BioPAX pathway converted from "Beta-catenin binds SOX proteins" in the Reactome database.Beta-catenin binds SOX proteinsBeta-catenin binds SOX proteinsThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97851001nucleoplasmGO0005654SRY,SOX2,SOX3,SOX4,SOX6,SOX7,SOX9,SOX17 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitySox3 [nucleoplasm]Sry [nucleoplasm]Sox4 [nucleoplasm]Sox7 [nucleoplasm]Sox9 [nucleoplasm]Sox2 [nucleoplasm]Sox6 [nucleoplasm]Sox17 [nucleoplasm]Reactomehttp://www.reactome.orgMus musculusNCBI Taxonomy10090UniProtP53784UniProtQ05738UniProtQ06831UniProtP40646UniProtQ04887UniProtP48432UniProtP40645UniProtQ61473Reactome DB_ID: 97274811UniProt:Q02248 Ctnnb1Ctnnb1CatnbCtnnb1FUNCTION Key downstream component of the canonical Wnt signaling pathway (PubMed:15132997). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (By similarity). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (PubMed:16325582, PubMed:18093941). Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2. Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (By similarity). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (PubMed:21325504). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (PubMed:15132997).SUBUNIT Two separate complex-associated pools are found in the cytoplasm. The majority is present as component of an E-cadherin/ catenin adhesion complex composed of at least E-cadherin/CDH1 and beta-catenin/CTNNB1, and possibly alpha-catenin/CTNNA1; the complex is located to adherens junctions. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1. Binds SLC9A3R1. Interacts with PTPRU (via the cytoplasmic juxtamembrane domain) and with EMD. Interacts with SESTD1 and TRPC4. Interacts with CAV1. Interacts with PTPRJ. Interacts with PKT7. Interacts with FAT1 (via the cytoplasmic domain). Interacts with CDK2, NDRG2 and NANOS1. Interacts with NEK2 and CDK5. Interacts with CARM1, CXADR, PCDH11Y and PTK6. Interacts with RAPGEF2. Interacts with SOX7; this interaction may lead to proteasomal degradation of active CTNNB1 and thus inhibition of Wnt/beta-catenin-stimulated transcription. Identified in a complex with HINT1 and MITF. Interacts with FHIT. Interacts with FERMT2. Identified in a complex with TCF4 and FERMT2. Another cytoplasmic pool is part of a large complex containing AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. Wnt-dependent activation of DVL antagonizes the action of GSK3B. When GSK3B activity is inhibited the complex dissociates, CTNNB1 is dephosphorylated and is no longer targeted for destruction. The stabilized protein translocates to the nucleus, where it binds TCF/LEF-1 family members, TBP, BCL9, BCL9L and possibly also RUVBL1 and CHD8. Interacts with TAX1BP3 (via the PDZ domain); this interaction inhibits the transcriptional activity of CTNNB1. Interacts with AJAP1, BAIAP1 and CTNNA3. Interacts with TRPV4; the TRPV4 and CTNNB1 complex can interact with CDH1. Interacts with VCL. The CTNNB1 and TCF4 complex interacts with PML. Interacts with XIRP1. Binds CTNNBIP and EP300. CTNNB1 forms a ternary complex with LEF1 and EP300 that is disrupted by CTNNBIP1 binding. Interacts directly with AXIN1; the interaction is regulated by CDK2 phosphorylation of AXIN1. Interacts with GLIS2. Interacts with SCRIB. Interacts with TNIK and TCF7L2. Interacts with SLC30A9. Interacts with RORA. May interact with P-cadherin/CDH3. Interacts with RNF220 (By similarity). Interacts with CTNND2 (By similarity). Interacts (via the C-terminal region) with CBY1 (By similarity). The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9') (By similarity). Interacts with DLG5 (PubMed:25232112). Interacts with FAM53B; promoting translocation to the nucleus. Interacts with TMEM170B (By similarity). Interacts with AHI1 (By similarity). Interacts with GID8 (By similarity). Component of an cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1 (By similarity). Forms a complex comprising APPL1, RUVBL2, APPL2, HDAC1 and HDAC2 (By similarity). Interacts with IRF2BPL; mediates the ubiquitination and degradation of CTNNB1 (By similarity). Interacts with AMFR (PubMed:31073040). Interacts with LMBR1L (PubMed:31073040). Interacts with SOX30; prevents interaction of CTNNB1 with TCF7L2/TCF4 and leads to inhibition of Wnt signaling (By similarity). Interacts with SOX9; inhibiting CTNNB1 activity by competing with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (PubMed:15132997).TISSUE SPECIFICITY Expressed in cerebellar granule neurons (at protein level).PTM Phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase. Phosphorylation proceeds then from Thr-41 to Ser-33. Phosphorylated by NEK2. EGF stimulates tyrosine phosphorylation. Phosphorylation on Tyr-654 decreases CDH1 binding and enhances TBP binding (By similarity). Phosphorylated on Ser-33 and Ser-37 by HIPK2. This phosphorylation triggers proteasomal degradation. Phosphorylation at Ser-552 by AMPK promotes stabilizion of the protein, enhancing TCF/LEF-mediated transcription. Phosphorylation on Ser-191 and Ser-246 by CDK5. Phosphorylation by CDK2 regulates insulin internalization (By similarity). Phosphorylation by PTK6 at Tyr-64, Tyr-142, Tyr-331 and/or Tyr-333 with the predominant site at Tyr-64 is not essential for inhibition of transcriptional activity (By similarity).PTM Ubiquitinated by the SCF(BTRC) E3 ligase complex when phosphorylated by GSK3B, leading to its degradation (By similarity). Ubiquitinated by a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X, leading to its subsequent proteasomal degradation (By similarity). Ubiquitinated and degraded following interaction with SOX9 (Probable).PTM S-nitrosylation at Cys-619 within adherens junctions promotes VEGF-induced, NO-dependent endothelial cell permeability by disrupting interaction with E-cadherin, thus mediating disassembly adherens junctions.PTM O-glycosylation at Ser-23 decreases nuclear localization and transcriptional activity, and increases localization to the plasma membrane and interaction with E-cadherin CDH1.PTM Deacetylated at Lys-49 by SIRT1.DISRUPTION PHENOTYPE Sympathetic ganglia-specific conditional knockout mice lead to a reduction in sympathetic ganglia size and in progenitor cell number, but does not alter sympathetic innervation of peripheral target organs.SIMILARITY Belongs to the beta-catenin family.UniProtQ02248Chain Coordinates1EQUAL781EQUALReactome DB_ID: 97851021CTNNB1:SRY,SOX2,SOX3,SOX4,SOX6,SOX7,SOX9,SOX17 [nucleoplasm]CTNNB1:SRY,SOX2,SOX3,SOX4,SOX6,SOX7,SOX9,SOX17Converted from EntitySet in ReactomeReactome DB_ID: 97851001Reactome DB_ID: 972748111EQUAL781EQUALReactome Database ID Release 759785102Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9785102ReactomeR-MMU-56269151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5626915.1Reactome Database ID Release 759785104Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9785104ReactomeR-MMU-56269381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5626938.1SOX protein family members are the transcription factors that regulate many different development processes and also control homeostasis in adult tissues. SOX proteins can be either transcriptional activators or repressors depending on the cellular context and their associated interacting proteins (Kormish et al. 2010). There are over twenty SOX proteins encoded in mammalian genome of which many of these can physically interact with beta-catenin and TCF (T-cell factor) transcription factors and modulate the Wnt signaling. Evidences suggest that SOX proteins have widespread role in modulating Wnt signaling in development and disease. In most cases SOX proteins repress WNT transcriptional responses, however some SOX proteins appear to enhance WNT-regulated gene expression. The precise mechanism by which SOX proteins regulate beta-catenin/TCF activity are still unclear. Differential recruitment of transcriptional co-activators or co-repressors is one mechanism by which SOX factors can either enhance or repress Wnt-target gene transcription. Another mechanism by which some SOX proteins repress Wnt signaling is by promoting proteosome-mediated beta-catenin degradation (Kormish et al. 2010). <br>Human SRY binds beta-catenin through a N-terminal domain (Bernard et al. 2008), SOX6 interacts via a centrally located leucine zipper (LZ/Q) element (Iguchi et al. 2007), and mammalian SOX7, SOX9 and SOX17 all bind beta-catenin via their C-terminal regions (Zorn et al., 1999; Takash et al., 2001; Akiyama et al., 2004; Sinner et al., 2007, Kormish et al. 2010). SRY and SOX9 function in part by suppressing canonical Wnt signaling by promoting beta-catenin phosphorylation in the nucleus (Topol et al. 2009). SOX9 and SRY are involved in the regulation of mammalian sex determination and mutation in human SRY and SOX9 results in sex reversal, with female development in XY individuals (Bernard et al. 2008). SOX2 binds beta-catenin and promotes cell proliferation by transcriptionally activating the Wnt target Cyclin D1 gene in breast cancer cells (Chen et al., 2008), whereas SOX6 represses Cyclin D1 transcription in pancreatic cells (Iguchi et al., 2007). SOX7 and SOX17 reduce cyclin-D1 expression and repress proliferation by stimulating beta-catenin degradation (Sinner et al. 2007, Zhang et al. 2008, 2009).15132997Pubmed2004Interactions between Sox9 and beta-catenin control chondrocyte differentiationAkiyama, HaruhikoLyons, Jon PMori-Akiyama, YukoYang, XiaohongZhang, RenZhang, ZhaopingDeng, Jian MinTaketo, Makoto MNakamura, TakashiBehringer, Richard RMcCrea, Pierre Dde Crombrugghe, BenoitGenes Dev. 18:1072-8719631281Pubmed2010All purpose Sox: The many roles of Sox proteins in gene expressionWegner, MichaelInt. J. Biochem. Cell Biol. 42:381-9019854293Pubmed2010Acquisition of SOX transcription factor specificity through protein-protein interaction, modulation of Wnt signalling and post-translational modificationBernard, PascalHarley, Vincent RInt. J. Biochem. Cell Biol. 42:400-1017875931Pubmed2007Sox17 and Sox4 differentially regulate beta-catenin/T-cell factor activity and proliferation of colon carcinoma cellsSinner, DéboraKordich, Jennifer JSpence, Jason ROpoka, RobertRankin, ScottLin, Suh-Chin JJonatan, DivaZorn, Aaron MWells, James MMol. Cell. Biol. 27:7802-1517698607Pubmed2007Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epitheliumBastide, PaulineDarido, CharbelPannequin, JulieKist, RalfRobine, SylvieMarty-Double, ChristianeBibeau, FrédéricScherer, GerdJoubert, DominiqueHollande, FrédéricBlache, PhilippeJay, PhilippeJ. Cell Biol. 178:635-4819047045Pubmed2009Sox9 inhibits Wnt signaling by promoting beta-catenin phosphorylation in the nucleusTopol, LiliaChen, WenSong, HaiDay, Timothy FYang, YingziJ. Biol. Chem. 284:3323-3324291232Pubmed2014?-Catenin, a Sox2 binding partner, regulates the DNA binding and transcriptional activity of Sox2 in breast cancer cellsYe, XiaoxiaWu, FangWu, ChengshengWang, PengJung, KarenGopal, KeshavMa, YupoLi, LiangLai, RaymondCell. Signal. 26:492-50119655378Pubmed2010Interactions between SOX factors and Wnt/beta-catenin signaling in development and diseaseKormish, Jay DSinner, DéboraZorn, Aaron MDev. Dyn. 239:56-6818413743Pubmed2008Epigenetic inactivation of the canonical Wnt antagonist SRY-box containing gene 17 in colorectal cancerZhang, WGlöckner, Sabine CGuo, MingzhouMachida, Emi OtaWang, David HEaswaran, HariharanVan Neste, LeanderHerman, James GSchuebel, Kornel EWatkins, D NeilAhuja, NitaBaylin, Stephen BCancer Res. 68:2764-7210549281Pubmed1999Regulation of Wnt signaling by Sox proteins: XSox17 alpha/beta and XSox3 physically interact with beta-cateninZorn, Aaron MBarish, G DWilliams, B OLavender, PKlymkowsky, M WVarmus, H EMol. Cell 4:487-9811691915Pubmed2001SOX7 transcription factor: sequence, chromosomal localisation, expression, transactivation and interference with Wnt signallingTakash, WCañizares, JBonneaud, NPoulat, FMattei, M GJay, PBerta, PNucleic Acids Res. 29:4274-8319108950Pubmed2009SOX7, down-regulated in colorectal cancer, induces apoptosis and inhibits proliferation of colorectal cancer cellsZhang, YuHuang, ShuyanDong, WeiLi, LinFeng, YunpengPan, LinaHan, ZhenkunWang, XiuliRen, GuolingSu, DongmeiHuang, BaiquLu, JunCancer Lett. 277:29-3718456656Pubmed2008The molecular mechanism governing the oncogenic potential of SOX2 in breast cancerChen, YupengShi, LeiZhang, LirongLi, RuifangLiang, JingYu, WenhuaSun, LuyangYang, XiaohanWang, YanZhang, YuShang, YongfengJ. Biol. Chem. 283:17969-7818819930Pubmed2008Sox7 Is an independent checkpoint for beta-catenin function in prostate and colon epithelial cellsGuo, LizhengZhong, DianshengLau, StephenLiu, XiujuDong, Xue-YuanSun, XiaodongYang, Vincent WVertino, Paula MMoreno, Carlos SVarma, VijayDong, Jin-TangZhou, WeiMol. Cancer Res. 6:1421-3018598779Pubmed2008Human SRY inhibits beta-catenin-mediated transcriptionBernard, PascalSim, HelenaKnower, KevinVilain, EricHarley, VincentInt. J. Biochem. Cell Biol. 40:2889-90017412698Pubmed2007SOX6 suppresses cyclin D1 promoter activity by interacting with beta-catenin and histone deacetylase 1, and its down-regulation induces pancreatic beta-cell proliferationIguchi, HaruhisaUrashima, YasuyoInagaki, YosukeIkeda, YukioOkamura, MasashiTanaka, TUchida, AoiYamamoto, TTKodama, TSakai, JJ. Biol. Chem. 282:19052-6117218525Pubmed2007Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13Melichar, Heather JNarayan, KavithaDer, Sandy DHiraoka, YoshikiGardiol, NoemieJeannet, GregoireHeld, WernerChambers, Cynthia AKang, JoonsooScience 315:230-3inferred by electronic annotationIEAGOIEA