BioPAX pathway converted from "GLI translocates to the nucleus" in the Reactome database. GLI translocates to the nucleus GLI 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> Reactome DB_ID: 10561621 1 ciliary tip GO 0097542 UniProt:P19538 ci ci CG2125 ci-D ci FUNCTION Has a dual function as a transcriptional activator and a repressor of the hedgehog (Hh) pathway. The full-length ci form (ciFL), acts as an activator (ciA) while ciR, its C-terminally truncated form, acts as a repressor. Involved in segment polarity. Required for the normal development of the posterior half of each embryonic segment. Engrailed protein directly represses ci expression in posterior compartment cells. Essential component of a hh-signaling pathway which regulates the Duox-dependent gut immune response to bacterial uracil; required to activate Cad99C-dependent endosome formation, norpA-dependent Ca2+ mobilization and p38 MAPK, which are essential steps in the Duox-dependent production of reactive oxygen species (ROS) in response to intestinal bacterial infection (PubMed:25639794).SUBUNIT Interacts with RDX (PubMed:16740475). Interacts with cos (PubMed:9244298, PubMed:15691767). Interacts with slmb; the interaction is enhanced by phosphorylation by CkIalpha and dco (PubMed:16326393).DEVELOPMENTAL STAGE In embryos, expressed uniformly throughout the blastoderm stage and gastrulation (from stage 5). During stage 10, ci is eliminated from the posterior compartment of each segment forming 15 segmentally repeating stripes at the end of the short phase of germ-band extension.PTM Polyubiquitinated by RDX in the presence of CUL3, which results in proteasomal degradation.PTM Phosphorylated on multiple sites by protein kinase A (PKA) and phosphorylation by PKA primes further phosphorylation by CK1 and GSK3. Phosphorylation is essential for its proteolytic processing. cos recruits multiple kinases to promote efficient phosphorylation of ci while Hh signaling inhibits phosphorylation by restricting the accessibility of ci to the kinases (PubMed:15691767). Phosphorylation by CkIalpha and dco enhances binding to Slmb, the F-box recognition component of the SCF(slmb) E3 ubiquitin-protein ligase required for ci processing (PubMed:16326393).PTM Transcriptional repressor ciR, a C-terminally truncated form, is generated from the full-length ci (ciFL/ci-155) through proteolytic processing. Hh suppresses the formation of ci75 and promotes the conversion of ci155 into a transcriptional activator (ci155A).DISRUPTION PHENOTYPE RNAi-mediated knockdown severely reduces adult survival following the ingestion of E.carotovora. Abolishes Cad99C-dependent formation of endosomes and DUOX-dependent up-regulation of reactive oxygen species (ROS) in the intestines of adults fed bacteria-derived uracil.SIMILARITY Belongs to the GLI C2H2-type zinc-finger protein family. Reactome http://www.reactome.org Drosophila melanogaster NCBI Taxonomy 7227 UniProt P19538 phosphorylated residue at unknown position phosphorylated residue [MOD:00696] Chain Coordinates 1 EQUAL 1586 EQUAL Reactome DB_ID: 10561609 1 nucleoplasm GO 0005654 phosphorylated residue at unknown position 1 EQUAL 1106 EQUAL Reactome Database ID Release 78 10561630 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10561630 Reactome R-DME-5635843 1 Reactome stable identifier. Use this 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-5635843.1 Activation of SMO downstream of Hh ligand binding results in the dissociation of the SUFU:GLI complex and the translocation of the full-length GLI proteins to the nucleus where it is converted to a short-lived transcriptionally active form (Pan et al, 2006; Kim et al, 2009; Wen et al, 2010; Humke et al, 2010; Tukachinsky et al, 2010; reviewed in Briscoe and Therond, 2013). 16611981 Pubmed 2006 Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation Pan, Yong Bai, Chunyang Brian Joyner, Alexandra L Wang, Baolin Mol. Cell. Biol. 26:3365-77 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 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 19996169 Pubmed 2009 Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus Kim, Jynho Kato, Masaki Beachy, Philip A Proc. Natl. Acad. Sci. U.S.A. 106:21666-71 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 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 inferred by electronic annotation IEA GO IEA