BioPAX pathway converted from "Hedgehog pathway" in the Reactome database. Hedgehog pathway Hedgehog pathway 在Hedgehog signalling pathway, as in the Wingless pathway, there are two main sets of signalling events. One comes into play when the Hedgehog (N-HH) ligand is bound to its cell surface receptor, Patched (PTC) and the other set occurs when the ligand isn't bound to it.

In Hedgehog sending cells, full-length Hedgehog ligand (HH) undergoes an autoprocessing event culminating in cleavage of itself into an N-terminal fragment (N-HH) modified by cholesterol and a C-terminal fragment (C-HH) which is no longer used in the pathway. N-HH is further processed through the action of the protein-cysteine N-palmitoyltransferase, Rasp (RASP), which palmitoylates the ligand. N-HH is secreted extracellularly with the assistance of the membrane protein, Dispatched (DISP). Efficient movement of N-HH requires heparan sulphate proteoglycans (HSPGs) such as Dally (DALLY) and Dally-like protein (DLP), which can aid the accumulation of N-HH at the cell surface and facilitate intercellular transport of ligand.

In cells not exposed to HH, the transmembrane protein PTC inhibits the transmembrane residing Smoothened (SMO). In the cytosol, full-length Cubitus Interruptus protein (CI) forms a complex with the Suppressor of Fused protein (SU(FU)) and the large kinesin-like scaffold protein, Costal2 (COS), which also binds the Ser/Thr protein kinase, Fused (FU). COS recruits the Ser/Thr kinases: protein kinase A (PKA-C1); Shaggy (SGG); casein kinase I alpha (CKIalpha); and casein kinase I epsilon (DCO). These phosphorylate CI which is now recognised by Slimb (SLMB) which is part of the SCF ubiquitin ligase complex. CI is ubiquitinated and partially degraded by the proteasome resulting in a truncated CI (CI75) which transports to the nucleus where it acts as a repressor of transcription.

However, if N-HH ligand is in the vicinity of the Hedgehog receiving cell, it binds to PTC, reducing the inhibiting effect PTC has on SMO. This leads to increased phosphorylation of SMO by PKA-C1 and CKIalpha, accompanied by a conformational change, increased stability and enhanced surface accumulation. CI associates with SMO via COS and is no longer efficiently phosphorylated and proteolysed after SMO activation. FU, COS and SU(FU) are phosphorylated and full-length CI gains greater access to the nucleus, where it activates transcription. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2006-12-07 16:49:12 Formation and transport of the N-HH ligand Formation and transport of the N-HH ligand Spatzle (SPZ) dimer binding leads to Toll (TL) receptor homodimerisation and activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2006-12-08 11:30:45 Autocleavage of HH Autocleavage of HH The autoprocessing event results in cleavage of Hedgehog (HH) between Gly207 and Cys208, coupled to the covalent addition of cholesterol to Gly207 via an ester linkage to form N-HH. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 176478 1 cytosol GO 0005829 cholesterol [ChEBI:16113] cholesterol cholest-5-en-3beta-ol Reactome //www.joaskin.com ChEBI 16113 Reactome DB_ID: 205973 1 UniProt:Q02936 hh hh hh CG4637 功能细胞间信号的变化ety of patterning events during development. Establishes the anterior-posterior axis of the embryonic segments and patterns the larval imaginal disks. Binds to the patched (ptc) receptor, which functions in association with smoothened (smo), to activate the transcription of target genes wingless (wg), decapentaplegic (dpp) and ptc. In the absence of hh, ptc represses the constitutive signaling activity of smo through fused (fu). Essential component of a 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). During photoreceptor differentiation, it up-regulates transcription of Ubr3, which in turn promotes the hh-signaling pathway by mediating the ubiquitination and degradation of cos (PubMed:27195754).FUNCTION The hedgehog protein N-product constitutes the active species in both local and long-range signaling, whereas the C-terminal product has no signaling activity. It acts as a morphogen, and diffuses long distances despite its lipidation. Heparan sulfate proteoglycans of the extracellular matrix play an essential role in diffusion. Lipophorin is required for diffusion, probably by acting as vehicle for its movement, explaining how it can spread over long distances despite its lipidation.FUNCTION The hedgehog protein C-product, which mediates the autocatalytic activity, has no signaling activity.SUBUNIT Interacts with shf.TISSUE SPECIFICITY In embryos, expression starts at stage 5 as a few stripes at the anterior and posterior ends, this expands to 17 stripes during stages 8-11 (PubMed:8166882, PubMed:1280560, PubMed:1340474). Expression is also seen in CNS and some PNS cells until stage 13-14, and in foregut, hindgut and salivary glands (PubMed:1340474). In larvae, expression is seen in the posterior compartment of the wing, leg and antennal imaginal disks (PubMed:1394430, PubMed:1340474). In adults, high level of expression in specific regions of the proventriculus and hindgut, with slightly lower levels of expression in the posterior midgut (PubMed:25639794). Relatively low levels of expression in the anterior midgut region (PubMed:25639794).DEVELOPMENTAL STAGE Expressed in embryos, larvae and pupae at high levels with maximum expression in 6-12 hours embryos and 0-24 hours pupae (PubMed:8166882, PubMed:1394430, PubMed:1280560, PubMed:1340474). Low levels of expression are seen in adults (PubMed:8166882, PubMed:1394430).INDUCTION Strongly up-regulated in the anterior midgut and the posterior midgut in response to bacterial uracil.PTM The C-terminal domain displays autoproteolytic activity. Cleavage of the full-length hedgehog protein is followed by the covalent attachment of a cholesterol moiety to the C-terminus of the newly generated N-terminal fragment (N-product).PTM Cholesterol attachment plays an essential role in restricting the spatial distribution of hedgehog activity to the cell surface.PTM N-terminal palmitoylation of the hedgehog N-product is required for the embryonic and larval patterning activities of the hedgehog signal. Rasp acts within the secretory pathway to catalyze the N-terminal palmitoylation of Hh.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 hedgehog family. Drosophila melanogaster NCBI Taxonomy 7227 UniProt Q02936 Chain Coordinates 35 EQUAL 421 EQUAL Reactome DB_ID: 206215 1 35 EQUAL 207 EQUAL Reactome DB_ID: 206216 1 208 EQUAL 421 EQUAL Reactome Database ID Release 77 209313 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209313 Reactome R-DME-209313 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209313.3 15189162 Pubmed 2004 Novel lipid modifications of secreted protein signals Mann, RK 海滩,PA Annu Rev Biochem 73:891-923 8824192 Pubmed 1996 Cholesterol modification of hedgehog signaling proteins in animal development Porter, JA Young, KE 海滩,PA Science 274:255-9 2.3.1 N-HH is palmitoylated by RASP N-HH is palmitoylated by RASP After removal of an N-terminal signal sequence, RASP, a protein-cysteine N-palmitoyltransferase, palmitoylates the new N-terminus (CGPGR..) via a thiol intermediate that resolves into a stable amide linkage. Palmitoylation efficiency is increased by prior addition of cholesterol at the C-terminus. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 206215 1 35 EQUAL 207 EQUAL Reactome DB_ID: 76168 1 early endosome GO 0005769 hexadecanoic acid [ChEBI:15756] hexadecanoic acid ChEBI 15756 Reactome DB_ID: 206215 1 35 EQUAL 207 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 205927 UniProt:Q9VZU2 rasp rasp ski cmn rasp sit CG11495 FUNCTION Required in hedgehog (hh) expressing cells for production of appropriate signaling activity in embryos and in the imaginal precursors of adult tissues. Acts within the secretory pathway to catalyze N-terminal palmitoylation of Hh; this lipid modification is required for the embryonic and larval patterning activities of the Hh signal. Not required for Wg signaling.DEVELOPMENTAL STAGE Expressed both maternally and zygotically.SIMILARITY Belongs to the membrane-bound acyltransferase family. HHAT subfamily. UniProt Q9VZU2 GO 0016409 GO molecular function Reactome Database ID Release 77 208928 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=208928 Reactome Database ID Release 77 209357 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209357 Reactome R-DME-209357 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209357.3 11861468 Pubmed 2002 Rasp, a putative transmembrane acyltransferase, is required for Hedgehog signaling Micchelli, CA The, I Selva, E Mogila, V Perrimon, N Development 129:843-51 11486055 Pubmed 2001 Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal Chamoun, Z Mann, RK Nellen, D von Kessler, DP Bellotto, M 海滩,PA Basler, K Science 293:2080-4 N-HH moves from the cytosol to the extracellular region N-HH moves from the cytosol to the extracellular region With the help of the transmembrane protein Dispatched (DISP), N-HH is secreted from the cytosol to the extracellular region. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 206215 1 35 EQUAL 207 EQUAL Reactome DB_ID: 206055 1 plasma membrane GO 0005886 UniProt:Q9VNJ5 disp disp disp CG2019 FUNCTION Segment polarity protein which functions in hedgehog (Hh) signaling. Regulates the trafficking and the release of cholesterol-modified hedgehog protein from cells of the posterior compartment (P cells) and is hence required for the effective production of the Hh signal.DEVELOPMENTAL STAGE Ubiquitously expressed throughout the embryo and the imaginal discs.DISRUPTION PHENOTYPE Death during embryogenesis with a strong segment-polarity phenotype.SIMILARITY Belongs to the dispatched family. UniProt Q9VNJ5 Reactome DB_ID: 205888 1 extracellular region GO 0005576 35 EQUAL 207 EQUAL Reactome DB_ID: 206055 1 Reactome Database ID Release 77 209271 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209271 Reactome R-DME-209271 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209271.3 10619433 Pubmed 1999 Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells Burke, R Nellen, D Bellotto, M Hafen, E Senti, KA Dickson, BJ Basler, K Cell 99:803-15 N-HH binds to the transmembrane HSPG proteins N-HH binds to the transmembrane HSPG proteins N-HH movement between cells is facilitated by the glypicans aka heparan sulphate proteoglycan proteins (HSPGs), Dally (DALLY) and Dally-like protein (DLP) which require heparan sulphate modification by the Exostosin (EXT) family proteins tout-velu (TTV), brother of tout-velu (BOTV) and sister of tout-velu (EXT2) for this purpose. N-HH can form multimers, associated with enhanced movement of vertebrate Sonic Hedgehog, and can associate with lipophorin-containing lipophorin particles which appear to enhance N-HH movement. The protein Shifted (SHF) also facilitates HH movement. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Converted from EntitySet in Reactome Reactome DB_ID: 206547 1 HSPG [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DALLY [plasma membrane] DLP [plasma membrane] UniProt Q24114 UniProt Q9GPL5 Reactome DB_ID: 205888 1 35 EQUAL 207 EQUAL Reactome DB_ID: 207018 1 N-HH:HSPG [plasma membrane] N-HH:HSPG Converted from EntitySet in Reactome Reactome DB_ID: 206547 1 Reactome DB_ID: 205888 1 35 EQUAL 207 EQUAL Reactome Database ID Release 77 207018 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=207018 Reactome R-DME-207018 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-207018.1 Reactome Database ID Release 77 209272 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209272 Reactome R-DME-209272 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209272.3 15563523 Pubmed 2004 Functions of heparan sulfate proteoglycans in cell signaling during development Lin, X Development 131:6009-21 10549295 Pubmed 1999 Hedgehog movement is regulated through tout velu-dependent synthesis of a heparan sulfate proteoglycan The, I Bellaiche, Y Perrimon, N Mol Cell 4:633-9 15875013 Pubmed 2005 Lipoprotein particles are required for Hedgehog and Wingless signalling Panáková, D Sprong, H Marois, E Thiele, C Eaton, S Nature 435:58-65 14729575 Pubmed 2004 Drosophila glypicans control the cell-to-cell movement of Hedgehog by a dynamin-independent process Han, C Belenkaya, TY Wang, B Lin, X Development 131:601-11 11395778 Pubmed 2001 A freely diffusible form of Sonic hedgehog mediates long-range signalling Zeng, X Goetz, JA Suber, LM Scott WJ, Jr Schreiner, CM Robbins, DJ Nature 411:716-20 18198278 Pubmed 2008 Patched, the receptor of Hedgehog, is a lipoprotein receptor Callejo, A Culi, J Guerrero, I Proc Natl Acad Sci U S A 105:912-7 Reactome Database ID Release 77 209471 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209471 Reactome R-DME-209471 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209471.2 14556242 Pubmed 2003 The hedgehog signaling network Cohen MM, Jr Am J Med Genet A 123:5-28 N-HH ligand not bound to PTC receptor complex N-HH ligand not bound to PTC receptor complex Spatzle (SPZ) dimer binding leads to Toll (TL) receptor homodimerisation and activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2006-12-08 11:30:45 Assembly of the CI containing complexes Assembly of the CI containing complexes Spatzle (SPZ) dimer binding leads to Toll (TL) receptor homodimerisation and activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2006-12-08 11:30:45 Formation of the 'scaffold complex' Formation of the 'scaffold complex' The kinesin-related protein, Costal2 (COS), forms a microtubule-associated 'scaffold complex' with Cubitus Interruptus (CI) and the Ser/Thr protein kinase Fused (FU). CI also associates directly with the Supressor of Fused (SU(FU)) protein in a separate complex. Complexes containing CI, COS, FU and SU(FU) are detectable but rare. The Ser/Thr protein kinases: Protein kinase A (PKA-C1), Shaggy (SGG), Casein kinase I alpha (CKIalpha), and Casein kinase I epsilon (DCO) all bind to the scaffold protein COS. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 205931 1 UniProt:P12370 Pka-C1 Pka-C1 DC0 CG4379 Pka-C1 CdkA FUNCTION Serine/threonine-protein kinase involved in memory formation (PubMed:29473541). Promotes long-term memory by phosphorylating meng and by regulating CrebB protein stability and activity (PubMed:29473541). As part of ethanol response in the glia, mediates ethanol-induced structural remodeling of actin cytoskeleton and perineurial membrane topology when anchored to the membrane (PubMed:29444420).ACTIVITY REGULATION Activated by cAMP.SUBUNIT Composed of two regulatory chains and two catalytic chains.TISSUE SPECIFICITY More abundant in adult head than adult body.SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily. UniProt P12370 2 EQUAL 353 EQUAL Reactome DB_ID: 205729 1 UniProt:O76324 dco dco dco CG2048 dbt FUNCTION Involved in circadian rhythms, viability and molecular oscillations of the clock genes period (per) and timeless (tim). Dbt reduces the stability and thus the accumulation of monomeric per proteins, probably through phosphorylation. No evident circadian oscillation is detected in head. Together with CkIalpha, regulates processing of ci by phosphorylating it which promotes its binding to slmb, the F-box recognition component of the SCF(slmb) E3 ubiquitin-protein ligase (PubMed:16326393).SUBUNIT Forms a complex with per (PubMed:9674431). Interacts with Dlish (PubMed:27692068).TISSUE SPECIFICITY Expressed in photoreceptor cells of the eyes as well as in the region situated between the optic lobe and the central brain.SIMILARITY Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily. UniProt O76324 Reactome DB_ID: 205716 1 UniProt:P18431 sgg sgg sgg CG2621 gsk3 zw3 几个发育事件所需功能such as syncytial blastoderm formation and embryonic segmentation. Is involved in transcriptional regulation. Required for arm phosphorylation. Wg signaling operates by inactivating the sgg repression of en autoactivation. Negatively controls the neuromuscular junction (NMJ) growth in presynaptic motoneurons. Plays a role in the regulation of microtubule dynamics and actin cytoskeleton during embryogenesis. Required for phosphorylation of sra in activated eggs. Essential for completion of meiosis, possibly by triggering calcineurin activation via sra phosphorylation. Phosphorylates microtubule-associated protein futsch in axons.SUBUNIT Interacts with cos.TISSUE SPECIFICITY Expressed in ovaries and activated eggs (at protein level). Expression is over all the embryo at all stages, no local accumulation is observed.DEVELOPMENTAL STAGE Isoform SGG46 is expressed at low levels in 12-24 hours embryos. Isoform Zygotic and isoform SGG39 are expressed in 12-24 hours embryos and present throughout the larval, pupal and adult stages (at protein level). Isoform Zygotic is expressed maternally and zygotically but reduced throughout later embryonic development. Expression persists throughout larval stages.DISRUPTION PHENOTYPE Mutants display an overdeveloped neuromuscular junction (NMJ), with the number of boutons greatly increased.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily. UniProt P18431 Reactome DB_ID: 206210 1 UniProt:P54367 CkIalpha CkIalpha CKI CkIalpha CG2028 酪蛋白激酶操作上定义的函数by their preferential utilization of acidic proteins such as caseins as substrates. Can phosphorylate a large number of proteins. Negative regulator of wg signaling (PubMed:22095083). Phosphorylates arm directly or indirectly and stimulates its degradation which prevents inappropriate wg signaling (PubMed:11955436, PubMed:11927557, PubMed:22095083). Phosphorylates smo which promotes its accumulation at the cell surface and its signaling activity in response to hh (PubMed:15616566). Together with dco, regulates proteolytic processing of ci by phosphorylating it which promotes its binding to slmb, the F-box recognition component of the SCF(slmb) E3 ubiquitin-protein ligase required for ci processing (PubMed:16326393). Inhibits condensin II interphase activity by promoting degradation of the Cap-H2 regulatory subunit and limiting the levels of chromatin-bound Cap-H2 which regulates interphase chromosome organization (PubMed:25723539).ACTIVITY REGULATION Activity increases following DNA damage.SUBUNIT Interacts with cos.DEVELOPMENTAL STAGE Expressed during early embryogenesis and in adult females (at protein level).PTM Phosphorylated. The dephosphorylated kinase is active in the cytoplasm while the active kinase in the nucleus is phosphorylated.SIMILARITY Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily. UniProt P54367 Reactome DB_ID: 205872 1 UniProt:P23647 fu fu CG6551 fu 函数可能丝氨酸/ threonine-protein激酶;maternally required for correct patterning in the posterior part of each embryonic metamere. May be involved in control of cell division during metamorphosis and ovarian development. May interact with costal-2.TISSUE SPECIFICITY Expressed in all imaginal disks, higher level in wing disk.DEVELOPMENTAL STAGE Expressed both maternally and zygotically, low expression is present in males, larvae and pupae.SIMILARITY Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. UniProt P23647 Reactome DB_ID: 205832 1 UniProt:O16844 cos cos cos2 cos CG1708 costal-2 FUNCTION Regulates cubitus interruptus (ci) processing by recruiting multiple kinases to promote its efficient phosphorylation. Scaffolds multiple kinases and ci into proximity to promote its hyperphosphorylation, which then targets it for SCFSlimb/proteasome-mediated processing to generate its repressor form. Hh signaling inhibits ci phosphorylation by interfering with the cos-ci-kinases complex formation. Negatively regulates hh-signaling pathways during various processes, including photoreceptor differentiation (PubMed:25639794, PubMed:27195754). May negatively regulate a hh-signaling pathway which functions in the intestinal immune response to bacterial uracil by activating the Duox-dependent production of reactive oxygen species (ROS) (PubMed:25639794).SUBUNIT Homodimer (Potential). Binds microtubules. Interacts with ci, smo, sgg, CkIalpha and protein kinase A catalytic subunit (PubMed:15691767, PubMed:9244298). Interacts (via kinesin motor domain) with Ubr3 (PubMed:27195754).DEVELOPMENTAL STAGE Present at high levels during the first 4 hours of embryogenesis and at moderate levels between 4-12 hours.PTM Polyubiquitinated by Ubr3, which leads to proteasomal degradation.DISRUPTION PHENOTYPE RNAi-mediated knockdown results in the increased expression of reactive oxygen species (ROS) in the gut of 7 day old conventionally reared adult flies. No increased ROS expression in germ-free adults and in response to bacteria-derived uracil.SIMILARITY Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. KIF27 subfamily. UniProt O16844 Reactome DB_ID: 206046 1 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. UniProt P19538 Reactome DB_ID: 206721 1 COS:CI:FU:PKA-C1:SGG:CKIalpha:DCO [cytosol] COS:CI:FU:PKA-C1:SGG:CKIalpha:DCO Reactome DB_ID: 205931 1 2 EQUAL 353 EQUAL Reactome DB_ID: 205729 1 Reactome DB_ID: 205716 1 Reactome DB_ID: 206210 1 Reactome DB_ID: 205872 1 Reactome DB_ID: 205832 1 Reactome DB_ID: 206046 1 Reactome Database ID Release 77 206721 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206721 Reactome R-DME-206721 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206721.1 Reactome Database ID Release 77 209331 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209331 Reactome R-DME-209331 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209331.3 10825151 Pubmed 2000 Identification of a tetrameric hedgehog signaling complex Stegman, MA Vallance, JE Elangovan, G Sosinski, J Cheng, Y Robbins, DJ J Biol Chem 275:21809-12 15063184 Pubmed 2004 Multiple Cos2/Ci interactions regulate Ci subcellular localization through microtubule dependent and independent mechanisms Wang, G Jiang, J Dev Biol 268:493-505 11090136 Pubmed 2000 Interactions with Costal2 and suppressor of fused regulate nuclear translocation and activity of cubitus interruptus Wang, G Amanai, K Wang, B Jiang, J Genes Dev 14:2893-905 14636583 Pubmed 2003 Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2 Lum, L Zhang, C Oh, S Mann, RK von Kessler, DP Taipale, J Weis-Garcia, F Gong, R Wang, B 海滩,PA Mol Cell 12:1261-74 15691767 Pubmed 2005 Hedgehog-regulated Costal2-kinase complexes control phosphorylation and proteolytic processing of Cubitus interruptus Zhang, W Zhao, Y Tong, C Wang, G Wang, B Jia, J Jiang, J Dev Cell 8:267-78 9601642 Pubmed 1998 Suppressor of fused links fused and Cubitus interruptus on the hedgehog signalling pathway Monnier, V Dussillol, F Alves, G Lamour-Isnard, C Plessis, A Curr Biol 8:583-6 11914126 Pubmed 2002 Hedgehog signal transduction proteins: contacts of the Fused kinase and Ci transcription factor with the kinesin-related protein Costal2 Monnier, V Ho, KS Sanial, M Scott, MP Plessis, A BMC Dev Biol 2:4 11955435 Pubmed 2002 Proteolysis of the Hedgehog signaling effector Cubitus interruptus requires phosphorylation by Glycogen Synthase Kinase 3 and Casein Kinase 1 Price, MA Kalderon, D Cell 108:823-35 Formation of the CI:SU(FU) complex Formation of the CI:SU(FU) complex Cubitus Interruptus (CI) forms a separate complex with the Supressor of Fused (SU(FU)) protein. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 206046 1 Reactome DB_ID: 206064 1 UniProt:Q27279 Su(fu) Su(fu) Su(fu) suppressoroffused CG6054 PEST protein Su(Fu) protein Suppressor of fused protein UniProt Q27279 Reactome DB_ID: 206802 1 CI:SU(FU) [cytosol] CI:SU(FU) Reactome DB_ID: 206046 1 Reactome DB_ID: 206064 1 Reactome Database ID Release 77 206802 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206802 Reactome R-DME-206802 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206802.1 Reactome Database ID Release 77 216136 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216136 Reactome R-DME-216136 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216136.3 Phosphorylation of CI Phosphorylation of CI Spatzle (SPZ) dimer binding leads to Toll (TL) receptor homodimerisation and activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2006-12-08 11:30:45 2.7.11 Phosphorylation of CI by PKA-C1 Phosphorylation of CI by PKA-C1 Cubitus Interruptus (CI) is primed for phosphorylation by Protein kinase A (PKA-C1) at Ser838, Ser856, and Ser892. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 113592 3 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 206721 1 Reactome DB_ID: 206916 1 COS:Phospho (3 sites) CI:FU:PKA-C1:SGG:CKIalpha:DCO [cytosol] COS:Phospho (3 sites) CI:FU:PKA-C1:SGG:CKIalpha:DCO Reactome DB_ID: 205938 1 O-phospho-L-serine at 838 838 EQUAL O-phospho-L-serine [MOD:00046] O-phospho-L-serine at 856 856 EQUAL O-phospho-L-serine at 892 892 EQUAL Reactome DB_ID: 205931 1 2 EQUAL 353 EQUAL Reactome DB_ID: 205729 1 Reactome DB_ID: 205716 1 Reactome DB_ID: 206210 1 Reactome DB_ID: 205872 1 Reactome DB_ID: 205832 1 Reactome Database ID Release 77 206916 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206916 Reactome R-DME-206916 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206916.1 Reactome DB_ID: 29370 3 ADP(3-) [ChEBI:456216] ADP(3-) ADPtrianion 5'-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 206865 CNK:PHL:Phospho (2 sites) KSR:AVE:DSOR1:CK2:PAR-1:PP2A-29B:MTS [cytosol] CNK:PHL:Phospho (2 sites) KSR:AVE:DSOR1:CK2:PAR-1:PP2A-29B:MTS Reactome DB_ID: 205807 1 UniProt:Q8ML92 ave ave ave CG30476 FUNCTION Required for normal photoreceptor differentiation between Ras and Raf for EGFR signaling in the eye and for mitogen-activated protein kinase phosphorylation. Probably acts together with Cnk to promote Raf activation, perhaps by recruiting an activating kinase.SUBUNIT Interacts with the SAM domain of cnk.DEVELOPMENTAL STAGE Expressed ubiquitously throughout development.MISCELLANEOUS 'Aveugle' means 'blind' in French. UniProt Q8ML92 Reactome DB_ID: 206624 1 CK2 [cytosol] CK2 Reactome DB_ID: 206276 2 UniProt:P08182 CkIIbeta 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 Reactome DB_ID: 206181 2 UniProt:P08181 CkIIalpha CkIIalpha Cask-II-a CG17520 CkIIalpha 酪蛋白激酶操作上定义的函数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 2 EQUAL 236 EQUAL Reactome Database ID Release 77 206624 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206624 Reactome R-DME-206624 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206624.1 Reactome DB_ID: 205928 1 UniProt:Q7KNQ9 cnk cnk cnk CG6556 Dmel_CG6556 SIMILARITY Contains 1 PDZ (DHR) domain.SIMILARITY Contains 1 PH domain. UniProt Q7KNQ9 Reactome DB_ID: 205713 1 UniProt:P11346 Raf Raf phl Raf ph CG2845 FUNCTION Serine/threonine kinase required in the early embryo for the formation of terminal structure (PubMed:3135183, PubMed:8423783). Also required during the proliferation of imaginal cells (PubMed:3135183). May act downstream of Ras85D in the tor signal transduction pathway (PubMed:8423783). During larval development, mediates Ptth/tor signaling leading to the production of ecdysone, a hormone required for the initiation of metamorphosis (PubMed:19965758).ACTIVITY REGULATION In quiescent cells, maintained in an inactive state via an intramolecular interaction between the protein kinase and N-terminal domains (By similarity). Following mitogen-mediated cell activation, binds via its RGB domain to active Ras85D (GTP-bound) which releases the inhibitory intramolecular interaction between the two domains (By similarity). This allows the Dsor1/MEK1-mediated dimerization of ksr and Raf which activates Raf (PubMed:29433126).SUBUNIT Interacts with Dsor1/MEK1 and ksr; Dsor1 binding to ksr probably promotes ksr and Raf dimerization and ksr-mediated Raf transactivation.DEVELOPMENTAL STAGE Expressed both maternally and zygotically. Zygotically expressed throughout embryogenesis.PTM Extensively phosphorylated 1 to 2 hours after egg laying.DISRUPTION PHENOTYPE RNAi-mediated knockdown in the prothoracic gland (PG) delays the onset of pupariation by prolonging the L3 larval stage.SIMILARITY Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily. UniProt P11346 Reactome DB_ID: 205968 1 UniProt:Q24324 Dsor1 Dsor1 Dsor1 CG15793 FUNCTION Required downstream of Raf in the sevenless (sev), torso (tor), and Drosophila EGF receptor homolog (DER) signal transduction pathways. Involved in both positive regulation (at the posterior terminus) and negative regulation (at the anterior domain) of tll, as in other terminal class gene products, maybe via the ERK-A kinase.SUBUNIT Interacts with Raf and ksr; Dsor1 binding to ksr probably promotes ksr and Raf dimerization and ksr-mediated Raf transactivation.DEVELOPMENTAL STAGE Expressed both maternally and zygotically.PTM Phosphorylation on Ser/Thr by MAP kinase kinase kinases regulates positively the kinase activity.SIMILARITY Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. UniProt Q24324 Reactome DB_ID: 206133 1 UniProt:Q95U75 par-1 par-1 CG8201 par-1 SIMILARITY Belongs to the protein kinase superfamily. UniProt Q95U75 Reactome DB_ID: 206606 1 PP2A-29B:MTS [cytosol] PP2A-29B:MTS Reactome DB_ID: 206147 1 UniProt:P23696 mts mts CG7109 Pp2A-28D PP2A mts PTM Reversibly methyl esterified on Leu-309 by leucine carboxyl methyltransferase 1 (LCMT1) and protein phosphatase methylesterase 1 (PPME1). Carboxyl methylation influences the affinity of the catalytic subunit for the different regulatory subunits, thereby modulating the PP2A holoenzyme's substrate specificity, enzyme activity and cellular localization (By similarity).SIMILARITY Belongs to the PPP phosphatase family. PP-2A subfamily. UniProt P23696 Reactome DB_ID: 205936 1 UniProt:P36179 Pp2A-29B Pp2A-29B CG17291 Pp2A-29B 函数的PR65亚基蛋白磷酸酶2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit.SUBUNIT PP2A exists in several trimeric forms, all of which consist of a core composed of a catalytic subunit associated with a 65 kDa regulatory subunit (PR65) (subunit A). The core complex associates with a third, variable subunit (subunit B), which confers distinct properties to the holoenzyme.TISSUE SPECIFICITY Expression varies in tissues throughout development. Highly distributed expression in early embryos. In late embryonal development, found at high levels in nervous system and gonads. In third instar larvae, found in brain, imaginal disks and salivary glands.DEVELOPMENTAL STAGE Expressed both maternally and zygotically. Expressed at lower levels in larvae and adult.DOMAIN Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure.SIMILARITY Belongs to the phosphatase 2A regulatory subunit A family. UniProt P36179 2 EQUAL 591 EQUAL Reactome Database ID Release 77 206606 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206606 Reactome R-DME-206606 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206606.1 Reactome DB_ID: 206130 1 UniProt:Q24170 ksr ksr ksr CG2899 CATALYTIC ACTIVITY ATP + a protein = ADP + a phosphoprotein.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. UniProt Q24170 O-phospho-L-serine at unknown position O-phospho-L-serine at unknown position Reactome Database ID Release 77 206865 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206865 Reactome r -测距装置- 206865 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206865.1 GO 0004674 GO molecular function Reactome Database ID Release 77 208927 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=208927 Reactome Database ID Release 77 209196 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209196 Reactome R-DME-209196 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209196.3 9482888 Pubmed 1998 Protein kinase A directly regulates the activity and proteolysis of cubitus interruptus Chen, Y Gallaher, N Goodman, RH Smolik, SM Proc Natl Acad Sci U S A 95:2349-54 10477300 Pubmed 1999 Proteolysis of cubitus interruptus in Drosophila requires phosphorylation by protein kinase A Price, MA Kalderon, D Development 126:4331-9 10557210 Pubmed 1999 Protein kinase A antagonizes Hedgehog signaling by regulating both the activator and repressor forms of Cubitus interruptus Wang, G Wang, B Jiang, J Genes Dev 13:2828-37 10409506 Pubmed 1999 Mutants of cubitus interruptus that are independent of PKA regulation are independent of hedgehog signaling Chen, Y Cardinaux, JR Goodman, RH Smolik, SM Development 126:3607-16 2.7.11 Phosphorylation of CI by CKIalphaepsilon (CKIalpha/DCO) Phosphorylation of CI by CKIalphaepsilon (CKIalpha/DCO) The priming phosphorylations of Cubitus Interruptus (CI) results in additional phosphorylation by kinases CKIalphaepsilon (CKIalpha/DCO) at Ser841, Ser844, Thr845, Ser849, Ser852, Ser859, Ser862, and Ser895. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 206916 1 Reactome DB_ID: 113592 8 Reactome DB_ID: 206924 1 COS:Phospho (11 sites) CI:FU:PKA-C1:SGG:CKIalpha:DCO [cytosol] COS:Phospho (11 sites) CI:FU:PKA-C1:SGG:CKIalpha:DCO Reactome DB_ID: 205757 1 O-phospho-L-serine at 838 838 EQUAL O-phospho-L-serine at 856 856 EQUAL O-phospho-L-serine at 892 892 EQUAL O-phospho-L-serine at 841 841 EQUAL O-phospho-L-serine at 844 844 EQUAL O-phospho-L-serine at 859 859 EQUAL O-phospho-L-serine at 862 862 EQUAL O-phospho-L-serine at 895 895 EQUAL O-phospho-L-threonine at 845 845 EQUAL O-phospho-L-threonine [MOD:00047] O-phospho-L-serine at 849 849 EQUAL O-phospho-L-serine at 852 852 EQUAL Reactome DB_ID: 205931 1 2 EQUAL 353 EQUAL Reactome DB_ID: 205729 1 Reactome DB_ID: 205716 1 Reactome DB_ID: 206210 1 Reactome DB_ID: 205872 1 Reactome DB_ID: 205832 1 Reactome Database ID Release 77 206924 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206924 Reactome R-DME-206924 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206924.1 Reactome DB_ID: 29370 8 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 206577 CKIalphaepsilon [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DCO [cytosol] CKIalpha [cytosol] Reactome Database ID Release 77 208910 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=208910 Reactome Database ID Release 77 209293 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209293 Reactome R-DME-209293 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209293.3 17925225 Pubmed 2007 Regulation of Ci-SCFSlimb binding, Ci proteolysis, and hedgehog pathway activity by Ci phosphorylation Smelkinson, MG Zhou, Q Kalderon, D Dev Cell 13:481-95 16326393 Pubmed 2005 Phosphorylation by double-time/CKIepsilon and CKIalpha targets cubitus interruptus for Slimb/beta-TRCP-mediated proteolytic processing Jia, J Zhang, Lei Zhang, Q Tong, C Wang, B Hou, F Amanai, K Jiang, J Dev Cell 9:819-30 2.7.11 Phosphorylation of CI by SGG Phosphorylation of CI by SGG Previous phosphorylation of Cubitus Interruptus (CI) at Ser856 and Ser892 primes Shaggy (SGG) phosphorylation at Ser884 and Ser888. Ser852 can also be phosphorylated by SGG if it hasn't been previously phosphorylated by CKIalpha/DCO. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 206924 1 Reactome DB_ID: 113592 2 Reactome DB_ID: 206997 1 COS:Phospho (13 sites) CI:FU:PKA-C1:SGG:CKIalpha:DCO [cytosol] COS:Phospho (13 sites) CI:FU:PKA-C1:SGG:CKIalpha:DCO Reactome DB_ID: 205931 1 2 EQUAL 353 EQUAL Reactome DB_ID: 205729 1 Reactome DB_ID: 205801 1 O-phospho-L-serine at 838 838 EQUAL O-phospho-L-serine at 856 856 EQUAL O-phospho-L-serine at 892 892 EQUAL O-phospho-L-serine at 841 841 EQUAL O-phospho-L-serine at 844 844 EQUAL O-phospho-L-serine at 859 859 EQUAL O-phospho-L-serine at 862 862 EQUAL O-phospho-L-serine at 895 895 EQUAL O-phospho-L-serine at 852 852 EQUAL O-phospho-L-serine at 884 884 EQUAL O-phospho-L-serine at 888 888 EQUAL O-phospho-L-threonine at 845 845 EQUAL O-phospho-L-serine at 849 849 EQUAL Reactome DB_ID: 205716 1 Reactome DB_ID: 206210 1 Reactome DB_ID: 205872 1 Reactome DB_ID: 205832 1 Reactome Database ID Release 77 206997 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206997 Reactome R-DME-206997 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206997.1 Reactome DB_ID: 29370 2 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 206898 Phospho AXN:Phospho APC:PP2A:CKIalpha:DCO:SGG [cytosol] Phospho AXN:Phospho APC:PP2A:CKIalpha:DCO:SGG Reactome DB_ID: 206136 1 UniProt:Q9V407 Axn Axn Axn CG7926 FUNCTION Inhibitor of the WG signaling pathway. Down-regulates beta-catenin (armadillo=ARM). Probably facilitate the phosphorylation of beta-catenin and APC by GSK3B (zeste-white 3=ZW3).SUBUNIT Interacts with ZW3 and ARM. The interaction between AXN and ARM occurs via the armadillo repeats contained in ARM.DEVELOPMENTAL STAGE Ubiquitously expressed throughout the development. UniProt Q9V407 O-phospho-L-serine at 529 529 EQUAL Reactome DB_ID: 205729 1 Reactome DB_ID: 206938 1 PP2A [cytosol] PP2A Reactome DB_ID: 205790 1 UniProt:P36872 tws tws tws aar CG6235 Pp2A-85F 函数可以执行一个底物识别的乐趣ction or could be responsible for targeting the enzyme complex to the appropriate subcellular compartment.SUBUNIT PP2A exists in several trimeric forms, all of which consist of a core composed of a catalytic subunit associated with a 65 kDa regulatory subunit (PR65) (subunit A). The core complex associates with a third, variable subunit (subunit B), which confers distinct properties to the holoenzyme.SIMILARITY Belongs to the phosphatase 2A regulatory subunit B family.CAUTION It is uncertain whether Met-1, Met-18, Met-33 or Met-44 is the initiator. UniProt P36872 Reactome DB_ID: 206147 1 Reactome DB_ID: 205936 1 2 EQUAL 591 EQUAL Reactome Database ID Release 77 206938 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206938 Reactome R-DME-206938 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206938.1 Converted from EntitySet in Reactome Reactome DB_ID: 206562 1 Phospho APC [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Phospho APC2 [cytosol] Phospho APC [cytosol] UniProt Q9Y1T2 UniProt P91667 Reactome DB_ID: 206210 1 Reactome DB_ID: 205716 1 Reactome Database ID Release 77 206898 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206898 Reactome R-DME-206898 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206898.1 Reactome Database ID Release 77 208897 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=208897 Reactome Database ID Release 77 209172 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209172 Reactome R-DME-209172 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209172.3 11912487 Pubmed 2002 Shaggy/GSK3 antagonizes Hedgehog signalling by regulating Cubitus interruptus Jia, J Amanai, K Wang, G Tang, J Wang, B Jiang, J Nature 416:548-52 2.7.11 Further phosphorylation of CI by CKIalphaepsilon Further phosphorylation of CI by CKIalphaepsilon Previous phosphorylation of Cubitus Interruptus (CI) at Ser852 and Ser888 primes further phosphorylation by CKIalphaepsilon (CKIalpha/DCO) at Ser855, Ser858, and Ser891. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 113592 3 Reactome DB_ID: 206997 1 Reactome DB_ID: 206766 1 COS:Phospho (16 sites) CI:FU:PKA-C1:SGG:CKIalpha:DCO [cytosol] COS:Phospho (16 sites) CI:FU:PKA-C1:SGG:CKIalpha:DCO Reactome DB_ID: 206294 1 O-phospho-L-serine at 838 838 EQUAL O-phospho-L-serine at 856 856 EQUAL O-phospho-L-serine at 892 892 EQUAL O-phospho-L-serine at 841 841 EQUAL O-phospho-L-serine at 844 844 EQUAL O-phospho-L-serine at 859 859 EQUAL O-phospho-L-serine at 862 862 EQUAL O-phospho-L-serine at 895 895 EQUAL O-phospho-L-serine at 852 852 EQUAL O-phospho-L-serine at 884 884 EQUAL O-phospho-L-serine at 888 888 EQUAL O-phospho-L-serine at 855 855 EQUAL O-phospho-L-serine在858 858 EQUAL O-phospho-L-serine at 891 891 EQUAL O-phospho-L-threonine at 845 845 EQUAL O-phospho-L-serine at 849 849 EQUAL Reactome DB_ID: 205931 1 2 EQUAL 353 EQUAL Reactome DB_ID: 205729 1 Reactome DB_ID: 205716 1 Reactome DB_ID: 206210 1 Reactome DB_ID: 205872 1 Reactome DB_ID: 205832 1 Reactome Database ID Release 77 206766 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206766 Reactome R-DME-206766 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206766.1 Reactome DB_ID: 29370 3 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 206577 Reactome Database ID Release 77 209187 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209187 Reactome R-DME-209187 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209187.3 Reactome Database ID Release 77 209190 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209190 Reactome R-DME-209190 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209190.2 Reactome Database ID Release 77 209159 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209159 Reactome R-DME-209159 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209159.2 Ubiquitination and proteolysis of phosphorylated CI Ubiquitination and proteolysis of phosphorylated CI Spatzle (SPZ) dimer binding leads to Toll (TL) receptor homodimerisation and activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2006-12-08 11:30:45 6.3.2.19 SLMB binds to and ubiquitinates phosphorylated CI SLMB binds to and ubiquitinates phosphorylated CI Phosphorylated Cubitus Interruptus (CI) is now recognised by Slimb (SLMB), which is part of the SCF (Skp1, Cdc53, and F-box) ubiquitin ligase complex. CI associates with SLMB via its phosphorylated residues and is then ubiquitinated by the SCF ubiquitin ligase complex. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Converted from EntitySet in Reactome Reactome DB_ID: 206204 1 UBI-P63E [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity UBI-P63E 1 [cytosol] UBI-P63E 7 [cytosol] UBI-P63E 9 [cytosol] UBI-P63E 8 [cytosol] UBI-P63E 3 [cytosol] UBI-P63E 12 [cytosol] UBI-P63E 2 [cytosol] UBI-P63E 10 [cytosol] UBI-P63E 4 [cytosol] UBI-P63E 11 [cytosol] UBI-P63E 5 [cytosol] UBI-P63E 6 [cytosol] UniProt P0CG69 UniProt P18101 UniProt P15357 Reactome DB_ID: 206766 1 Reactome DB_ID: 206788 1 SLMB:SKPA:LIN19:ROC1A:EFF [cytosol] SLMB:SKPA:LIN19:ROC1A:EFF Reactome DB_ID: 205902 1 UniProt:Q9W5E1 Roc1a Roc1a Roc1a CG16982 函数多个自洽场(SKP1-CUL1的核心组成部分-F-box protein) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. Through the RING-type zinc finger, seems to recruit the E2 ubiquitination enzyme to the complex and brings it into close proximity to the substrate. Required for the specific SCF-dependent proteolysis of CI, but not that of ARM, suggesting that it also participates in the selection of substrates inside the SCF complex (PubMed:12062088). During early metamorphosis, part of the SCF-slmb complex that negatively regulates the InR/PI3K/TOR pathway to activate the pruning of unnecessary larval ddaC dendrites and mushroom body axons (PubMed:24068890). The SCF-slmb complex also regulates asymmetrical division of neuroblasts and inhibits ectopic neuroblast formation partly through SAK and Akt1 (PubMed:24413555). Also part of an SCF complex required for caspase activation during sperm differentiation (Probable).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Component of SCF E3 ubiquitin-protein ligase complexes consisting of Skpa, Cul1, Roc1a and an F-box protein. In larvae neuroblast self renewal and asymmetric division, as well as ddaC dendrite and mushroom body axon pruning, the complex contains the F-box protein slmb (SCF-slmb) (PubMed:24068890, PubMed:24413555). Interacts directly with Cul1 and Slmb (PubMed:11500045). In caspase activation during sperm differentiation, the complex contains the F-box protein ntc (Probable).TISSUE SPECIFICITY Widely expressed. Expressed in embryonic, larval and adult tissues.DEVELOPMENTAL STAGE Expressed both maternally and zygotically.DOMAIN The RING-type zinc finger domain is essential for ubiquitin ligase activity. It coordinates an additional third zinc ion (By similarity).DISRUPTION PHENOTYPE Severe pruning defect in ddaC neurons (PubMed:24068890). Also shows defects in ddaD and ddaE neuron pruning and in ddaF apoptosis (PubMed:24068890). RNAi-mediated knockdown results in apical detachment of scolopidial cells in Johnston's organ (PubMed:27331610).SIMILARITY Belongs to the RING-box family. UniProt Q9W5E1 Reactome DB_ID: 206299 1 UniProt:O44382 slmb slmb slimb CG3412 slmb Slimb UniProt O44382 Reactome DB_ID: 206151 1 UniProt:Q24311 Cul1 Cul1 Cul1 cul-1 lin19 CG1877 函数多个自洽场(SKP1-CUL1的核心组成部分-F-box protein) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. During early metamorphosis, part of the SCF-slmb complex that negatively regulates the InR/PI3K/TOR pathway to activate the pruning of unnecessary larval ddaC dendrites and mushroom body axons (PubMed:24068890). The SCF-slmb complex also regulates asymmetrical division of neuroblasts and inhibits ectopic neuroblast formation partly through SAK and Akt1 (PubMed:24413555). Also part of an SCF complex required for caspase activation during sperm differentiation (PubMed:20392747). Necessary for auditory transduction: plays a role in Johnston's organ organization by acting in the regulation of zip and ck function in scolopidial apical attachment (PubMed:27331610). May function by acting in a Ubr3-mediated pathway that negatively regulates the ubiquitination of zip, consequently affecting its interaction with ck (PubMed:27331610).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Component of SCF E3 ubiquitin-protein ligase complexes consisting of Skpa, Cul1, Roc1a and an F-box protein. In larval neuroblast self renewal and asymmetric division, as well as ddaC dendrite and mushroom body axon pruning, the complex contains the F-box protein slmb (SCF-slmb) (PubMed:24068890, PubMed:24413555). In caspase activation during sperm differentiation, the complex contains the F-box protein ntc (PubMed:20392747). Interacts directly with Roc1a (PubMed:11500045). Interacts with Fsn (PubMed:20123973). Interacts with Dlish (PubMed:27692068). Interacts with Cad99C (via the cytoplasmic domain) (PubMed:27331610). Interacts with Sans (PubMed:27331610).TISSUE SPECIFICITY Expressed in testis.PTM Neddylated (PubMed:12183637, PubMed:18493598). Deneddylated via its interaction with the COP9 signalosome (CSN) complex (PubMed:12183637).DISRUPTION PHENOTYPE Severe dendrite pruning defects in ddaC neurons at 16 hours after puparium formation (APF) and axon pruning defects in mushroom body gamma neurons at 24 hours APF. RNAi-mediated knockdown results in a significant increase in Akt1 protein levels and activity in ddaC somas (PubMed:24068890). In the larval brain there is a large increase in the number of neuroblasts, 40% of which show a spindle misorientation at metaphase (PubMed:24413555). RNAi-mediated knockdown results in apical detachment of scolopidial cells in Johnston's organ (PubMed:27331610).SIMILARITY Belongs to the cullin family. UniProt Q24311 Reactome DB_ID: 205785 1 UniProt:O77430 skpA skpA EG:115C2.4 Dmel_CG16983 Dredd skpA CG16983 SkpA, isoform A SkpA, isoform B SkpA, isoform C SkpA, isoform D SkpA, isoform E SkpA, isoform F SkpA, isoform G EG:115C2.4 protein HL01263p SKPA UniProt O77430 Reactome DB_ID: 205773 1 UniProt:P25867 eff eff CG7425 eff UbcD1 FUNCTION Catalyzes the covalent attachment of ubiquitin to other proteins. Mediates the selective degradation of short-lived and abnormal proteins. Required for proper telomere behavior during cell divisions and possibly for ubiquitination of proteins involved in postmeiotic stages of spermatogenesis. Deletion mutations are lethal in homozygotes.PATHWAY Protein modification; protein ubiquitination.SIMILARITY Belongs to the ubiquitin-conjugating enzyme family. UniProt P25867 Reactome Database ID Release 77 206788 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206788 Reactome R-DME-206788 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206788.1 Reactome DB_ID: 207011 1 SLMB:SKPA:LIN19:ROC1A:EFF:COS:Phospho (16 sites) CI:UBI-P63E:FU:PKA-C1:SGG:CKIalpha:DCO [cytosol] SLMB:SKPA:LIN19:ROC1A:EFF:COS:Phospho (16 sites) CI:UBI-P63E:FU:PKA-C1:SGG:CKIalpha:DCO Converted from EntitySet in Reactome Reactome DB_ID: 206204 1 Reactome DB_ID: 206766 1 Reactome DB_ID: 206788 1 Reactome Database ID Release 77 207011 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=207011 Reactome R-DME-207011 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-207011.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 207002 SLMB:SKPA:LIN19:ROC1A:EFF:Phospho (4 sites) ARM:Phospho (3 sites) AXN:Phospho (6 sites) APC:PP2A:CKIalpha:DCO:SGG [cytosol] SLMB:SKPA:LIN19:ROC1A:EFF:Phospho (4 sites) ARM:Phospho (3 sites) AXN:Phospho (6 sites) APC:PP2A:CKIalpha:DCO:SGG Reactome DB_ID: 207028 1 Phospho (4 sites) ARM:Phospho (3 sites) AXN:Phospho (6 sites) APC:PP2A:CKIalpha:DCO:SGG [cytosol] Phospho (4 sites) ARM:Phospho (3 sites) AXN:Phospho (6 sites) APC:PP2A:CKIalpha:DCO:SGG Reactome DB_ID: 205960 1 UniProt:P18824 arm arm CG11579 arm FUNCTION Isoform neural may associate with CadN and participate in the transmission of developmental information. Can associate with alpha-catenin. Isoform cytoplasmic accumulates through wg signaling; arm function in wg signal transduction is required early in development for determination of neuroblast fate. Arm and Abl proteins function cooperatively at adherens junctions in both the CNS and epidermis.SUBUNIT Interacts with Mer and Moe at the adherens junction (PubMed:8666669). Interacts with Inx2 (PubMed:15047872). Interacts with alpha-Cat (PubMed:25653389). Interacts with Myo31DF (PubMed:16598259, PubMed:22491943).TISSUE SPECIFICITY Isoform cytoplasmic accumulates at low levels in axons, at high levels in specific cells along the CNS midline and in leg and eye imaginal disks. Isoform neural accumulates in the axon tracts of the CNS. Both isoforms accumulate in the peripheral nervous system.DEVELOPMENTAL STAGE Present at all stages, but reaches the highest levels during early to mid-embryogenesis. Isoform cytoplasmic is the predominant one from the cellular blastoderm stage until germ-band retraction. Isoform neural is first seen after germ band retraction.PTM Phosphorylated on Ser, Thr and Tyr residues (PubMed:7529201). Level of phosphorylation varies both during embryonic development and from embryonic tissue to tissue (PubMed:7529201). Sgg is required for phosphorylation and wg signal negatively regulates arm phosphorylation (PubMed:7529201). Hypophosphorylated form of arm increases in steady-state levels (PubMed:7529201). Phosphorylated directly or indirectly by CkIalpha which stimulates its degradation (PubMed:11927557).SIMILARITY Belongs to the beta-catenin family. UniProt P18824 O-phospho-L-serine at 44 44 EQUAL O-phospho-L-serine at 48 48 EQUAL O-phospho-L-threonine at 52 52 EQUAL O-phospho-L-serine at 56 56 EQUAL Reactome DB_ID: 205729 1 Reactome DB_ID: 206938 1 Reactome DB_ID: 206210 1 Reactome DB_ID: 205716 1 Converted from EntitySet in Reactome Reactome DB_ID: 206566 1 Phospho (6 sites) APC [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Phospho (6 sites) APC [cytosol] Phospho (6 sites) APC2 [cytosol] Reactome DB_ID: 206169 1 O-phospho-L-serine at 529 529 EQUAL O-phospho-L-threonine at 517 517 EQUAL O-phospho-L-serine at 522 522 EQUAL Reactome Database ID Release 77 207028 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=207028 Reactome R-DME-207028 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-207028.1 Reactome DB_ID: 206788 1 Reactome Database ID Release 77 207002 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=207002 Reactome R-DME-207002 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-207002.1 GO 0004842 GO molecular function Reactome Database ID Release 77 208868 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=208868 Reactome Database ID Release 77 209224 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209224 Reactome R-DME-209224 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209224.3 16386907 Pubmed 2006 Processing of the Drosophila hedgehog signaling effector Ci-155 to the repressor Ci-75 is mediated by direct binding to the SCF component Slimb Smelkinson, MG Kalderon, D Curr Biol 16:110-6 Ubiquitinated and phosphorylated CI is partially degraded by the proteasome complex Ubiquitinated and phosphorylated CI is partially degraded by the proteasome complex Ubiquitinated和磷酸化尺骨中断us (CI) is processed by the proteasome complex resulting in a truncated product, CI75, with a C-terminus somewhere between residues 650-700 (Aza-Blanc et al., 1997) or 611-760 (Methot and Basler, 1999). It is thought that the zinc-finger domain and C-terminal simple sequences arrest proteasome digestion from the C-terminus. Some CI is likely to be fully proteolysed by the proteasome. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 207011 1 Converted from EntitySet in Reactome Reactome DB_ID: 206204 1 Reactome DB_ID: 206171 1 Reactome DB_ID: 206900 1 COS:FU:PKA-C1:SGG:CKIalpha:DCO [cytosol] COS:FU:PKA-C1:SGG:CKIalpha:DCO Reactome DB_ID: 205931 1 2 EQUAL 353 EQUAL Reactome DB_ID: 205729 1 Reactome DB_ID: 205716 1 Reactome DB_ID: 206210 1 Reactome DB_ID: 205872 1 Reactome DB_ID: 205832 1 Reactome Database ID Release 77 206900 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206900 Reactome R-DME-206900 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206900.1 Reactome DB_ID: 206788 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 206968 26S proteasome [cytosol] 26S proteasome Reactome DB_ID: 205917 1 UniProt:Q9VNA5 Prosbeta7 Prosbeta7 Prosbeta4 Prosb4 CG12000 Prosbeta7 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 Reactome DB_ID: 206270 1 UniProt:P26270 Rpn8 Rpn8 Mov34 Rpn8 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 Reactome DB_ID: 206127 1 UniProt:Q8SYQ2 l(2)05070 l(2)05070 l(2)05070 CG8392 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 Q8SYQ2 Reactome DB_ID: 206228 1 UniProt:Q9V405 Rpt3 Rpt3 CG16916 Rpt3-RA Rpt3 Dmel_CG16916 SIMILARITY Belongs to the AAA ATPase family. UniProt Q9V405 Reactome DB_ID: 206031 1 UniProt:Q9VUJ1 Prosbeta2 Prosbeta2 Prosbeta2 Dmel_CG3329 Pros-beta-2 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 Reactome DB_ID: 206131 1 UniProt:Q7KLV9 Rpn6 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 Reactome DB_ID: 205764 1 UniProt:Q95083 Prosalpha5 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 Reactome DB_ID: 205719 1 UniProt:P40304 Prosbeta6 Prosbeta6 PROS-26 Pros26 CG4097 l(3)73Ai Prosbeta6 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 P40304 Reactome DB_ID: 206118 1 UniProt:Q9VKZ8 CG5384 CG5384 Dmel_CG5384 CG5384 CATALYTIC ACTIVITY Ubiquitin C-terminal thioester + H(2)O = ubiquitin + a thiol.SIMILARITY Belongs to the peptidase C19 family. UniProt Q9VKZ8 Reactome DB_ID: 206285 1 UniProt:Q9VJJ0 CG17331 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 Reactome DB_ID: 205958 1 UniProt:Q9V5C6 Prosalpha7 Prosalpha7 CG1519 Prosalpha7 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 Reactome DB_ID: 206081 1 UniProt:Q9VM46 Sem1 Sem1 Sem1 CG13779 FUNCTION Subunit of the 26S proteasome which plays a role in ubiquitin-dependent proteolysis.SUBUNIT Part of the 26S proteasome.SIMILARITY Belongs to the DSS1/SEM1 family. UniProt Q9VM46 Reactome DB_ID: 206288 1 UniProt:Q9Y1A7 mnd mnd mnd CG3297 Dmel_CG3297 Minidiscs, isoform A Minidiscs, isoform C Minidiscs, isoform D LD25378p Minidiscs UniProt Q9Y1A7 Reactome DB_ID: 206038 1 UniProt:Q9V436 Rpn12 Rpn12 CG4157 Rpn12 Dmel_CG4157 Rpn12 26S proteasome regulatory complex subunit p30 RE36854p UniProt Q9V436 Reactome DB_ID: 206026 1 UniProt:O18413 Rpt6 Rpt6 Ug Rpt6 DUG Pros45 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 Reactome DB_ID: 206106 1 UniProt:Q9V3V6 Tbp-1 Tbp-1 Dmel_CG10370 Tbp-1 CG10370 SIMILARITY Belongs to the AAA ATPase family. UniProt Q9V3V6 Reactome DB_ID: 205893 1 UniProt:Q9V3H2 Rpn11 Rpn11 CG18174 Rpn11 yip5 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 Reactome DB_ID: 205697 1 UniProt:Q9NHX7 Prosbeta5 Prosbeta5 Prosbeta5 beta5 Pros-beta-5 CG12323 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 Q9NHX7 Reactome DB_ID: 205693 1 UniProt:Q7KMP8 Rpn9 Rpn9 Dmel_CG10230 CG10230 Rpn9 Rpn9, isoform A 26S proteasome regulatory complex subunit p39A LD17530p UniProt Q7KMP8 Reactome DB_ID: 206158 1 UniProt:Q9XYN7 Prosbeta3 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 Reactome DB_ID: 205848 1 UniProt:Q9V3G7 Rpn7 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 Reactome DB_ID: 206189 1 UniProt:Q9XZ61 Uch-L3 Uch-L3 Uch-L3 CG31639 CG3431 Dmel_CG3431 Ubiquitin C-terminal hydrolase 26S proteasome regulatory complex subunit p37A AT10619p LD24440p UniProt Q9XZ61 Reactome DB_ID: 206179 1 UniProt:P22769 Prosalpha4 Prosalpha4 CG3422 PROS-28.1 Prosalpha4 Pros28.1 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 Reactome DB_ID: 206091 1 UniProt:Q9VW54 Rpn1 Rpn1 Dmel_CG7762 Rpn1 CG7762 Rpn1 26S proteasome regulatory complex subunit p97 Putative uncharacterized protein UniProt Q9VW54 Reactome DB_ID: 206229 1 UniProt:Q9V3Z4 Rpn5 Rpn5 CG1100 Rpn5 Dmel_CG1100 SIMILARITY Contains 1 PCI domain. UniProt Q9V3Z4 Reactome DB_ID: 205708 1 UniProt:P55035 Rpn10 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 Reactome DB_ID: 206188 1 UniProt:P12881 Prosalpha6 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 Reactome DB_ID: 206278 1 UniProt:P40301 Prosalpha2 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 Reactome DB_ID: 205701 1 UniProt:P25161 Rpn3 Rpn3 Rpn3 CG42641 Dox-A2 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 Reactome DB_ID: 205939 1 UniProt:Q9U7A2 Rpt4 Rpt4 CG3455 Rpt4 SIMILARITY Belongs to the AAA ATPase family. UniProt Q9U7A2 Reactome DB_ID: 205706 1 UniProt:Q9V3P6 Rpn2 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 Reactome DB_ID: 205787 1 UniProt:Q9XZJ4 Prosalpha1 Prosalpha1 Prosalpha1 CG18495 Prosalpha6 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 Reactome DB_ID: 205898 1 UniProt:Q7KMQ0 Rpt1 Rpt1 Dmel_CG1341 CG1341 Rpt1 SIMILARITY Belongs to the AAA ATPase family. UniProt Q7KMQ0 Reactome DB_ID: 206110 1 UniProt:P48601 Rpt2 Rpt2 CG5289 Rpt2 Pros26.4 P26s4 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 Reactome Database ID Release 77 206968 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206968 Reactome R-DME-206968 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206968.1 GO 0004175 GO molecular function Reactome Database ID Release 77 208900 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=208900 Reactome Database ID Release 77 209278 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209278 Reactome R-DME-209278 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209278.3 9215627 Pubmed 1997 Proteolysis that is inhibited by hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor Aza-Blanc, P Ramirez-Weber, FA Laget, MP Schwartz, C Kornberg, Thomas B Cell 89:1043-53 10102270 Pubmed 1999 刺猬控制肢体发展通过调节the activities of distinct transcriptional activator and repressor forms of Cubitus interruptus Methot, N Basler, K Cell 96:819-31 16299518 Pubmed 2005 A conserved processing mechanism regulates the activity of transcription factors Cubitus interruptus and NF-kappaB Tian, L Holmgren, RA Matouschek, A Nat Struct Mol Biol 12:1045-53 10458606 Pubmed 1999 Nuclear trafficking of Cubitus interruptus in the transcriptional regulation of Hedgehog target gene expression Chen, CH von Kessler, DP Park, W Wang, B Ma, Y 海滩,PA Cell 98:305-16 12231619 Pubmed 2002 Degrading Ci: who is Cul-pable? Jiang, J Genes Dev 16:2315-21 Reactome Database ID Release 77 209360 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209360 Reactome R-DME-209360 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209360.2 CI75 transports from the cytosol to the nucleus CI75 transports from the cytosol to the nucleus Truncated Cubitus Interruptus (CI75) translocates from the cytosol to the nucleus. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 206171 1 Reactome DB_ID: 205741 1 nucleoplasm GO 0005654 Reactome Database ID Release 77 209370 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209370 Reactome R-DME-209370 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209370.3 CI75 inhibits transcription CI75 inhibits transcription Upon arrival in the nucleus, truncated Cubitus Interruptus (CI75) represses transcription. Sensitive target genes include hh and dpp, but not ptc and repression depends on direct DNA-binding sites for CI75. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 205741 1 Reactome DB_ID: 205741 1 Reactome Database ID Release 77 209252 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209252 Reactome R-DME-209252 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209252.3 10862738 Pubmed 2000 The repressor and activator forms of Cubitus interruptus control Hedgehog target genes through common generic gli-binding sites Müller, B Basler, K Development 127:2999-3007 Reactome Database ID Release 77 209446 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209446 Reactome R-DME-209446 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209446.2 N-HH ligand bound to PTC receptor complex N-HH ligand bound to PTC receptor complex Spatzle (SPZ) dimer binding leads to Toll (TL) receptor homodimerisation and activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2006-12-08 11:30:45 Assembly of the 'signalling complexes' Assembly of the 'signalling complexes' Spatzle (SPZ) dimer binding leads to Toll (TL) receptor homodimerisation and activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2006-12-08 11:30:45 COS binds to SMO COS binds to SMO SMO:COS:FU:CI complexes are present prior to Hedgehog signalling owing to direct binding of Smoothened (SMO) to both Coastal2 (COS) and the Ser/Thr kinase Fused (FU). Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 216188 1 COS:CI:FU [cytosol] COS:CI:FU Reactome DB_ID: 205872 1 Reactome DB_ID: 205832 1 Reactome DB_ID: 206046 1 Reactome Database ID Release 77 216188 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216188 Reactome R-DME-216188 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216188.1 Reactome DB_ID: 206086 1 UniProt:P91682 smo smo smo CG11561 功能段极性和所需的蛋白质rect patterning of every segment. G protein-coupled receptor that associates with the patched protein (ptc) to transduce the hedgehog (hh) signal through the activation of an inhibitory G-protein. In the absence of hh, ptc represses the constitutive signaling activity of smo through fused (fu). 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 cos.DEVELOPMENTAL STAGE Expressed at all developmental stages, though the levels vary.PTM Phosphorylation by CkIalpha and PKA regulates smo accumulation at the cell surface and its signaling activity in response to hh.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 G-protein coupled receptor Fz/Smo family.CAUTION It is uncertain whether Met-1, Met-9, Met-13 or Met-14 is the initiator. UniProt P91682 32 EQUAL 1036 EQUAL Reactome DB_ID: 216146 1 SMO:COS:CI:FU [plasma membrane] SMO:COS:CI:FU Reactome DB_ID: 216188 1 Reactome DB_ID: 206086 1 32 EQUAL 1036 EQUAL Reactome Database ID Release 77 216146 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216146 Reactome R-DME-216146 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216146.1 Reactome Database ID Release 77 216222 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216222 Reactome R-DME-216222 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216222.3 14614827 Pubmed 2003 Identification of a functional interaction between the transmembrane protein Smoothened and the kinesin-related protein Costal2 Ogden, SK Ascano M, Jr Stegman, MA Suber, LM Hooper, JE Robbins, DJ Curr Biol 13:1998-2003 14523402 Pubmed 2003 Stability and association of Smoothened, Costal2 and Fused with Cubitus interruptus are regulated by Hedgehog Ruel, L Rodriguez, R Gallet, A Lavenant-Staccini, L Therond, PP Nat Cell Biol 5:907-13 14597665 Pubmed 2003 Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail Jia, J Tong, C Jiang, J Genes Dev 17:2709-20 17182028 Pubmed 2007 The last 59 amino acids of Smoothened cytoplasmic tail directly bind the protein kinase Fused and negatively regulate the Hedgehog pathway Malpel, S Claret, S Sanial, M Brigui, A Piolot, T Daviet L Martin-Lannerée, S Plessis, A Dev Biol 303:121-33 N-HH binds to PTC receptor complex N-HH binds to PTC receptor complex N-HH bound to Dally-like protein (DLP) is presented to Patched (PTC) receptor and Induced Hedgehog/Brother of Induced Hedgehog (IHOG/BOI) co-receptor to form a ternary complex at the plasma membrane. N-HH binds directly to PTC. Binding is enhanced by the putative co-receptor, IHOG/BOI, which is a type I transmembrane protein that can bind N-HH directly in the presence of Heparin. Signal transduction is also enhanced by DLP, implying that heparan sulphate proteoglycan (HSPG)-associated N-HH may be the most potent form of Hedgehog. Binding of N-HH to PTC leads to PTC internalisation and lysosomal degradation, resulting in a reduction of extracellular N-HH levels and a relief of repression of Smoothened (SMO) by PTC, which depends on the opposing actions of free PTC and N-HH bound PTC. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 216284 1 N-HH:DLP [plasma membrane] N-HH:DLP Reactome DB_ID: 206027 1 UniProt:Q9GPL5 dlp dlp dlp CG32146 FUNCTION Cell surface proteoglycan that bears heparan sulfate (By similarity).SIMILARITY Belongs to the glypican family. Reactome DB_ID: 205888 1 35 EQUAL 207 EQUAL Reactome Database ID Release 77 216284 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216284 Reactome R-DME-216284 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216284.1 Reactome DB_ID: 206021 1 UniProt:P18502 ptc ptc CG2411 ptc FUNCTION Segmentation polarity protein. Acts as a receptor for the hedgehog protein (HH). Associates with the smoothened protein (SMO) to transduce the hedgehog signal leading to the activation of wingless, decapentaplegic and patched itself. Participates in cell interactions that establish pattern within the segment and the imaginal disks during development. In the absence of HH, represses the constitutive signaling activity of smo through fused (FU).SIMILARITY Belongs to the patched family. UniProt P18502 Converted from EntitySet in Reactome Reactome DB_ID: 216135 1 IHOG/BOI dimer [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome DB_ID: 216226 1 N-HH:DLP:IHOG/BOI dimer:PTC [plasma membrane] N-HH:DLP:IHOG/BOI dimer:PTC Reactome DB_ID: 206021 1 Reactome DB_ID: 206027 1 Reactome DB_ID: 205888 1 35 EQUAL 207 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 216135 1 Reactome Database ID Release 77 216226 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216226 Reactome R-DME-216226 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216226.1 Reactome Database ID Release 77 209178 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209178 Reactome R-DME-209178 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209178.3 15300262 Pubmed 2004 Reading the Hedgehog morphogen gradient by measuring the ratio of bound to unbound Patched protein Casali, A Struhl, G Nature 431:76-80 16041759 Pubmed 2005 Mechanisms of Hedgehog gradient formation and interpretation Torroja, C Gorfinkiel, N Guerrero, I J Neurobiol 64:334-56 8906787 Pubmed 1996 The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog Stone, DM Hynes, M Armanini, M Swanson, TA Gu, Q Johnson, RL Scott, MP Pennica, D Goddard, A Phillips, H Noll, M Hooper, JE de Sauvage, F Rosenthal, A 自然384:129-34 17077139 Pubmed 2006 Structure of a heparin-dependent complex of Hedgehog and Ihog McLellan, JS Yao, S Zheng, X Geisbrecht, BV Ghirlando, R 海滩,PA Leahy, DJ Proc Natl Acad Sci U S A 103:17208-13 8898207 Pubmed 1996 Dual roles for patched in sequestering and transducing Hedgehog Chen, Y Struhl, G Cell 87:553-63 8906794 Pubmed 1996 Biochemical evidence that patched is the Hedgehog receptor Marigo, V Davey, RA Zuo, Y Cunningham, JM Tabin, CJ Nature 384:176-9 12663920 Pubmed 2003 Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells Lum, L Yao, S Mozer, B Rovescalli, A Von Kessler, D Nirenberg, M 海滩,PA Science 299:2039-45 16630821 Pubmed 2006 The ihog cell-surface proteins bind Hedgehog and mediate pathway activation Yao, S Lum, L 海滩,P Cell 125:343-57 Reactome Database ID Release 77 209338 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209338 Reactome R-DME-209338 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209338.2 Activation of SMO Activation of SMO Spatzle (SPZ) dimer binding leads to Toll (TL) receptor homodimerisation and activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2008-03-11 15:41:17 Phosphorylation of SMO Phosphorylation of SMO Spatzle (SPZ) dimer binding leads to Toll (TL) receptor homodimerisation and activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2006-12-08 11:30:45 2.7.11 Phosphorylation of SMO by PKA-C1 Phosphorylation of SMO by PKA-C1 The Ser/Thr kinase, Protein kinase A (PKA-C1) carries out priming phosphorylation of the transmembrane protein Smoothened (SMO) at Ser667, Ser687, and Ser740. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 216146 1 Reactome DB_ID: 113592 3 Reactome DB_ID: 216105 1 Phospho (3 sites) SMO:COS:CI:FU [plasma membrane] Phospho (3 sites) SMO:COS:CI:FU Reactome DB_ID: 216188 1 Reactome DB_ID: 206009 1 O-phospho-L-serine at 667 667 EQUAL O-phospho-L-serine at 687 687 EQUAL O-phospho-L-serine at 740 740 EQUAL 32 EQUAL 1036 EQUAL Reactome Database ID Release 77 216105 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216105 Reactome R-DME-216105 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216105.1 Reactome DB_ID: 29370 3 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 206865 Reactome Database ID Release 77 209341 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209341 Reactome R-DME-209341 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209341.3 15592457 Pubmed 2005 Drosophila Smoothened phosphorylation sites essential for Hedgehog signal transduction Apionishev, S Katanayeva, NM Marks, SA Kalderon, D Tomlinson, A Nat Cell Biol 7:86-92 15598741 Pubmed 2004 Extensive phosphorylation of Smoothened in Hedgehog pathway activation Zhang, C Williams, EH Guo, Y Lum, L 海滩,PA Proc Natl Acad Sci U S A 101:17900-7 15616566 Pubmed 2004 Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I Jia, J Tong, C Wang, B Luo, L Jiang, J Nature 432:1045-50 2.7.11 Phosphorylation of SMO by CKIalpha Phosphorylation of SMO by CKIalpha Priming phosphorylation of the transmembrane protein Smoothened (SMO) leads to additional phosphorylation by Casein kinase I alpha (CKIalpha) at Ser670, Ser673, Ser690, Ser693, Ser743, and Ser746. Even though SMO has been shown to be explicitly phosphorylated by CKIalpha, phosphorylation of these residues by other CK1 isoforms cannot be ruled out. In addition, other residues are probably phosphorylated by unidentified kinases. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 216105 1 Reactome DB_ID: 113592 6 Reactome DB_ID: 206727 1 Phospho (9 sites) SMO:COS:CI:FU [plasma membrane] Phospho (9 sites) SMO:COS:CI:FU Reactome DB_ID: 205802 1 O-phospho-L-serine at 667 667 EQUAL O-phospho-L-serine at 687 687 EQUAL O-phospho-L-serine at 740 740 EQUAL O-phospho-L-serine at 670 670 EQUAL O-phospho-L-serine at 673 673 EQUAL O-phospho-L-serine at 690 690 EQUAL O-phospho-L-serine at 693 693 EQUAL O-phospho-L-serine at 743 743 EQUAL O-phospho-L-serine at 746 746 EQUAL 32 EQUAL 1036 EQUAL Reactome DB_ID: 216188 1 Reactome Database ID Release 77 206727 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206727 Reactome R-DME-206727 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206727.1 Reactome DB_ID: 29370 6 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 206666 ARM:Phospho (3 sites) AXN:Phospho (6 sites) APC:PP2A:CKIalpha:DCO:SGG [cytosol] ARM:Phospho (3 sites) AXN:Phospho (6 sites) APC:PP2A:CKIalpha:DCO:SGG Reactome DB_ID: 205729 1 Reactome DB_ID: 206938 1 Reactome DB_ID: 206210 1 Reactome DB_ID: 205716 1 Converted from EntitySet in Reactome Reactome DB_ID: 206566 1 Reactome DB_ID: 205774 1 Reactome DB_ID: 206169 1 O-phospho-L-serine at 529 529 EQUAL O-phospho-L-threonine at 517 517 EQUAL O-phospho-L-serine at 522 522 EQUAL Reactome Database ID Release 77 206666 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206666 Reactome R-DME-206666 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206666.1 Reactome Database ID Release 77 208918 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=208918 Reactome Database ID Release 77 209168 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209168 Reactome R-DME-209168 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209168.3 Reactome Database ID Release 77 209214 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209214 Reactome R-DME-209214 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209214.2 Phosphorylated SMO changes conformation and is activated Phosphorylated SMO changes conformation and is activated The Smoothened (SMO) large terminal cytoplasmic domain changes conformation in response to phosphorylation and becomes active. The localisation of SMO and its partners shifts from internal vesicles towards the plasma membrane. SMO stability increases results in the SMO:COS:FU:CI complexes at the plasma membrane becoming more abundant.

Activation of SMO leads to reduced association of the Ser/Thr protein kinases: Protein kinase A (PKA-C1), Shaggy (SGG), Casein kinase 1 alpha (CKIalpha), and Casein kinase I epsilon (DCO) with Costal2 (COS). This leads to a reduced phosphorylation of Cubitus Interruptus (CI) and inhibition of CI proteolysis and processing. This increases full-length CI protein levels. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 206727 1 Reactome DB_ID: 216158 1 Phospho (9 sites) Act SMO:COS:CI:FU [plasma membrane] Phospho (9 sites) Act SMO:COS:CI:FU Reactome DB_ID: 205802 1 O-phospho-L-serine at 667 667 EQUAL O-phospho-L-serine at 687 687 EQUAL O-phospho-L-serine at 740 740 EQUAL O-phospho-L-serine at 670 670 EQUAL O-phospho-L-serine at 673 673 EQUAL O-phospho-L-serine at 690 690 EQUAL O-phospho-L-serine at 693 693 EQUAL O-phospho-L-serine at 743 743 EQUAL O-phospho-L-serine at 746 746 EQUAL 32 EQUAL 1036 EQUAL Reactome DB_ID: 216188 1 Reactome Database ID Release 77 216158 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216158 Reactome R-DME-216158 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216158.1 Reactome Database ID Release 77 216202 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216202 Reactome R-DME-216202 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216202.3 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 17960137 Pubmed 2007 Hedgehog regulates smoothened activity by inducing a conformational switch Zhao, Y Tong, C Jiang, J 自然450:252-8 2.7.11 Autophosphorylated FU phosphorylates COS Autophosphorylated FU phosphorylates COS The Ser/Thr protein kinase, Fused (FU), is capable of autophosphorylation and is proposed to be activated by phosphorylation on at least Thr158 and probably on other residues too. Costal2 (COS), bound to the phosphorylated transmembrane receptor Smoothened (SMO), is itself phosphorylated by FU at Ser572 and Ser931. Both FU and COS promote phosphorylation of SMO and its accumulation at the plasma membrane resulting in a positive feedback loop. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 216158 1 Reactome DB_ID: 113592 3 Reactome DB_ID: 206734 1 Phospho (9 sites) Act SMO:Phospho (2 sites) COS:CI:Phospho FU [plasma membrane] Phospho (9 sites) Act SMO:Phospho (2 sites) COS:CI:Phospho FU Reactome DB_ID: 205802 1 O-phospho-L-serine at 667 667 EQUAL O-phospho-L-serine at 687 687 EQUAL O-phospho-L-serine at 740 740 EQUAL O-phospho-L-serine at 670 670 EQUAL O-phospho-L-serine at 673 673 EQUAL O-phospho-L-serine at 690 690 EQUAL O-phospho-L-serine at 693 693 EQUAL O-phospho-L-serine at 743 743 EQUAL O-phospho-L-serine at 746 746 EQUAL 32 EQUAL 1036 EQUAL Reactome DB_ID: 206809 1 Phospho (2 sites) COS:CI:Phospho FU [cytosol] Phospho (2 sites) COS:CI:Phospho FU Reactome DB_ID: 206282 1 O-phospho-L-serine at 572 572 EQUAL O-phospho-L-serine at 931 931 EQUAL Reactome DB_ID: 206046 1 Reactome DB_ID: 205779 1 O-phospho-L-threonine at 158 158 EQUAL Reactome Database ID Release 77 206809 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206809 Reactome R-DME-206809 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206809.1 Reactome Database ID Release 77 206734 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206734 Reactome R-DME-206734 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206734.1 Reactome DB_ID: 29370 3 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 205872 Reactome Database ID Release 77 208942 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=208942 Reactome Database ID Release 77 209253 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209253 Reactome R-DME-209253 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209253.3 11934882 Pubmed 2002 Hedgehog-stimulated phosphorylation of the kinesin-related protein Costal2 is mediated by the serine/threonine kinase fused Nybakken, KE Turck, CW Robbins, DJ Bishop, JM J Biol Chem 277:24638-47 17671093 Pubmed 2007 Fused-Costal2 protein complex regulates Hedgehog-induced Smo phosphorylation and cell-surface accumulation Liu, Y Cao, X Jiang, J Jia, J Genes Dev 21:1949-63 18211840 Pubmed 2008 Hedgehog signaling: a smoothened conformational switch Kalderon, D Curr Biol 18:R64-6 17881487 Pubmed 2007 Phosphorylation of the atypical kinesin Costal2 by the kinase Fused induces the partial disassembly of the Smoothened-Fused-Costal2-Cubitus interruptus complex in Hedgehog signalling Ruel, L Gallet, A Raisin, S Truchi, A Staccini-Lavenant, L Cervantes, A Therond, PP Development 134:3677-89 11495917 Pubmed 2001 The fused protein kinase regulates Hedgehog-stimulated transcriptional activation in Drosophila Schneider 2 cells Fukumoto, T Watanabe-Fukunaga, R Fujisawa, K Nagata, S Fukunaga, R J Biol Chem 276:38441-8 Reactome Database ID Release 77 216217 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216217 Reactome R-DME-216217 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216217.2 Activation of CI Activation of CI Spatzle (SPZ) dimer binding leads to Toll (TL) receptor homodimerisation and activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2008-03-11 15:41:17 Dissociation of CI from COS Dissociation of CI from COS Coastal2 (COS) phosphorylated on Ser572 has reduced affinity for Cubitus Interruptus (CI). This may contribute to partial dissociation of CI from COS complexes. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 206734 1 Reactome DB_ID: 206634 1 Phospho (9 sites) Act SMO:Phospho (2 sites) COS:Phospho FU [plasma membrane] Phospho (9 sites) Act SMO:Phospho (2 sites) COS:Phospho FU Reactome DB_ID: 205802 1 O-phospho-L-serine at 667 667 EQUAL O-phospho-L-serine at 687 687 EQUAL O-phospho-L-serine at 740 740 EQUAL O-phospho-L-serine at 670 670 EQUAL O-phospho-L-serine at 673 673 EQUAL O-phospho-L-serine at 690 690 EQUAL O-phospho-L-serine at 693 693 EQUAL O-phospho-L-serine at 743 743 EQUAL O-phospho-L-serine at 746 746 EQUAL 32 EQUAL 1036 EQUAL Reactome DB_ID: 206977 1 Phospho (2 sites) COS:Phospho FU [cytosol] Phospho (2 sites) COS:Phospho FU Reactome DB_ID: 206282 1 O-phospho-L-serine at 572 572 EQUAL O-phospho-L-serine at 931 931 EQUAL Reactome DB_ID: 205779 1 O-phospho-L-threonine at 158 158 EQUAL Reactome Database ID Release 77 206977 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206977 Reactome R-DME-206977 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206977.1 Reactome Database ID Release 77 206634 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=206634 Reactome R-DME-206634 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-206634.1 Reactome DB_ID: 206046 1 Reactome Database ID Release 77 216133 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216133 Reactome R-DME-216133 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216133.3 2.7.11 Liberation of CI from SU(FU) repression Liberation of CI from SU(FU) repression Cubitus Interruptus (CI) that is spared from proteolysis is liberated from the repressive effects of its direct binding partner, Supressor of Fused (SU(FU)), by Fused (FU) Ser/Thr kinase activity. FU is believed to phosphorylate SU(FU) but it is not known if this relieves repression. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 113592 1 Reactome DB_ID: 206802 1 Reactome DB_ID: 206634 1 Reactome DB_ID: 205950 1 phosphorylated residue at unknown position phosphorylated residue [MOD:00696] Reactome DB_ID: 206634 1 Reactome DB_ID: 29370 1 Reactome DB_ID: 206046 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 205872 Reactome Database ID Release 77 209220 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209220 Reactome R-DME-209220 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209220.3 15750186 Pubmed 2005 Differential regulation of Hedgehog target gene transcription by Costal2 and Suppressor of Fused Ho, KS Suyama, K Fish, M Scott, MP Development 132:1401-12 CI transports from the cytosol to the nucleus CI transports from the cytosol to the nucleus Cubitus Interruptus (CI) access to the nucleus increases in response to Hedgehog signalling, most likely due to reduced cytoplasmic tethering by both Coastal2 (COS) and Suppressor of Fused (SU(FU)) complexes. However, the vast majority of CI is cytoplasmic. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 206046 1 Reactome DB_ID: 205911 1 Reactome Database ID Release 77 209163 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209163 Reactome R-DME-209163 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209163.3 10862750 Pubmed 2000 Nuclear import of cubitus interruptus is regulated by hedgehog via a mechanism distinct from Ci stabilization and Ci activation Wang, QT Holmgren, RA Development 127:3131-9 10952898 Pubmed 2000 Suppressor of fused opposes hedgehog signal transduction by impeding nuclear accumulation of the activator form of Cubitus interruptus Methot, N Basler, K Development 127:4001-10 10529426 Pubmed 1999 The subcellular localization and activity of Drosophila cubitus interruptus are regulated at multiple levels Wang, QT Holmgren, RA Development 126:5097-106 CI activates transcription CI activates transcription Cubitus Interruptus (CI) activates transcription of ptc and several tissue-specific target genes that include direct CI binding sites in their regulatory sequences. CREB binding protein, CBP (NEJ) co-activator contributes to transcriptional activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 205911 1 Reactome DB_ID: 205911 1 Reactome Database ID Release 77 209215 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209215 Reactome R-DME-209215 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209215.3 9109493 Pubmed 1997 Drosophila CBP is a co-activator of cubitus interruptus in hedgehog signalling Akimaru, H Chen, Y Dai, P Hou, DX Nonaka, M Smolik, SM Armstrong, S Goodman, RH Ishii, S Nature 386:735-8 9122207 Pubmed 1997 Hedgehog signaling regulates transcription through cubitus interruptus, a sequence-specific DNA binding protein Von Ohlen, T Lessing, D Nusse, Roel Hooper, JE Proc Natl Acad Sci U S A 94:2404-9 9431812 Pubmed 1997 Hedgehog signaling regulates transcription through Gli/Ci binding sites in the wingless enhancer Von Ohlen, T Hooper, JE Mech Dev 68:149-56 8769644 Pubmed 1996 Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins Alexandre, C Jacinto, A Ingham, PW Genes Dev 10:2003-13 11997517 Pubmed 2002 The acetyltransferase activity of CBP is required for wingless activation and H4 acetylation in Drosophila melanogaster Ludlam, WH 泰勒,MH Tanner, KG Denu, JM Goodman, RH Smolik, SM Mol Cell Biol 22:3832-41 Reactome Database ID Release 77 216119 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216119 Reactome R-DME-216119 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216119.2 Nuclear CI is degraded Nuclear CI is degraded Spatzle (SPZ) dimer binding leads to Toll (TL) receptor homodimerisation and activation. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2008-03-11 15:41:17 6.3.2.19 RDX binds to and ubiquitinates CI RDX binds to and ubiquitinates CI HIB or Roadkill (RDX) is transcriptionally induced by Hedgehog signalling and binds directly to Cubitus Interruptus (CI), likely in competition with Supressor of Fused (SU(FU)), to link CI with a Cul3 aka guftagu (GFT)-based E3 ubiquitin ligase complex, leading to degradation of active nuclear CI. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 216104 1 RDX:GFT:ROC1B [nucleoplasm] RDX:GFT:ROC1B Reactome DB_ID: 216275 1 UniProt:Q9VFP2 rdx rdx HIB rdx CG12537 FUNCTION Involved in segment polarity. In complex with gft/CUL3, promotes ubiquitination of ci and its subsequent degradation by the proteasome, which results in hh signaling attenuation. This regulation may be important during eye formation for proper packing of ommatidia into a hexagonal array.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Interacts with ci and gft/CUL3.TISSUE SPECIFICITY Expressed near the anterio-posterior compartment boundary of antenna, leg and wing disks.DEVELOPMENTAL STAGE Expressed maternally in stage 1 embryos. Isoform 1 and isoform 4 are expressed zygotically in stage 4 in pole cells. By stage 8, expressed in 14 segmentally repeating stripes. During stage 9 and 10, expression appears in neuroblasts. After stage 14, expression is restricted to clypeolabrum, anal plate and salivary glands.INDUCTION By hh during segmentation.DOMAIN The MATH domain interacts with ci.DOMAIN The BTB (POZ) domain interacts with gft/CUL3.SIMILARITY Belongs to the Tdpoz family. UniProt Q9VFP2 Reactome DB_ID: 216234 1 UniProt:Q9V475 gft gft gft Dmel_CG11861 CG11861 SIMILARITY Belongs to the cullin family. UniProt Q9V475 Reactome DB_ID: 216255 1 UniProt:Q9NHX0 Roc1b Roc1b Roc1b CG16988 ROC2 自洽场的功能组件(SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Through the RING-type zinc finger, seems to recruit the E2 ubiquitination enzyme to the complex and brings it into close proximity to the substrate (By similarity).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Part of a SCF complex consisting of Skpa (SKP1), Cul1, Roc1B and a F-box protein.TISSUE SPECIFICITY Highly expressed in early embryos, and in pupae. Widely expressed in adult males, while it is weakly expressed in adult females.DOMAIN The RING-type zinc finger domain is essential for ubiquitin ligase activity. It coordinates an additional third zinc ion (By similarity).SIMILARITY Belongs to the RING-box family.CAUTION It is uncertain whether Met-1 or Met-16 is the initiator. UniProt Q9NHX0 Reactome Database ID Release 77 216104 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216104 Reactome R-DME-216104 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216104.1 Converted from EntitySet in Reactome Reactome DB_ID: 216110 1 UBI-P63E [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity UBI-P63E 6 [nucleoplasm] UBI-P63E 9 [nucleoplasm] UBI-P63E 3 [nucleoplasm] UBI-P63E 4 [nucleoplasm] UBI-P63E 5 [nucleoplasm] UBI-P63E 1 [nucleoplasm] UBI-P63E 2 [nucleoplasm] UBI-P63E 10 [nucleoplasm] UBI-P63E 11 [nucleoplasm] UBI-P63E 8 [nucleoplasm] UBI-P63E 7 [nucleoplasm] Reactome DB_ID: 205911 1 Reactome DB_ID: 216204 1 RDX:GFT:ROC1B:CI:UBI-P63E [nucleoplasm] RDX:GFT:ROC1B:CI:UBI-P63E Reactome DB_ID: 216275 1 Reactome DB_ID: 216234 1 Converted from EntitySet in Reactome Reactome DB_ID: 216110 1 Reactome DB_ID: 216255 1 Reactome DB_ID: 205911 1 Reactome Database ID Release 77 216204 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216204 Reactome R-DME-216204 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216204.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 216104 Reactome Database ID Release 77 216164 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216164 Reactome Database ID Release 77 216283 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216283 Reactome R-DME-216283 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216283.3 15331761 Pubmed 2004 Targeted disruption of Drosophila Roc1b reveals functional differences in the Roc subunit of Cullin-dependent E3 ubiquitin ligases Donaldson, TD Noureddine, MA Reynolds, PJ Bradford, W Duronio, RJ Mol Biol Cell 15:4892-903 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 17102630 Pubmed 2006 Regulation of Hh/Gli signaling by dual ubiquitin pathways Jiang, J Cell Cycle 5:2457-63 16651542 Pubmed 2006 Roadkill attenuates Hedgehog responses through degradation of Cubitus interruptus Kent, D Bush, EW Hooper, JE Development 133:2001-10 Ubiquitinated CI is degraded by the proteasome complex Ubiquitinated CI is degraded by the proteasome complex The ubiquitinated Cubitus Interruptus (CI) is marked for degradation in the nucleus by the 26S proteasome complex. Authored: Williams, MG, 2006-12-07 16:49:12 Reviewed: Kalderon, D, 2008-03-17 11:00:25 Edited: Williams, MG, 2014-05-20 Reactome DB_ID: 216204 1 Reactome DB_ID: 216104 1 Converted from EntitySet in Reactome Reactome DB_ID: 216110 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 216160 26S proteasome [nucleoplasm] 26S proteasome Reactome DB_ID: 216176 1 Reactome DB_ID: 216163 1 Reactome DB_ID: 216224 1 Reactome DB_ID: 216267 1 Reactome DB_ID: 216289 1 Reactome DB_ID: 216264 1 Reactome DB_ID: 216212 1 Reactome DB_ID: 216200 1 Reactome DB_ID: 216274 1 Reactome DB_ID: 216153 1 Reactome DB_ID: 216172 1 Reactome DB_ID: 216223 1 Reactome DB_ID: 216106 1 Reactome DB_ID: 216125 1 Reactome DB_ID: 216278 1 Reactome DB_ID: 216242 1 Reactome DB_ID: 216210 1 Reactome DB_ID: 216225 1 Reactome DB_ID: 216177 1 Reactome DB_ID: 216279 1 Reactome DB_ID: 216186 1 Reactome DB_ID: 216161 1 Reactome DB_ID: 216113 1 Reactome DB_ID: 216230 1 Reactome DB_ID: 216268 1 Reactome DB_ID: 216237 1 Reactome DB_ID: 216236 1 Reactome DB_ID: 216244 1 Reactome DB_ID: 216138 1 Reactome DB_ID: 216143 1 Reactome DB_ID: 216196 1 Reactome DB_ID: 216129 1 Reactome DB_ID: 216166 1 Reactome DB_ID: 216116 1 Reactome Database ID Release 77 216160 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216160 Reactome R-DME-216160 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216160.1 Reactome Database ID Release 77 216287 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216287 Reactome Database ID Release 77 216282 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216282 Reactome R-DME-216282 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216282.3 Reactome Database ID Release 77 216167 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=216167 Reactome R-DME-216167 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-216167.2 Reactome Database ID Release 77 209452 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209452 Reactome R-DME-209452 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209452.2 Reactome Database ID Release 77 209392 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=209392 Reactome R-DME-209392 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-209392.1 16596340 Pubmed 2006 Decoding the Hedgehog signal in animal development Jia, J Jiang, J Cell Mol Life Sci 63:1249-65 15803137 Pubmed 2005 Communicating with Hedgehogs Hooper, JE Scott, MP Nat Rev Mol Cell Biol 6:306-17 15104233 Pubmed 2004 Regulation of Hedgehog signaling: a complex story Ogden, SK Ascano M, Jr Stegman, MA Robbins, DJ Biochem Pharmacol 67:805-14 15205520 Pubmed 2004 The Hedgehog response network: sensors, switches, and routers Lum, L 海滩,PA Science 304:1755-9 16339192 Pubmed 2006 Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates Huangfu, D Anderson, KV Development 133:3-14 16246157 Pubmed 2005 The mechanism of hedgehog signal transduction Kalderon, D Biochem Soc Trans 33:1509-12 12200154 Pubmed 2002 Hedgehog signal transduction: recent findings Nybakken, K Perrimon, N Curr Opin Genet Dev 12:503-11 GO 0007224 GO biological process