BioPAX pathway converted from "PTEN Regulation" in the Reactome database. PTEN Regulation 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> Regulation of PTEN gene transcription 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> LEFT-TO-RIGHT SALL4 recruits NuRD to PTEN gene 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> NuRD complex Reactome DB_ID: 10741462 nucleoplasm GENE ONTOLOGY GO:0005654 MBD3 MBD-like A0A0B4KGZ0 Reactome DB_ID: 10734345 UniProt:A0A0B4KGZ0 MBD-like Drosophila melanogaster NCBI Taxonomy 7227 UniProt A0A0B4KGZ0 1 EQUAL 291 EQUAL Reactome Database ID Release 83 10734345 Database 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=10734345 Reactome R-DME-4657010 1 Reactome 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-DME-4657010.1 Reactome http://www.reactome.org 1 Converted from EntitySet in Reactome Mi-2 Reactome DB_ID: 10734343 Converted from EntitySet in Reactome Homologues of CHD4 Reactome DB_ID: 10734335 CHD4 O16102 Reactome DB_ID: 10734328 UniProt:O16102 UniProt O16102 1 EQUAL 1912 EQUAL Reactome Database ID Release 83 10734328 Database 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=10734328 Reactome R-DME-3702078 1 Reactome 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-DME-3702078.1 CHD4 O97159 Reactome DB_ID: 10734333 UniProt:O97159 UniProt O97159 1 EQUAL 1912 EQUAL Reactome Database ID Release 83 10734333 Database 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=10734333 Reactome R-DME-3702078-2 1 Reactome 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-DME-3702078-2.1 Reactome Database ID Release 83 10734335 Database 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=10734335 Reactome R-DME-3702078-3 1 Reactome 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-DME-3702078-3.1 Converted from EntitySet in Reactome Homologues of CHD3 Reactome DB_ID: 10734341 CHD3 O16102 Reactome DB_ID: 10734337 1 EQUAL 2000 EQUAL Reactome Database ID Release 83 10734337 Database 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=10734337 Reactome R-DME-4657012 1 Reactome 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-DME-4657012.1 CHD3 O97159 Reactome DB_ID: 10734339 1 EQUAL 2000 EQUAL Reactome Database ID Release 83 10734339 Database 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=10734339 Reactome R-DME-4657012-2 1 Reactome 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-DME-4657012-2.1 Reactome Database ID Release 83 10734341 Database 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=10734341 Reactome R-DME-4657012-3 1 Reactome 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-DME-4657012-3.1 Reactome Database ID Release 83 10734343 Database 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=10734343 Reactome R-DME-4657021 1 Reactome 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-DME-4657021.1 1 Converted from EntitySet in Reactome (GATAD2A, GATAD2B) Reactome DB_ID: 10734354 simj GATAD2A M9PF79 Reactome DB_ID: 10734350 UniProt:M9PF79 simj UniProt M9PF79 1 EQUAL 633 EQUAL Reactome Database ID Release 83 10734350 Database 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=10734350 Reactome R-DME-3702077 1 Reactome 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-DME-3702077.1 Reactome Database ID Release 83 10734354 Database 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=10734354 Reactome R-DME-4657014 1 Reactome 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-DME-4657014.1 1 RBBP4 Caf1-55 Q24572 Reactome DB_ID: 10706765 UniProt:Q24572 Caf1-55 UniProt Q24572 2 EQUAL 425 EQUAL Reactome Database ID Release 83 10706765 Database 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=10706765 Reactome R-DME-212223 1 Reactome 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-DME-212223.1 2 MTA1 MTA1-like A0A0B4KG70 Reactome DB_ID: 10716450 UniProt:A0A0B4KG70 MTA1-like UniProt A0A0B4KG70 1 EQUAL 715 EQUAL Reactome Database ID Release 83 10716450 Database 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=10716450 Reactome R-DME-3465550 1 Reactome 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-DME-3465550.1 1 HDAC1:HDAC2 Reactome DB_ID: 10704920 HDAC1 HDAC1 Q94517 Reactome DB_ID: 10688492 UniProt:Q94517 HDAC1 HDAC1 Rpd3 CG7471 FUNCTION Catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:11571273, PubMed:28245922, PubMed:12408863). Histone deacetylation may constitute a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:11571273, PubMed:8955276, PubMed:15545624, PubMed:15306652). For instance, deacetylation of histone H3 may be a prerequisite for the subsequent recruitment of the histone methyltransferase Su(var)3-9 to histones (PubMed:11571273). Involved in position-effect variegation (PEV) (PubMed:11571273). In the larval brain, part of a regulatory network including the transcriptional repressors klu, dpn and E(spl)mgamma-HLH which is required for type II neuroblast self-renewal and for maintaining erm in an inactive state in intermediate neural progenitors (INP) (PubMed:28245922).SUBUNIT Component of a form of the Esc/E(z) complex present specifically during early embryogenesis which is composed of Caf1-55, esc, E(z), Su(z)12, Pcl and HDAC1 (PubMed:12533794, PubMed:12408863, PubMed:12697833). The Esc/E(z) complex may also associate with Pcl and HDAC1 during early embryogenesis (PubMed:12697833). This complex is distinct from the PRC1 complex, which contains many other PcG proteins like Pc, Ph, Psc, Su(z)2 (PubMed:12533794). The 2 complexes however cooperate and interact together during the first 3 hours of development to establish PcG silencing (PubMed:12533794). Interacts with the histone methyltransferase Su(var)3-9 (PubMed:11571273). Component of a complex that contains at least HDAC1, CoRest and Su(var)3-3/Hdm (PubMed:15306652). Component of the DREAM complex at least composed of Myb, Caf1-55, mip40, mip120, mip130, E2f2, Dp, Rbf, Rbf2, lin-52, HDAC1 and l(3)mbt (PubMed:15545624). Interacts with the chromatin-remodeler Mi-2 (PubMed:18250149).DISRUPTION PHENOTYPE RNAi-mediated knockdown results in loss of type II neuroblasts.SIMILARITY Belongs to the histone deacetylase family. HD type 1 subfamily. UniProt Q94517 1 EQUAL 482 EQUAL Reactome Database ID Release 83 10688492 Database 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=10688492 Reactome R-DME-205021 1 Reactome 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-DME-205021.1 1 HDAC1 HDAC2 Q94517 Reactome DB_ID: 10688518 1 EQUAL 488 EQUAL Reactome Database ID Release 83 10688518 Database 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=10688518 Reactome R-DME-205135 1 Reactome 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-DME-205135.1 1 Reactome Database ID Release 83 10704920 Database 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=10704920 Reactome R-DME-4657004 1 Reactome 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-DME-4657004.1 1 Reactome Database ID Release 83 10741462 Database 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=10741462 Reactome R-DME-4657018 1 Reactome 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-DME-4657018.1 SALL4:PTEN gene Reactome DB_ID: 10741458 Ghost homologue of PTEN gene Reactome DB_ID: 10741456 Reactome Database ID Release 83 10741456 Database 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=10741456 Reactome R-DME-5632949 1 Reactome 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-DME-5632949.1 1 Converted from EntitySet in Reactome Homologues of SALL4 Reactome DB_ID: 10714693 salm SALL4 P39770 Reactome DB_ID: 10714686 UniProt:P39770 salm UniProt P39770 1 EQUAL 1053 EQUAL Reactome Database ID Release 83 10714686 Database 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=10714686 Reactome R-DME-452644 1 Reactome 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-DME-452644.1 salr SALL4 Q9VKH3 Reactome DB_ID: 10714691 UniProt:Q9VKH3 salr UniProt Q9VKH3 1 EQUAL 1053 EQUAL Reactome Database ID Release 83 10714691 Database 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=10714691 Reactome R-DME-452644-2 1 Reactome 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-DME-452644-2.1 Reactome Database ID Release 83 10714693 Database 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=10714693 Reactome R-DME-452644-3 1 Reactome 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-DME-452644-3.1 1 Reactome Database ID Release 83 10741458 Database 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=10741458 Reactome R-DME-8943729 1 Reactome 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-DME-8943729.1 SALL4:NuRD:PTEN gene Reactome DB_ID: 10741466 1 SALL4:NuRD Reactome DB_ID: 10741464 1 1 Reactome Database ID Release 83 10741464 Database 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=10741464 Reactome R-DME-8943778 1 Reactome 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-DME-8943778.1 1 Reactome Database ID Release 83 10741466 Database 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=10741466 Reactome R-DME-8943781 1 Reactome 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-DME-8943781.1 Reactome Database ID Release 83 10741468 Database 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=10741468 Reactome R-DME-8943780 1 Reactome 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-DME-8943780.1 SALL4 recruits the transcriptional repressor complex NuRD, containing histone deacetylases HDAC1 and HDAC2, to the PTEN gene promoter (Lu et al 2009, Gao et al. 2013). SALL4 may also recruit DNA methyltransferases (DNMTs) to the PTEN promoter (Yang et al. 2012). 23287862 Pubmed 2013 Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex Gao, Chong Dimitrov, Todor Yong, Kol Jia Tatetsu, Hiro Jeong, Ha-Won Luo, Hongbo R Bradner, James E Tenen, Daniel G Chai, Li Blood 121:1413-21 19440552 Pubmed 2009 Stem cell factor SALL4 represses the transcriptions of PTEN and SALL1 through an epigenetic repressor complex Lu, J Jeong, HW Kong, N Yang, Y Carroll, J Luo, HR Silberstein, LE Yupoma, LE Chai, L PLoS One 4:e5577 22128185 Pubmed 2012 Stem cell gene SALL4 suppresses transcription through recruitment of DNA methyltransferases Yang, Jianchang Corsello, Tyler R Ma, Yupo J. Biol. Chem. 287:1996-2005 inferred from electronic annotation EVIDENCE CODE ECO:0000203 LEFT-TO-RIGHT MECOM (EVI1) recruits polycomb repressor complexes (PRCs) to the PTEN gene promoter 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> MECOM:PTEN gene Reactome DB_ID: 10741499 1 Converted from EntitySet in Reactome Homologues of MECOM Reactome DB_ID: 10741495 MECOM Dmel\CG1663 Q4V6W8 Reactome DB_ID: 10741473 UniProt:Q4V6W8 Dmel\CG1663 UniProt Q4V6W8 1 EQUAL 1051 EQUAL Reactome Database ID Release 83 10741473 Database 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=10741473 Reactome R-DME-8943897 1 Reactome 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-DME-8943897.1 ham MECOM Q8I7Z8 Reactome DB_ID: 10741478 UniProt:Q8I7Z8 ham UniProt Q8I7Z8 1 EQUAL 1051 EQUAL Reactome Database ID Release 83 10741478 Database 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=10741478 Reactome R-DME-8943897-2 1 Reactome 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-DME-8943897-2.1 MECOM Q8T051 Reactome DB_ID: 10741483 UniProt:Q8T051 UniProt Q8T051 1 EQUAL 1051 EQUAL Reactome Database ID Release 83 10741483 Database 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=10741483 Reactome R-DME-8943897-3 1 Reactome 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-DME-8943897-3.1 MECOM Q9VEF3 Reactome DB_ID: 10741488 UniProt:Q9VEF3 UniProt Q9VEF3 1 EQUAL 1051 EQUAL Reactome Database ID Release 83 10741488 Database 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=10741488 Reactome R-DME-8943897-4 1 Reactome 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-DME-8943897-4.1 MECOM Dmel\CG10348 Q9VJ55 Reactome DB_ID: 10741493 UniProt:Q9VJ55 Dmel\CG10348 UniProt Q9VJ55 1 EQUAL 1051 EQUAL Reactome Database ID Release 83 10741493 Database 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=10741493 Reactome R-DME-8943897-5 1 Reactome 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-DME-8943897-5.1 Reactome Database ID Release 83 10741495 Database 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=10741495 Reactome R-DME-8943897-6 1 Reactome 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-DME-8943897-6.1 1 Reactome Database ID Release 83 10741499 Database 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=10741499 Reactome R-DME-8943810 1 Reactome 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-DME-8943810.1 Converted from EntitySet in Reactome PRC1.4,PRC2 (EZH2) core Reactome DB_ID: 10741497 PRC2 (EZH2) Core Reactome DB_ID: 10715537 E(z) EZH2 P42124 Reactome DB_ID: 10715530 UniProt:P42124 E(z) UniProt P42124 1 EQUAL 746 EQUAL Reactome Database ID Release 83 10715530 Database 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=10715530 Reactome R-DME-212298 1 Reactome 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-DME-212298.1 1 EED escl Q9VKD5 Reactome DB_ID: 10715525 UniProt:Q9VKD5 escl UniProt Q9VKD5 1 EQUAL 441 EQUAL Reactome Database ID Release 83 10715525 Database 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=10715525 Reactome R-DME-212278 1 Reactome 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-DME-212278.1 1 1 SUZ12 Su(z)12 Q9NJG9 Reactome DB_ID: 10715535 UniProt:Q9NJG9 Su(z)12 UniProt Q9NJG9 1 EQUAL 739 EQUAL Reactome Database ID Release 83 10715535 Database 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=10715535 Reactome R-DME-212217 1 Reactome 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-DME-212217.1 1 Reactome Database ID Release 83 10715537 Database 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=10715537 Reactome R-DME-212285 1 Reactome 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-DME-212285.1 PRC1.4 Reactome DB_ID: 10715497 Pc CBX6 P26017 Reactome DB_ID: 10715495 UniProt:P26017 Pc UniProt P26017 1 EQUAL 412 EQUAL Reactome Database ID Release 83 10715495 Database 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=10715495 Reactome R-DME-3229071 1 Reactome 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-DME-3229071.1 1 Sce RING1 Q9VB08 Reactome DB_ID: 10715094 UniProt:Q9VB08 Sce UniProt Q9VB08 1 EQUAL 406 EQUAL Reactome Database ID Release 83 10715094 Database 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=10715094 Reactome R-DME-389113 1 Reactome 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-DME-389113.1 1 Q9VHA0 SCMH1-2 Reactome DB_ID: 10715044 UniProt:Q9VHA0 UniProt Q9VHA0 1 EQUAL 660 EQUAL Reactome Database ID Release 83 10715044 Database 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=10715044 Reactome R-DME-389122 1 Reactome 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-DME-389122.1 1 Converted from EntitySet in Reactome Homologues of BMI1 Reactome DB_ID: 10715056 BMI1 Su(z)2 P25172 Reactome DB_ID: 10715049 UniProt:P25172 Su(z)2 UniProt P25172 1 EQUAL 326 EQUAL Reactome Database ID Release 83 10715049 Database 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=10715049 Reactome R-DME-389121 1 Reactome 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-DME-389121.1 Psc BMI1 P35820 Reactome DB_ID: 10715054 UniProt:P35820 Psc UniProt P35820 1 EQUAL 326 EQUAL Reactome Database ID Release 83 10715054 Database 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=10715054 Reactome R-DME-389121-2 1 Reactome 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-DME-389121-2.1 Reactome Database ID Release 83 10715056 Database 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=10715056 Reactome R-DME-389121-3 1 Reactome 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-DME-389121-3.1 1 Converted from EntitySet in Reactome PHC1,PHC2,PHC3 Reactome DB_ID: 10715089 PHC1 Samuel Q9VKL0 Reactome DB_ID: 10715065 UniProt:Q9VKL0 Samuel UniProt Q9VKL0 1 EQUAL 1004 EQUAL Reactome Database ID Release 83 10715065 Database 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=10715065 Reactome R-DME-389111 1 Reactome 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-DME-389111.1 Converted from EntitySet in Reactome Homologues of PHC2 Reactome DB_ID: 10715079 PHC2 P39769 Reactome DB_ID: 10715070 UniProt:P39769 UniProt P39769 1 EQUAL 858 EQUAL Reactome Database ID Release 83 10715070 Database 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=10715070 Reactome R-DME-389112 1 Reactome 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-DME-389112.1 PHC2 Samuel Q9VKL0 Reactome DB_ID: 10715072 1 EQUAL 858 EQUAL Reactome Database ID Release 83 10715072 Database 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=10715072 Reactome R-DME-389112-2 1 Reactome 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-DME-389112-2.1 ph-d PHC2 Q9W523 Reactome DB_ID: 10715077 UniProt:Q9W523 ph-d UniProt Q9W523 1 EQUAL 858 EQUAL Reactome Database ID Release 83 10715077 Database 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=10715077 Reactome R-DME-389112-3 1 Reactome 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-DME-389112-3.1 Reactome Database ID Release 83 10715079 Database 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=10715079 Reactome R-DME-389112-4 1 Reactome 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-DME-389112-4.1 Converted from EntitySet in Reactome Homologues of PHC3 Reactome DB_ID: 10715087 PHC3 P39769 Reactome DB_ID: 10715081 1 EQUAL 983 EQUAL Reactome Database ID Release 83 10715081 Database 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=10715081 Reactome R-DME-389116 1 Reactome 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-DME-389116.1 PHC3 Samuel Q9VKL0 Reactome DB_ID: 10715083 1 EQUAL 983 EQUAL Reactome Database ID Release 83 10715083 Database 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=10715083 Reactome R-DME-389116-2 1 Reactome 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-DME-389116-2.1 ph-d PHC3 Q9W523 Reactome DB_ID: 10715085 1 EQUAL 983 EQUAL Reactome Database ID Release 83 10715085 Database 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=10715085 Reactome R-DME-389116-3 1 Reactome 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-DME-389116-3.1 Reactome Database ID Release 83 10715087 Database 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=10715087 Reactome R-DME-389116-4 1 Reactome 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-DME-389116-4.1 Reactome Database ID Release 83 10715089 Database 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=10715089 Reactome R-DME-9007200 1 Reactome 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-DME-9007200.1 1 Reactome Database ID Release 83 10715497 Database 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=10715497 Reactome R-DME-3229073 1 Reactome 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-DME-3229073.1 Reactome Database ID Release 83 10741497 Database 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=10741497 Reactome R-DME-8943822 1 Reactome 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-DME-8943822.1 MECOM:(PRC1.4,PRC2 (EZH2) core):PTEN gene Reactome DB_ID: 10741503 1 MECOM:(PRC1.4,PRC2 (EZH2) core) Reactome DB_ID: 10741501 1 1 Reactome Database ID Release 83 10741501 Database 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=10741501 Reactome R-DME-8943820 1 Reactome 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-DME-8943820.1 1 Reactome Database ID Release 83 10741503 Database 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=10741503 Reactome R-DME-8943821 1 Reactome 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-DME-8943821.1 Reactome Database ID Release 83 10741505 Database 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=10741505 Reactome R-DME-8943817 1 Reactome 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-DME-8943817.1 The transcription factor MECOM (EVI1) can associate with the polycomb repressor complexes (PRCs) and recruit them to the promoter of the PTEN gene (Song et al. 2009). Both the BMI1-containing PRC, supposedly PRC1.4, and the EZH2-containing PRC2 complex are recruited to the PTEN promoter, resulting in transcriptional silencing of the PTEN gene (Song et al. 2009, Yoshimi et al. 2011). Since the exact composition of the EZH2-containing PRC2 at the PTEN promoter is not known, the core EZH2-PRC2 complex is shown. 19884659 Pubmed 2009 The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells Song, Li-Bing Li, J Liao, Wen-Ting Feng, Yan Yu, Chun-Ping Hu, Li-Juan Kong, Qing-Li Xu, Li-Hua Zhang, Xing Liu, Wan-Li Li, Man-Zhi Zhang, L Kang, Tie-Bang Fu, Li-Wu Huang, Wen-Lin Xia, Yun-Fei Tsao, Sai Wah Li, Mengfeng Band, Vimla Band, Hamid Shi, Qing-Hua Zeng, Yi-Xin Zeng, Mu-Sheng J. Clin. Invest. 119:3626-36 21289308 Pubmed 2011 Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins Yoshimi, Akihide Goyama, Susumu Watanabe-Okochi, Naoko Yoshiki, Yumiko Nannya, Yasuhito Nitta, Eriko Arai, Shunya Sato, Tomohiko Shimabe, Munetake Nakagawa, Masahiro Imai, Yoichi Kitamura, Toshio Kurokawa, Mineo Blood 117:3617-28 LEFT-TO-RIGHT 2.7.11.1 mTORC1 phosphorylates MAF1 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> Maf1 MAF1 Q7PL26 Reactome DB_ID: 10741648 cytosol GENE ONTOLOGY GO:0005829 UniProt:Q7PL26 Maf1 UniProt Q7PL26 1 EQUAL 256 EQUAL Reactome Database ID Release 83 10741648 Database 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=10741648 Reactome R-DME-8944460 1 Reactome 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-DME-8944460.1 ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 113592 ATP(4-) [ChEBI:30616] ATP(4-) ATP atp Adenosine 5'-triphosphate ChEBI CHEBI:30616 Reactome Database ID Release 83 113592 Database 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=113592 Reactome R-ALL-113592 5 Reactome 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-ALL-113592.5 COMPOUND C00002 additional information MI MI:0361 3 Q7PL26 phospho-Maf1 p-S60,S68,S75-MAF1 Reactome DB_ID: 10741653 60 EQUAL O-phospho-L-serine MOD MOD:00046 68 EQUAL 75 EQUAL 1 EQUAL 256 EQUAL Reactome Database ID Release 83 10741653 Database 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=10741653 Reactome R-DME-8944455 1 Reactome 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-DME-8944455.1 ADP Adenosine 5'-diphosphate ADP(3-) Reactome DB_ID: 29370 ADP(3-) [ChEBI:456216] ADP(3-) ADP 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP trianion ChEBI CHEBI:456216 Reactome Database ID Release 83 29370 Database 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=29370 Reactome R-ALL-29370 5 Reactome 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-ALL-29370.5 COMPOUND C00008 3 ACTIVATION Active mTORC1 complex Reactome DB_ID: 10680606 lysosomal membrane GENE ONTOLOGY GO:0005765 mTORC1:Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9 Reactome DB_ID: 10680604 Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9 Reactome DB_ID: 10680602 Ragulator:RagA,B:GTP:RagC,D:GDP Reactome DB_ID: 10680600 Ragulator Reactome DB_ID: 10680570 Q9V8I2 Lamtor2 LAMTOR2 Reactome DB_ID: 10680553 UniProt:Q9V8I2 Lamtor2 UniProt Q9V8I2 1 EQUAL 125 EQUAL Reactome Database ID Release 83 10680553 Database 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=10680553 Reactome R-DME-5653583 1 Reactome 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-DME-5653583.1 1 Q9VZL6 Lamtor4 LAMTOR4 Reactome DB_ID: 10680563 UniProt:Q9VZL6 Lamtor4 UniProt Q9VZL6 1 EQUAL 99 EQUAL Reactome Database ID Release 83 10680563 Database 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=10680563 Reactome R-DME-5655432 1 Reactome 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-DME-5655432.1 1 O96824 Lamtor5 LAMTOR5 Reactome DB_ID: 10680568 UniProt:O96824 Lamtor5 UniProt O96824 1 EQUAL 91 EQUAL Reactome Database ID Release 83 10680568 Database 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=10680568 Reactome R-DME-5655441 1 Reactome 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-DME-5655441.1 1 Q9VJD2 Lamtor3 LAMTOR3 Reactome DB_ID: 10680558 UniProt:Q9VJD2 Lamtor3 UniProt Q9VJD2 1 EQUAL 124 EQUAL Reactome Database ID Release 83 10680558 Database 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=10680558 Reactome R-DME-5653581 1 Reactome 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-DME-5653581.1 1 Q9VW73 Lamtor1 LAMTOR1 Reactome DB_ID: 10680548 UniProt:Q9VW73 Lamtor1 UniProt Q9VW73 2 EQUAL 161 EQUAL Reactome Database ID Release 83 10680548 Database 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=10680548 Reactome R-DME-5653582 1 Reactome 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-DME-5653582.1 1 Reactome Database ID Release 83 10680570 Database 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=10680570 Reactome R-DME-5653921 1 Reactome 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-DME-5653921.1 1 RagA,B:GTP:RagC,D:GDP Reactome DB_ID: 10680598 Converted from EntitySet in Reactome RRAGA, RRAGB:GTP Reactome DB_ID: 10680583 RRAGA:GTP Reactome DB_ID: 10680577 RRAGA RagA-B Q9VHJ4 Reactome DB_ID: 10680575 UniProt:Q9VHJ4 RagA-B UniProt Q9VHJ4 1 EQUAL 313 EQUAL Reactome Database ID Release 83 10680575 Database 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=10680575 Reactome R-DME-5653577 1 Reactome 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-DME-5653577.1 1 GTP Guanosine 5'-triphosphate GTP)(4-) Reactome DB_ID: 29438 GTP(4-) [ChEBI:37565] GTP(4-) GTP gtp guanosine 5'-triphosphate(4-) ChEBI CHEBI:37565 Reactome Database ID Release 83 29438 Database 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=29438 Reactome R-ALL-29438 4 Reactome 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-ALL-29438.4 COMPOUND C00044 1 Reactome Database ID Release 83 10680577 Database 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=10680577 Reactome R-DME-5653978 1 Reactome 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-DME-5653978.1 RRAGB:GTP Reactome DB_ID: 10680581 RRAGB RagA-B Q9VHJ4 Reactome DB_ID: 10680579 1 EQUAL 374 EQUAL Reactome Database ID Release 83 10680579 Database 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=10680579 Reactome R-DME-5653579 1 Reactome 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-DME-5653579.1 1 1 Reactome Database ID Release 83 10680581 Database 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=10680581 Reactome R-DME-5653976 1 Reactome 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-DME-5653976.1 Reactome Database ID Release 83 10680583 Database 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=10680583 Reactome R-DME-5653946 1 Reactome 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-DME-5653946.1 1 Converted from EntitySet in Reactome RRAGC,RRAGD:GDP Reactome DB_ID: 10680596 RRAGC:GDP Reactome DB_ID: 10680590 GDP Guanosine 5'-diphosphate Guanosine diphosphate GDP(3-) Reactome DB_ID: 29420 GDP(3-) [ChEBI:58189] GDP(3-) 5'-O-[(phosphonatooxy)phosphinato]guanosine guanosine 5'-diphosphate(3-) GDP guanosine 5'-diphosphate trianion guanosine 5'-diphosphate GDP trianion ChEBI CHEBI:58189 Reactome Database ID Release 83 29420 Database 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=29420 Reactome R-ALL-29420 3 Reactome 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-ALL-29420.3 COMPOUND C00035 1 RRAGC RagC-D Q7K519 Reactome DB_ID: 10680588 UniProt:Q7K519 RagC-D UniProt Q7K519 2 EQUAL 399 EQUAL Reactome Database ID Release 83 10680588 Database 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=10680588 Reactome R-DME-5653949 1 Reactome 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-DME-5653949.1 1 Reactome Database ID Release 83 10680590 Database 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=10680590 Reactome R-DME-5653973 1 Reactome 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-DME-5653973.1 RRAGD:GDP Reactome DB_ID: 10680594 RRAGD RagC-D Q7K519 Reactome DB_ID: 10680592 1 EQUAL 400 EQUAL Reactome Database ID Release 83 10680592 Database 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=10680592 Reactome R-DME-5653953 1 Reactome 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-DME-5653953.1 1 1 Reactome Database ID Release 83 10680594 Database 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=10680594 Reactome R-DME-5653970 1 Reactome 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-DME-5653970.1 Reactome Database ID Release 83 10680596 Database 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=10680596 Reactome R-DME-5653964 1 Reactome 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-DME-5653964.1 1 Reactome Database ID Release 83 10680598 Database 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=10680598 Reactome R-DME-5653945 1 Reactome 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-DME-5653945.1 1 Reactome Database ID Release 83 10680600 Database 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=10680600 Reactome R-DME-5653979 1 Reactome 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-DME-5653979.1 1 Ghost homologue of SLC38A9 Reactome DB_ID: 10680543 Reactome Database ID Release 83 10680543 Database 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=10680543 Reactome R-DME-5215938 1 Reactome 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-DME-5215938.1 1 Reactome Database ID Release 83 10680602 Database 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=10680602 Reactome R-DME-8952725 1 Reactome 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-DME-8952725.1 1 mTORC1 Reactome DB_ID: 10680541 Lst8 MLST8 Q9W328 Reactome DB_ID: 10680529 UniProt:Q9W328 Lst8 UniProt Q9W328 1 EQUAL 326 EQUAL Reactome Database ID Release 83 10680529 Database 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=10680529 Reactome R-DME-165676 1 Reactome 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-DME-165676.1 1 RPTOR raptor Q9W437 Reactome DB_ID: 10680539 UniProt:Q9W437 raptor UniProt Q9W437 1 EQUAL 1335 EQUAL Reactome Database ID Release 83 10680539 Database 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=10680539 Reactome R-DME-3006727 1 Reactome 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-DME-3006727.1 1 Tor MTOR Q9VK45 Reactome DB_ID: 10680534 UniProt:Q9VK45 Tor UniProt Q9VK45 1 EQUAL 2549 EQUAL Reactome Database ID Release 83 10680534 Database 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=10680534 Reactome R-DME-165662 1 Reactome 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-DME-165662.1 1 Reactome Database ID Release 83 10680541 Database 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=10680541 Reactome R-DME-377400 1 Reactome 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-DME-377400.1 1 Reactome Database ID Release 83 10680604 Database 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=10680604 Reactome R-DME-5653972 1 Reactome 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-DME-5653972.1 1 RHEB:GTP Reactome DB_ID: 10680522 1 RHEB Q9VND8 Reactome DB_ID: 10680518 UniProt:Q9VND8 Rheb Rheb CG1081 FUNCTION Binds GTP and exhibits intrinsic GTPase activity (By similarity). Activates the protein kinase activity of TORC1, and thereby plays a role in the regulation of apoptosis (PubMed:22493059). Stimulates the phosphorylation of S6K through activation of TORC1 signaling (PubMed:22493059). May also have a role in activating TORC2 signaling (PubMed:22493059).SIMILARITY Belongs to the small GTPase superfamily. Rheb family. UniProt Q9VND8 1 EQUAL 181 EQUAL Reactome Database ID Release 83 10680518 Database 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=10680518 Reactome R-DME-165190 1 Reactome 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-DME-165190.1 1 Reactome Database ID Release 83 10680522 Database 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=10680522 Reactome R-DME-165189 1 Reactome 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-DME-165189.1 1 Reactome Database ID Release 83 10680606 Database 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=10680606 Reactome R-DME-165678 1 Reactome 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-DME-165678.1 GENE ONTOLOGY GO:0004674 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 83 10741654 Database 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=10741654 Reactome Database ID Release 83 10741656 Database 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=10741656 Reactome R-DME-8944454 1 Reactome 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-DME-8944454.1 Activated mTORC1 complex phosphorylates the transcription factor MAF1 on serine residues S60, S68 and S75 (Shor et al. 2010, Michels et al. 2010). mTORC1-mediated phosphorylation of MAF1 inhibits translocation of MAF1 to the nucleus (Shor et al. 2010). 20233713 Pubmed 2010 Requirement of the mTOR kinase for the regulation of Maf1 phosphorylation and control of RNA polymerase III-dependent transcription in cancer cells Shor, Boris Wu, Jiang Shakey, Quazi Toral-Barza, Lourdes Shi, Celine Follettie, Max Yu, Ker J. Biol. Chem. 285:15380-92 20516213 Pubmed 2010 mTORC1 directly phosphorylates and regulates human MAF1 Michels, Annemieke A Robitaille, Aaron M Buczynski-Ruchonnet, Diane Hodroj, Wassim Reina, Jaime H Hall, Michael N Hernandez, Nouria Mol. Cell. Biol. 30:3749-57 LEFT-TO-RIGHT MAF1 translocates to the nucleus 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> Maf1 MAF1 Q7PL26 Reactome DB_ID: 10741646 1 EQUAL 256 EQUAL Reactome Database ID Release 83 10741646 Database 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=10741646 Reactome R-DME-8944422 1 Reactome 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-DME-8944422.1 Reactome Database ID Release 83 10741658 Database 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=10741658 Reactome R-DME-8944457 1 Reactome 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-DME-8944457.1 Phosphorylation of MAF1 by the activated mTORC1 complex inhibits translocation of MAF1 to the nucleus, and hence its transcriptional activity, but the mechanism has not been elucidated (Shor et al. 2010). INHIBITION Reactome Database ID Release 83 10741659 Database 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=10741659 Reactome Database ID Release 83 10751491 Database 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=10751491 Reactome R-DME-8943724 1 Reactome 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-DME-8943724.1 Transcription of the PTEN gene is regulated at multiple levels. Epigenetic repression involves the recruitment of Mi-2/NuRD upon SALL4 binding to the PTEN promoter (Yang et al. 2008, Lu et al. 2009) or EVI1-mediated recruitment of the polycomb repressor complex (PRC) to the PTEN promoter (Song et al. 2009, Yoshimi et al. 2011). Transcriptional regulation is also elicited by negative regulators, including NR2E1:ATN1 (atrophin-1) complex, JUN (c-Jun), SNAIL and SLUG (Zhang et al. 2006, Vasudevan et al. 2007, Escriva et al. 2008, Uygur et al. 2015) and positive regulators such as TP53 (p53), MAF1, ATF2, EGR1 or PPARG (Stambolic et al. 2001, Virolle et al. 2001, Patel et al. 2001, Shen et al. 2006, Li et al. 2016). 18172008 Pubmed 2008 Repression of PTEN phosphatase by Snail1 transcriptional factor during gamma radiation-induced apoptosis Escrivà, Maria Peiró, Sandra Herranz, Nicolás Villagrasa, Patricia Dave, Natàlia Montserrat-Sentís, Bàrbara Murray, Stephen A Francí, Clara Gridley, T Virtanen, Ismo García de Herreros, Antonio Mol. Cell. Biol. 28:1528-40 26910647 Pubmed 2016 MAF1 suppresses AKT-mTOR signaling and liver cancer through activation of PTEN transcription Li, Yue Tsang, Chi Kwan Wang, Suihai Li, Xiao-Xing Yang, Yang Fu, Liwu Huang, Wenlin Li, Ming Wang, Hui-Yun Zheng, X F Steven Hepatology 63:1928-42 11781575 Pubmed 2001 The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling Virolle, T Adamson, Eileen D Baron, V Birle, D Mercola, D Mustelin, T de Belle, I Nat. Cell Biol. 3:1124-8 25728608 Pubmed 2015 SLUG is a direct transcriptional repressor of PTEN tumor suppressor Uygur, Berna Abramo, Katrina Leikina, Evgenia Vary, Calvin Liaw, Lucy Wu, Wen-Shu Prostate 75:907-16 17974977 Pubmed 2007 Suppression of PTEN expression is essential for antiapoptosis and cellular transformation by oncogenic Ras Vasudevan, Krishna Murthi Burikhanov, Ravshan Goswami, Anindya Rangnekar, Vivek M Cancer Res. 67:10343-50 18487508 Pubmed 2008 SALL4 is a key regulator of survival and apoptosis in human leukemic cells Yang, Jianchang Chai, Li Gao, Chong Fowles, Taylor C Alipio, Zaida Dang, Hien Xu, Dan Fink, Louis M Ward, David C Ma, Yupo Blood 112:805-13 16702404 Pubmed 2006 Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1 Zhang, Chun-Li Zou, Yuhua Yu, Ruth T Gage, Fred H Evans, Ronald M Genes Dev. 20:1308-20 16418168 Pubmed 2006 Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) mediates p38 MAPK stress signal-induced inhibition of insulin signaling. A cross-talk between stress signaling and insulin signaling in resistin-treated human endothelial cells Shen, Ying H Zhang, Lin Gan, Yehua Wang, Xinwen Wang, Jian LeMaire, Scott A Coselli, Joseph S Wang, Xing Li J. Biol. Chem. 281:7727-36 11378386 Pubmed 2001 Tumor suppressor and anti-inflammatory actions of PPARgamma agonists are mediated via upregulation of PTEN Patel, L Pass, I Coxon, P Downes, C P Smith, S A MacPhee, C H Curr. Biol. 11:764-8 11545734 Pubmed 2001 Regulation of PTEN transcription by p53 Stambolic, V MacPherson, D Sas, D Lin, Y Snow, B Jang, Y Benchimol, S Mak, T W Mol. Cell 8:317-25 Regulation of PTEN localization 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> LEFT-TO-RIGHT PTEN undergoes monoubiquitination 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> Pten PTEN Q7KMQ6 Reactome DB_ID: 10685016 UniProt:Q7KMQ6 Pten Pten CG5671 Dmel_CG5671 <submittedName ref="1 2 3 4"> <fullName>Pten, isoform B</fullName> </submittedName> <submittedName> <fullName>IP16020p</fullName> </submittedName> <submittedName> <fullName>Phosphatase PTEN</fullName> </submittedName> UniProt Q7KMQ6 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10685016 Database 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=10685016 Reactome R-DME-199420 1 Reactome 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-DME-199420.1 Converted from EntitySet in Reactome Ub ubiquitin Reactome DB_ID: 10671899 UBI-P63E 12 ubiquitin 12 Reactome DB_ID: 1221561 UniProt:P18101 RpL40 RpL40 Ubi-f UBI-F52 CG2960 SUBUNIT 60S ribosomal protein is part of the 60S ribosomal subunit.MISCELLANEOUS In Drosophila ubiquitin is encoded by 3 different genes. RpL40 and RpS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. Ubi-p63E gene codes for a polyubiquitin precursor with 10 exact head to tail repeats.MISCELLANEOUS For a better understanding, features related to ubiquitin are only indicated for the first chain.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family. UniProt P18101 1 EQUAL 76 EQUAL Reactome Database ID Release 83 1221561 Database 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=1221561 Reactome R-DME-1221561 1 Reactome 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-DME-1221561.1 Q9W418 Ubi-p5E UBA52(1-76) Reactome DB_ID: 10671881 UniProt:Q9W418 Ubi-p5E UniProt Q9W418 1 EQUAL 76 EQUAL Reactome Database ID Release 83 10671881 Database 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=10671881 Reactome R-DME-939203 1 Reactome 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-DME-939203.1 UBI-P63E 1 ubiquitin 1 Reactome DB_ID: 1221567 UniProt:P0CG69 Ubi-p63E Ubi-p63E Ubi-m CG11624 FUNCTION Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-48-linked is involved in protein degradation via the proteasome. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity).MISCELLANEOUS In Drosophila ubiquitin is encoded by 3 different genes. RpL40 and RpS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. Ubi-p63E gene codes for a polyubiquitin precursor with 10 exact head to tail repeats.MISCELLANEOUS For the sake of clarity sequence features are annotated only for the first chain, and are not repeated for each of the following chains.SIMILARITY Belongs to the ubiquitin family. UniProt P0CG69 1 EQUAL 76 EQUAL Reactome Database ID Release 83 1221567 Database 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=1221567 Reactome R-DME-1221567 1 Reactome 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-DME-1221567.1 UBI-P63E 2 ubiquitin 2 Reactome DB_ID: 1221557 77 EQUAL 152 EQUAL Reactome Database ID Release 83 1221557 Database 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=1221557 Reactome R-DME-1221557 1 Reactome 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-DME-1221557.1 UBI-P63E 3 ubiquitin 3 Reactome DB_ID: 1221559 153 EQUAL 228 EQUAL Reactome Database ID Release 83 1221559 Database 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=1221559 Reactome R-DME-1221559 1 Reactome 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-DME-1221559.1 UBI-P63E 11 ubiquitin 11 Reactome DB_ID: 1221562 UniProt:P15357 RpS27A RpS27A UB3-D UBI-F80 Ubi-m CG5271 FUNCTION Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-48-linked is involved in protein degradation via the proteasome. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity).FUNCTION Ribosomal protein S27a is a component of the 40S subunit of the ribosome.SUBUNIT Ribosomal protein S27a is part of the 40S ribosomal subunit.MISCELLANEOUS In Drosophila ubiquitin is encoded by 3 different genes. RpL40 and RpS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. Ubi-p63E gene codes for a polyubiquitin precursor with exact head to tail repeats.MISCELLANEOUS For a better understanding, features related to ubiquitin are only indicated for the first chain.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the eukaryotic ribosomal protein eS31 family. UniProt P15357 1 EQUAL 76 EQUAL Reactome Database ID Release 83 1221562 Database 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=1221562 Reactome R-DME-1221562 1 Reactome 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-DME-1221562.1 RpS27A UBC(77-152) P15357 Reactome DB_ID: 10671883 77 EQUAL 152 EQUAL Reactome Database ID Release 83 10671883 Database 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=10671883 Reactome R-DME-939164 1 Reactome 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-DME-939164.1 Reactome Database ID Release 83 10671899 Database 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=10671899 Reactome R-DME-113595 1 Reactome 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-DME-113595.1 Pten MonoUb-K13,K289-PTEN Q7KMQ6 Reactome DB_ID: 10734443 13 EQUAL ubiquitinylated lysine MOD MOD:01148 289 EQUAL 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10734443 Database 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=10734443 Reactome R-DME-6807247 1 Reactome 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-DME-6807247.1 ACTIVATION Converted from EntitySet in Reactome XIAP,NEDD4 Reactome DB_ID: 10734451 Converted from EntitySet in Reactome Homologues of XIAP Reactome DB_ID: 10678802 XIAP Q24306 Reactome DB_ID: 10678796 UniProt:Q24306 Diap1 Diap1 Iap1 th CG12284 FUNCTION Anti-apoptotic protein which functions as a caspase regulator, using its E3 ubiquitin-protein ligase activity to smother caspase activity. Binds, ubiquitinates and inactivates initiator caspase Dronc, and effector caspases Drice and Dcp-1. Acts as a Nedd8-E3 ubiquitin-protein ligase for Drice. Suppresses apoptosis by targeting the apoptosome for ubiquitination and inactivation. Plays an important role in cell motility. Overexpression suppresses rpr and hid-dependent cell death in the eye. Interaction of Diap1 with Dronc is required to suppress Dronc-mediated cell death through Diap1-mediated ubiquitination of Dronc. Acts as a positive regulator of Wnt signaling.SUBUNIT Interacts (via BIR 2 domain) with Dronc (via residues 114-125). Rpr, hid and grim can outcompete Dronc for binding Diap1 therefore removing Diap1-mediated ubiquitination. Interacts (via BIR 2 domain) with HtrA2; this displaces any bound Dronc. Interacts with Strica (PubMed:11550090). The N-terminally cleaved form interacts with Ubr3 (via UBR-type zinc finger) (PubMed:25146930, PubMed:26383956); the interaction promotes the recruitment and uniquitination of substrate capases such as Dronc (PubMed:25146930).DEVELOPMENTAL STAGE Detected in wing disks (at protein level).PTM Ubiquitinated and degraded by HtrA2 in apoptotic cells; proteolytic cleavage at specific sites in the BIR domain linker region generating inactive fragments. Mutation of one site reduces but does not abolish cleavage as another site is selected by the protease.SIMILARITY Belongs to the IAP family. UniProt Q24306 1 EQUAL 497 EQUAL Reactome Database ID Release 83 10678796 Database 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=10678796 Reactome R-DME-50849 1 Reactome 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-DME-50849.1 XIAP Q24307 Reactome DB_ID: 10678800 UniProt:Q24307 Diap2 Diap2 DIHA Iap2 Ilp CG8293 FUNCTION Required for activation of NF-kappaB transcription factors in the immune deficiency (Imd) signaling cascade which is essential for innate immune responses upon infection by Gram-negative bacteria (PubMed:16894030, PubMed:17068333). Promotes cytoplasmic cleavage of Rel and its translocation to the nucleus where it drives expression of antimicrobial peptides (PubMed:17068333, PubMed:24374974). Binds, polyubiquitinates and activates Dredd which is required for Rel-mediated induction of antimicrobial peptides (PubMed:22549468). Anti-apoptotic protein which binds, ubiquitinates and inactivates the effector caspase Drice (PubMed:18166655). Suppresses rpr and hid-dependent cell death in the eye (PubMed:8548811). However, has also been shown to have little, if any, role in the regulation of the canonical caspase-dependent apoptosis pathway (PubMed:17068333). Plays a role in regulating the expression of ion channels (PubMed:24374974).SUBUNIT Interacts with the caspase Strica (PubMed:11550090). Interacts (via BIR2 domain) with rpr and grim (PubMed:18166655). Interacts (via the BIR2 and BIR3 domains) with hid (PubMed:18166655). Interacts (via BIR3 domain) with Drice (PubMed:18166655). Interacts with Dredd; likely to bind Dredd simultaneously with Fadd to form a trimeric complex (PubMed:22549468).TISSUE SPECIFICITY Expressed in both principal and stellar cells of the Malphigian tubules.DEVELOPMENTAL STAGE Expressed in Malpighian tubules from the 3rd instar larval stage and expression continues in pupae and adults with highest levels in adults (at protein level).INDUCTION Constitutively expressed (PubMed:17068333). Up-regulated by bacterial lipopolysaccharides (LPS) in Malpighian tubules but not in salivary glands (PubMed:24374974).PTM Caspase-dependent cleavage is required for suppression of Drice-mediated cell death.DISRUPTION PHENOTYPE Normal development and viability (PubMed:16894030, PubMed:17068333). Acute sensitivity to infection by Gram-negative bacteria with failure to induce expression of antibacterial peptide genes and inability to mount a proper innate immune response (PubMed:16894030, PubMed:17068333, PubMed:24374974). Loss of cleavage and nuclear translocation of Rel (PubMed:17068333, PubMed:24374974). Increased activity of the effector caspase Drice and increased apoptosis following x-ray irradiation (PubMed:18166655). Reduced ion channel expression in Malpighian tubules (PubMed:24374974).SIMILARITY Belongs to the IAP family. UniProt Q24307 1 EQUAL 497 EQUAL Reactome Database ID Release 83 10678800 Database 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=10678800 Reactome R-DME-50849-2 1 Reactome 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-DME-50849-2.1 Reactome Database ID Release 83 10678802 Database 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=10678802 Reactome R-DME-50849-3 1 Reactome 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-DME-50849-3.1 Nedd4 NEDD4 Q9VVI3 Reactome DB_ID: 10703939 UniProt:Q9VVI3 Nedd4 UniProt Q9VVI3 1 EQUAL 1319 EQUAL Reactome Database ID Release 83 10703939 Database 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=10703939 Reactome R-DME-975992 1 Reactome 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-DME-975992.1 Reactome Database ID Release 83 10734451 Database 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=10734451 Reactome R-DME-6807260 1 Reactome 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-DME-6807260.1 GENE ONTOLOGY GO:0061630 Reactome Database ID Release 83 10734452 Database 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=10734452 Reactome Database ID Release 83 10734454 Database 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=10734454 Reactome R-DME-6807106 1 Reactome 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-DME-6807106.1 When present at low levels in the cell, the E3 ubiquitin ligase XIAP monoubiquitinates PTEN (Van Themsche et al. 2009). NEDD4 (NEDD4-1) can also monoubiquitinate PTEN (Trotman et al. 2007). Monoubiquitination of PTEN on at least lysine residues K13 and K289 causes translocation of PTEN from the cytosol to the nucleus (Trotman et al. 2007, Van Themsche et al. 2009). 19473982 Pubmed 2009 X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization Van Themsche, Céline Leblanc, Valérie Parent, Sophie Asselin, Eric J. Biol. Chem. 284:20462-6 17218261 Pubmed 2007 Ubiquitination regulates PTEN nuclear import and tumor suppression Trotman, Lloyd C Wang, Xinjiang Alimonti, Andrea Chen, Zhenbang Teruya-Feldstein, Julie Yang, Haijuan Pavletich, Nikola P Carver, Brett S Cordon-Cardo, Carlos Erdjument-Bromage, H Tempst, P Chi, Sung-Gil Kim, Hyo-Jong Misteli, Tom Jiang, Xuejun Pandolfi, Pier Paolo Cell 128:141-56 LEFT-TO-RIGHT Monoubiquitinated PTEN translocates to the nucleus 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> Pten MonoUb-K13,K289-PTEN Q7KMQ6 Reactome DB_ID: 10734447 13 EQUAL 289 EQUAL 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10734447 Database 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=10734447 Reactome R-DME-6807264 1 Reactome 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-DME-6807264.1 Reactome Database ID Release 83 10734449 Database 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=10734449 Reactome R-DME-6807105 1 Reactome 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-DME-6807105.1 Monoubiquitinated PTEN translocates to the nucleus. Lysine residues K13 and K289 of PTEN are important monoubiquitination targets and their mutation abrogates PTEN nuclear localization (Trotman et al. 2007). LEFT-TO-RIGHT 3.4.19.12 USP7 deubiquitinates monoubiquitinated PTEN 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> H2O water Reactome DB_ID: 113518 water [ChEBI:15377] water ChEBI CHEBI:15377 Reactome Database ID Release 83 113518 Database 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=113518 Reactome R-ALL-113518 3 Reactome 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-ALL-113518.3 COMPOUND C00001 Pten PTEN Q7KMQ6 Reactome DB_ID: 10724993 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10724993 Database 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=10724993 Reactome R-DME-6807273 1 Reactome 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-DME-6807273.1 Converted from EntitySet in Reactome Ub Ubiquitin UBIQ_HUMAN Reactome DB_ID: 10671363 RpL40 RPS27A(1-76) P18101 Reactome DB_ID: 10671336 1 EQUAL 76 EQUAL Reactome Database ID Release 83 10671336 Database 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=10671336 Reactome R-DME-939849 1 Reactome 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-DME-939849.1 Q9W418 Ubi-p5E UBA52(1-76) Reactome DB_ID: 10671341 1 EQUAL 76 EQUAL Reactome Database ID Release 83 10671341 Database 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=10671341 Reactome R-DME-939844 1 Reactome 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-DME-939844.1 UBI-P63E 1 ubiquitin 1 Reactome DB_ID: 1221576 1 EQUAL 76 EQUAL Reactome Database ID Release 83 1221576 Database 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=1221576 Reactome R-DME-1221576 1 Reactome 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-DME-1221576.1 UBI-P63E 2 ubiquitin 2 Reactome DB_ID: 1221586 77 EQUAL 152 EQUAL Reactome Database ID Release 83 1221586 Database 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=1221586 Reactome R-DME-1221586 1 Reactome 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-DME-1221586.1 UBI-P63E 3 ubiquitin 3 Reactome DB_ID: 1221575 153 EQUAL 228 EQUAL Reactome Database ID Release 83 1221575 Database 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=1221575 Reactome R-DME-1221575 1 Reactome 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-DME-1221575.1 UBI-P63E 11 ubiquitin 11 Reactome DB_ID: 1221592 1 EQUAL 76 EQUAL Reactome Database ID Release 83 1221592 Database 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=1221592 Reactome R-DME-1221592 1 Reactome 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-DME-1221592.1 RpS27A UBC(77-152) P15357 Reactome DB_ID: 10671347 77 EQUAL 152 EQUAL Reactome Database ID Release 83 10671347 Database 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=10671347 Reactome R-DME-939869 1 Reactome 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-DME-939869.1 Reactome Database ID Release 83 10671363 Database 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=10671363 Reactome R-DME-68524 1 Reactome 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-DME-68524.1 2 ACTIVATION Usp7 USP7 Q9VYQ8 Reactome DB_ID: 10715277 UniProt:Q9VYQ8 Usp7 UniProt Q9VYQ8 1 EQUAL 1102 EQUAL Reactome Database ID Release 83 10715277 Database 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=10715277 Reactome R-DME-3215278 1 Reactome 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-DME-3215278.1 GENE ONTOLOGY GO:0004843 Reactome Database ID Release 83 10715278 Database 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=10715278 Reactome Database ID Release 83 10734456 Database 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=10734456 Reactome R-DME-6807118 1 Reactome 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-DME-6807118.1 USP7 (HAUSP) deubiquitinates monoubiquitinated nuclear PTEN, thus promoting relocalization of PTEN to the cytosol. USP7-mediated deubiquitination of PTEN is negatively regulated by PML in the presence of DAXX, but the exact mechanism has not been elucidated (Song et al. 2008). 18716620 Pubmed 2008 The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network Song, MS Salmena, Leonardo Carracedo, Arkaitz Egia, Ainara Lo-Coco, F Teruya-Feldstein, Julie Pandolfi, Pier Paolo Nature 455:813-7 LEFT-TO-RIGHT Deubiquitinated PTEN translocates to the cytosol 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> Reactome Database ID Release 83 10734458 Database 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=10734458 Reactome R-DME-6807126 1 Reactome 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-DME-6807126.1 After nuclear monoubiquitinated PTEN gets deubiquitinated by USP7 (HAUSP), it translocates to the cytosol (Song et al. 2008). Reactome Database ID Release 83 10751367 Database 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=10751367 Reactome R-DME-8948747 1 Reactome 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-DME-8948747.1 When monoubiquitinated by E3 ubiquitin ligases XIAP and NEDD4, PTEN translocates from the cytosol to the nucleus (Trotman et al. 2007, Van Themsche et al. 2009). USP7 (HAUSP)-mediated deubiquitination of monoubiquitinated nuclear PTEN promotes relocalization of PTEN to the cytosol (Song et al. 2008). Regulation of PTEN stability and activity 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> LEFT-TO-RIGHT NEDD4, WWP2, CHIP and XIAP polyubiquitinate PTEN 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> 3 Pten PolyUb-PTEN Q7KMQ6 Reactome DB_ID: 10734461 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10734461 Database 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=10734461 Reactome R-DME-6807280 1 Reactome 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-DME-6807280.1 ACTIVATION Converted from EntitySet in Reactome NEDD4,STUB1,WWP2 and XIAP Reactome DB_ID: 10734465 STUB1 STUB1 Q9XYW6 Reactome DB_ID: 10703915 UniProt:Q9XYW6 STUB1 UniProt Q9XYW6 1 EQUAL 303 EQUAL Reactome Database ID Release 83 10703915 Database 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=10703915 Reactome R-DME-975970 1 Reactome 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-DME-975970.1 WWP2 Su(dx) Q9Y0H4 Reactome DB_ID: 10734463 UniProt:Q9Y0H4 Su(dx) UniProt Q9Y0H4 1 EQUAL 870 EQUAL Reactome Database ID Release 83 10734463 Database 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=10734463 Reactome R-DME-6807279 1 Reactome 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-DME-6807279.1 Reactome Database ID Release 83 10734465 Database 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=10734465 Reactome R-DME-6807286 1 Reactome 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-DME-6807286.1 Reactome Database ID Release 83 10734466 Database 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=10734466 Reactome Database ID Release 83 10734468 Database 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=10734468 Reactome R-DME-6807134 1 Reactome 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-DME-6807134.1 Several ubiquitin ligases, including NEDD4 (Wang et al. 2007), STUB1 (CHIP) (Ahmed et al. 2012), WWP2 (Maddika et al. 2011) and XIAP (Van Themsche et al. 2009) can polyubiquitinate PTEN, targeting it for degradation. 17218260 Pubmed 2007 NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN Wang, Xinjiang Trotman, Lloyd C Koppie, Theresa Alimonti, Andrea Chen, Zhenbang Gao, Zhonghua Wang, Junru Erdjument-Bromage, H Tempst, P Cordon-Cardo, Carlos Pandolfi, Pier Paolo Jiang, Xuejun Cell 128:129-39 21532586 Pubmed 2011 WWP2 is an E3 ubiquitin ligase for PTEN Maddika, Subbareddy Kavela, Sridhar Rani, Neelam Palicharla, Vivek Reddy Pokorny, Jenny L Sarkaria, Jann N Chen, J Nat. Cell Biol. 13:728-33 22427670 Pubmed 2012 The chaperone-assisted E3 ligase C terminus of Hsc70-interacting protein (CHIP) targets PTEN for proteasomal degradation Ahmed, Syed Feroj Deb, Satamita Paul, Indranil Chatterjee, Anirban Mandal, Tapashi Chatterjee, Uttara Ghosh, Mrinal K J. Biol. Chem. 287:15996-6006 LEFT-TO-RIGHT 2.7.11.1 AKT phosphorylates MKRN1 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> Mkrn1 MKRN1 Q9VP20 Reactome DB_ID: 10704168 UniProt:Q9VP20 Mkrn1 UniProt Q9VP20 1 EQUAL 482 EQUAL Reactome Database ID Release 83 10704168 Database 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=10704168 Reactome R-DME-976042 1 Reactome 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-DME-976042.1 Q9VP20 phospho-Mkrn1 p-S109-MKRN1 Reactome DB_ID: 10741818 109 EQUAL 1 EQUAL 482 EQUAL Reactome Database ID Release 83 10741818 Database 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=10741818 Reactome R-DME-8948758 1 Reactome 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-DME-8948758.1 ACTIVATION activeUnit: #Protein87 Converted from EntitySet in Reactome Active AKT p-T,p-S-AKT Reactome DB_ID: 10684671 Q8INB9 phospho-p-T308,S473-AKT1 Reactome DB_ID: 10684665 UniProt:Q8INB9 Akt1 Akt1 CG4006 FUNCTION Serine/threonine kinase involved in various developmental processes (PubMed:9601646, PubMed:10587646, PubMed:10962553, PubMed:11740943, PubMed:12172554, PubMed:11872800, PubMed:14525946, PubMed:12893776, PubMed:15466161, PubMed:15712201). During early embryogenesis, acts as a survival protein (PubMed:9601646, PubMed:10962553). During mid-embryogenesis, phosphorylates and activates trh, a transcription factor required for tracheal cell fate determination (PubMed:11740943). Also regulates tracheal cell migration (PubMed:11740943, PubMed:14525946). Later in development, acts downstream of PI3K and Pk61C/PDK1 in the insulin receptor transduction pathway which regulates cell growth and organ size, by phosphorylating and antagonizing FOXO transcription factor (PubMed:10587646, PubMed:10962553, PubMed:11752451, PubMed:12893776, PubMed:25329475, PubMed:29025897, PubMed:24603715). Controls follicle cell size during oogenesis (PubMed:15712201). May also stimulate cell growth by phosphorylating Gig/Tsc2 and inactivating the Tsc complex (PubMed:12172554, PubMed:15466161). Dephosphorylation of 'Ser-586' by Phlpp triggers apoptosis and suppression of tumor growth (PubMed:10962553).SUBUNIT Interacts with trbl.TISSUE SPECIFICITY Ubiquitously expressed. Present in ovary, where it is concentrated at the basal side of follicle cells.DEVELOPMENTAL STAGE Expressed both maternally and zygotically. Strongly expressed in embryo and pupa. Weakly expressed in larva. Mildly expressed in adult.DOMAIN Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI(3)K) results in its targeting to the plasma membrane.PTM Phosphorylated and activated by Pk61C/PDK1 (PubMed:11344272). Phosphorylated on Ser-586 by the TORC2 complex (PubMed:10962553, PubMed:15718470, PubMed:22493059).DISRUPTION PHENOTYPE Death at the first instar larval stage (PubMed:9601646). Conditional RNAi-mediated knockdown in the female germline reduces ovary size (PubMed:24786828). RNAi-mediated knockdown in both larval salivary glands and fat body, results in small salivary glands displaying ectopic lipid storage and reduced expression of CdsA (PubMed:24603715).SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily. UniProt Q8INB9 308 EQUAL O-phospho-L-threonine MOD MOD:00047 473 EQUAL 1 EQUAL 480 EQUAL Reactome Database ID Release 83 10684665 Database 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=10684665 Reactome R-DME-198356 1 Reactome 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-DME-198356.1 Q8INB9 phospho-p-T309,S474-AKT2 Reactome DB_ID: 10677737 309 EQUAL 474 EQUAL 1 EQUAL 481 EQUAL Reactome Database ID Release 83 10677737 Database 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=10677737 Reactome R-DME-202062 1 Reactome 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-DME-202062.1 Q8INB9 phospho-p-T305,S472-AKT3 Reactome DB_ID: 10684669 305 EQUAL 472 EQUAL 1 EQUAL 479 EQUAL Reactome Database ID Release 83 10684669 Database 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=10684669 Reactome R-DME-3009367 1 Reactome 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-DME-3009367.1 Reactome Database ID Release 83 10684671 Database 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=10684671 Reactome R-DME-202074 1 Reactome 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-DME-202074.1 Reactome Database ID Release 83 10684672 Database 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=10684672 Reactome Database ID Release 83 10741820 Database 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=10741820 Reactome R-DME-8948757 1 Reactome 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-DME-8948757.1 GENE ONTOLOGY GO:0043491 gene ontology term for cellular process MI MI:0359 AKT1 (and possibly AKT2 and AKT3), activated in response to EGF treatment, phosphorylates MKRN1, an E3 ubiquitin ligase, on serine residue S109. AKT-mediated phosphorylation results in stabilization of MKRN1, protecting it from ubiquitination and proteasome-mediated degradation (Lee et al. 2015). 26183061 Pubmed 2015 PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis Lee, Min-Sik Jeong, Man-Hyung Lee, Hyun-Woo Han, Hyun-Ji Ko, Aram Hewitt, SM Kim, Jae-Hoon Chun, Kyung-Hee Chung, Joon-Yong Lee, Cheolju Cho, Hanbyoul Song, Jaewhan Nat Commun 6:7769 LEFT-TO-RIGHT MKRN1 polyubiquitinates PTEN 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> 3 Pten K48polyUb-K289-PTEN Q7KMQ6 Reactome DB_ID: 10734471 289 EQUAL 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10734471 Database 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=10734471 Reactome R-DME-8948777 1 Reactome 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-DME-8948777.1 ACTIVATION Reactome Database ID Release 83 10741821 Database 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=10741821 Reactome Database ID Release 83 10741823 Database 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=10741823 Reactome R-DME-8948775 1 Reactome 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-DME-8948775.1 The C-terminal region of the E3 ubiquitin ligase MKRN1 interacts with PTEN and polyubiquitinates it on lysine residue K289, via K48 linkage. AKT-mediated phosphorylation of MKRN1 on serine residue S109 is a pre-requisite for MKRN1 stabilization and MKRN1-mediated ubiquitination of PTEN. MKRN1 is implicated as an oncogene in cervical cancer (Lee et al. 2015). LEFT-TO-RIGHT 2.4.2.30 TNKS and TNKS2 PARylate PTEN 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> NAD NAD+ NAD(+) Nicotinamide adenine dinucleotide DPN Diphosphopyridine nucleotide Reactome DB_ID: 29360 NAD(1-) [ChEBI:57540] NAD(1-) adenosine 5'-{3-[1-(3-carbamoylpyridinio)-1,4-anhydro-D-ribitol-5-yl] diphosphate} NAD(+) NAD anion ChEBI CHEBI:57540 Reactome Database ID Release 83 29360 Database 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=29360 Reactome R-ALL-29360 5 Reactome 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-ALL-29360.5 COMPOUND C00003 3 Q7KMQ6 phospho-Pten RibC-E40,E150,D326-PTEN Reactome DB_ID: 10741825 40 EQUAL adenosine diphosphoribosyl (ADP-ribosyl) modified residue MOD MOD:00752 150 EQUAL 326 EQUAL 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10741825 Database 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=10741825 Reactome R-DME-8948798 1 Reactome 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-DME-8948798.1 NAM nicotinamide Reactome DB_ID: 197277 nicotinamide [ChEBI:17154] nicotinamide ChEBI CHEBI:17154 Reactome Database ID Release 83 197277 Database 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=197277 Reactome R-ALL-197277 3 Reactome 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-ALL-197277.3 COMPOUND C00153 3 ACTIVATION Converted from EntitySet in Reactome TNKS1/2 Reactome DB_ID: 10716479 TNKS2 Q9VBP3 Reactome DB_ID: 10716475 UniProt:Q9VBP3 UniProt Q9VBP3 1 EQUAL 1166 EQUAL Reactome Database ID Release 83 10716475 Database 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=10716475 Reactome R-DME-3640824 1 Reactome 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-DME-3640824.1 TNKS Q9VBP3 Reactome DB_ID: 10716477 1 EQUAL 1327 EQUAL Reactome Database ID Release 83 10716477 Database 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=10716477 Reactome R-DME-3640825 1 Reactome 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-DME-3640825.1 Reactome Database ID Release 83 10716479 Database 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=10716479 Reactome R-DME-3640826 1 Reactome 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-DME-3640826.1 GENE ONTOLOGY GO:0003950 Reactome Database ID Release 83 10741826 Database 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=10741826 Reactome Database ID Release 83 10741828 Database 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=10741828 Reactome R-DME-8948800 1 Reactome 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-DME-8948800.1 PTEN can bind tankyrases TNKS (TNKS1) and TNKS2. The interaction involves the tankyrase binding motif at the N-terminus of PTEN (RYQEDG). TNKS and TNKS2 poly-ADP-ribosylate (PARylate) PTEN on glutamic acid residues E40 and E150 and on aspartic acid residue D326. PTEN PARylation is a pre-requisite for RNF146-mediated ubiquitination of PTEN (Li et al. 2015). 25547115 Pubmed 2015 Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth Li, N Zhang, Yajie Han, Xin Liang, Ke Wang, Jiadong Feng, Lin Wang, W Songyang, Z Lin, Chunru Yang, Liuqing Yu, Yonghao Chen, J Genes Dev. 29:157-70 LEFT-TO-RIGHT RNF146 polyubiquitinates PARylated PTEN 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> 9 Q7KMQ6 phospho-Pten PolyUb-K324,K344,K349-RibC-E40,E150,D326-PTEN Reactome DB_ID: 10736579 342 EQUAL 344 EQUAL 349 EQUAL 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10736579 Database 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=10736579 Reactome R-DME-8948841 1 Reactome 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-DME-8948841.1 ACTIVATION Rnf146 RNF146 B7Z078 Reactome DB_ID: 10716465 UniProt:B7Z078 Rnf146 UniProt B7Z078 1 EQUAL 359 EQUAL Reactome Database ID Release 83 10716465 Database 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=10716465 Reactome R-DME-3640827 1 Reactome 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-DME-3640827.1 Reactome Database ID Release 83 10741829 Database 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=10741829 Reactome Database ID Release 83 10741831 Database 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=10741831 Reactome R-DME-8948832 1 Reactome 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-DME-8948832.1 The E3 ubiquitin ligase RNF146 possesses a PAR recognition domain (WWE) which binds to PARylated PTEN. RNF146 polyubiquitinates PARylated PTEN, with lysine residues K342, K344 and K349 as major ubiquitination sites. RNF146-mediated ubiquitination targets PTEN for proteasome-mediated degradation (Li et al. 2015). LEFT-TO-RIGHT Proteasome degrades polyubiquitinated PTEN 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> Converted from EntitySet in Reactome PolyUb-PTEN, K48polyUb-K289-PTEN, PolyUb-K324,K344,K349-RibC-E40,E150,D326-PTEN Reactome DB_ID: 10736581 Reactome Database ID Release 83 10736581 Database 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=10736581 Reactome R-DME-8948842 1 Reactome 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-DME-8948842.1 3 ACTIVATION 26S proteasome Reactome DB_ID: 10672015 PSMD5 Q9VYG1 Reactome DB_ID: 10671983 UniProt:Q9VYG1 UniProt Q9VYG1 2 EQUAL 504 EQUAL Reactome Database ID Release 83 10671983 Database 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=10671983 Reactome R-DME-68802 1 Reactome 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-DME-68802.1 1 PSMA1 Prosalpha6 P12881 Reactome DB_ID: 10671903 UniProt:P12881 Prosalpha6 Prosalpha6 PROS-35 Pros35 CG4904 FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel (By similarity). Interacts with PI31.SIMILARITY Belongs to the peptidase T1A family. UniProt P12881 1 EQUAL 263 EQUAL Reactome Database ID Release 83 10671903 Database 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=10671903 Reactome R-DME-68724 1 Reactome 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-DME-68724.1 1 Ghost homologue of PSMD10 Reactome DB_ID: 10671969 Reactome Database ID Release 83 10671969 Database 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=10671969 Reactome R-DME-68788 1 Reactome 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-DME-68788.1 1 PSMA8 Prosalpha4 P22769 Reactome DB_ID: 10672003 UniProt:P22769 Prosalpha4 Prosalpha4 PROS-28.1 Pros28.1 CG3422 FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel (By similarity). Interacts with PI31; this interaction is reduced by PI31 ADP-ribosylation.SIMILARITY Belongs to the peptidase T1A family. UniProt P22769 1 EQUAL 256 EQUAL Reactome Database ID Release 83 10672003 Database 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=10672003 Reactome R-DME-947610 1 Reactome 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-DME-947610.1 1 Rpn6 PSMD11 Q7KLV9 Reactome DB_ID: 10671971 UniProt:Q7KLV9 Rpn6 Rpn6 CG10149 FUNCTION Component of the lid subcomplex of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. In the complex, RPN6 is required for proteasome assembly (By similarity). May act as linker between 19S regulatory subunit and the 20S proteasome core.SUBUNIT Component of the lid subcomplex of the 19S proteasome regulatory particle complex (also named PA700 complex). The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. Interacts with alien/CSN2. Interacts with Prosalpha2 and Rpt6.DEVELOPMENTAL STAGE Highly expressed in the female germline, more precisely in the nurse cells of maturing egg chambers. Also detected in the somatic follicle cells. Highly expressed during oogenesis and early blastoderm embryos. After the beginning of zygotic transcription, present in the elongating germband and later in the mesodermal region and the developing hindgut and posterior midgut. In late embryos, shortly before hatching, becomes restricted to the brain hemispheres, the central nervous system, the embryonic gonads and the gut. In third instar larval tissues, expressed in the larval brain and in all imaginal disks.DISRUPTION PHENOTYPE Embryos develop and hatch normally but fail to outlive early larval stages. During the first and second instar larval stages larvae become immobile and sluggish and die without any observable defects. Lethality is probably the result of additive defects in overall cell proliferation rather than of distinct developmental disorders.SIMILARITY Belongs to the proteasome subunit S9 family. UniProt Q7KLV9 2 EQUAL 422 EQUAL Reactome Database ID Release 83 10671971 Database 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=10671971 Reactome R-DME-68790 1 Reactome 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-DME-68790.1 1 PSMC1 P48601 Reactome DB_ID: 10671955 UniProt:P48601 Rpt2 Rpt2 P26s4 Pros26.4 CG5289 FUNCTION The 26S proteasome is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex (By similarity).SUBUNIT Interacts with PSMD5.SIMILARITY Belongs to the AAA ATPase family. UniProt P48601 2 EQUAL 440 EQUAL Reactome Database ID Release 83 10671955 Database 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=10671955 Reactome R-DME-68768 1 Reactome 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-DME-68768.1 1 Rpt4 PSMC6 Q9W414 Reactome DB_ID: 10671965 UniProt:Q9W414 Rpt4 UniProt Q9W414 1 EQUAL 389 EQUAL Reactome Database ID Release 83 10671965 Database 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=10671965 Reactome R-DME-68783 1 Reactome 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-DME-68783.1 1 PSMB3 Prosbeta3 Q9XYN7 Reactome DB_ID: 10671935 UniProt:Q9XYN7 Prosbeta3 Prosbeta3 CG11981 FUNCTION Non-catalytic component of the proteasome, a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel (By similarity).SIMILARITY Belongs to the peptidase T1B family. UniProt Q9XYN7 2 EQUAL 205 EQUAL Reactome Database ID Release 83 10671935 Database 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=10671935 Reactome R-DME-68747 1 Reactome 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-DME-68747.1 1 REG PSME1 Q9V3P3 Reactome DB_ID: 10671993 UniProt:Q9V3P3 REG UniProt Q9V3P3 1 EQUAL 249 EQUAL Reactome Database ID Release 83 10671993 Database 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=10671993 Reactome R-DME-68812 1 Reactome 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-DME-68812.1 1 Ghost homologue of PSME4 Reactome DB_ID: 10672001 Reactome Database ID Release 83 10672001 Database 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=10672001 Reactome R-DME-947606 1 Reactome 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-DME-947606.1 1 PSMB7 Prosbeta2 Q9VUJ1 Reactome DB_ID: 10671943 UniProt:Q9VUJ1 Prosbeta2 Prosbeta2 Pros-beta-2 CG3329 Dmel_CG3329 FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity (By similarity).CATALYTIC ACTIVITY Cleavage of peptide bonds with very broad specificity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits (By similarity).SIMILARITY Belongs to the peptidase T1B family. UniProt Q9VUJ1 44 EQUAL 277 EQUAL Reactome Database ID Release 83 10671943 Database 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=10671943 Reactome R-DME-68759 1 Reactome 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-DME-68759.1 1 PSMB2 Prosbeta4 Q9VJJ0 Reactome DB_ID: 10671933 UniProt:Q9VJJ0 CG17331 CG17331 Dmel_CG17331 FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity (By similarity).CATALYTIC ACTIVITY Cleavage of peptide bonds with very broad specificity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits (By similarity).SIMILARITY Belongs to the peptidase T1B family. UniProt Q9VJJ0 1 EQUAL 201 EQUAL Reactome Database ID Release 83 10671933 Database 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=10671933 Reactome R-DME-68744 1 Reactome 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-DME-68744.1 1 Rpn5 PSMD12 Q9V3Z4 Reactome DB_ID: 10671973 UniProt:Q9V3Z4 Rpn5 Rpn5 CG1100 Dmel_CG1100 SIMILARITY Contains 1 PCI domain. UniProt Q9V3Z4 2 EQUAL 456 EQUAL Reactome Database ID Release 83 10671973 Database 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=10671973 Reactome R-DME-68792 1 Reactome 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-DME-68792.1 1 Rpn12 PSMD8 Q9V436 Reactome DB_ID: 10671989 UniProt:Q9V436 Rpn12 Rpn12 CG4157 Dmel_CG4157 <submittedName> <fullName>Rpn12</fullName> </submittedName> <submittedName> <fullName>26S proteasome regulatory complex subunit p30</fullName> </submittedName> <submittedName> <fullName>RE36854p</fullName> </submittedName> UniProt Q9V436 1 EQUAL 350 EQUAL Reactome Database ID Release 83 10671989 Database 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=10671989 Reactome R-DME-68808 1 Reactome 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-DME-68808.1 1 PSMB4 Prosbeta7 Q9VNA5 Reactome DB_ID: 10671937 UniProt:Q9VNA5 Prosbeta7 Prosbeta7 Prosb4 Prosbeta4 CG12000 FUNCTION Non-catalytic component of the proteasome, a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity (By similarity).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel (By similarity).SIMILARITY Belongs to the peptidase T1B family. UniProt Q9VNA5 46 EQUAL 264 EQUAL Reactome Database ID Release 83 10671937 Database 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=10671937 Reactome R-DME-68750 1 Reactome 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-DME-68750.1 1 Rpt1 PSMC2 Q7KMQ0 Reactome DB_ID: 10671957 UniProt:Q7KMQ0 Rpt1 Rpt1 CG1341 Dmel_CG1341 SIMILARITY Belongs to the AAA ATPase family. UniProt Q7KMQ0 2 EQUAL 433 EQUAL Reactome Database ID Release 83 10671957 Database 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=10671957 Reactome R-DME-68771 1 Reactome 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-DME-68771.1 1 Rpn9 PSMD13 Q7KMP8 Reactome DB_ID: 10671975 UniProt:Q7KMP8 Rpn9 Rpn9 CG10230 Dmel_CG10230 <submittedName> <fullName>Rpn9, isoform A</fullName> </submittedName> <submittedName> <fullName>26S proteasome regulatory complex subunit p39A</fullName> </submittedName> <submittedName> <fullName>LD17530p</fullName> </submittedName> UniProt Q7KMP8 1 EQUAL 376 EQUAL Reactome Database ID Release 83 10671975 Database 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=10671975 Reactome R-DME-68794 1 Reactome 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-DME-68794.1 1 PSMA6 Prosalpha1 Q9XZJ4 Reactome DB_ID: 10671913 UniProt:Q9XZJ4 Prosalpha1 Prosalpha1 Prosalpha6 CG18495 FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity (By similarity).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel (By similarity). Interacts with PI31.SIMILARITY Belongs to the peptidase T1A family. UniProt Q9XZJ4 1 EQUAL 246 EQUAL Reactome Database ID Release 83 10671913 Database 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=10671913 Reactome R-DME-68734 1 Reactome 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-DME-68734.1 1 PSMD14 Q9V3H2 Reactome DB_ID: 10671901 UniProt:Q9V3H2 Rpn11 Rpn11 yip5 CG18174 FUNCTION Metalloprotease component of the 26S proteasome that specifically cleaves 'Lys-63'-linked polyubiquitin chains. The 26S proteasome is involved in the ATP-dependent degradation of ubiquitinated proteins. The function of the 'Lys-63'-specific deubiquitination of the proteasome is unclear (By similarity).SUBUNIT Component of the 19S regulatory cap of the 26S proteasome.SIMILARITY Belongs to the peptidase M67A family. PSMD14 subfamily. UniProt Q9V3H2 1 EQUAL 310 EQUAL Reactome Database ID Release 83 10671901 Database 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=10671901 Reactome R-DME-68722 1 Reactome 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-DME-68722.1 1 PSMB9 Prosbeta1 A0AQH0 Reactome DB_ID: 10671953 UniProt:A0AQH0 Prosbeta1 UniProt A0AQH0 21 EQUAL 219 EQUAL Reactome Database ID Release 83 10671953 Database 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=10671953 Reactome R-DME-68765 1 Reactome 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-DME-68765.1 1 Rpn8 PSMD7 P26270 Reactome DB_ID: 10671987 UniProt:P26270 Rpn8 Rpn8 Mov34 CG3416 FUNCTION Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.SIMILARITY Belongs to the peptidase M67A family. UniProt P26270 1 EQUAL 324 EQUAL Reactome Database ID Release 83 10671987 Database 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=10671987 Reactome R-DME-68806 1 Reactome 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-DME-68806.1 1 PSMB5 Prosbeta5 Q7K148 Reactome DB_ID: 10671939 UniProt:Q7K148 Prosbeta5 UniProt Q7K148 60 EQUAL 263 EQUAL Reactome Database ID Release 83 10671939 Database 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=10671939 Reactome R-DME-68753 1 Reactome 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-DME-68753.1 1 PSMA4 Prosalpha3 P18053 Reactome DB_ID: 10671909 UniProt:P18053 Prosalpha3 UniProt P18053 1 EQUAL 261 EQUAL Reactome Database ID Release 83 10671909 Database 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=10671909 Reactome R-DME-68730 1 Reactome 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-DME-68730.1 1 Rpt3 PSMC4 Q9V405 Reactome DB_ID: 10671961 UniProt:Q9V405 Rpt3 Rpt3 Rpt3-RA CG16916 Dmel_CG16916 SIMILARITY Belongs to the AAA ATPase family. UniProt Q9V405 1 EQUAL 418 EQUAL Reactome Database ID Release 83 10671961 Database 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=10671961 Reactome R-DME-68777 1 Reactome 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-DME-68777.1 1 Rpn1 PSMD2 Q9VW54 Reactome DB_ID: 10671977 UniProt:Q9VW54 Rpn1 Rpn1 CG7762 Dmel_CG7762 <submittedName> <fullName>Rpn1</fullName> </submittedName> <submittedName> <fullName>26S proteasome regulatory complex subunit p97</fullName> </submittedName> <submittedName> <fullName>Putative uncharacterized protein</fullName> </submittedName> UniProt Q9VW54 1 EQUAL 908 EQUAL Reactome Database ID Release 83 10671977 Database 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=10671977 Reactome R-DME-68796 1 Reactome 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-DME-68796.1 1 Rpn2 PSMD1 Q9V3P6 Reactome DB_ID: 10671967 UniProt:Q9V3P6 Rpn2 Rpn2 CG11888 FUNCTION Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.SIMILARITY Belongs to the proteasome subunit S1 family. UniProt Q9V3P6 1 EQUAL 953 EQUAL Reactome Database ID Release 83 10671967 Database 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=10671967 Reactome R-DME-68786 1 Reactome 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-DME-68786.1 1 PSMA3 Prosalpha7 Q9V5C6 Reactome DB_ID: 10671907 UniProt:Q9V5C6 Prosalpha7 Prosalpha7 CG1519 FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity (By similarity).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel (By similarity). Interacts with ntc.SIMILARITY Belongs to the peptidase T1A family. UniProt Q9V5C6 2 EQUAL 255 EQUAL Reactome Database ID Release 83 10671907 Database 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=10671907 Reactome R-DME-68728 1 Reactome 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-DME-68728.1 1 Converted from EntitySet in Reactome Homologues of PSMB8 Reactome DB_ID: 10671951 PSMB8 Prosbeta5 Q7K148 Reactome DB_ID: 10671945 73 EQUAL 276 EQUAL Reactome Database ID Release 83 10671945 Database 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=10671945 Reactome R-DME-68762 1 Reactome 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-DME-68762.1 PSMB8 Prosbeta5R2 Q8INY4 Reactome DB_ID: 10671947 UniProt:Q8INY4 Prosbeta5R2 UniProt Q8INY4 73 EQUAL 276 EQUAL Reactome Database ID Release 83 10671947 Database 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=10671947 Reactome R-DME-68762-2 1 Reactome 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-DME-68762-2.1 PSMB8 Prosbeta5R1 Q9W1S5 Reactome DB_ID: 10671949 UniProt:Q9W1S5 Prosbeta5R1 UniProt Q9W1S5 73 EQUAL 276 EQUAL Reactome Database ID Release 83 10671949 Database 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=10671949 Reactome R-DME-68762-3 1 Reactome 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-DME-68762-3.1 Reactome Database ID Release 83 10671951 Database 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=10671951 Reactome R-DME-68762-4 1 Reactome 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-DME-68762-4.1 1 Rpn10 PSMD4 P55035 Reactome DB_ID: 10671981 UniProt:P55035 Rpn10 Rpn10 PROS-54 Pros54 CG7619 FUNCTION Binds and presumably selects ubiquitin-conjugates for destruction.SUBUNIT The 26S proteasome is composed of a core protease, known as the 20S proteasome, capped at one or both ends by the 19S regulatory complex (RC). The RC is composed of at least 18 different subunits in two subcomplexes, the base and the lid, which form the portions proximal and distal to the 20S proteolytic core, respectively (By similarity). Interacts with Ubc4.SIMILARITY Belongs to the proteasome subunit S5A family. UniProt P55035 1 EQUAL 377 EQUAL Reactome Database ID Release 83 10671981 Database 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=10671981 Reactome R-DME-68800 1 Reactome 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-DME-68800.1 1 PSMA5 Prosalpha5 Q95083 Reactome DB_ID: 10671911 UniProt:Q95083 Prosalpha5 Prosalpha5 ProsMA5 CG10938 FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel (By similarity).SIMILARITY Belongs to the peptidase T1A family. UniProt Q95083 1 EQUAL 241 EQUAL Reactome Database ID Release 83 10671911 Database 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=10671911 Reactome R-DME-68732 1 Reactome 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-DME-68732.1 1 Converted from EntitySet in Reactome Homologues of PSMB10 Reactome DB_ID: 10671931 PSMB10 Prosbeta2R2 Q8T915 Reactome DB_ID: 10671925 UniProt:Q8T915 Prosbeta2R2 UniProt Q8T915 40 EQUAL 273 EQUAL Reactome Database ID Release 83 10671925 Database 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=10671925 Reactome R-DME-68741 1 Reactome 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-DME-68741.1 PSMB10 Prosbeta2 Q9VUJ1 Reactome DB_ID: 10671927 40 EQUAL 273 EQUAL Reactome Database ID Release 83 10671927 Database 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=10671927 Reactome R-DME-68741-2 1 Reactome 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-DME-68741-2.1 PSMB10 Prosbeta2R1 Q9W470 Reactome DB_ID: 10671929 UniProt:Q9W470 Prosbeta2R1 UniProt Q9W470 40 EQUAL 273 EQUAL Reactome Database ID Release 83 10671929 Database 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=10671929 Reactome R-DME-68741-3 1 Reactome 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-DME-68741-3.1 Reactome Database ID Release 83 10671931 Database 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=10671931 Reactome R-DME-68741-4 1 Reactome 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-DME-68741-4.1 1 Ghost homologue of SEM1 Reactome DB_ID: 10672013 Reactome Database ID Release 83 10672013 Database 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=10672013 Reactome R-DME-8866674 1 Reactome 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-DME-8866674.1 1 Ghost homologue of PSMB1 Reactome DB_ID: 10671923 Reactome Database ID Release 83 10671923 Database 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=10671923 Reactome R-DME-68738 1 Reactome 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-DME-68738.1 1 REG PSME2 Q9V3P3 Reactome DB_ID: 10671995 2 EQUAL 239 EQUAL Reactome Database ID Release 83 10671995 Database 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=10671995 Reactome R-DME-68814 1 Reactome 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-DME-68814.1 1 PI31 PSMF1 Q9V637 Reactome DB_ID: 10671999 UniProt:Q9V637 PI31 UniProt Q9V637 1 EQUAL 271 EQUAL Reactome Database ID Release 83 10671999 Database 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=10671999 Reactome R-DME-68818 1 Reactome 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-DME-68818.1 1 Converted from EntitySet in Reactome Homologues of PSMB11 Reactome DB_ID: 10672011 PSMB11 Prosbeta5 Q7K148 Reactome DB_ID: 10672005 50 EQUAL 300 EQUAL Reactome Database ID Release 83 10672005 Database 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=10672005 Reactome R-DME-947607 1 Reactome 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-DME-947607.1 PSMB11 Prosbeta5R2 Q8INY4 Reactome DB_ID: 10672007 50 EQUAL 300 EQUAL Reactome Database ID Release 83 10672007 Database 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=10672007 Reactome R-DME-947607-2 1 Reactome 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-DME-947607-2.1 PSMB11 Prosbeta5R1 Q9W1S5 Reactome DB_ID: 10672009 50 EQUAL 300 EQUAL Reactome Database ID Release 83 10672009 Database 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=10672009 Reactome R-DME-947607-3 1 Reactome 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-DME-947607-3.1 Reactome Database ID Release 83 10672011 Database 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=10672011 Reactome R-DME-947607-4 1 Reactome 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-DME-947607-4.1 1 Rpt5 PSMC3 Q9V3V6 Reactome DB_ID: 10671959 UniProt:Q9V3V6 Tbp-1 Tbp-1 CG10370 Dmel_CG10370 SIMILARITY Belongs to the AAA ATPase family. UniProt Q9V3V6 1 EQUAL 439 EQUAL Reactome Database ID Release 83 10671959 Database 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=10671959 Reactome R-DME-68774 1 Reactome 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-DME-68774.1 1 Rpn3 PSMD3 P25161 Reactome DB_ID: 10671979 UniProt:P25161 Rpn3 Rpn3 Dox-A2 CG42641 FUNCTION Acts as a regulatory subunit of the 26 proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.SUBUNIT The 26S proteasome is composed of a core protease, known as the 20S proteasome, capped at one or both ends by the 19S regulatory complex (RC). The RC is composed of at least 18 different subunits in two subcomplexes, the base and the lid, which form the portions proximal and distal to the 20S proteolytic core, respectively (By similarity).TISSUE SPECIFICITY Blood (crystal) cells and cuticle.SIMILARITY Belongs to the proteasome subunit S3 family.CAUTION Was originally thought to be the diphenol oxidase A2 component involved in catecholamine metabolism, melanin formation, and sclerotization of the cuticle. UniProt P25161 1 EQUAL 534 EQUAL Reactome Database ID Release 83 10671979 Database 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=10671979 Reactome R-DME-68798 1 Reactome 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-DME-68798.1 1 PSMA2 Prosalpha2 P40301 Reactome DB_ID: 10671905 UniProt:P40301 Prosalpha2 Prosalpha2 PROS-25 Pros25 CG5266 FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel (By similarity). Interacts with Rpn6.SIMILARITY Belongs to the peptidase T1A family. UniProt P40301 2 EQUAL 234 EQUAL Reactome Database ID Release 83 10671905 Database 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=10671905 Reactome R-DME-68726 1 Reactome 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-DME-68726.1 1 Converted from EntitySet in Reactome Homologues of PSMA7 Reactome DB_ID: 10671921 PSMA7 Prosalpha4 P22769 Reactome DB_ID: 10671915 1 EQUAL 248 EQUAL Reactome Database ID Release 83 10671915 Database 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=10671915 Reactome R-DME-68736 1 Reactome 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-DME-68736.1 PSMA7 Prosalpha4T1 Q24178 Reactome DB_ID: 10671917 UniProt:Q24178 Prosalpha4T1 UniProt Q24178 1 EQUAL 248 EQUAL Reactome Database ID Release 83 10671917 Database 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=10671917 Reactome R-DME-68736-2 1 Reactome 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-DME-68736-2.1 PSMA7 Prosalpha4T2 Q27575 Reactome DB_ID: 10671919 UniProt:Q27575 Prosalpha4T2 UniProt Q27575 1 EQUAL 248 EQUAL Reactome Database ID Release 83 10671919 Database 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=10671919 Reactome R-DME-68736-3 1 Reactome 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-DME-68736-3.1 Reactome Database ID Release 83 10671921 Database 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=10671921 Reactome R-DME-68736-4 1 Reactome 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-DME-68736-4.1 1 PSMC5 O18413 Reactome DB_ID: 10671963 UniProt:O18413 Rpt6 Rpt6 DUG Pros45 Ug CG1489 FUNCTION The 26S proteasome is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex (By similarity).SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. Interacts with Rpn6 (PubMed:22187461). Interacts with imd and Usp2 isoform A (PubMed:25027767).SIMILARITY Belongs to the AAA ATPase family. UniProt O18413 2 EQUAL 406 EQUAL Reactome Database ID Release 83 10671963 Database 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=10671963 Reactome R-DME-68780 1 Reactome 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-DME-68780.1 1 PSMB6 Prosbeta1 A0AQH0 Reactome DB_ID: 10671941 35 EQUAL 239 EQUAL Reactome Database ID Release 83 10671941 Database 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=10671941 Reactome R-DME-68756 1 Reactome 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-DME-68756.1 1 Rpn7 PSMD6 Q9V3G7 Reactome DB_ID: 10671985 UniProt:Q9V3G7 Rpn7 Rpn7 CG5378 FUNCTION Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.SIMILARITY Belongs to the proteasome subunit S10 family. UniProt Q9V3G7 1 EQUAL 389 EQUAL Reactome Database ID Release 83 10671985 Database 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=10671985 Reactome R-DME-68804 1 Reactome 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-DME-68804.1 1 PSMD9 Q9VFS8 Reactome DB_ID: 10671991 UniProt:Q9VFS8 UniProt Q9VFS8 1 EQUAL 223 EQUAL Reactome Database ID Release 83 10671991 Database 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=10671991 Reactome R-DME-68810 1 Reactome 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-DME-68810.1 1 REG PSME3 Q9V3P3 Reactome DB_ID: 10671997 2 EQUAL 254 EQUAL Reactome Database ID Release 83 10671997 Database 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=10671997 Reactome R-DME-68816 1 Reactome 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-DME-68816.1 1 Reactome Database ID Release 83 10672015 Database 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=10672015 Reactome R-DME-68819 1 Reactome 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-DME-68819.1 GENE ONTOLOGY GO:0004175 Reactome Database ID Release 83 10672016 Database 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=10672016 Reactome Database ID Release 83 10736583 Database 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=10736583 Reactome R-DME-8850992 1 Reactome 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-DME-8850992.1 PTEN, polyubiquitinated by either NEDD4 (Wang et al. 2007), STUB1 (CHIP) (Ahmed et al. 2011), WWP2 (Maddika et al. 2011), XIAP (Van Themsche et al. 2009), MKRN1 (Lee et al. 2015) or RNF146 (Li et al. 2015), is degraded by the proteasome. LEFT-TO-RIGHT 3.4.19.12 USP13 and OTUD3 deubiquitinate PTEN 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> H2O water Reactome DB_ID: 29356 Reactome Database ID Release 83 29356 Database 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=29356 Reactome R-ALL-29356 5 Reactome 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-ALL-29356.5 COMPOUND C00001 3 ACTIVATION Converted from EntitySet in Reactome USP13,OTUD3 Reactome DB_ID: 10734478 USP13 Q9VZU7 Reactome DB_ID: 10727035 UniProt:Q9VZU7 UniProt Q9VZU7 1 EQUAL 863 EQUAL Reactome Database ID Release 83 10727035 Database 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=10727035 Reactome R-DME-6781893 1 Reactome 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-DME-6781893.1 otu OTUD3 P10383 Reactome DB_ID: 10734476 UniProt:P10383 otu UniProt P10383 1 EQUAL 398 EQUAL Reactome Database ID Release 83 10734476 Database 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=10734476 Reactome R-DME-8873955 1 Reactome 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-DME-8873955.1 Reactome Database ID Release 83 10734478 Database 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=10734478 Reactome R-DME-8948849 1 Reactome 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-DME-8948849.1 Reactome Database ID Release 83 10734479 Database 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=10734479 Reactome Database ID Release 83 10734481 Database 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=10734481 Reactome R-DME-6807206 1 Reactome 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-DME-6807206.1 Several ubiquitin proteases deubiquitinate polyubiquitinated PTEN. USP13 and OTUD3 prolong the half-life of PTEN by preventing its proteasome-mediated degradation. Loss of USP13 or OTUD3 expression promotes AKT activation and cancer aggressiveness (Zhang et al. 2013, Yuan et al. 2015). 24270891 Pubmed 2013 Deubiquitylation and stabilization of PTEN by USP13 Zhang, Jinsong Zhang, Peijing Wei, Yongkun Piao, Hai-Long Wang, W Maddika, Subbareddy Wang, Min Chen, Dahu Sun, Yutong Hung, Mien-Chie Chen, J Ma, Li Nat. Cell Biol. 15:1486-94 26280536 Pubmed 2015 Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis Yuan, Lin Lv, Yanrong Li, Hongchang Gao, Haidong Song, Shanshan Zhang, Yuan Xing, Guichun Kong, Xiangzhen Wang, Lijing Li, Yang Zhou, Tao Gao, Daming Xiao, Zhi-Xiong Yin, Yuxin Wei, Wenyi He, Fuchu Zhang, Lingqiang Nat. Cell Biol. 17:1169-81 LEFT-TO-RIGHT PTEN binds FRK 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> Q9V9J3 phospho-p-Y387-FRK Reactome DB_ID: 10736016 UniProt:Q9V9J3 Src42A Src42A Src41 TK5 CG44128 FUNCTION Required directly or indirectly for the phosphorylation of drpr which is necessary for the interaction of drpr with shark and subsequent glial phagocytic activity (PubMed:18432193). Together with drpr and shark, promotes the migration of macrophages to sites of wounding as part of a signaling cascade where Scr42a detects production of hydrogen peroxide at wound sites which triggers phosphorylation of drpr and subsequent recruitment and activation of shark (PubMed:26028435). Essential for correct eye morphogenesis (ommatidial R7 neuron formation) which requires the Ras1/MAPK signal transduction pathway (PubMed:8682295). May be involved in the regulation of cytoskeleton organization and cell-cell contacts in developing ommatidia (PubMed:8682295). During embryogenesis, involved in regulation of dorsal closure where it may have a role in activating the JNK pathway in leading edge cells during this process (PubMed:16831834).TISSUE SPECIFICITY Ubiquitous in early embryos, in stages 13-16 expression is seen in visceral mesoderm, hindgut, brain, anal pads and ventral ganglions. In larvae, expression is in CNS, wing disk, leg disk and photoreceptor precursors in the eye-antenna disks posterior to the morphogenetic furrow.DEVELOPMENTAL STAGE In early embryos expression is very low, expression increases during embryogenesis. Also expressed in larvae and pupae.DISRUPTION PHENOTYPE Following epithelial wounding, no migration of macrophages to wound sites (PubMed:26028435). RNAi-mediated knockdown in glial cells potently suppresses glial phagocytic activity with drpr not recruited to severed maxillary palp axons, blockage of glial hypertrophy, blockage of drpr up-regulation after antennal ablation and reduced clearance of severed axons in the central nervous system (PubMed:18432193).SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. UniProt Q9V9J3 387 EQUAL O4'-phospho-L-tyrosine MOD MOD:00048 1 EQUAL 505 EQUAL Reactome Database ID Release 83 10736016 Database 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=10736016 Reactome R-DME-8847965 1 Reactome 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-DME-8847965.1 PTEN:p-Y387-FRK Reactome DB_ID: 10736018 1 1 Reactome Database ID Release 83 10736018 Database 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=10736018 Reactome R-DME-8847960 1 Reactome 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-DME-8847960.1 Reactome Database ID Release 83 10736020 Database 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=10736020 Reactome R-DME-8847968 1 Reactome 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-DME-8847968.1 FRK (RAK), a SRC family member kinase, binds PTEN. The interaction involves the SH3 domain of FRK and the C2 domain of PTEN (Yim et al. 2009). Like other SRC family members, FRK is autophosphorylated on a C-terminal tyrosine residue Y387. FRK possesses a nuclear localization signal and is found in both nucleus and the cytosol (Cance et al. 1994). 19345329 Pubmed 2009 Rak functions as a tumor suppressor by regulating PTEN protein stability and function Yim, Eun-Kyoung Peng, Guang Dai, Hui Hu, Ruozhen Li, Kaiyi Lu, Yiling Mills, Gordon B Meric-Bernstam, Funda Hennessy, Bryan T Craven, Rolf J Lin, Shiaw-Yih Cancer Cell 15:304-14 7696183 Pubmed 1994 Rak, a novel nuclear tyrosine kinase expressed in epithelial cells Cance, W G Craven, R J Bergman, M Xu, L Alitalo, K Liu, E T Cell Growth Differ. 5:1347-55 LEFT-TO-RIGHT 2.7.10.2 FRK phosphorylates PTEN 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> Q7KMQ6 phospho-Pten p-Y336-PTEN Reactome DB_ID: 10736023 336 EQUAL 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10736023 Database 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=10736023 Reactome R-DME-8847980 1 Reactome 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-DME-8847980.1 ACTIVATION activeUnit: #Protein155 GENE ONTOLOGY GO:0004713 Reactome Database ID Release 83 10736024 Database 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=10736024 Reactome Database ID Release 83 10736026 Database 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=10736026 Reactome R-DME-8847977 1 Reactome 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-DME-8847977.1 FRK tyrosine kinase (RAK) phosphorylates PTEN on tyrosine residue Y336. FRK-mediated phosphorylation inhibits NEDD4-mediated polyubiquitination and subsequent degradation of PTEN, thus increasing PTEN half-life. FRK-mediated phosphorylation also increases PTEN enzymatic activity (Yim et al. 2009). LEFT-TO-RIGHT 2.7.11.1 Casein kinase II phosphorylates PTEN 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> 5 Q7KMQ6 phospho-Pten p-3S,2T-PTEN Reactome DB_ID: 10736569 370 EQUAL 380 EQUAL 382 EQUAL 383 EQUAL 385 EQUAL 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10736569 Database 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=10736569 Reactome R-DME-8850936 1 Reactome 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-DME-8850936.1 5 ACTIVATION Casein kinase II Reactome DB_ID: 10685706 Converted from EntitySet in Reactome CSNK2(A1:A1/A1:A2/A2:A2) CKII alpha catalytic subunit Reactome DB_ID: 10685704 CSNK2A1 dimer Reactome DB_ID: 10685696 P08181 CSNK2A1 Reactome DB_ID: 10685694 UniProt:P08181 CkIIalpha CkIIalpha Cask-II-a CG17520 FUNCTION Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. The alpha chain contains the catalytic site. May participate in Wnt signaling.SUBUNIT Tetramer of two alpha and two beta chains.DISRUPTION PHENOTYPE RNAi-mediated knockdown results in mislocalization of mbm in interphase cells with partial localization to the cytoplasm as well as nucleolar expression.SIMILARITY Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CK2 subfamily. UniProt P08181 1 EQUAL 391 EQUAL Reactome Database ID Release 83 10685694 Database 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=10685694 Reactome R-DME-201713 1 Reactome 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-DME-201713.1 2 Reactome Database ID Release 83 10685696 Database 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=10685696 Reactome R-DME-5083621 1 Reactome 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-DME-5083621.1 CSNK2A2 dimer Reactome DB_ID: 10685700 P08181 CSNK2A2 Reactome DB_ID: 10685698 1 EQUAL 350 EQUAL Reactome Database ID Release 83 10685698 Database 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=10685698 Reactome R-DME-201721 1 Reactome 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-DME-201721.1 2 Reactome Database ID Release 83 10685700 Database 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=10685700 Reactome R-DME-5083620 1 Reactome 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-DME-5083620.1 CSNK2A1:CSNK2A2 Reactome DB_ID: 10685702 1 1 Reactome Database ID Release 83 10685702 Database 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=10685702 Reactome R-DME-5083623 1 Reactome 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-DME-5083623.1 Reactome Database ID Release 83 10685704 Database 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=10685704 Reactome R-DME-5083624 1 Reactome 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-DME-5083624.1 2 CSNK2B CkIIbeta P08182 Reactome DB_ID: 10685690 UniProt:P08182 CkIIbeta CkIIbeta Cask-II-b CG15224 FUNCTION Participates in Wnt signaling (By similarity). Plays a complex role in regulating the basal catalytic activity of the alpha subunit.SUBUNIT Tetramer of two alpha and two beta subunits.PTM Phosphorylated by alpha subunit.SIMILARITY Belongs to the casein kinase 2 subunit beta family. UniProt P08182 2 EQUAL 215 EQUAL Reactome Database ID Release 83 10685690 Database 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=10685690 Reactome R-DME-201693 1 Reactome 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-DME-201693.1 2 Reactome Database ID Release 83 10685706 Database 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=10685706 Reactome R-DME-201711 1 Reactome 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-DME-201711.1 Reactome Database ID Release 83 10685707 Database 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=10685707 Reactome Database ID Release 83 10736571 Database 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=10736571 Reactome R-DME-8850945 1 Reactome 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-DME-8850945.1 Casein kinase II (CK2) constitutively phosphorylates the C-terminal tail of PTEN on serine and threonine residues S370, S380, T382, T383 and S385. S370 and S385 are the main CK2 phosphorylation sites in PTEN (Torres and Pulido 2001, Miller et al. 2002). CK2-mediated phosphorylation increases PTEN protein stability (Torres and Pulido 2001) but results in ~30% reduction in PTEN lipid phosphatase activity (Miller et al. 2002). 11035045 Pubmed 2001 The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation Torres, J Pulido, R J. Biol. Chem. 276:993-8 12297295 Pubmed 2002 Direct identification of PTEN phosphorylation sites Miller, Susan J Lou, David Y Seldin, David C Lane, William S Neel, Benjamin G FEBS Lett. 528:145-53 Reactome Database ID Release 83 10751371 Database 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=10751371 Reactome R-DME-8948751 1 Reactome 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-DME-8948751.1 PTEN protein stability is regulated by ubiquitin ligases, such as NEDD4, WWP2, STUB1 (CHIP), XIAP, MKRN1 and RNF146, which polyubiquitinate PTEN in response to different stimuli and thus target it for proteasome-mediated degradation (Wang et al. 2007, Van Themsche et al. 2009, Maddika et al. 2011, Ahmed et al. 2012, Lee et al. 2015, Li et al. 2015). Several ubiquitin proteases, such as USP13 and OTUD3, can remove polyubiquitin chains from PTEN and rescue it from degradation (Zhang et al. 2013, Yuan et al. 2015). TRIM27 (RFP) is an E3 ubiquitin ligase that polyubiquitinates PTEN on multiple lysines in the C2 domain of PTEN using K27 linkage between ubiquitin molecules. TRIM27 mediated ubiquitination inhibits PTEN lipid phosphatase activity, but does not affect PTEN protein localization or stability (Lee et al. 2013).<br>PTEN phosphorylation by the tyrosine kinase FRK (RAK) inhibits NEDD4 mediated polyubiquitination and subsequent degradation of PTEN, thus increasing PTEN half life. FRK mediated phosphorylation also increases PTEN enzymatic activity (Yim et al. 2009). Casein kinase 2 (CK2) mediated phosphorylation of the C-terminus of PTEN on multiple serine and threonine residues increases PTEN protein stability (Torres and Pulido 2001) but results in ~30% reduction in PTEN lipid phosphatase activity (Miller et al. 2002).<br>PREX2, a RAC1 guanine nucleotide exchange factor (GEF) can binds to PTEN and inhibit its catalytic activity (Fine et al. 2009). 19729658 Pubmed 2009 Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a Fine, Barry Hodakoski, Cindy Koujak, Susan Su, Tao Saal, Lao H Maurer, Matthew Hopkins, Benjamin Keniry, Megan Sulis, ML Mense, Sarah Hibshoosh, Hanina Parsons, R Science 325:1261-5 24367090 Pubmed 2014 Regulation of PTEN inhibition by the pleckstrin homology domain of P-REX2 during insulin signaling and glucose homeostasis Hodakoski, Cindy Hopkins, Benjamin D Barrows, Douglas Mense, Sarah M Keniry, Megan Anderson, Karen E Kern, Philip A Hawkins, Phillip T Stephens, Len R Parsons, R Proc. Natl. Acad. Sci. U.S.A. 111:155-60 Reactome Database ID Release 83 10751369 Database 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=10751369 Reactome R-DME-6807070 1 Reactome 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-DME-6807070.1 PTEN is regulated at the level of gene transcription, mRNA translation, localization and protein stability.<p>Transcription of the PTEN gene is regulated at multiple levels. Epigenetic repression involves the recruitment of Mi-2/NuRD upon SALL4 binding to the PTEN promoter (Yang et al. 2008, Lu et al. 2009) or EVI1-mediated recruitment of the polycomb repressor complex (PRC) to the PTEN promoter (Song et al. 2009, Yoshimi et al. 2011). Transcriptional regulation is also elicited by negative regulators, including NR2E1:ATN1 (atrophin-1) complex, JUN (c-Jun), SNAIL and SLUG (Zhang et al. 2006, Vasudevan et al. 2007, Escriva et al. 2008, Uygur et al. 2015) and positive regulators such as TP53 (p53), MAF1, ATF2, EGR1 or PPARG (Stambolic et al. 2001, Virolle et al. 2001, Patel et al. 2001, Shen et al. 2006, Li et al. 2016).<p>MicroRNAs miR-26A1, miR-26A2, miR-22, miR-25, miR-302, miR-214, miR-17-5p, miR-19 and miR-205 bind PTEN mRNA and inhibit its translation into protein. These microRNAs are altered in cancer and can account for changes in PTEN levels (Meng et al. 2007, Xiao et al. 2008, Yang et al. 2008, Huse et al. 2009, Kim et al. 2010, Poliseno, Salmena, Riccardi et al. 2010, Cai et al. 2013). In addition, coding and non-coding RNAs can prevent microRNAs from binding to PTEN mRNA. These RNAs are termed competing endogenous RNAs or ceRNAs. Transcripts of the pseudogene PTENP1 and mRNAs transcribed from SERINC1, VAPA and CNOT6L genes exhibit this activity (Poliseno, Salmena, Zhang et al. 2010, Tay et al. 2011, Tay et al. 2014).<p>PTEN can translocate from the cytosol to the nucleus after undergoing monoubiquitination. PTEN's ability to localize to the nucleus contributes to its tumor suppressive role (Trotman et al. 2007). The ubiquitin protease USP7 (HAUSP) targets monoubiquitinated PTEN in the nucleus, resulting in PTEN deubiquitination and nuclear exclusion. PML, via an unknown mechanism that involves USP7- and PML-interacting protein DAXX, inhibits USP7-mediated deubiquitination of PTEN, thus promoting PTEN nuclear localization. Disruption of PML function in acute promyelocytic leukemia, through a chromosomal translocation that results in expression of a fusion protein PML-RARA, leads to aberrant PTEN localization (Song et al. 2008).<p>Several ubiquitin ligases, including NEDD4, WWP2, STUB1 (CHIP), RNF146, XIAP and MKRN1, polyubiquitinate PTEN and target it for proteasome-mediated degradation (Wang et al. 2007, Van Themsche et al. 2009, Ahmed et al. 2011, Maddika et al. 2011, Lee et al. 2015, Li et al. 2015). The ubiquitin proteases USP13 and OTUD3, frequently down-regulated in breast cancer, remove polyubiquitin chains from PTEN, thus preventing its degradation and increasing its half-life (Zhang et al. 2013, Yuan et al. 2015). The catalytic activity of PTEN is negatively regulated by PREX2 binding (Fine et al. 2009, Hodakoski et al. 2014) and TRIM27-mediated ubiquitination (Lee et al. 2013), most likely through altered PTEN conformation.<p>In addition to ubiquitination, PTEN also undergoes SUMOylation (Gonzalez-Santamaria et al. 2012, Da Silva Ferrada et al. 2013, Lang et al. 2015, Leslie et al. 2016). SUMOylation of the C2 domain of PTEN may regulate PTEN association with the plasma membrane (Shenoy et al. 2012) as well as nuclear localization of PTEN (Bassi et al. 2013, Collaud et al. 2016). PIASx-alpha, a splicing isorom of E3 SUMO-protein ligase PIAS2 has been implicated in PTEN SUMOylation (Wang et al. 2014). SUMOylation of PTEN may be regulated by activated AKT (Lin et al. 2016). Reactions describing PTEN SUMOylation will be annotated when mechanistic details become available.<p>Phosphorylation affects the stability and activity of PTEN. FRK tyrosine kinase (RAK) phosphorylates PTEN on tyrosine residue Y336, which increases PTEN half-life by inhibiting NEDD4-mediated polyubiquitination and subsequent degradation of PTEN. FRK-mediated phosphorylation also increases PTEN enzymatic activity (Yim et al. 2009). Casein kinase II (CK2) constitutively phosphorylates the C-terminal tail of PTEN on serine and threonine residues S370, S380, T382, T383 and S385. CK2-mediated phosphorylation increases PTEN protein stability (Torres and Pulido 2001) but results in ~30% reduction in PTEN lipid phosphatase activity (Miller et al. 2002).<p>PTEN localization and activity are affected by acetylation of its lysine residues (Okumura et al. 2006, Ikenoue et al. 2008, Meng et al. 2016). PTEN can undergo oxidation, which affects its function, but the mechanism is poorly understood (Tan et al. 2015, Shen et al. 2015, Verrastro et al. 2016). 22000013 Pubmed 2011 Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs Tay, Yvonne Kats, Lev Salmena, Leonardo Weiss, Dror Tan, Shen Mynn Ala, Ugo Karreth, Florian Poliseno, Laura Provero, Paolo Di Cunto, Ferdinando Lieberman, Judy Rigoutsos, Isidore Pandolfi, Pier Paolo Cell 147:344-57 23888040 Pubmed 2013 Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress Bassi, C Ho, J Srikumar, T Dowling, R J O Gorrini, C Miller, S J Mak, T W Neel, B G Raught, B Stambolic, V Science 341:395-9 24344134 Pubmed 2014 PIASxα ligase enhances SUMO1 modification of PTEN protein as a SUMO E3 ligase Wang, Weibin Chen, Yifan Wang, Shuya Hu, Ningguang Cao, Zhengyi Wang, Wengong Tong, Tanjun Zhang, Xiaowei J. Biol. Chem. 289:3217-30 25867063 Pubmed 2016 SUMO modification of Akt regulates global SUMOylation and substrate SUMOylation specificity through Akt phosphorylation of Ubc9 and SUMO1 Lin, C H Liu, S Y Lee, E H Y Oncogene 35:595-607 19487573 Pubmed 2009 The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo Huse, Jason T Brennan, Cameron Hambardzumyan, Dolores Wee, Boyoung Pena, John Rouhanifard, Sara H Sohn-Lee, Cherin le Sage, Carlos Agami, Reuven Tuschl, Thomas Holland, Eric C Genes Dev. 23:1327-37 20388916 Pubmed 2010 Identification of the miR-106b~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation Poliseno, Laura Salmena, Leonardo Riccardi, Luisa Fornari, Alessandro Song, MS Hobbs, Robin M Sportoletti, Paolo Varmeh, Shorheh Egia, Ainara Fedele, Giuseppe Rameh, Lucia Loda, Massimo Pandolfi, Pier Paolo Sci Signal 3:ra29 23073177 Pubmed 2012 Membrane association of the PTEN tumor suppressor: electrostatic interaction with phosphatidylserine-containing bilayers and regulatory role of the C-terminal tail Shenoy, Siddharth S Nanda, Hirsh Lösche, Mathias J. Struct. Biol. 180:394-408 25224693 Pubmed 2015 Analysis of PTEN ubiquitylation and SUMOylation using molecular traps Lang, Valérie Aillet, Fabienne Da Silva-Ferrada, Elisa Xolalpa, Wendy Zabaleta, Lorea Rivas, Carmen Rodriguez, Manuel S Methods 77:112-8 26561776 Pubmed 2016 Reversible oxidation of phosphatase and tensin homolog (PTEN) alters its interactions with signaling and regulatory proteins Verrastro, Ivan Tveen-Jensen, Karina Woscholski, Rudiger Spickett, Corinne M Pitt, Andrew R Free Radic. Biol. Med. 90:24-34 26862215 Pubmed 2016 The PTEN protein: cellular localization and post-translational regulation Leslie, Nick R Kriplani, Nisha Hermida, Miguel A Alvarez-Garcia, Virginia Wise, Helen M Biochem. Soc. Trans. 44:273-8 18199536 Pubmed 2008 MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN Yang, Hua Kong, William He, Lili Zhao, Jian-Jun O'Donnell, Joshua D Wang, Jiawang Wenham, Robert M Coppola, Domenico Kruk, Patricia A Nicosia, Santo V Cheng, Jin Q Cancer Res. 68:425-33 17681183 Pubmed 2007 MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer Meng, Fanyin Henson, Roger Wehbe-Janek, Hania Ghoshal, Kalpana Jacob, Samson T Patel, Tushar Gastroenterology 133:647-58 23856247 Pubmed 2013 miR-205 targets PTEN and PHLPP2 to augment AKT signaling and drive malignant phenotypes in non-small cell lung cancer Cai, Junchao Fang, Lishan Huang, Yongbo Li, Rong Yuan, Jie Yang, Y Zhu, Xun Chen, Baixue Wu, Jueheng Li, Mengfeng Cancer Res. 73:5402-15 20577206 Pubmed 2010 A coding-independent function of gene and pseudogene mRNAs regulates tumour biology Poliseno, Laura Salmena, Leonardo Zhang, Jiangwen Carver, Brett Haveman, William J Pandolfi, Pier Paolo Nature 465:1033-8 26279303 Pubmed 2016 PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition Meng, Z Jia, L-F Gan, Y-H Oncogene 35:2333-44 16829519 Pubmed 2006 PCAF modulates PTEN activity Okumura, Koichi Mendoza, Michelle Bachoo, Robert M DePinho, Ronald A Cavenee, Webster K Furnari, Frank B J. Biol. Chem. 281:26562-8 23604351 Pubmed 2013 Analysis of SUMOylated proteins using SUMO-traps Da Silva-Ferrada, Elisa Xolalpa, Wendy Lang, Valérie Aillet, Fabienne Martin-Ruiz, Itziar de la Cruz-Herrera, Carlos F Lopitz-Otsoa, Fernando Carracedo, Arkaitz Goldenberg, SJ Rivas, Carmen England, Patrick Rodriguez, Manuel S Sci Rep 3:1690 18757404 Pubmed 2008 PTEN acetylation modulates its interaction with PDZ domain Ikenoue, T Inoki, Ken Zhao, B Guan, KL Cancer Res. 68:6908-12 23419514 Pubmed 2013 RFP-mediated ubiquitination of PTEN modulates its effect on AKT activation Lee, James T Shan, Jing Zhong, Jiayun Li, Muyang Zhou, Brenda Zhou, Amanda Parsons, R Gu, Wei Cell Res. 23:552-64 20080666 Pubmed 2010 Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship Kim, Hyunsoo Huang, Wei Jiang, Xiuli Pennicooke, Brenton Park, Peter J Johnson, Mark D Proc. Natl. Acad. Sci. U.S.A. 107:2183-8 25737250 Pubmed 2015 Differential thiol oxidation of the signaling proteins Akt, PTEN or PP2A determines whether Akt phosphorylation is enhanced or inhibited by oxidative stress in C2C12 myotubes derived from skeletal muscle Tan, Pearl Lin Shavlakadze, Tea Grounds, Miranda D Arthur, Peter G Int. J. Biochem. Cell Biol. 62:72-9 26415504 Pubmed 2015 AIF inhibits tumor metastasis by protecting PTEN from oxidation Shen, Shao-Ming Guo, Meng Xiong, Zhong Yu, Yun Zhao, Xu-Yun Zhang, Fei-Fei Chen, Guo-Qiang EMBO Rep. 16:1563-80 18327259 Pubmed 2008 Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes Xiao, Changchun Srinivasan, Lakshmi Calado, Dinis Pedro Patterson, Heide Christine Zhang, Baochun Wang, Jing Henderson, Joel M Kutok, Jeffrey L Rajewsky, Klaus Nat. Immunol. 9:405-14 23013792 Pubmed 2012 Regulation of the tumor suppressor PTEN by SUMO González-Santamaría, J Campagna, M Ortega-Molina, A Marcos-Villar, L de la Cruz-Herrera, C F González, D Gallego, P Lopitz-Otsoa, F Esteban, M Rodriguez, M S Serrano, M Rivas, C Cell Death Dis 3:e393 25884169 Pubmed 2015 Lung neuroendocrine tumors: correlation of ubiquitinylation and sumoylation with nucleo-cytosolic partitioning of PTEN Collaud, Stéphane Tischler, Verena Atanassoff, Andrej Wiedl, Thomas Komminoth, Paul Oehlschlegel, Christian Weder, Walter Soltermann, A BMC Cancer 15:74 24429633 Pubmed 2014 The multilayered complexity of ceRNA crosstalk and competition Tay, Yvonne Rinn, John Pandolfi, Pier Paolo Nature 505:344-52