Panther Pathway: P00025 This is the current model for the Hedgehog signaling pathway. The best data for mechanism of signaling has been worked out in Drosophila, so this model is based largely on Drosophila data. Hedgehog target genes vary from tissue to tissue, so the identities of individual target genes have not been listed. The main difference between the Drosophila and mammalian Hedgehog signaling pathways is the fact that there are three mammalian homologs of Cubitus interruptus, Gli1 Gli2 and Gli3. Some or all of the mammalian homologs may be proteolytically processed, but the data are controversial. There are two mammalian Ptc genes and three mammalian Hedgehog genes as well. The pathway for Sonic Hedgehog appears to be most similar to the Drosophila hedgehog pathway. Medline=11731473 Medline=11861165 Medline=12200154 Medline=14738752 PMID: 11731473 PMID: 11861165 PMID: 12200154 PMID: 14738752 4.0 s21 PROTEIN p3 s22 PROTEIN p1 s22 PROTEIN p3 s46 PROTEIN p4 s46 PROTEIN p5 s46 PROTEIN p2 s48 PROTEIN p4 s48 PROTEIN p2 s48 PROTEIN p5 s69 PROTEIN p4 s69 PROTEIN p5 s69 PROTEIN p2 s89 PROTEIN p12 s89 PROTEIN p6 s102 PROTEIN p12 s102 PROTEIN p6 s103 PROTEIN p12 s113 PROTEIN p6 s113 PROTEIN p12 s113 PROTEIN p16 s118 PROTEIN p12 s118 PROTEIN p6 s84 PROTEIN p4 s84 PROTEIN p5 s84 PROTEIN p12 s84 PROTEIN p6 s84 PROTEIN p2 s84 PROTEIN p7 s88 PROTEIN p12 s88 PROTEIN p5 s88 PROTEIN p6 s88 PROTEIN p4 s88 PROTEIN p2 s143 PROTEIN p11 s143 PROTEIN p6 s127 PROTEIN p12 s128 PROTEIN p12 s140 PROTEIN p21 s140 PROTEIN p12 s127 PROTEIN p20 s128 PROTEIN p20 s140 PROTEIN p20 Long Name: Patched Synonym: Ptc,Ptc1 Accession: P00689 s21 PROTEIN p1 s103 PROTEIN p6 s118 PROTEIN p16 SQUARE_CLOSEUP_NORTHEAST OVAL OVAL OVAL OVAL OVAL OVAL inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive Ho Karen SRI International Receiving cell Endosome lipid raft nucleus lysosome Long Name: ATP Synonym: Synonym not specified Accession: S01691 inside SIMPLE_MOLECULE ATP Long Name: ADP Synonym: Synonym not specified Accession: S01693 inside SIMPLE_MOLECULE ADP Long Name: Patched Synonym: Ptc,Ptc1 Accession: P00689 transmembrane PROTEIN p1 Long Name: a31_degraded Synonym: Synonym not specified Accession: U02280 inside DEGRADED a31_degraded Long Name: e.g., ptc Synonym: Synonym not specified Accession: G01526 inside GENE gn1 Long Name: GSK3 Synonym: Glycogen synthase kinase3,Glycogen synthase kinase3 beta,sgg,shaggy,zeste-white 3 Accession: P00692 inside PROTEIN p13 Long Name: Slimb Synonym: Supernumerary limbs,beta TRCP,beta transducin Accession: P00683 inside PROTEIN p16 Long Name: Proteasome Synonym: Synonym not specified Accession: P00695 inside PROTEIN p17 Long Name: Debra Synonym: Dbr,Determiner of breaking down of Ci Activator Accession: P00694 inside PROTEIN p18 Long Name: Ubiquitin Synonym: Synonym not specified Accession: S01692 inside SIMPLE_MOLECULE Ubiquitin Long Name: a202_degraded Synonym: Synonym not specified Accession: U02281 inside DEGRADED a202_degraded Long Name: Sap18 Synonym: Sin3-associated polypeptide 18 Accession: P00697 inside PROTEIN p21 Long Name: PKA Synonym: Protein kinase A,cAMP-dependent Protein Kinase A Accession: P00682 inside PROTEIN p8 Long Name: Hedgehog Synonym: Hh,Shh,Sonic hedgehog Accession: P00688 inside PROTEIN p3 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05221 Heterodimer Member Info: Hedgehog#PROTEIN#Hedgehog#P00688#Hh|Shh|Sonic hedgehog#;Patched#PROTEIN#Patched#P00689#Ptc|Ptc1# transmembrane COMPLEX Complex_br_(Patched/Hedgehog) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05219 Heterodimer Member Info: Hedgehog#PROTEIN#Hedgehog#P00688#Hh|Shh|Sonic hedgehog#;Patched#PROTEIN#Patched#P00689#Ptc|Ptc1# transmembrane COMPLEX Complex_br_(Patched/Hedgehog) Long Name: Long Name: Smoothened Synonym: Synonym not specified Accession: U05226 Heterodimer Member Info: Smoothened#PROTEIN#Smoothened#P00685#Smo#;Fused#PROTEIN#Fused#P00686#Fu#;Costal2#PROTEIN#Costal2#P00698#Cos-2|Cos2|Costal-2# transmembrane COMPLEX Complex_br_(Costal2/Fused/_br_Smoothened) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05228 Heterodimer Member Info: Smoothened#PROTEIN#Smoothened#P00685#Smo#;Fused#PROTEIN#Fused#P00686#Fu#;Costal2#PROTEIN#Costal2#P00698#Cos-2|Cos2|Costal-2# transmembrane COMPLEX Complex_br_(Costal2/Smoothened/_br_Fused) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05229 Heterodimer Member Info: Smoothened#PROTEIN#Smoothened#P00685#Smo#;Fused#PROTEIN#Fused#P00686#Fu#;Costal2#PROTEIN#Costal2#P00698#Cos-2|Cos2|Costal-2# transmembrane COMPLEX Complex_br_(Costal2/Fused/_br_Smoothened) Long Name: CBP Synonym: CREB binding protein,p300 Accession: P00691 inside PROTEIN p11 Long Name: Microtubule Synonym: Synonym not specified Accession: P00696 inside PROTEIN p10 Long Name: Casine kinase I Synonym: CKI,Doubletime Accession: P00681 inside PROTEIN p14 Long Name: Cubitus interruptus Synonym: Ci,CiFL,Gli1,Gli2,Gli3 Accession: P00690 inside PROTEIN p6 Long Name: Long Name: Su(fu) Synonym: Synonym not specified Accession: U05218 Heterodimer Member Info: Cubitus interruptus#PROTEIN#Cubitus interruptus#P00690#Ci|CiFL|Gli1|Gli2|Gli3#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused# inside COMPLEX Complex_br_(Su(fu)/Cubitus_space_interruptus) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05225 Heterodimer Member Info: Cubitus interruptus#PROTEIN#Cubitus interruptus#P00690#Ci|CiFL|Gli1|Gli2|Gli3#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused# inside COMPLEX Complex_br_(Su(fu)/Cubitus_space_interruptus) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05227 Heterodimer Member Info: Cubitus interruptus#PROTEIN#Cubitus interruptus#P00690#Ci|CiFL|Gli1|Gli2|Gli3#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused# inside COMPLEX Complex_br_(Su(fu)/Cubitus_space_interruptus) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05222 Heterodimer Member Info: Slimb#PROTEIN#Slimb#P00683#Supernumerary limbs|beta TRCP|beta transducin#;Cubitus interruptus#PROTEIN#Cubitus interruptus#P00690#Ci|CiFL|Gli1|Gli2|Gli3#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused# inside COMPLEX Complex_br_(Cubitus_space_interruptus/Su(fu)/_br_Slimb) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05224 Heterodimer Member Info: Slimb#PROTEIN#Slimb#P00683#Supernumerary limbs|beta TRCP|beta transducin#;Cubitus interruptus#PROTEIN#Cubitus interruptus#P00690#Ci|CiFL|Gli1|Gli2|Gli3#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused# inside COMPLEX Complex_br_(Su(fu)/Slimb/_br_Cubitus_space_interruptus) Long Name: Cubitus interruptus Synonym: Ci,CiFL,Gli1,Gli2,Gli3 Accession: P00690 inside PROTEIN p6 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05232 Heterodimer Member Info: MIcrotubule#PROTEIN#MIcrotubule#P00684#microtubules|tubulin|tubulin alpha|tubulin beta#;Smoothened#PROTEIN#Smoothened#P00685#Smo#;Fused#PROTEIN#Fused#P00686#Fu#;Cubitus interruptus#PROTEIN#Cubitus interruptus#P00690#Ci|CiFL|Gli1|Gli2|Gli3#;Costal2#PROTEIN#Costal2#P00698#Cos-2|Cos2|Costal-2#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused# transmembrane COMPLEX Complex_br_(Costal2/Fused/_br_Su(fu)/Cubitus_space_interruptus/_br_Smoothened/MIcrotubule) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05223 Heterodimer Member Info: Smoothened#PROTEIN#Smoothened#P00685#Smo#;Fused#PROTEIN#Fused#P00686#Fu#;Cubitus interruptus#PROTEIN#Cubitus interruptus#P00690#Ci|CiFL|Gli1|Gli2|Gli3#;Costal2#PROTEIN#Costal2#P00698#Cos-2|Cos2|Costal-2#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused# transmembrane COMPLEX Complex_br_(Su(fu)/Fused/_br_Cubitus_space_interruptus/Costal2/_br_Smoothened) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05231 Heterodimer Member Info: Cubitus interruptus#PROTEIN#Cubitus interruptus#P00690#Ci|CiFL|Gli1|Gli2|Gli3#;CBP#PROTEIN#CBP#P00691#CREB binding protein|p300# inside COMPLEX Complex_br_(CBP/Cubitus_space_interruptus) Long Name: Long Name: Cubitus interruptus repressor Synonym: Synonym not specified Accession: U05230 Heterodimer Member Info: Cubitus interruptus repressor#PROTEIN#Cubitus interruptus repressor#P00687#CiR#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused# inside COMPLEX Complex_br_(Cubitus_space_interruptus_space_repressor/Su(fu)) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05220 Heterodimer Member Info: Cubitus interruptus repressor#PROTEIN#Cubitus interruptus repressor#P00687#CiR#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused# inside COMPLEX Complex_br_(Cubitus_space_interruptus_space_repressor/Su(fu)) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05217 Heterodimer Member Info: Cubitus interruptus repressor#PROTEIN#Cubitus interruptus repressor#P00687#CiR#;Sap18#PROTEIN#Sap18#P00697#Sin3-associated polypeptide 18#;Su(fu)#PROTEIN#Su(fu)#P00699#Suppressor of Fused# inside COMPLEX Complex_br_(Sap18/Su(fu)/_br_Cubitus_space_interruptus_space_repressor) Long Name: Ubiquitin ligase Synonym: Synonym not specified Accession: P00693 inside PROTEIN p19 inside RNA rn1 HETERODIMER_ASSOCIATION 0.3325942350332594,0.3747228381374723 a26 a25 a30 TRANSPORT a30 a31 STATE_TRANSITION a31 a36 TRANSPORT 0.21712798660204058,-0.005185694069377966 a95 a55 a30 STATE_TRANSITION 0.3735269811168802,0.0 0.5941169905310915,0.0 a55 a12 a57 a13 a30 DISSOCIATION 0.27034748318657686,8.613948149505113E-4 0.0058352677642457,0.5856959887386024 a115 a94 a123 a30 DISSOCIATION -0.0027787426189642694,0.47238624522403616 a123 a124 a95 TRANSPORT a124 a46 STATE_TRANSITION 0.39999999999999947,0.0 0.5999999999999996,0.0 a149 a153 a150 a154 a47 STATE_TRANSITION 0.40000000000000036,0.0 0.5999999999999996,0.0 a150 a157 a155 a151 a158 a156 a125 a126 HETERODIMER_ASSOCIATION 0.47368421052631593,0.5263157894736841 a159 a151 a175 STATE_TRANSITION 0.4500000000000002,0.0 0.6499999999999995,0.0 a175 a184 a183 a181 STATE_TRANSITION a183 a199 a160 TRANSPORT a199 a200 STATE_TRANSITION a202 a203 KNOWN_TRANSITION_OMITTED a115 a149 HETERODIMER_ASSOCIATION 0.5341614906832266,0.46583850931676984 a215 a200 a222 STATE_TRANSITION a46 a223 a57 HETERODIMER_ASSOCIATION 0.439300411522634,0.1851851851851869 a223 a96 a227 TRANSPORT 0.6082570257109519,0.0021872355750478523 a149 a202 a161 TRANSCRIPTION a102 sa86 a227 a222 STATE_TRANSITION sa87 a161 a30