:ComplexPortal
Biological Process regulation of transcription by RNA polymerase II1 PublicationNAS:BHF-UCL
Biological Process RNA polymerase I preinitiation complex assemblyIEA:GOC

Nucleus
Colocalizes with long non-coding RNA Evf2 in nuclear RNA clouds.

Rhabdoid tumor predisposition syndrome 2 (RTPS2):
A familial cancer syndrome predisposing to renal or extrarenal malignant rhabdoid tumors and to a variety of tumors of the central nervous system, including choroid plexus carcinoma, medulloblastoma, and central primitive neuroectodermal tumors. Rhabdoid tumors are the most aggressive and lethal malignancies occurring in early childhood.
Coffin-Siris syndrome 4 (CSS4):
A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported.