7vrb

<table><tr><td colspan='2'>[[7vrb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VRB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VRB FirstGlance]. <br>

</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7vrb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vrb OCA], [https://pdbe.org/7vrb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vrb RCSB], [https://www.ebi.ac.uk/pdbsum/7vrb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vrb ProSAT]</span></td></tr>

== Disease ==

[https://www.uniprot.org/uniprot/SMCA4_HUMAN SMCA4_HUMAN] Defects in SMARCA4 are the cause of rhabdoid tumor predisposition syndrome type 2 (RTPS2) [MIM:[https://omim.org/entry/613325 613325]. RTPS2 is 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.<ref>PMID:20137775</ref> Defects in SMARCA4 are the cause of mental retardation autosomal dominant type 16 (MRD16) [MIM:[https://omim.org/entry/614609 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 adaptative 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.<ref>PMID:22426308</ref> [https://www.uniprot.org/uniprot/SSXT_HUMAN SSXT_HUMAN] Synovial sarcoma. A chromosomal aberration involving SS18 may be a cause of synovial sarcoma. Translocation t(X;18)(p11.2;q11.2). The translocation is specifically found in more than 80% of synovial sarcoma. The fusion products SSXT-SSX1 or SSXT-SSX2 are probably responsible for transforming activity. Heterogeneity in the position of the breakpoint can occur (low frequency).<ref>PMID:7495284</ref> <ref>PMID:7539744</ref>

== Function ==

[https://www.uniprot.org/uniprot/SMCA4_HUMAN SMCA4_HUMAN] 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.<ref>PMID:12837248</ref> <ref>PMID:19571879</ref> <ref>PMID:20418909</ref> [https://www.uniprot.org/uniprot/SSXT_HUMAN SSXT_HUMAN] Appears to function synergistically with RBM14 as a transcriptional coactivator. Isoform 1 and isoform 2 function in nuclear receptor coactivation. Isoform 1 and isoform 2 function in general transcriptional coactivation. Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:29374058).<ref>PMID:15919756</ref> <ref>PMID:29374058</ref>

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Oncoprotein SS18-SSX is a hallmark of synovial sarcomas. However, as a part of the SS18-SSX fusion protein, SS18's function remains unclear. Here, we depict the structures of both human SS18/BRG1 and yeast SNF11/SNF2 subcomplexes. Both subcomplexes assemble into heterodimers that share a similar conformation, suggesting that SNF11 might be a homologue of SS18 in chromatin remodeling complexes. Importantly, our study shows that the self-association of the intrinsically disordered region, QPGY domain, leads to liquid-liquid phase separation (LLPS) of SS18 or SS18-SSX and the subsequent recruitment of BRG1 into phase-separated condensates. Moreover, our results show that the tyrosine residues in the QPGY domain play a decisive role in the LLPS of SS18 or SS18-SSX. Perturbations of either SS18-SSX LLPS or SS18-SSX's binding to BRG1 impair NIH3T3 cell transformation by SS18-SSX. Our data demonstrate that both LLPS and assembling into chromatin remodelers contribute to the oncogenic activity of SS18-SSX in synovial sarcomas.

Phase transition and remodeling complex assembly are important for SS18-SSX oncogenic activity in synovial sarcomas.,Cheng Y, Shen Z, Gao Y, Chen F, Xu H, Mo Q, Chu X, Peng CL, McKenzie TT, Palacios BE, Hu J, Zhou H, Long J Nat Commun. 2022 May 18;13(1):2724. doi: 10.1038/s41467-022-30447-9. PMID:35585082<ref>PMID:35585082</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

<div class="pdbe-citations 7vrb" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Homo sapiens]]