BioPAX pathway converted from "TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)" in the Reactome database.TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)This 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>SMURF1 binds phosphorylated PARD6ASMURF1 binds phosphorylated PARD6AThis 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>Reactome DB_ID: 101427211cell junctionGO0030054Tight Junction Complex:TGFB1:TGFBR2:p-TGFBR1:p-PARD6A:RHOA [cell junction]Tight Junction Complex:TGFB1:TGFBR2:p-TGFBR1:p-PARD6A:RHOAReactome DB_ID: 101427191Tight Junction Complex:p-PARD6A:RHOA [cell junction]Tight Junction Complex:p-PARD6A:RHOAReactome DB_ID: 101427041UniProt:I3LVS7RHOAReactomehttp://www.reactome.orgSus scrofaNCBI Taxonomy9823UniProtI3LVS7Chain Coordinates1EQUAL190EQUALReactome DB_ID: 101427001UniProt:F1ST04CGNUniProtF1ST041EQUAL1197EQUALReactome DB_ID: 101427061UniProt:A0A287A1S5UniProtA0A287A1S51EQUAL1173EQUALReactome DB_ID: 101427171PARD3:p-PARD6A:PRKCZ [cell junction]PARD3:p-PARD6A:PRKCZReactome DB_ID: 101427081UniProt:F1RUR8PARD3UniProtF1RUR81EQUAL1356EQUALReactome DB_ID: 101427151plasma membraneGO0005886UniProt:A0A286ZZ01PARD6AUniProtA0A286ZZ01O-phospho-L-serine at 345 (in Homo sapiens)345EQUALO-phospho-L-serine [MOD:00046]1EQUAL346EQUALReactome DB_ID: 101427121UniProt:A0A286ZSY3PRKCZUniProtA0A286ZSY31EQUAL592EQUALReactome Database ID Release 7510142717Database 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=10142717ReactomeR-SSC-21345281Reactome 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-SSC-2134528.1Reactome DB_ID: 101427021UniProt:B2ZI35UniProtB2ZI3528EQUAL299EQUALReactome Database ID Release 7510142719Database 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=10142719ReactomeR-SSC-21345291Reactome 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-SSC-2134529.1Reactome DB_ID: 101426961TGFB1:TGFBR2:p-TGFBR1 [plasma membrane]TGFB1:TGFBR2:p-TGFBR1Reactome DB_ID: 101426821extracellular regionGO0005576Dimeric TGFB1 [extracellular region]Dimeric TGFB1Reactome DB_ID: 101426802Ghost homologue of TGFB1 [extracellular region]Ghost homologue of TGFB1Reactome Database ID Release 7510142682Database 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=10142682ReactomeR-SSC-1708521Reactome 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-SSC-170852.1Reactome DB_ID: 101426941p-TGFBR1 [plasma membrane]p-TGFBR1Reactome DB_ID: 101426922UniProt:K7GSM3TGFBR1UniProtK7GSM3O-phospho-L-serine at 165 (in Homo sapiens)165EQUALO-phospho-L-threonine at 185 (in Homo sapiens)185EQUALO-phospho-L-threonine [MOD:00047]O-phospho-L-threonine at 186 (in Homo sapiens)186EQUALO-phospho-L-serine at 187 (in Homo sapiens)187EQUALO-phospho-L-serine at 189 (in Homo sapiens)189EQUALO-phospho-L-serine at 191 (in Homo sapiens)191EQUAL34EQUAL503EQUALReactome Database ID Release 7510142694Database 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=10142694ReactomeR-SSC-1708631Reactome 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-SSC-170863.1Reactome DB_ID: 101426781TGFBR2 homodimer [plasma membrane]TGFBR2 homodimerReactome DB_ID: 101426762Ghost homologue of TGFBR2 [plasma membrane]Ghost homologue of TGFBR2Reactome Database ID Release 7510142678Database 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=10142678ReactomeR-SSC-1708661Reactome 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-SSC-170866.1Reactome Database ID Release 7510142696Database 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=10142696ReactomeR-SSC-1708411Reactome 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-SSC-170841.1Reactome Database ID Release 7510142721Database 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=10142721ReactomeR-SSC-21345341Reactome 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-SSC-2134534.1Reactome DB_ID: 101087821cytosolGO0005829UniProt:I3LTD6SMURF1UniProtI3LTD61EQUAL757EQUALReactome DB_ID: 101427231Tight Junction Complex:TGFB1:TGFBR2:p-TGFBR1:p-PARD6A:RHOA:SMURF1 [plasma membrane]Tight Junction Complex:TGFB1:TGFBR2:p-TGFBR1:p-PARD6A:RHOA:SMURF1Reactome DB_ID: 101427211Reactome DB_ID: 1010878211EQUAL757EQUALReactome Database ID Release 7510142723Database 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=10142723ReactomeR-SSC-21609291Reactome 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-SSC-2160929.1Reactome Database ID Release 7510142729Database 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=10142729ReactomeR-SSC-21609321Reactome 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-SSC-2160932.1SMURF1 ubiquitin ligase is recruited to tight junctions by binding to phosphorylated PARD6A (Ozdamar et al. 2005).15761148Pubmed2005Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticityOzdamar, BBose, RBarrios-Rodiles, MWang, HRZhang, YWrana, JLScience 307:1603-9inferred by electronic annotationIEAGOIEASMURF1 ubiquitinates RHOASMURF1 ubiquitinates RHOAThis 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>Reactome DB_ID: 101427231Converted from EntitySet in ReactomeReactome DB_ID: 100912091Ub [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityUBB [cytosol]RPS27A [cytosol]UBA52(1-76) [cytosol]UniProtA7U5U2UniProtA0A287AZA7UniProtP63053Reactome DB_ID: 101427251Tight Junction Complex:TGFB1:TGFBR2:p-TGFBR1:p-PARD6A:Ub-RHOA:SMURF1 [cell junction]Tight Junction Complex:TGFB1:TGFBR2:p-TGFBR1:p-PARD6A:Ub-RHOA:SMURF1Reactome DB_ID: 101427231Converted from EntitySet in ReactomeReactome DB_ID: 100912091Reactome Database ID Release 7510142725Database 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=10142725ReactomeR-SSC-21609341Reactome 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-SSC-2160934.1Reactome Database ID Release 7510142731Database 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=10142731ReactomeR-SSC-21609351Reactome 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-SSC-2160935.1SMURF1, recruited to tight junctions through association with phosphorylated PARD6A, ubiquitinates RHOA, leading to RHOA degradation and disassembly of tight junctions (Ozdamar et al. 2005). Disassembly of tight junctions is an important step in epithelial to mesenchymal transition. SMURF1, but not SMURF2, decreases RHOA level, and this effect is proteasome dependent (Wang et al. 2003). 14657501Pubmed2003Regulation of cell polarity and protrusion formation by targeting RhoA for degradationWang, HRZhang, YOzdamar, BOgunjimi, AAAlexandrova, EThomsen, GHWrana, JLScience 302:1775-9inferred by electronic annotationIEAGOIEADisassembly of tight junctionsDisassembly of tight junctionsThis 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>Reactome DB_ID: 101427251Reactome Database ID Release 7510142727Database 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=10142727ReactomeR-SSC-21609311Reactome 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-SSC-2160931.1Ubiquitination of RHOA by SMURF1 leads to disassembly of tight junctions, an important step in epithelial to mesenchymal transition.inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510186891Database 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=10186891ReactomeR-SSC-21737911Reactome 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-SSC-2173791.1GO0007179GO biological processIn normal cells and in the early stages of cancer development, signaling by TGF-beta plays a tumor suppressive role, as SMAD2/3:SMAD4-mediated transcription inhibits cell division by downregulating MYC oncogene transcription and stimulating transcription of CDKN2B tumor suppressor gene. In advanced cancers however, TGF-beta signaling promotes metastasis by stimulating epithelial to mesenchymal transition (EMT). <br>TGFBR1 is recruited to tight junctions by binding PARD6A, a component of tight junctions. After TGF-beta stimulation, activated TGFBR2 binds TGFBR1 at tight junctions, and phosphorylates both TGFBR1 and PARD6A. Phosphorylated PARD6A recruits SMURF1 to tight junctions. SMURF1 is able to ubiquitinate RHOA, a component of tight junctions needed for tight junction maintenance, leading to disassembly of tight junctions, an important step in EMT (Wang et al. 2003, Ozdamar et al. 2005).inferred by electronic annotationIEAGOIEA