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SMARCA4 a member of the SWI/SNF nucleosome remodeling complex with ATP-dependent DNA helicase activity. SWI/SNF complexes are required for mammalian development and are mutated in ~20% of all human primary tumors. Mutated in 35% (13/37) of NSCLC and 5% (1/19) of SCLC human lung cancer cell lines . A 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. Belongs to the neural progenitor-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). Component of the BAF53 complex which acetylates histone H4 and H2A within nucleosomes. Transcriptional coactivator of nuclear hormone receptors. Acts as a corepressor of ZEB1 to regulate E-cadherin transcription, and is required for induction of epithelial-mesenchymal transition (EMT) by ZEB1. Can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. SMARCA4, in consort with ZEB1, represses the transcription of E-cadherin and promotes the epithelial-to-mesenchymal transisition (EMT). SMARCA4 is required for stem cell maintenance in the mouse intestinal epithelium. Its loss inhibits aberrant Wnt-signalling and prevents tumorigenesis in the mouse small intestine. SMARCA4 mutations are the cause of 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. Belongs to the SNF2/RAD54 helicase family. The human protein includes 5 isoforms produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Cell cycle regulation; EC 3.6.1.-; EC 3.6.4.-; Helicase; Nuclear receptor co-regulator; Transcription, coactivator/corepressor; Tumor suppressor
Chromosomal Location of Human Ortholog: 19p13.2
Cellular Component: extracellular space; membrane; nuclear chromatin; nucleolus; nucleoplasm; nucleus; protein complex; SWI/SNF complex
Molecular Function: androgen receptor binding; DNA-dependent ATPase activity; nucleosomal DNA binding; p53 binding; protein binding; protein N-terminus binding; Tat protein binding; transcription coactivator activity; transcription corepressor activity; transcription factor binding
Biological Process: ATP-dependent chromatin remodeling; chromatin remodeling; establishment and/or maintenance of chromatin architecture; negative regulation of cell growth; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription from RNA polymerase II promoter, mitotic; negative regulation of transcription, DNA-dependent; nucleosome disassembly; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; positive regulation of Wnt receptor signaling pathway
Disease: Mental Retardation, Autosomal Dominant 16; Rhabdoid Tumor Predisposition Syndrome 2
Reference #:  P51532 (UniProtKB)
Alt. Names/Synonyms: ATP-dependent helicase SMARCA4; BAF190; BAF190A; brahma protein-like 1; BRG1; BRG1-associated factor 190A; BRM/SWI2-related gene 1; FLJ39786; homeotic gene regulator; hSNF2b; Mitotic growth and transcription activator; nuclear protein GRB1; Protein brahma homolog 1; Protein BRG-1; RTPS2; SMARCA4; SMCA4; SNF2; SNF2-beta; SNF2-like 4; SNF2B; SNF2L4; SNF2LB; sucrose nonfermenting-like 4; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4; SWI2; Transcription activator BRG1
Gene Symbols: SMARCA4
Molecular weight: 184,646 Da
Basal Isoelectric point: 7.83  Predict pI for various phosphorylation states
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