InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SMARCA4

Summary

InnateDB Protein

IDBP-372046.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SMARCA4

Protein Name

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4

Synonyms

BAF190; BAF190A; BRG1; hSNF2b; MRD16; RTPS2; SNF2; SNF2L4; SNF2LB; SWI2;

Species

Homo sapiens

Ensembl Protein

ENSP00000414727

InnateDB Gene

IDBG-28592 (SMARCA4)

Protein Structure

UniProt Annotation

Function

Transcriptional coactivator cooperating with nuclear hormone receptors to potentiate transcriptional activation. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-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 a 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 post-mitotic 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 post-mitotic 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). Also involved in vitamin D-coupled transcription regulation via its association with the WINAC complex, a chromatin-remodeling complex recruited by vitamin D receptor (VDR), which is required for the ligand-bound VDR-mediated transrepression of the CYP27B1 gene. Acts as a corepressor of ZEB1 to regulate E-cadherin transcription and is required for induction of epithelial- mesenchymal transition (EMT) by ZEB1. {ECO:0000250, ECO:0000269PubMed:12837248, ECO:0000269PubMed:19571879, ECO:0000269PubMed:20418909}.

Subcellular Localization

Nucleus {ECO:0000255PROSITE- ProRule:PRU00549, ECO:0000269PubMed:20418909}.

Disease Associations

Rhabdoid tumor predisposition syndrome 2 (RTPS2) [MIM:613325]: 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. {ECO:0000269PubMed:20137775}. Note=The disease is caused by mutations affecting the gene represented in this entry.Mental retardation, autosomal dominant 16 (MRD16) [MIM:614609]: A disease characterized by multiple congenital anomalies and mental retardation. Mental retardation is defined by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD16 patients manifest developmental delay, absent or hypoplastic fifth fingernails or toenails, thick eyebrows and long eyelashes, hirsutism. Additional findings include hypotonia, microcephaly, seizures, a Dandy-Walker malformation, and vision and hearing problems. {ECO:0000269PubMed:22426308}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Colocalizes with ZEB1 in E-cadherin-negative cells from established lines, and stroma of normal colon as well as in de-differentiated epithelial cells at the invasion front of colorectal carcinomas (at protein level). {ECO:0000269PubMed:20418909}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 331 experimentally validated interaction(s) in this database.
They are also associated with 92 interaction(s) predicted by orthology.

Experimentally validated
Total	331 [view]
Protein-Protein	305 [view]
Protein-DNA	24 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	92 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000980	RNA polymerase II distal enhancer sequence-specific DNA binding
GO:0001105	RNA polymerase II transcription coactivator activity
GO:0002039	p53 binding
GO:0003677	DNA binding
GO:0003713	transcription coactivator activity
GO:0003714	transcription corepressor activity
GO:0004386	helicase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008094	DNA-dependent ATPase activity
GO:0016817	hydrolase activity, acting on acid anhydrides
GO:0016818	hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
GO:0030957	Tat protein binding
GO:0031492	nucleosomal DNA binding
GO:0047485	protein N-terminus binding
GO:0050681	androgen receptor binding
GO:0070577	lysine-acetylated histone binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0003407	neural retina development
GO:0006200	ATP catabolic process
GO:0006337	nucleosome disassembly
GO:0006338	chromatin remodeling
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006357	regulation of transcription from RNA polymerase II promoter
GO:0007070	negative regulation of transcription from RNA polymerase II promoter during mitosis
GO:0030308	negative regulation of cell growth
GO:0043044	ATP-dependent chromatin remodeling
GO:0043923	positive regulation by host of viral transcription
GO:0045087	innate immune response (InnateDB)
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0060766	negative regulation of androgen receptor signaling pathway
GO:2000134	negative regulation of G1/S transition of mitotic cell cycle

Cellular Component

GO:0000790	nuclear chromatin
GO:0005615	extracellular space
GO:0005634	nucleus
GO:0005730	nucleolus
GO:0016020	membrane
GO:0016514	SWI/SNF complex
GO:0043234	protein complex
GO:0071564	npBAF complex
GO:0071565	nBAF complex

Protein Structure and Domains

PDB ID

InterPro

IPR000330 SNF2-related
IPR001487 Bromodomain
IPR001650 Helicase, C-terminal
IPR006576 BRK domain
IPR013999 HAS subgroup
IPR014001 Helicase, superfamily 1/2, ATP-binding domain
IPR014012 Helicase/SANT-associated, DNA binding
IPR014978 Glutamine-Leucine-Glutamine, QLQ
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00176
PF00439
PF00271
PF07533
PF07529
PF08880

PRINTS

PR00503

PIRSF

SMART

SM00297
SM00490
SM00592
SM00573
SM00487
SM00951

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt