KEGG   PATHWAY: hsa04340
hsa04340                    Pathway                                
Hedgehog signaling pathway - Homo sapiens (human)
The Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for transduction of the Hedgehog signal in vertebrates. In Hh's absence, the Ptch receptor localizes to the cilium, where it inhibits Smo activation. Gli proteins are phosphorylated by PKA, CKI and GSK3B and partially degraded into truncated Gli repressor form (GliR) that suppresses Hh target gene transcription in the nucleus. In Hh's presence, Ptch disappears from the cilium, and activated Smo contributes to the translocation of the protein complex Gli, Sufu, Kif7 to ciliary tip, where Gli dissociates from the negative regulator Sufu. The production of Gli activator form (GliA) occurs and the increased nuclear accumulation of GliA results in activation transcription of Hh target genes.
Environmental Information Processing; Signal transduction
Pathway map
hsa04340  Hedgehog signaling pathway

nt06217  HH signaling
nt06269  Basal cell carcinoma
nt06501  HH signaling
N00062  Hedgehog signaling pathway
N01537  Hedgehog signaling pathway, HH ligand secretion
N01538  Hedgehog signaling pathway, PTCH coreceptor
D09992  Vismodegib (USAN/INN)
D10119  Sonidegib (USAN/INN)
D10324  Patidegib (USAN)
D10325  Patidegib hydrochloride (USAN)
D10636  Glasdegib (USAN/INN)
D10671  Taladegib (USAN/INN)
D10729  Sonidegib phosphate (USAN)
D11107  Glasdegib maleate (JAN)
D11322  Umbralisib (USAN/INN)
D11323  Umbralisib tosylate (USAN)
Homo sapiens (human) [GN:hsa]
5727  PTCH1; patched 1 [KO:K06225]
8643  PTCH2; patched 2 [KO:K11101]
6608  SMO; smoothened, frizzled class receptor [KO:K06226]
23432  GPR161; G protein-coupled receptor 161 [KO:K08439]
5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:]
122011  CSNK1A1L; casein kinase 1 alpha 1 like [KO:K08957] [EC:]
1452  CSNK1A1; casein kinase 1 alpha 1 [KO:K08957] [EC:]
1455  CSNK1G2; casein kinase 1 gamma 2 [KO:K08958] [EC:]
1456  CSNK1G3; casein kinase 1 gamma 3 [KO:K08958] [EC:]
53944  CSNK1G1; casein kinase 1 gamma 1 [KO:K08958] [EC:]
1453  CSNK1D; casein kinase 1 delta [KO:K08959] [EC:]
1454  CSNK1E; casein kinase 1 epsilon [KO:K08960] [EC:]
102800317  TPTEP2-CSNK1E; TPTEP2-CSNK1E readthrough [KO:K08960] [EC:]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
2735  GLI1; GLI family zinc finger 1 [KO:K16797]
2736  GLI2; GLI family zinc finger 2 [KO:K16798]
2737  GLI3; GLI family zinc finger 3 [KO:K06230]
51684  SUFU; SUFU negative regulator of hedgehog signaling [KO:K06229]
374654  KIF7; kinesin family member 7 [KO:K18806]
64399  HHIP; hedgehog interacting protein [KO:K06231]
595  CCND1; cyclin D1 [KO:K04503]
894  CCND2; cyclin D2 [KO:K10151]
596  BCL2; BCL2 apoptosis regulator [KO:K02161]
8454  CUL1; cullin 1 [KO:K03347]
8945  BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
23291  FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
55733  HHAT; hedgehog acyltransferase [KO:K24678] [EC:2.3.1.-]
57467  HHATL; hedgehog acyltransferase like [KO:K24679]
6469  SHH; sonic hedgehog signaling molecule [KO:K11988]
3549  IHH; Indian hedgehog signaling molecule [KO:K11989]
50846  DHH; desert hedgehog signaling molecule [KO:K11990]
84976  DISP1; dispatched RND transporter family member 1 [KO:K24680]
57758  SCUBE2; signal peptide, CUB domain and EGF like domain containing 2 [KO:K24706]
91653  BOC; BOC cell adhesion associated, oncogene regulated [KO:K20020]
50937  CDON; cell adhesion associated, oncogene regulated [KO:K20033]
2619  GAS1; growth arrest specific 1 [KO:K06232]
4036  LRP2; LDL receptor related protein 2 [KO:K06233]
730094  MOSMO; modulator of smoothened [KO:K23663]
1954  MEGF8; multiple EGF like domains 8 [KO:K23664]
23295  MGRN1; mahogunin ring finger 1 [KO:K10604] [EC:]
57154  SMURF1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:]
64750  SMURF2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:]
156  GRK2; G protein-coupled receptor kinase 2 [KO:K00910] [EC:]
157  GRK3; G protein-coupled receptor kinase 3 [KO:K00910] [EC:]
2121  EVC; EvC ciliary complex subunit 1 [KO:K19605]
132884  EVC2; EvC ciliary complex subunit 2 [KO:K19608]
84455  EFCAB7; EF-hand calcium binding domain 7 [KO:K23852]
23288  IQCE; IQ motif containing E [KO:K24677]
408  ARRB1; arrestin beta 1 [KO:K04439]
409  ARRB2; arrestin beta 2 [KO:K04439]
11127  KIF3A; kinesin family member 3A [KO:K10394]
8452  CUL3; cullin 3 [KO:K03869]
8405  SPOP; speckle type BTB/POZ protein [KO:K10523]
339745  SPOPL; speckle type BTB/POZ protein like [KO:K10523]
C00575  3',5'-Cyclic AMP
Xavier GM, Seppala M, Barrell W, Birjandi AA, Geoghegan F, Cobourne MT
Hedgehog receptor function during craniofacial development.
Dev Biol 415:198-215 (2016)
Briscoe J, Therond PP
The mechanisms of Hedgehog signalling and its roles in development and disease.
Nat Rev Mol Cell Biol 14:416-29 (2013)
Alman BA
The role of hedgehog signalling in skeletal health and disease.
Nat Rev Rheumatol 11:552-60 (2015)
Mooney CJ, Hakimjavadi R, Fitzpatrick E, Kennedy E, Walls D, Morrow D, Redmond EM, Cahill PA
Hedgehog and Resident Vascular Stem Cell Fate.
Stem Cells Int 2015:468428 (2015)
Sasai N, Briscoe J
Primary cilia and graded Sonic Hedgehog signaling.
Wiley Interdiscip Rev Dev Biol 1:753-72 (2012)
Heretsch P, Tzagkaroulaki L, Giannis A
Modulators of the hedgehog signaling pathway.
Bioorg Med Chem 18:6613-24 (2010)
Anderson E, Peluso S, Lettice LA, Hill RE
Human limb abnormalities caused by disruption of hedgehog signaling.
Trends Genet 28:364-73 (2012)
Rohatgi R, Scott MP
Cell biology. Arrestin' movement in cilia.
Science 320:1726-7 (2008)
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.
Elife 3:e02555 (2014)
Ok CY, Singh RR, Vega F
Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms.
Am J Pathol 180:2-11 (2012)
Hsia EY, Gui Y, Zheng X
Regulation of Hedgehog signaling by ubiquitination.
Front Biol (Beijing) 10:203-220 (2015)
Pusapati GV, Kong JH, Patel BB, Krishnan A, Sagner A, Kinnebrew M, Briscoe J, Aravind L, Rohatgi R
CRISPR Screens Uncover Genes that Regulate Target Cell Sensitivity to the Morphogen Sonic Hedgehog.
Dev Cell 44:113-129.e8 (2018)
Pusapati GV, Hughes CE, Dorn KV, Zhang D, Sugianto P, Aravind L, Rohatgi R
EFCAB7 and IQCE regulate hedgehog signaling by tethering the EVC-EVC2 complex to the base of primary cilia.
Dev Cell 28:483-96 (2014)
Rodgers UR, Lanyon-Hogg T, Masumoto N, Ritzefeld M, Burke R, Blagg J, Magee AI, Tate EW
Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells.
ACS Chem Biol 11:3256-3262 (2016)
hsa04120  Ubiquitin mediated proteolysis
KO pathway

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