Biomarker: SMARCA4

Histology type: Dedifferentiated endometrial carcinomas (DDECs)/undifferentiated endometrial carcinomas (UDECs)

Country: Canada

Region: BC

Followed up time :

Conclusion: ARID1B, SMARCA4 and SMARCB1 immunohistochemistry can be used to aid in the differentiation betweenDedifferentiated endometrial carcinomas (DDECs)/undifferentiated endometrial carcinomas (UDECs) andneuroendocrine carcinoma (NEC).

Sample type : tissues

Sample method: immunohistochemistry

Expression pattern : upregulated

Funtion Uniprot: 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). In brown adipose tissue, involved in the regulation of thermogenic genes expression (By similarity).

UniProt Link: https://www.uniprot.org/uniprotkb/P51532

Biological function from UniProt: #Neurogenesis #Transcription #Transcription regulation

Molecular function from UniProt:

Tissue specificity from UniProt: 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).

Subcellular UniProt: #Nucleus

Recommended name: Transcription activator BRG1

Gene name from HGNC: SMARCA4

HPA class: Cancer-related genes Disease related genes Human disease related genes Plasma proteins

AlphaFold DB: P51532

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P51532

HPA link: https://www.proteinatlas.org/ENSG00000127616-SMARCA4

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Squamous epithelium - Innate immune response (mainly)

Single cell type specificity Low cell type specificity

Immune cell specificity: Low immune cell specificity

Cancer prognostic summary HPA Prognostic marker in liver cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000127616-SMARCA4/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000127616-SMARCA4/pathology/endometrial+cancer

OMIM: 603254

OMIM link2: https://www.omim.org/entry/603254