Hedgehog 'off' state (Homo sapiens)

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43, 66, 68, 8779, 8017, 19, 26, 35, 551, 3-5, 7...52, 74, 816, 10, 47, 48, 60...22, 5516, 38, 42, 64, 73...17, 26, 35, 6548, 66, 8016, 29, 78, 90, 912287, 9352, 8122, 26, 35, 55, 6553, 78, 9079, 8026, 352, 8, 9, 11, 12, 14...26, 3522, 55, 706, 10, 47, 60, 7948, 66, 802252, 8122, 5526, 55, 70, 7452, 74, 8115, 18, 23, 30, 34...749, 20, 27, 31, 32, 36...16, 53, 78, 902, 8, 9, 11, 12, 14...cytosolnucleoplasmendocytic vesicle lumenciliumOFD1 UBC(381-456) ADCY8 ITCH ITCH PSME4 PSMB1 PSMD11 PSMD1 CUL1 PRKACG SUFU ATPPPiBTRC GPR161 PSMD12 UBB(77-152) ADCY7 PSMD3 IFT-A complexUBC(533-608) IFT140 PSMA7 GLI2 PSMC4 PTCH1 gene PSMD8 UBB(153-228) PSMA5 UBC(153-228) ADCY6 microtubuleITCHPSMB10 GLI:SUFUPSMD11 p10S-GLI3:SUFUNUMB:ITCH:ub-pS-GLI1:SUFUIFT57 pS-GLI1:SUFUGLI1,2,3PSMB10 PRKACA Mg2+ GLI3 IFT172 PSMA4 TTC21B UBC(305-380) PSMD6 GLI2 genePSMD9 SMO dimerSHFM1 GNAS2 PSMD5 PSMB6 UBC(609-684) FUZ RPS27A(1-76) SUFU UBC(305-380) UBA52(1-76) PSMF1 PSMD7 CSNK1A1UBC(533-608) PSMD10 PSMA7 PRKAR1B UBC(533-608) PSMD14 GLI1 gene 26S proteasomeUBC(609-684) UBC(1-76) SMO PSMB1 NUMB PSMB7 ADCY2 PSMC4 UBC(381-456) GLI3R PSMC6 PSMB8 microtubule UBC(457-532) 26S proteasomecAMP GLI2 UBB(77-152) INTU SUFU UBC(609-684) p11S-GLI2 ciliary basal bodyregulators of Hhub-pS-GLI1 GSK3BPSME3 NUMB p13S-GLI3 GLI1 PRKAR2B PRKACG IFT122 GLI3RGLI3 BTRC p11S-GLI2:SUFUIFT88 PSMD5 PSMD14 UBC(457-532) IFT52 TULP3 ub-p13S-GLI3 PSMD2 IFT122 PSME2 NUMBPKA tetramerGLI3 WDR35 PSMC5 GLI2:SUFUub-pS-GLI1 UBB(1-76) GPR161UBC(457-532) UBC(1-76) ADPPSMA3 ADCY3 PSMA4 GLI1SKP1 PSME3 ADCY9 PSMF1 SUFU GLI3:SUFUGLI2 PSMB5 GLI3RSUFU PSMD13 UbPSMC2 PSMA2 IFT140 ADCY10 SUFU PSMC5 GLI2 PSMC1 PCP regulators of HhCUL1 PSMA1 PSMA8 GLI1 TULP3 KIF7 p4S-GLI2:SUFUPSME2 ADCY5 PSMB4 UBC(77-152) SUFU PRKAR1B SUFU PTCH1 geneGLI3R ub-p11S-GLI2 PSMA5 anterograde IFTregulators of HhGLI1 gene:GLI3RGLI1 SUFUPSMD13 WDR19 UBC(229-304) UBC(77-152) PSMB9 retrograde IFTregulators of HhADCY1 GLI3R UbTTC21B WDR35 UBB(153-228) SMO PSMB3 MKS1 GLI1 RPS27A(1-76) RBX1 PSMB8 4xub-p13S-Gli3:SUFUPSMC1 GLI2 GPR161:IFT-A:TULP3UBB(1-76) PSMD10 ADPp6S-GLI3 IFT122 cAMPBTRC:CUL1:RBX1:SKP1WDR35 GLI:SUFUWDR19 KIF3A UBC(381-456) p6S-GLI3:SUFUp8S-GLI2 PRKAR1A UBC(305-380) UBC(77-152) PKA regulatorysubunits:cAMPATPPRKAR2A PRKAR2B IFT-A complex:TULP3UBB(77-152) GLI3 ub-p11S-GLI2:SUFUPSMC2 UBC(229-304) p10S-GLI3 TTC21B pS-GLI1 PSMD6 ADCY4 PSMD12 PSMB11 ub-pS-GLI1:SUFUSUFU RBX1 ADPPSMD3 p8S-GLI2:SUFUATPSUFU DYNC2H1 UbPSME1 SKP1 PRKAR2A PSMB11 GLI3 PTCH1PSMA2 IFT140 BTRC:CUL1:RBX1:SKP1PSMB2 SUFU PSMD1 PSMB7 SUFU PSMB6 TTC21B G alpha (s):GTPSUFU ATPATPp4S-GLI2 UBC(1-76) ADPTULP3IFT122 PSMD7 NUMB:ITCHGLI2GLI2 gene:GLI3RATPUBA52(1-76) PSMA1 GLI:SUFUPSMB3 UBC(153-228) PSMC3 PTCH1 gene:GLI3RWDR19 PSMD2 PSMD9 PSMB9 PSMA6 PSMA8 KIF7UBA52(1-76) PKA catalyticsubunitUBB(153-228) GTP PSMB4 PRKAR1A UBB(1-76) ADPGLI2 gene SHFM1 PSMB2 ATPGLI1 SMO dimerSUFU GLI1 genePSME4 PSMD4 PSMC3 PRKACB UBC(153-228) KIF7:microtubuleRPS27A(1-76) ATPSUFU PSMD4 PSMA3 adenylatecyclases:Mg2+SUFU PSMB5 PSMC6 p13S-GLI3:SUFUPSMA6 ADPPSME1 UBC(229-304) GLI1:SUFUPRKACB PRKACA ADPGNAS1 RPGRIP1L PSMD8 SUFU 21, 244510, 4726, 35802126, 3526, 3526, 35162126, 3521, 241680


Description

Hedgehog is a secreted morphogen that has evolutionarily conserved roles in body organization by regulating the activity of the Ci/Gli transcription factor family. In Drosophila in the absence of Hh signaling, full-length Ci is partially degraded by the proteasome to generate a truncated repressor form that translocates to the nucleus to represses Hh-responsive genes. Binding of Hh ligand to the Patched (PTC) receptor allows the 7-pass transmembrane protein Smoothened (SMO) to be activated in an unknown manner, disrupting the partial proteolysis of Ci and allowing the full length activator form to accumulate (reviewed in Ingham et al, 2011; Briscoe and Therond, 2013).
While many of the core components of Hh signaling are conserved from flies to humans, the pathways do show points of significant divergence. Notably, the human genome encodes three Ci homologues, GLI1, 2 and 3 that each play slightly different roles in regulating Hh responsive genes. GLI3 is the primary repressor of Hh signaling in vertebrates, and is converted to the truncated GLI3R repressor form in the absence of Hh. GLI2 is a potent activator of transcription in the presence of Hh but contributes only minimally to the repression function. While a minor fraction of GLI2 protein is processed into the repressor form in the absence of Hh, the majority is either fully degraded by the proteasome or sequestered in the full-length form in the cytosol by protein-protein interactions. GLI1 lacks the repression domain and appears to be an obligate transcriptional activator (reviewed in Briscoe and Therond, 2013).
Vertebrate but not fly Hh signaling also depends on the movement of pathway components through the primary cilium. The primary cilium is a non-motile microtubule based structure whose construction and maintenance depends on intraflagellar transport (IFT). Anterograde IFT moves molecules from the ciliary base along the axoneme to the ciliary tip in a manner that requires the microtubule-plus-end directed kinesin KIF3 motor complex and the IFT-B protein complex, while retrograde IFT back to the ciliary base depends on the minus-end directed dynein motor and the IFT-A complex. Genetic screens have identified a number of cilia-related proteins that are required both to maintain Hh in the 'off' state and to transduce the signal when the pathway is activated (reviewed in Hui and Angers, 2011; Goetz and Anderson, 2010). View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 5610787
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: Rothfels, Karen

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Bibliography

View all...
  1. Dunaeva M, Michelson P, Kogerman P, Toftgard R.; ''Characterization of the physical interaction of Gli proteins with SUFU proteins.''; PubMed Europe PMC
  2. Zeng H, Hoover AN, Liu A.; ''PCP effector gene Inturned is an important regulator of cilia formation and embryonic development in mammals.''; PubMed Europe PMC
  3. Humke EW, Dorn KV, Milenkovic L, Scott MP, Rohatgi R.; ''The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins.''; PubMed Europe PMC
  4. Kise Y, Morinaka A, Teglund S, Miki H.; ''Sufu recruits GSK3beta for efficient processing of Gli3.''; PubMed Europe PMC
  5. Paces-Fessy M, Boucher D, Petit E, Paute-Briand S, Blanchet-Tournier MF.; ''The negative regulator of Gli, Suppressor of fused (Sufu), interacts with SAP18, Galectin3 and other nuclear proteins.''; PubMed Europe PMC
  6. Lee EY, Ji H, Ouyang Z, Zhou B, Ma W, Vokes SA, McMahon AP, Wong WH, Scott MP.; ''Hedgehog pathway-regulated gene networks in cerebellum development and tumorigenesis.''; PubMed Europe PMC
  7. Svärd J, Heby-Henricson K, Persson-Lek M, Rozell B, Lauth M, Bergström A, Ericson J, Toftgård R, Teglund S.; ''Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway.''; PubMed Europe PMC
  8. Huangfu D, Anderson KV.; ''Cilia and Hedgehog responsiveness in the mouse.''; PubMed Europe PMC
  9. Haycraft CJ, Banizs B, Aydin-Son Y, Zhang Q, Michaud EJ, Yoder BK.; ''Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function.''; PubMed Europe PMC
  10. Agren M, Kogerman P, Kleman MI, Wessling M, Toftgård R.; ''Expression of the PTCH1 tumor suppressor gene is regulated by alternative promoters and a single functional Gli-binding site.''; PubMed Europe PMC
  11. Houde C, Dickinson RJ, Houtzager VM, Cullum R, Montpetit R, Metzler M, Simpson EM, Roy S, Hayden MR, Hoodless PA, Nicholson DW.; ''Hippi is essential for node cilia assembly and Sonic hedgehog signaling.''; PubMed Europe PMC
  12. Vierkotten J, Dildrop R, Peters T, Wang B, Rüther U.; ''Ftm is a novel basal body protein of cilia involved in Shh signalling.''; PubMed Europe PMC
  13. Monnier V, Dussillol F, Alves G, Lamour-Isnard C, Plessis A.; ''Suppressor of fused links fused and Cubitus interruptus on the hedgehog signalling pathway.''; PubMed Europe PMC
  14. Ferrante MI, Zullo A, Barra A, Bimonte S, Messaddeq N, Studer M, Dollé P, Franco B.; ''Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification.''; PubMed Europe PMC
  15. Huangfu D, Anderson KV.; ''Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates.''; PubMed Europe PMC
  16. Mukhopadhyay S, Wen X, Chih B, Nelson CD, Lane WS, Scales SJ, Jackson PK.; ''TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia.''; PubMed Europe PMC
  17. Schrader EK, Harstad KG, Holmgren RA, Matouschek A.; ''A three-part signal governs differential processing of Gli1 and Gli3 proteins by the proteasome.''; PubMed Europe PMC
  18. Yue S, Tang LY, Tang Y, Tang Y, Shen QH, Ding J, Chen Y, Zhang Z, Yu TT, Zhang YE, Cheng SY.; ''Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception.''; PubMed Europe PMC
  19. Wang B, Fallon JF, Beachy PA.; ''Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb.''; PubMed Europe PMC
  20. Liem KF, He M, Ocbina PJ, Anderson KV.; ''Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling.''; PubMed Europe PMC
  21. Wei SJ, Williams JG, Dang H, Darden TA, Betz BL, Humble MM, Chang FM, Trempus CS, Johnson K, Cannon RE, Tennant RW.; ''Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation.''; PubMed Europe PMC
  22. Pan Y, Bai CB, Joyner AL, Wang B.; ''Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation.''; PubMed Europe PMC
  23. Tuson M, He M, Anderson KV.; ''Protein kinase A acts at the basal body of the primary cilium to prevent Gli2 activation and ventralization of the mouse neural tube.''; PubMed Europe PMC
  24. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC
  25. Taylor MD, Liu L, Raffel C, Hui CC, Mainprize TG, Zhang X, Agatep R, Chiappa S, Gao L, Lowrance A, Hao A, Goldstein AM, Stavrou T, Scherer SW, Dura WT, Wainwright B, Squire JA, Rutka JT, Hogg D.; ''Mutations in SUFU predispose to medulloblastoma.''; PubMed Europe PMC
  26. Tempé D, Casas M, Karaz S, Blanchet-Tournier MF, Concordet JP.; ''Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP.''; PubMed Europe PMC
  27. He M, Subramanian R, Bangs F, Omelchenko T, Liem KF, Kapoor TM, Anderson KV.; ''The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment.''; PubMed Europe PMC
  28. Jia J, Kolterud A, Zeng H, Hoover A, Teglund S, Toftgård R, Liu A.; ''Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia.''; PubMed Europe PMC
  29. Norman RX, Ko HW, Huang V, Eun CM, Abler LL, Zhang Z, Sun X, Eggenschwiler JT.; ''Tubby-like protein 3 (TULP3) regulates patterning in the mouse embryo through inhibition of Hedgehog signaling.''; PubMed Europe PMC
  30. Denef N, Neubüser D, Perez L, Cohen SM.; ''Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened.''; PubMed Europe PMC
  31. Tukachinsky H, Lopez LV, Salic A.; ''A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes.''; PubMed Europe PMC
  32. Cheung HO, Zhang X, Ribeiro A, Mo R, Makino S, Puviindran V, Law KK, Briscoe J, Hui CC.; ''The kinesin protein Kif7 is a critical regulator of Gli transcription factors in mammalian hedgehog signaling.''; PubMed Europe PMC
  33. Pearse RV, Collier LS, Scott MP, Tabin CJ.; ''Vertebrate homologs of Drosophila suppressor of fused interact with the gli family of transcriptional regulators.''; PubMed Europe PMC
  34. Ayers KL, Thérond PP.; ''Evaluating Smoothened as a G-protein-coupled receptor for Hedgehog signalling.''; PubMed Europe PMC
  35. Wang B, Li Y.; ''Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing.''; PubMed Europe PMC
  36. Maurya AK, Ben J, Zhao Z, Lee RT, Niah W, Ng AS, Iyu A, Yu W, Elworthy S, van Eeden FJ, Ingham PW.; ''Positive and negative regulation of Gli activity by Kif7 in the zebrafish embryo.''; PubMed Europe PMC
  37. Rohatgi R, Milenkovic L, Scott MP.; ''Patched1 regulates hedgehog signaling at the primary cilium.''; PubMed Europe PMC
  38. Santagata S, Boggon TJ, Baird CL, Gomez CA, Zhao J, Shan WS, Myszka DG, Shapiro L.; ''G-protein signaling through tubby proteins.''; PubMed Europe PMC
  39. Chen Y, Sasai N, Ma G, Yue T, Jia J, Briscoe J, Jiang J.; ''Sonic Hedgehog dependent phosphorylation by CK1α and GRK2 is required for ciliary accumulation and activation of smoothened.''; PubMed Europe PMC
  40. Endoh-Yamagami S, Evangelista M, Wilson D, Wen X, Theunissen JW, Phamluong K, Davis M, Scales SJ, Solloway MJ, de Sauvage FJ, Peterson AS.; ''The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development.''; PubMed Europe PMC
  41. Huang S, Zhang Z, Zhang C, Lv X, Zheng X, Chen Z, Sun L, Wang H, Zhu Y, Zhang J, Yang S, Lu Y, Sun Q, Tao Y, Liu F, Zhao Y, Chen D.; ''Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover.''; PubMed Europe PMC
  42. Pal K, Mukhopadhyay S.; ''Primary cilium and sonic hedgehog signaling during neural tube patterning: role of GPCRs and second messengers.''; PubMed Europe PMC
  43. Goetz SC, Anderson KV.; ''The primary cilium: a signalling centre during vertebrate development.''; PubMed Europe PMC
  44. Chen Y, Li S, Tong C, Zhao Y, Wang B, Liu Y, Jia J, Jiang J.; ''G protein-coupled receptor kinase 2 promotes high-level Hedgehog signaling by regulating the active state of Smo through kinase-dependent and kinase-independent mechanisms in Drosophila.''; PubMed Europe PMC
  45. Zhao Y, Tong C, Jiang J.; ''Hedgehog regulates smoothened activity by inducing a conformational switch.''; PubMed Europe PMC
  46. Dwyer JR, Sever N, Carlson M, Nelson SF, Beachy PA, Parhami F.; ''Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells.''; PubMed Europe PMC
  47. Vokes SA, Ji H, Wong WH, McMahon AP.; ''A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb.''; PubMed Europe PMC
  48. Kinzler KW, Vogelstein B.; ''The GLI gene encodes a nuclear protein which binds specific sequences in the human genome.''; PubMed Europe PMC
  49. Wang Y, Zhou Z, Walsh CT, McMahon AP.; ''Selective translocation of intracellular Smoothened to the primary cilium in response to Hedgehog pathway modulation.''; PubMed Europe PMC
  50. Wilson CW, Chen MH, Chuang PT.; ''Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium.''; PubMed Europe PMC
  51. Cortellino S, Wang C, Wang B, Bassi MR, Caretti E, Champeval D, Calmont A, Jarnik M, Burch J, Zaret KS, Larue L, Bellacosa A.; ''Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4.''; PubMed Europe PMC
  52. Di Marcotullio L, Ferretti E, Greco A, De Smaele E, Po A, Sico MA, Alimandi M, Giannini G, Maroder M, Screpanti I, Gulino A.; ''Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination.''; PubMed Europe PMC
  53. Sassone-Corsi P.; ''The cyclic AMP pathway.''; PubMed Europe PMC
  54. Corcoran RB, Scott MP.; ''Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells.''; PubMed Europe PMC
  55. Pan Y, Wang B.; ''A novel protein-processing domain in Gli2 and Gli3 differentially blocks complete protein degradation by the proteasome.''; PubMed Europe PMC
  56. Liu A, Wang B, Niswander LA.; ''Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors.''; PubMed Europe PMC
  57. Stone DM, Murone M, Luoh S, Ye W, Armanini MP, Gurney A, Phillips H, Brush J, Goddard A, de Sauvage FJ, Rosenthal A.; ''Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli.''; PubMed Europe PMC
  58. Rohatgi R, Scott MP.; ''Patching the gaps in Hedgehog signalling.''; PubMed Europe PMC
  59. Milenkovic L, Scott MP, Rohatgi R.; ''Lateral transport of Smoothened from the plasma membrane to the membrane of the cilium.''; PubMed Europe PMC
  60. Vokes SA, Ji H, McCuine S, Tenzen T, Giles S, Zhong S, Longabaugh WJ, Davidson EH, Wong WH, McMahon AP.; ''Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning.''; PubMed Europe PMC
  61. Pastorino L, Ghiorzo P, Nasti S, Battistuzzi L, Cusano R, Marzocchi C, Garrè ML, Clementi M, Scarrà GB.; ''Identification of a SUFU germline mutation in a family with Gorlin syndrome.''; PubMed Europe PMC
  62. Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DY, Reiter JF.; ''Vertebrate Smoothened functions at the primary cilium.''; PubMed Europe PMC
  63. Cheng SY, Bishop JM.; ''Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex.''; PubMed Europe PMC
  64. Qin J, Lin Y, Norman RX, Ko HW, Eggenschwiler JT.; ''Intraflagellar transport protein 122 antagonizes Sonic Hedgehog signaling and controls ciliary localization of pathway components.''; PubMed Europe PMC
  65. Wen X, Lai CK, Evangelista M, Hongo JA, de Sauvage FJ, Scales SJ.; ''Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation.''; PubMed Europe PMC
  66. Hui CC, Angers S.; ''Gli proteins in development and disease.''; PubMed Europe PMC
  67. Kim J, Kato M, Beachy PA.; ''Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus.''; PubMed Europe PMC
  68. Ingham PW, Nakano Y, Seger C.; ''Mechanisms and functions of Hedgehog signalling across the metazoa.''; PubMed Europe PMC
  69. Szczepny A, Wagstaff KM, Dias M, Gajewska K, Wang C, Davies RG, Kaur G, Ly-Huynh J, Loveland KL, Jans DA.; ''Overlapping binding sites for importin β1 and suppressor of fused (SuFu) on glioma-associated oncogene homologue 1 (Gli1) regulate its nuclear localization.''; PubMed Europe PMC
  70. Pan Y, Wang C, Wang B.; ''Phosphorylation of Gli2 by protein kinase A is required for Gli2 processing and degradation and the Sonic Hedgehog-regulated mouse development.''; PubMed Europe PMC
  71. May SR, Ashique AM, Karlen M, Wang B, Shen Y, Zarbalis K, Reiter J, Ericson J, Peterson AS.; ''Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli.''; PubMed Europe PMC
  72. Varjosalo M, Björklund M, Cheng F, Syvänen H, Kivioja T, Kilpinen S, Sun Z, Kallioniemi O, Stunnenberg HG, He WW, Ojala P, Taipale J.; ''Application of active and kinase-deficient kinome collection for identification of kinases regulating hedgehog signaling.''; PubMed Europe PMC
  73. Hwang SH, Mukhopadhyay S.; ''G-protein-coupled receptors and localized signaling in the primary cilium during ventral neural tube patterning.''; PubMed Europe PMC
  74. Huntzicker EG, Estay IS, Zhen H, Lokteva LA, Jackson PK, Oro AE.; ''Dual degradation signals control Gli protein stability and tumor formation.''; PubMed Europe PMC
  75. Taipale J, Cooper MK, Maiti T, Beachy PA.; ''Patched acts catalytically to suppress the activity of Smoothened.''; PubMed Europe PMC
  76. Nachtergaele S, Mydock LK, Krishnan K, Rammohan J, Schlesinger PH, Covey DF, Rohatgi R.; ''Oxysterols are allosteric activators of the oncoprotein Smoothened.''; PubMed Europe PMC
  77. Gray RS, Abitua PB, Wlodarczyk BJ, Szabo-Rogers HL, Blanchard O, Lee I, Weiss GS, Liu KJ, Marcotte EM, Wallingford JB, Finnell RH.; ''The planar cell polarity effector Fuz is essential for targeted membrane trafficking, ciliogenesis and mouse embryonic development.''; PubMed Europe PMC
  78. Mukhopadhyay S, Rohatgi R.; ''G-protein-coupled receptors, Hedgehog signaling and primary cilia.''; PubMed Europe PMC
  79. Dai P, Shinagawa T, Nomura T, Harada J, Kaul SC, Wadhwa R, Khan MM, Akimaru H, Sasaki H, Colmenares C, Ishii S.; ''Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3.''; PubMed Europe PMC
  80. Hu MC, Mo R, Bhella S, Wilson CW, Chuang PT, Hui CC, Rosenblum ND.; ''GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis.''; PubMed Europe PMC
  81. Di Marcotullio L, Greco A, Mazzà D, Canettieri G, Pietrosanti L, Infante P, Coni S, Moretti M, De Smaele E, Ferretti E, Screpanti I, Gulino A.; ''Numb activates the E3 ligase Itch to control Gli1 function through a novel degradation signal.''; PubMed Europe PMC
  82. Cooper AF, Yu KP, Brueckner M, Brailey LL, Johnson L, McGrath JM, Bale AE.; ''Cardiac and CNS defects in a mouse with targeted disruption of suppressor of fused.''; PubMed Europe PMC
  83. Chen MH, Wilson CW, Li YJ, Law KK, Lu CS, Gacayan R, Zhang X, Hui CC, Chuang PT.; ''Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved.''; PubMed Europe PMC
  84. Khaliullina H, Panáková D, Eugster C, Riedel F, Carvalho M, Eaton S.; ''Patched regulates Smoothened trafficking using lipoprotein-derived lipids.''; PubMed Europe PMC
  85. Huangfu D, Liu A, Rakeman AS, Murcia NS, Niswander L, Anderson KV.; ''Hedgehog signalling in the mouse requires intraflagellar transport proteins.''; PubMed Europe PMC
  86. Heydeck W, Zeng H, Liu A.; ''Planar cell polarity effector gene Fuzzy regulates cilia formation and Hedgehog signal transduction in mouse.''; PubMed Europe PMC
  87. Briscoe J, Thérond PP.; ''The mechanisms of Hedgehog signalling and its roles in development and disease.''; PubMed Europe PMC
  88. Tran PV, Haycraft CJ, Besschetnova TY, Turbe-Doan A, Stottmann RW, Herron BJ, Chesebro AL, Qiu H, Scherz PJ, Shah JV, Yoder BK, Beier DR.; ''THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia.''; PubMed Europe PMC
  89. Park TJ, Haigo SL, Wallingford JB.; ''Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and Hedgehog signaling.''; PubMed Europe PMC
  90. Mukhopadhyay S, Wen X, Ratti N, Loktev A, Rangell L, Scales SJ, Jackson PK.; ''The ciliary G-protein-coupled receptor Gpr161 negatively regulates the Sonic hedgehog pathway via cAMP signaling.''; PubMed Europe PMC
  91. Patterson VL, Damrau C, Paudyal A, Reeve B, Grimes DT, Stewart ME, Williams DJ, Siggers P, Greenfield A, Murdoch JN.; ''Mouse hitchhiker mutants have spina bifida, dorso-ventral patterning defects and polydactyly: identification of Tulp3 as a novel negative regulator of the Sonic hedgehog pathway.''; PubMed Europe PMC
  92. Weatherbee SD, Niswander LA, Anderson KV.; ''A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling.''; PubMed Europe PMC
  93. Hatayama M, Aruga J.; ''Gli protein nuclear localization signal.''; PubMed Europe PMC
  94. Mas C, Ruiz i Altaba A.; ''Small molecule modulation of HH-GLI signaling: current leads, trials and tribulations.''; PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
101477view11:34, 1 November 2018ReactomeTeamreactome version 66
101015view21:14, 31 October 2018ReactomeTeamreactome version 65
100551view19:48, 31 October 2018ReactomeTeamreactome version 64
100099view16:32, 31 October 2018ReactomeTeamreactome version 63
99649view15:04, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99251view12:45, 31 October 2018ReactomeTeamreactome version 62
93840view13:40, 16 August 2017ReactomeTeamreactome version 61
93396view11:22, 9 August 2017ReactomeTeamreactome version 61
87141view18:52, 18 July 2016MkutmonOntology Term : 'Hedgehog signaling pathway' added !
86481view09:19, 11 July 2016ReactomeTeamreactome version 56
83587view07:34, 26 November 2015EgonwAdded missing ENSG parts of the Ensembl IDs.
83062view09:50, 18 November 2015ReactomeTeamVersion54
81377view12:54, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-68819 (Reactome)
4xub-p13S-Gli3:SUFUComplexR-HSA-5610526 (Reactome)
ADCY1 ProteinQ08828 (Uniprot-TrEMBL)
ADCY10 ProteinQ96PN6 (Uniprot-TrEMBL)
ADCY2 ProteinQ08462 (Uniprot-TrEMBL)
ADCY3 ProteinO60266 (Uniprot-TrEMBL)
ADCY4 ProteinQ8NFM4 (Uniprot-TrEMBL)
ADCY5 ProteinO95622 (Uniprot-TrEMBL)
ADCY6 ProteinO43306 (Uniprot-TrEMBL)
ADCY7 ProteinP51828 (Uniprot-TrEMBL)
ADCY8 ProteinP40145 (Uniprot-TrEMBL)
ADCY9 ProteinO60503 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
BTRC ProteinQ9Y297 (Uniprot-TrEMBL)
BTRC:CUL1:RBX1:SKP1ComplexR-HSA-206748 (Reactome)
CSNK1A1ProteinP48729 (Uniprot-TrEMBL)
CUL1 ProteinQ13616 (Uniprot-TrEMBL)
DYNC2H1 ProteinQ8NCM8 (Uniprot-TrEMBL)
FUZ ProteinQ9BT04 (Uniprot-TrEMBL)
G alpha (s):GTPComplexR-HSA-164358 (Reactome)
GLI1 ProteinP08151 (Uniprot-TrEMBL)
GLI1 gene ProteinENSG00000111087 (Ensembl)
GLI1 gene:GLI3RComplexR-HSA-5617398 (Reactome)
GLI1 geneGeneProductENSG00000111087 (Ensembl)
GLI1,2,3ComplexR-HSA-5610616 (Reactome)
GLI1:SUFUComplexR-HSA-5610531 (Reactome)
GLI1ProteinP08151 (Uniprot-TrEMBL)
GLI2 ProteinP10070 (Uniprot-TrEMBL)
GLI2 gene ProteinENSG00000074047 (Ensembl)
GLI2 gene:GLI3RComplexR-HSA-5617399 (Reactome)
GLI2 geneGeneProductENSG00000074047 (Ensembl)
GLI2:SUFUComplexR-HSA-5610536 (Reactome)
GLI2ProteinP10070 (Uniprot-TrEMBL)
GLI3 ProteinP10071 (Uniprot-TrEMBL)
GLI3:SUFUComplexR-HSA-5610542 (Reactome)
GLI3R ProteinP10071 (Uniprot-TrEMBL)
GLI3RProteinP10071 (Uniprot-TrEMBL)
GLI:SUFUComplexR-HSA-5621780 (Reactome)
GLI:SUFUComplexR-HSA-5621783 (Reactome)
GLI:SUFUComplexR-HSA-5621787 (Reactome)
GNAS1 ProteinQ5JWF2 (Uniprot-TrEMBL)
GNAS2 ProteinP63092 (Uniprot-TrEMBL)
GPR161 ProteinQ8N6U8 (Uniprot-TrEMBL)
GPR161:IFT-A:TULP3ComplexR-HSA-5610579 (Reactome)
GPR161ProteinQ8N6U8 (Uniprot-TrEMBL)
GSK3BProteinP49841 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
IFT-A complex:TULP3ComplexR-HSA-5610556 (Reactome)
IFT-A complexComplexR-HSA-5610555 (Reactome)
IFT122 ProteinQ9HBG6 (Uniprot-TrEMBL)
IFT140 ProteinQ96RY7 (Uniprot-TrEMBL)
IFT172 ProteinQ9UG01 (Uniprot-TrEMBL)
IFT52 ProteinQ9Y366 (Uniprot-TrEMBL)
IFT57 ProteinQ9NWB7 (Uniprot-TrEMBL)
IFT88 ProteinQ13099 (Uniprot-TrEMBL)
INTU ProteinQ9ULD6 (Uniprot-TrEMBL)
ITCH ProteinQ96J02 (Uniprot-TrEMBL)
ITCHProteinQ96J02 (Uniprot-TrEMBL)
KIF3A ProteinQ9Y496 (Uniprot-TrEMBL)
KIF7 ProteinQ2M1P5 (Uniprot-TrEMBL)
KIF7:microtubuleComplexR-HSA-5610559 (Reactome)
KIF7ProteinQ2M1P5 (Uniprot-TrEMBL)
MKS1 ProteinQ9NXB0 (Uniprot-TrEMBL)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
NUMB ProteinP49757 (Uniprot-TrEMBL)
NUMB:ITCH:ub-pS-GLI1:SUFUComplexR-HSA-5610565 (Reactome)
NUMB:ITCHComplexR-HSA-5610562 (Reactome)
NUMBProteinP49757 (Uniprot-TrEMBL)
OFD1 ProteinO75665 (Uniprot-TrEMBL)
PCP regulators of HhComplexR-HSA-5610624 (Reactome)
PKA catalytic subunitComplexR-HSA-5610569 (Reactome)
PKA regulatory subunits:cAMPComplexR-HSA-5610566 (Reactome)
PKA tetramerComplexR-HSA-5610571 (Reactome)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKACA ProteinP17612 (Uniprot-TrEMBL)
PRKACB ProteinP22694 (Uniprot-TrEMBL)
PRKACG ProteinP22612 (Uniprot-TrEMBL)
PRKAR1A ProteinP10644 (Uniprot-TrEMBL)
PRKAR1B ProteinP31321 (Uniprot-TrEMBL)
PRKAR2A ProteinP13861 (Uniprot-TrEMBL)
PRKAR2B ProteinP31323 (Uniprot-TrEMBL)
PSMA1 ProteinP25786 (Uniprot-TrEMBL)
PSMA2 ProteinP25787 (Uniprot-TrEMBL)
PSMA3 ProteinP25788 (Uniprot-TrEMBL)
PSMA4 ProteinP25789 (Uniprot-TrEMBL)
PSMA5 ProteinP28066 (Uniprot-TrEMBL)
PSMA6 ProteinP60900 (Uniprot-TrEMBL)
PSMA7 ProteinO14818 (Uniprot-TrEMBL)
PSMA8 ProteinQ8TAA3 (Uniprot-TrEMBL)
PSMB1 ProteinP20618 (Uniprot-TrEMBL)
PSMB10 ProteinP40306 (Uniprot-TrEMBL)
PSMB11 ProteinA5LHX3 (Uniprot-TrEMBL)
PSMB2 ProteinP49721 (Uniprot-TrEMBL)
PSMB3 ProteinP49720 (Uniprot-TrEMBL)
PSMB4 ProteinP28070 (Uniprot-TrEMBL)
PSMB5 ProteinP28074 (Uniprot-TrEMBL)
PSMB6 ProteinP28072 (Uniprot-TrEMBL)
PSMB7 ProteinQ99436 (Uniprot-TrEMBL)
PSMB8 ProteinP28062 (Uniprot-TrEMBL)
PSMB9 ProteinP28065 (Uniprot-TrEMBL)
PSMC1 ProteinP62191 (Uniprot-TrEMBL)
PSMC2 ProteinP35998 (Uniprot-TrEMBL)
PSMC3 ProteinP17980 (Uniprot-TrEMBL)
PSMC4 ProteinP43686 (Uniprot-TrEMBL)
PSMC5 ProteinP62195 (Uniprot-TrEMBL)
PSMC6 ProteinP62333 (Uniprot-TrEMBL)
PSMD1 ProteinQ99460 (Uniprot-TrEMBL)
PSMD10 ProteinO75832 (Uniprot-TrEMBL)
PSMD11 ProteinO00231 (Uniprot-TrEMBL)
PSMD12 ProteinO00232 (Uniprot-TrEMBL)
PSMD13 ProteinQ9UNM6 (Uniprot-TrEMBL)
PSMD14 ProteinO00487 (Uniprot-TrEMBL)
PSMD2 ProteinQ13200 (Uniprot-TrEMBL)
PSMD3 ProteinO43242 (Uniprot-TrEMBL)
PSMD4 ProteinP55036 (Uniprot-TrEMBL)
PSMD5 ProteinQ16401 (Uniprot-TrEMBL)
PSMD6 ProteinQ15008 (Uniprot-TrEMBL)
PSMD7 ProteinP51665 (Uniprot-TrEMBL)
PSMD8 ProteinP48556 (Uniprot-TrEMBL)
PSMD9 ProteinO00233 (Uniprot-TrEMBL)
PSME1 ProteinQ06323 (Uniprot-TrEMBL)
PSME2 ProteinQ9UL46 (Uniprot-TrEMBL)
PSME3 ProteinP61289 (Uniprot-TrEMBL)
PSME4 ProteinQ14997 (Uniprot-TrEMBL)
PSMF1 ProteinQ92530 (Uniprot-TrEMBL)
PTCH1 gene ProteinENSG00000185920 (Ensembl)
PTCH1 gene:GLI3RComplexR-HSA-5612507 (Reactome)
PTCH1 geneGeneProductENSG00000185920 (Ensembl)
PTCH1ProteinQ13635 (Uniprot-TrEMBL)
RBX1 ProteinP62877 (Uniprot-TrEMBL)
RPGRIP1L ProteinQ68CZ1 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
SHFM1 ProteinP60896 (Uniprot-TrEMBL)
SKP1 ProteinP63208 (Uniprot-TrEMBL)
SMO ProteinQ99835 (Uniprot-TrEMBL)
SMO dimerComplexR-HSA-5610573 (Reactome)
SMO dimerComplexR-HSA-5610574 (Reactome)
SUFU ProteinQ9UMX1 (Uniprot-TrEMBL)
SUFUProteinQ9UMX1 (Uniprot-TrEMBL)
TTC21B ProteinQ7Z4L5 (Uniprot-TrEMBL)
TULP3 ProteinO75386 (Uniprot-TrEMBL)
TULP3ProteinO75386 (Uniprot-TrEMBL)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
UbComplexR-HSA-113595 (Reactome)
WDR19 ProteinQ8NEZ3 (Uniprot-TrEMBL)
WDR35 ProteinQ9P2L0 (Uniprot-TrEMBL)
adenylate cyclases:Mg2+ComplexR-HSA-5610577 (Reactome)
anterograde IFT regulators of HhComplexR-HSA-5610625 (Reactome)
cAMP MetaboliteCHEBI:17489 (ChEBI)
cAMPMetaboliteCHEBI:17489 (ChEBI)
ciliary basal body regulators of HhComplexR-HSA-5610628 (Reactome)
microtubule R-HSA-5610520 (Reactome)
microtubuleR-HSA-5610520 (Reactome)
p10S-GLI3 ProteinP10071 (Uniprot-TrEMBL)
p10S-GLI3:SUFUComplexR-HSA-5610581 (Reactome)
p11S-GLI2 ProteinP10070 (Uniprot-TrEMBL)
p11S-GLI2:SUFUComplexR-HSA-5610584 (Reactome)
p13S-GLI3 ProteinP10071 (Uniprot-TrEMBL)
p13S-GLI3:SUFUComplexR-HSA-5610587 (Reactome)
p4S-GLI2 ProteinP10070 (Uniprot-TrEMBL)
p4S-GLI2:SUFUComplexR-HSA-5610589 (Reactome)
p6S-GLI3 ProteinP10071 (Uniprot-TrEMBL)
p6S-GLI3:SUFUComplexR-HSA-5610595 (Reactome)
p8S-GLI2 ProteinP10070 (Uniprot-TrEMBL)
p8S-GLI2:SUFUComplexR-HSA-5610598 (Reactome)
pS-GLI1 ProteinP08151 (Uniprot-TrEMBL)
pS-GLI1:SUFUComplexR-HSA-5610605 (Reactome)
retrograde IFT regulators of HhComplexR-HSA-5610630 (Reactome)
ub-p11S-GLI2 ProteinP10070 (Uniprot-TrEMBL)
ub-p11S-GLI2:SUFUComplexR-HSA-5610608 (Reactome)
ub-p13S-GLI3 ProteinP10071 (Uniprot-TrEMBL)
ub-pS-GLI1 ProteinP08151 (Uniprot-TrEMBL)
ub-pS-GLI1:SUFUComplexR-HSA-5610612 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisR-HSA-5610754 (Reactome)
26S proteasomemim-catalysisR-HSA-5610757 (Reactome)
26S proteasomemim-catalysisR-HSA-5610758 (Reactome)
26S proteasomemim-catalysisR-HSA-5610760 (Reactome)
4xub-p13S-Gli3:SUFUArrowR-HSA-5610746 (Reactome)
4xub-p13S-Gli3:SUFUR-HSA-5610754 (Reactome)
ADPArrowR-HSA-5610717 (Reactome)
ADPArrowR-HSA-5610718 (Reactome)
ADPArrowR-HSA-5610720 (Reactome)
ADPArrowR-HSA-5610722 (Reactome)
ADPArrowR-HSA-5610730 (Reactome)
ADPArrowR-HSA-5610732 (Reactome)
ADPArrowR-HSA-5610741 (Reactome)
ATPR-HSA-5610717 (Reactome)
ATPR-HSA-5610718 (Reactome)
ATPR-HSA-5610720 (Reactome)
ATPR-HSA-5610722 (Reactome)
ATPR-HSA-5610727 (Reactome)
ATPR-HSA-5610730 (Reactome)
ATPR-HSA-5610732 (Reactome)
ATPR-HSA-5610741 (Reactome)
BTRC:CUL1:RBX1:SKP1mim-catalysisR-HSA-5610742 (Reactome)
BTRC:CUL1:RBX1:SKP1mim-catalysisR-HSA-5610745 (Reactome)
BTRC:CUL1:RBX1:SKP1mim-catalysisR-HSA-5610746 (Reactome)
CSNK1A1mim-catalysisR-HSA-5610718 (Reactome)
CSNK1A1mim-catalysisR-HSA-5610722 (Reactome)
G alpha (s):GTPArrowR-HSA-5610727 (Reactome)
GLI1 gene:GLI3RArrowR-HSA-5617408 (Reactome)
GLI1 gene:GLI3RTBarR-HSA-5617412 (Reactome)
GLI1 geneR-HSA-5617408 (Reactome)
GLI1 geneR-HSA-5617412 (Reactome)
GLI1,2,3R-HSA-5610723 (Reactome)
GLI1:SUFUR-HSA-5610741 (Reactome)
GLI1ArrowR-HSA-5617412 (Reactome)
GLI2 gene:GLI3RArrowR-HSA-5617410 (Reactome)
GLI2 gene:GLI3RTBarR-HSA-5617413 (Reactome)
GLI2 geneR-HSA-5617410 (Reactome)
GLI2 geneR-HSA-5617413 (Reactome)
GLI2:SUFUR-HSA-5610717 (Reactome)
GLI2ArrowR-HSA-5617413 (Reactome)
GLI3:SUFUR-HSA-5610720 (Reactome)
GLI3RArrowR-HSA-5610752 (Reactome)
GLI3RArrowR-HSA-5610754 (Reactome)
GLI3RR-HSA-5610752 (Reactome)
GLI3RR-HSA-5612508 (Reactome)
GLI3RR-HSA-5617408 (Reactome)
GLI3RR-HSA-5617410 (Reactome)
GLI:SUFUArrowR-HSA-5610723 (Reactome)
GLI:SUFUArrowR-HSA-5610766 (Reactome)
GLI:SUFUArrowR-HSA-5610767 (Reactome)
GLI:SUFUR-HSA-5610766 (Reactome)
GLI:SUFUR-HSA-5610767 (Reactome)
GPR161:IFT-A:TULP3ArrowR-HSA-5610725 (Reactome)
GPR161:IFT-A:TULP3ArrowR-HSA-5610727 (Reactome)
GPR161R-HSA-5610725 (Reactome)
GSK3Bmim-catalysisR-HSA-5610730 (Reactome)
GSK3Bmim-catalysisR-HSA-5610732 (Reactome)
IFT-A complex:TULP3ArrowR-HSA-5610726 (Reactome)
IFT-A complex:TULP3R-HSA-5610725 (Reactome)
IFT-A complexR-HSA-5610726 (Reactome)
ITCHR-HSA-5610735 (Reactome)
KIF7:microtubuleArrowR-HSA-5610733 (Reactome)
KIF7:microtubuleArrowR-HSA-5610767 (Reactome)
KIF7R-HSA-5610733 (Reactome)
NUMB:ITCH:ub-pS-GLI1:SUFUArrowR-HSA-5610737 (Reactome)
NUMB:ITCH:ub-pS-GLI1:SUFUR-HSA-5610760 (Reactome)
NUMB:ITCHArrowR-HSA-5610735 (Reactome)
NUMB:ITCHArrowR-HSA-5610760 (Reactome)
NUMB:ITCHR-HSA-5610737 (Reactome)
NUMB:ITCHmim-catalysisR-HSA-5610737 (Reactome)
NUMBR-HSA-5610735 (Reactome)
PCP regulators of HhArrowR-HSA-5610766 (Reactome)
PCP regulators of HhArrowR-HSA-5610767 (Reactome)
PKA catalytic subunitArrowR-HSA-5610749 (Reactome)
PKA catalytic subunitmim-catalysisR-HSA-5610717 (Reactome)
PKA catalytic subunitmim-catalysisR-HSA-5610720 (Reactome)
PKA catalytic subunitmim-catalysisR-HSA-5610741 (Reactome)
PKA regulatory subunits:cAMPArrowR-HSA-5610749 (Reactome)
PKA tetramerR-HSA-5610749 (Reactome)
PPiArrowR-HSA-5610727 (Reactome)
PTCH1 gene:GLI3RArrowR-HSA-5612508 (Reactome)
PTCH1 gene:GLI3RTBarR-HSA-5612510 (Reactome)
PTCH1 geneR-HSA-5612508 (Reactome)