BioPAX pathway converted from "Hedgehog 'on' state" in the Reactome database. Hedgehog 'on' state 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 PTCH is internalized 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> ptc-3 ub-PTCH1 H2L0G5 Reactome DB_ID: 10636432 ciliary membrane GENE ONTOLOGY GO:0060170 UniProt:H2L0G5 ptc-3 Caenorhabditis elegans NCBI Taxonomy 6239 UniProt H2L0G5 ubiquitinylated lysine MOD MOD:01148 1 EQUAL 1447 EQUAL Reactome Database ID Release 78 10636432 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=10636432 Reactome R-CEL-5632517 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-CEL-5632517.1 Reactome http://www.reactome.org ptc-3 ub-PTCH1 H2L0G5 Reactome DB_ID: 10636434 endocytic vesicle membrane GENE ONTOLOGY GO:0030666 1 EQUAL 1447 EQUAL Reactome Database ID Release 78 10636434 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=10636434 Reactome R-CEL-5632520 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-CEL-5632520.1 Reactome Database ID Release 78 10636436 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=10636436 Reactome R-CEL-5632677 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-CEL-5632677.1 After SMURF-dependent ubiquitination, PTCH1 is internalized to endocytic vesicles for degradation (Rohatgi et al, 2007; Huang et al, 2013; Yue et al, 2014). PTCH1 and SMO show reciprocal changes in localization upon Hh pathway activation, with PTCH moving from the primary cilium to internal vesicles while SMO becomes enriched in the primary cilium after ligand binding (Denef et al, 2000; Rohatgi et al, 2007; Corbit et al, 2005; Kovacs et al, 2008; reviewed in Goetz and Anderson). In mice, internalization of PTCH1 appears to be independent of SMO, while in flies, activated SMO is required to promote the SMURF-dependent downregulation of PTCH (Yue et al, 2014; Huang et al, 2013). 24302888 Pubmed 2013 Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover Huang, Shoujun Zhang, Zhao Zhang, Chunxia Lv, Xiangdong Zheng, Xiudeng Chen, Zhenping Sun, Liwei Wang, Hailong Zhu, Yuanxiang Zhang, Jing Yang, Shuyan Lu, Yi Sun, Qinmiao Tao, Yi Liu, Feng Zhao, Yun Chen, Dahua PLoS Biol. 11:e1001721 16136078 Pubmed 2005 Vertebrate Smoothened functions at the primary cilium Corbit, Kevin C Aanstad, Pia Singla, Veena Norman, Andrew R Stainier, Didier Y R Reiter, Jeremy F Nature 437:1018-21 17641202 Pubmed 2007 Patched1 regulates hedgehog signaling at the primary cilium Rohatgi, Rajat Milenkovic, Ljiljana Scott, Matthew P Science 317:372-6 24925320 Pubmed 2014 Requirement of Smurf-mediated endocytosis of Patched1 in Sonic Hedgehog signal reception Yue, Shen Tang, LY Tang, Ying Tang, Y Shen, Qiu-Hong Ding, Jie Chen, Yan Zhang, Zengdi Yu, Ting-Ting Zhang, Ying E Cheng, SY Elifee02555 10966113 Pubmed 2000 Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened Denef, N Neubüser, D Perez, L Cohen, SM Cell 102:521-31 18497258 Pubmed 2008 Beta-arrestin-mediated localization of smoothened to the primary cilium Kovacs, Jeffrey J Whalen, Erin J Liu, Renshui Xiao, Kunhong Kim, Jihee Chen, Minyong Wang, Jiangbo Chen, Wei Lefkowitz, Robert J Science 320:1777-81 inferred from electronic annotation EVIDENCE CODE ECO:0000203 LEFT-TO-RIGHT SPOP:CUL3:RBX1 ubiquitinates GLI2,3 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> ubq-1 UBA52(1-76) P0CG71 Reactome DB_ID: 10588842 nucleoplasm GENE ONTOLOGY GO:0005654 UniProt:P0CG71 ubq-1 UniProt P0CG71 1 EQUAL 76 EQUAL Reactome Database ID Release 78 10588842 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=10588842 Reactome R-CEL-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-CEL-939844.1 2p-GLI:SPOP:CUL3:RBX1 Reactome DB_ID: 10636544 SPOP:CUL3:RBX1 Reactome DB_ID: 10636536 CUL3 cul-3 Q17391 Reactome DB_ID: 10636534 UniProt:Q17391 cul-3 UniProt Q17391 1 EQUAL 768 EQUAL Reactome Database ID Release 78 10636534 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=10636534 Reactome R-CEL-5635033 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-CEL-5635033.1 2 RBX1 rbx-1 Q23457 Reactome DB_ID: 10588865 UniProt:Q23457 rbx-1 UniProt Q23457 2 EQUAL 108 EQUAL Reactome Database ID Release 78 10588865 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=10588865 Reactome R-CEL-1234142 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-CEL-1234142.1 2 Converted from EntitySet in Reactome SPOP dimer Reactome DB_ID: 10636532 SPOP dimer Reactome DB_ID: 10636526 Converted from EntitySet in Reactome Homologues of SPOP Reactome DB_ID: 10636524 SPOP bath-44 H2KYJ3 Reactome DB_ID: 10636497 UniProt:H2KYJ3 bath-44 UniProt H2KYJ3 1 EQUAL 374 EQUAL Reactome Database ID Release 78 10636497 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=10636497 Reactome R-CEL-5635035 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-CEL-5635035.1 SPOP bath-42 P34371 Reactome DB_ID: 10636502 UniProt:P34371 bath-42 UniProt P34371 1 EQUAL 374 EQUAL Reactome Database ID Release 78 10636502 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=10636502 Reactome R-CEL-5635035-2 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-CEL-5635035-2.1 SPOP bath-43 P34568 Reactome DB_ID: 10636507 UniProt:P34568 bath-43 UniProt P34568 1 EQUAL 374 EQUAL Reactome Database ID Release 78 10636507 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=10636507 Reactome R-CEL-5635035-3 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-CEL-5635035-3.1 SPOP bath-41 P41886 Reactome DB_ID: 10636512 UniProt:P41886 bath-41 UniProt P41886 1 EQUAL 374 EQUAL Reactome Database ID Release 78 10636512 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=10636512 Reactome R-CEL-5635035-4 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-CEL-5635035-4.1 SPOP mel-26 Q94420 Reactome DB_ID: 10636517 UniProt:Q94420 mel-26 UniProt Q94420 1 EQUAL 374 EQUAL Reactome Database ID Release 78 10636517 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=10636517 Reactome R-CEL-5635035-5 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-CEL-5635035-5.1 SPOP bath-40 Q9NF14 Reactome DB_ID: 10636522 UniProt:Q9NF14 bath-40 UniProt Q9NF14 1 EQUAL 374 EQUAL Reactome Database ID Release 78 10636522 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=10636522 Reactome R-CEL-5635035-6 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-CEL-5635035-6.1 Reactome Database ID Release 78 10636524 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=10636524 Reactome R-CEL-5635035-7 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-CEL-5635035-7.1 2 Reactome Database ID Release 78 10636526 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=10636526 Reactome R-CEL-5635066 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-CEL-5635066.1 SPOP:SPOPL Reactome DB_ID: 10636530 SPOPL bath-43 P34568 Reactome DB_ID: 10636528 1 EQUAL 392 EQUAL Reactome Database ID Release 78 10636528 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=10636528 Reactome R-CEL-5635036 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-CEL-5635036.1 1 1 Reactome Database ID Release 78 10636530 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=10636530 Reactome R-CEL-5635068 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-CEL-5635068.1 Reactome Database ID Release 78 10636532 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=10636532 Reactome R-CEL-5635065 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-CEL-5635065.1 1 Reactome Database ID Release 78 10636536 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=10636536 Reactome R-CEL-5635071 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-CEL-5635071.1 1 Ghost homologue of 2p-GLI2,3 Reactome DB_ID: 10636542 Reactome Database ID Release 78 10636542 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=10636542 Reactome R-CEL-5635080 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-CEL-5635080.1 1 Reactome Database ID Release 78 10636544 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=10636544 Reactome R-CEL-5635087 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-CEL-5635087.1 ub-2p-GLI2,3:SPOP:CUL3:RBX1 Reactome DB_ID: 10636538 1 Ghost homologue of ub-2p-GLI2,3 Reactome DB_ID: 10636492 Reactome Database ID Release 78 10636492 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=10636492 Reactome R-CEL-5635092 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-CEL-5635092.1 1 Reactome Database ID Release 78 10636538 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=10636538 Reactome R-CEL-5635095 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-CEL-5635095.1 ACTIVATION activeUnit: #Protein5 GENE ONTOLOGY GO:0061630 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 78 10636545 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=10636545 Reactome Database ID Release 78 10636547 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=10636547 Reactome R-CEL-5635856 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-CEL-5635856.1 The transcriptional activity of full-length activated Ci/GLI proteins is restricted by their rapid ubiquitin-mediated degradation after initiation of Hh signaling (Ohlmeyer et al, 1998; Humke et al, 2010; Tukachinsky et al, 2010; Wen et al, 2010). Ubiquitination of Ci, GLI2 and GLI3 is mediated by the E3 ligase complex SPOP:CUL3:RBX1, which ubiquitinates the transcription factors in a Hh-dependent manner (Zhang et al, 2006; Kent et al, 2006; Zhang et al, 2009; Chen et al, 2009). 9874371 Pubmed 1998 Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator Ohlmeyer, Johanna Talavera Kalderon, Daniel Nature 396:749-53 20360384 Pubmed 2010 The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins Humke, Eric W Dorn, Karolin V Milenkovic, Ljiljana Scott, Matthew P Rohatgi, Rajat Genes Dev. 24:670-82 20956384 Pubmed 2010 A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes Tukachinsky, Hanna Lopez, Lyle V Salic, Adrian J. Cell Biol. 191:415-28 20154143 Pubmed 2010 Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation Wen, Xiaohui Lai, Cary K Evangelista, Marie Hongo, Jo-Anne de Sauvage, Frederic J Scales, Suzie J Mol. Cell. Biol. 30:1910-22 16651542 Pubmed 2006 Roadkill attenuates Hedgehog responses through degradation of Cubitus interruptus Kent, D Bush, EW Hooper, JE Development 133:2001-10 19684112 Pubmed 2009 Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved Chen, Miao-Hsueh Wilson, Christopher W Li, Ya-Jun Law, Kelvin King Lo Lu, Chi-Sheng Gacayan, Rhodora Zhang, Xiaoyun Hui, Chi-Chung Chuang, Pao-Tien Genes Dev. 23:1910-28 19955409 Pubmed 2009 Multiple Ser/Thr-rich degrons mediate the degradation of Ci/Gli by the Cul3-HIB/SPOP E3 ubiquitin ligase Zhang, Qing Shi, Qing Chen, Yongbin Yue, Tao Li, Shuang Wang, Bing Jiang, Jin Proc. Natl. Acad. Sci. U.S.A. 106:21191-6 16740475 Pubmed 2006 A hedgehog-induced BTB protein modulates hedgehog signaling by degrading Ci/Gli transcription factor Zhang, Q Zhang, Lei Wang, B Ou, CY Chien, CT Jiang, J Dev Cell 10:719-29 LEFT-TO-RIGHT GLI2,3 are degraded by the proteasome 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> ACTIVATION 26S proteasome Reactome DB_ID: 10600179 pbs-2 PSMB10 O62102 Reactome DB_ID: 10600113 UniProt:O62102 pbs-2 UniProt O62102 40 EQUAL 273 EQUAL Reactome Database ID Release 78 10600113 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=10600113 Reactome R-CEL-174349 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-CEL-174349.1 1 PSME2 Q95PZ7 Reactome DB_ID: 10600171 UniProt:Q95PZ7 UniProt Q95PZ7 2 EQUAL 239 EQUAL Reactome Database ID Release 78 10600171 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=10600171 Reactome R-CEL-174350 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-CEL-174350.1 1 pas-3 PSMA4 Q9N599 Reactome DB_ID: 10600103 UniProt:Q9N599 pas-3 UniProt Q9N599 1 EQUAL 261 EQUAL Reactome Database ID Release 78 10600103 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=10600103 Reactome R-CEL-174324 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-CEL-174324.1 1 pbs-3 PSMB3 Q23237 Reactome DB_ID: 10600117 UniProt:Q23237 pbs-3 UniProt Q23237 2 EQUAL 205 EQUAL Reactome Database ID Release 78 10600117 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=10600117 Reactome R-CEL-174341 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-CEL-174341.1 1 rpt-1 PSMC2 Q18787 Reactome DB_ID: 10600133 UniProt:Q18787 rpt-1 UniProt Q18787 2 EQUAL 433 EQUAL Reactome Database ID Release 78 10600133 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=10600133 Reactome R-CEL-174332 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-CEL-174332.1 1 PSMD4 rpn-10 O61742 Reactome DB_ID: 10600157 UniProt:O61742 rpn-10 UniProt O61742 1 EQUAL 377 EQUAL Reactome Database ID Release 78 10600157 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=10600157 Reactome R-CEL-174330 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-CEL-174330.1 1 rpn-9 PSMD13 Q22253 Reactome DB_ID: 10600151 UniProt:Q22253 rpn-9 UniProt Q22253 1 EQUAL 376 EQUAL Reactome Database ID Release 78 10600151 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=10600151 Reactome R-CEL-174326 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-CEL-174326.1 1 pbs-6 PSMB1 P34286 Reactome DB_ID: 10600111 UniProt:P34286 pbs-6 UniProt P34286 29 EQUAL 241 EQUAL Reactome Database ID Release 78 10600111 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=10600111 Reactome R-CEL-174347 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-CEL-174347.1 1 rpt-4 PSMC6 O17071 Reactome DB_ID: 10600141 UniProt:O17071 rpt-4 UniProt O17071 1 EQUAL 389 EQUAL Reactome Database ID Release 78 10600141 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=10600141 Reactome R-CEL-174319 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-CEL-174319.1 1 pbs-1 PSMB6 Q966I8 Reactome DB_ID: 10600123 UniProt:Q966I8 pbs-1 UniProt Q966I8 35 EQUAL 239 EQUAL Reactome Database ID Release 78 10600123 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=10600123 Reactome R-CEL-174342 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-CEL-174342.1 1 rpn-1 PSMD2 Q9GZH5 Reactome DB_ID: 10600153 UniProt:Q9GZH5 rpn-1 UniProt Q9GZH5 1 EQUAL 908 EQUAL Reactome Database ID Release 78 10600153 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=10600153 Reactome R-CEL-174311 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-CEL-174311.1 1 PSMD11 rpn-6.1 Q20938 Reactome DB_ID: 10600147 UniProt:Q20938 rpn-6.1 UniProt Q20938 2 EQUAL 422 EQUAL Reactome Database ID Release 78 10600147 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=10600147 Reactome R-CEL-174327 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-CEL-174327.1 1 rpn-3 PSMD3 Q04908 Reactome DB_ID: 10600155 UniProt:Q04908 rpn-3 UniProt Q04908 1 EQUAL 534 EQUAL Reactome Database ID Release 78 10600155 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=10600155 Reactome R-CEL-174328 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-CEL-174328.1 1 pas-6 PSMA1 O44156 Reactome DB_ID: 10600097 UniProt:O44156 pas-6 UniProt O44156 1 EQUAL 263 EQUAL Reactome Database ID Release 78 10600097 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=10600097 Reactome R-CEL-174333 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-CEL-174333.1 1 rpn-8 PSMD7 O61792 Reactome DB_ID: 10600163 UniProt:O61792 rpn-8 UniProt O61792 1 EQUAL 324 EQUAL Reactome Database ID Release 78 10600163 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=10600163 Reactome R-CEL-174309 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-CEL-174309.1 1 pbs-1 PSMB9 Q966I8 Reactome DB_ID: 10600129 21 EQUAL 219 EQUAL Reactome Database ID Release 78 10600129 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=10600129 Reactome R-CEL-174334 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-CEL-174334.1 1 pas-4 PSMA7 Q95005 Reactome DB_ID: 10600109 UniProt:Q95005 pas-4 UniProt Q95005 1 EQUAL 248 EQUAL Reactome Database ID Release 78 10600109 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=10600109 Reactome R-CEL-174351 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-CEL-174351.1 1 pbs-2 PSMB7 O62102 Reactome DB_ID: 10600125 44 EQUAL 277 EQUAL Reactome Database ID Release 78 10600125 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=10600125 Reactome R-CEL-174331 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-CEL-174331.1 1 rpt-6 PSMC5 Q9XTT9 Reactome DB_ID: 10600139 UniProt:Q9XTT9 rpt-6 UniProt Q9XTT9 2 EQUAL 406 EQUAL Reactome Database ID Release 78 10600139 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=10600139 Reactome R-CEL-174312 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-CEL-174312.1 1 PSMD9 psmd-9 Q10920 Reactome DB_ID: 10600167 UniProt:Q10920 psmd-9 UniProt Q10920 1 EQUAL 223 EQUAL Reactome Database ID Release 78 10600167 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=10600167 Reactome R-CEL-174321 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-CEL-174321.1 1 pbs-5 PSMB5 Q9XUV0 Reactome DB_ID: 10600121 UniProt:Q9XUV0 pbs-5 UniProt Q9XUV0 60 EQUAL 263 EQUAL Reactome Database ID Release 78 10600121 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=10600121 Reactome R-CEL-174344 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-CEL-174344.1 1 pas-5 PSMA5 Q95008 Reactome DB_ID: 10600105 UniProt:Q95008 pas-5 UniProt Q95008 1 EQUAL 241 EQUAL Reactome Database ID Release 78 10600105 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=10600105 Reactome R-CEL-174340 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-CEL-174340.1 1 pbs-4 PSMB2 P91477 Reactome DB_ID: 10600115 UniProt:P91477 pbs-4 UniProt P91477 1 EQUAL 201 EQUAL Reactome Database ID Release 78 10600115 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=10600115 Reactome R-CEL-174335 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-CEL-174335.1 1 PSME3 Q95PZ7 Reactome DB_ID: 10600173 2 EQUAL 254 EQUAL Reactome Database ID Release 78 10600173 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=10600173 Reactome R-CEL-174310 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-CEL-174310.1 1 pas-2 PSMA2 Q27488 Reactome DB_ID: 10600099 UniProt:Q27488 pas-2 UniProt Q27488 2 EQUAL 234 EQUAL Reactome Database ID Release 78 10600099 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=10600099 Reactome R-CEL-174345 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-CEL-174345.1 1 pbs-7 PSMB4 P90868 Reactome DB_ID: 10600119 UniProt:P90868 pbs-7 UniProt P90868 46 EQUAL 264 EQUAL Reactome Database ID Release 78 10600119 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=10600119 Reactome R-CEL-174343 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-CEL-174343.1 1 rpt-5 PSMC3 O76371 Reactome DB_ID: 10600135 UniProt:O76371 rpt-5 UniProt O76371 1 EQUAL 439 EQUAL Reactome Database ID Release 78 10600135 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=10600135 Reactome R-CEL-174313 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-CEL-174313.1 1 rpn-5 PSMD12 Q19324 Reactome DB_ID: 10600149 UniProt:Q19324 rpn-5 UniProt Q19324 2 EQUAL 456 EQUAL Reactome Database ID Release 78 10600149 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=10600149 Reactome R-CEL-174339 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-CEL-174339.1 1 PSMD10 O45398 Reactome DB_ID: 10600145 UniProt:O45398 UniProt O45398 1 EQUAL 226 EQUAL Reactome Database ID Release 78 10600145 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=10600145 Reactome R-CEL-174322 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-CEL-174322.1 1 pas-7 PSMA3 Q09583 Reactome DB_ID: 10600101 UniProt:Q09583 pas-7 UniProt Q09583 2 EQUAL 255 EQUAL Reactome Database ID Release 78 10600101 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=10600101 Reactome R-CEL-174323 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-CEL-174323.1 1 rpt-3 PSMC4 P46502 Reactome DB_ID: 10600137 UniProt:P46502 rpt-3 UniProt P46502 1 EQUAL 418 EQUAL Reactome Database ID Release 78 10600137 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=10600137 Reactome R-CEL-174315 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-CEL-174315.1 1 rpn-11 PSMD14 O76577 Reactome DB_ID: 10600095 UniProt:O76577 rpn-11 UniProt O76577 1 EQUAL 310 EQUAL Reactome Database ID Release 78 10600095 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=10600095 Reactome R-CEL-174329 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-CEL-174329.1 1 PSME1 Q95PZ7 Reactome DB_ID: 10600169 1 EQUAL 249 EQUAL Reactome Database ID Release 78 10600169 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=10600169 Reactome R-CEL-174320 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-CEL-174320.1 1 pbs-5 PSMB8 Q9XUV0 Reactome DB_ID: 10600127 73 EQUAL 276 EQUAL Reactome Database ID Release 78 10600127 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=10600127 Reactome R-CEL-174336 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-CEL-174336.1 1 PSMD5 Q20058 Reactome DB_ID: 10600159 UniProt:Q20058 UniProt Q20058 2 EQUAL 504 EQUAL Reactome Database ID Release 78 10600159 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=10600159 Reactome R-CEL-174346 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-CEL-174346.1 1 rpn-7 PSMD6 Q20585 Reactome DB_ID: 10600161 UniProt:Q20585 rpn-7 UniProt Q20585 1 EQUAL 389 EQUAL Reactome Database ID Release 78 10600161 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=10600161 Reactome R-CEL-174316 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-CEL-174316.1 1 PSMD8 rpn-12 Q23449 Reactome DB_ID: 10600165 UniProt:Q23449 rpn-12 UniProt Q23449 1 EQUAL 350 EQUAL Reactome Database ID Release 78 10600165 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=10600165 Reactome R-CEL-174318 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-CEL-174318.1 1 Ghost homologue of PSMF1 Reactome DB_ID: 10600175 Reactome Database ID Release 78 10600175 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=10600175 Reactome R-CEL-174308 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-CEL-174308.1 1 rpt-2 PSMC1 O16368 Reactome DB_ID: 10600131 UniProt:O16368 rpt-2 UniProt O16368 2 EQUAL 440 EQUAL Reactome Database ID Release 78 10600131 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=10600131 Reactome R-CEL-174338 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-CEL-174338.1 1 pas-1 PSMA6 O17586 Reactome DB_ID: 10600107 UniProt:O17586 pas-1 UniProt O17586 1 EQUAL 246 EQUAL Reactome Database ID Release 78 10600107 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=10600107 Reactome R-CEL-174314 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-CEL-174314.1 1 rpn-2 PSMD1 Q18115 Reactome DB_ID: 10600143 UniProt:Q18115 rpn-2 UniProt Q18115 1 EQUAL 953 EQUAL Reactome Database ID Release 78 10600143 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=10600143 Reactome R-CEL-174348 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-CEL-174348.1 1 Ghost homologue of SHFM1 Reactome DB_ID: 10600177 Reactome Database ID Release 78 10600177 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=10600177 Reactome R-CEL-8866665 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-CEL-8866665.1 1 Reactome Database ID Release 78 10600179 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=10600179 Reactome R-CEL-177750 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-CEL-177750.1 GENE ONTOLOGY GO:0004175 Reactome Database ID Release 78 10600180 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=10600180 Reactome Database ID Release 78 10636540 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=10636540 Reactome R-CEL-5635854 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-CEL-5635854.1 SPOP:CUL3:RBX1-mediated ubiquitination of the transcriptionally active GLI proteins attenuates Hh-dependent signaling by promoting their degradation by the proteasome (Zhang et al, 2009; Chen et al, 2009; Humke et al, 2010; Tukachinsky et al, 2010; Wen et al, 2010). LEFT-TO-RIGHT NUMB binds ITCH 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> NUMB num-1 Q9XTY6 Reactome DB_ID: 10612204 plasma membrane GENE ONTOLOGY GO:0005886 UniProt:Q9XTY6 num-1 UniProt Q9XTY6 1 EQUAL 651 EQUAL Reactome Database ID Release 78 10612204 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=10612204 Reactome R-CEL-443595 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-CEL-443595.1 ITCH wwp-1 Q9N2Z7 Reactome DB_ID: 10618064 cytosol GENE ONTOLOGY GO:0005829 UniProt:Q9N2Z7 wwp-1 UniProt Q9N2Z7 1 EQUAL 903 EQUAL Reactome Database ID Release 78 10618064 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=10618064 Reactome R-CEL-975995 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-CEL-975995.1 NUMB:ITCH Reactome DB_ID: 10635233 1 1 Reactome Database ID Release 78 10635233 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=10635233 Reactome R-CEL-5610562 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-CEL-5610562.1 Reactome Database ID Release 78 10635235 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=10635235 Reactome R-CEL-5610735 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-CEL-5610735.1 NUMB is a negative regulator of Hh signaling that acts by promoting the ITCH-dependent ubiquitination of GLI1. ITCH is an E3 ligase that is kept in an inactive conformation by an intramolecular interaction between the HECT domain and a WW motif. Binding of the adaptor protein NUMB to the WW region of ITCH displaces the HECT domain and promotes the catalytic activity of the E3 ligase (di Marcotullio et al, 2006; 2011). 20818436 Pubmed 2011 Numb activates the E3 ligase Itch to control Gli1 function through a novel degradation signal Di Marcotullio, L Greco, A Mazzà, D Canettieri, G Pietrosanti, L Infante, P Coni, S Moretti, M De Smaele, E Ferretti, E Screpanti, I Gulino, A Oncogene 30:65-76 17115028 Pubmed 2006 Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination Di Marcotullio, L Ferretti, Elisabetta Greco, Azzura De Smaele, Enrico Po, Agnese Sico, Maria Anna Alimandi, M Giannini, Giuseppe Maroder, Marella Screpanti, I Gulino, Alberto Nat. Cell Biol. 8:1415-23 Reactome Database ID Release 78 10659095 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=10659095 Reactome R-CEL-5632684 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-CEL-5632684.1 Hedgehog is a secreted morphogen that has evolutionarily conserved roles in body organization by regulating the activity of the Ci/Gli transcription factor family. In Drosophila in the absence of Hh signaling, full-length Ci is partially degraded by the proteasome to generate a truncated repressor form that translocates to the nucleus to represses Hh-responsive genes. Binding of Hh ligand to the Patched (PTC) receptor allows the 7-pass transmembrane protein Smoothened (SMO) to be activated in an unknown manner, disrupting the partial proteolysis of Ci and allowing the full length activator form to accumulate (reviewed in Ingham et al, 2011; Briscoe and Therond, 2013). <br>While many of the core components of Hh signaling are conserved from flies to humans, the pathways do show points of significant divergence. Notably, the human genome encodes three Ci homologues, GLI1, 2 and 3 that each play slightly different roles in regulating Hh responsive genes. GLI3 is the primary repressor of Hh signaling in vertebrates, and is converted to the truncated GLI3R repressor form in the absence of Hh. GLI2 is a potent activator of transcription in the presence of Hh but contributes only minimally to the repression function. While a minor fraction of GLI2 protein is processed into the repressor form in the absence of Hh, the majority is either fully degraded by the proteasome or sequestered in the full-length form in the cytosol by protein-protein interactions. GLI1 lacks the repression domain and appears to be an obligate transcriptional activator (reviewed in Briscoe and Therond, 2013).<br> Vertebrate but not fly Hh signaling also depends on the movement of pathway components through the primary cilium. The primary cilium is a non-motile microtubule based structure whose construction and maintenance depends on intraflagellar transport (IFT). Anterograde IFT moves molecules from the ciliary base along the axoneme to the ciliary tip in a manner that requires the microtubule-plus-end directed kinesin KIF3 motor complex and the IFT-B protein complex, while retrograde IFT back to the ciliary base depends on the minus-end directed dynein motor and the IFT-A complex. Genetic screens have identified a number of cilia-related proteins that are required both to maintain Hh in the 'off' state and to transduce the signal when the pathway is activated (reviewed in Hui and Angers, 2011; Goetz and Anderson, 2010). 20395968 Pubmed 2010 The primary cilium: a signalling centre during vertebrate development Goetz, Sarah C Anderson, Kathryn V Nat. Rev. Genet. 11:331-44 21502959 Pubmed 2011 Mechanisms and functions of Hedgehog signalling across the metazoa Ingham, Philip W Nakano, Yoshiro Seger, Claudia Nat. Rev. Genet. 12:393-406 23719536 Pubmed 2013 The mechanisms of Hedgehog signalling and its roles in development and disease Briscoe, James Thérond, Pascal P Nat. Rev. Mol. Cell Biol. 14:416-29 21801010 Pubmed 2011 Gli proteins in development and disease Hui, Chi-Chung Angers, S Annu. Rev. Cell Dev. Biol. 27:513-37