KEGG   PATHWAY: hsa04340Help
Entry
hsa04340                    Pathway                                

Name
Hedgehog signaling pathway - Homo sapiens (human)
Description
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.
Class
Environmental Information Processing; Signal transduction
BRITE hierarchy
Pathway map
hsa04340  Hedgehog signaling pathway
hsa04340

Ortholog table
Module
hsa_M00678  Hedgehog signaling [PATH:hsa04340]
Network
N00062  Hedgehog signaling pathway
Disease
H00263  Acrocallosal syndrome
H00267  Holoprosencephaly
H00482  Brachydactyly
H00502  Pallister-Hall syndrome
H00503  Ellis-van Creveld syndrome
H00530  Joubert syndrome
H00646  Odontoonychodermal dysplasia
H00652  Solitary median maxillary central incisor syndrome
H00675  Acrocapitofemoral dysplasia
H00855  Triphalangeal thumb-polysyndactyly syndrome
H00886  Donnai-Barrow syndrome
H00895  Basal cell nevus syndrome
H01160  Schizencephaly
H01226  Polysyndactyly
H01667  Medulloblastoma
H02158  Weyers acrodental dysostosis
H02161  Greig cephalopolysyndactyly syndrome
Drug
D09992  Vismodegib (USAN/INN)
D10119  Sonidegib (USAN/INN)
D10324  Saridegib (USAN)
D10325  Saridegib hydrochloride (USAN)
D10636  Glasdegib (USAN/INN)
D10671  Taladegib (USAN/INN)
D10729  Sonidegib phosphate (USAN)
D11107  Glasdegib maleate (JAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
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:2.7.11.11]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
122011  CSNK1A1L; casein kinase 1 alpha 1 like [KO:K08957] [EC:2.7.11.1]
1452  CSNK1A1; casein kinase 1 alpha 1 [KO:K08957] [EC:2.7.11.1]
1455  CSNK1G2; casein kinase 1 gamma 2 [KO:K08958] [EC:2.7.11.1]
1456  CSNK1G3; casein kinase 1 gamma 3 [KO:K08958] [EC:2.7.11.1]
53944  CSNK1G1; casein kinase 1 gamma 1 [KO:K08958] [EC:2.7.11.1]
1453  CSNK1D; casein kinase 1 delta [KO:K08959] [EC:2.7.11.1]
1454  CSNK1E; casein kinase 1 epsilon [KO:K08960] [EC:2.7.11.1]
102800317  TPTEP2-CSNK1E; TPTEP2-CSNK1E readthrough [KO:K08960] [EC:2.7.11.1]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
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]
6469  SHH; sonic hedgehog [KO:K11988]
3549  IHH; indian hedgehog [KO:K11989]
50846  DHH; desert hedgehog [KO:K11990]
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]
57154  SMURF1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:2.3.2.26]
64750  SMURF2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:2.3.2.26]
156  GRK2; G protein-coupled receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
157  GRK3; G protein-coupled receptor kinase 3 [KO:K00910] [EC:2.7.11.15]
2121  EVC; EvC ciliary complex subunit 1 [KO:K19605]
132884  EVC2; EvC ciliary complex subunit 2 [KO:K19608]
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]
Compound
C00575  3',5'-Cyclic AMP
Reference
  Authors
Xavier GM, Seppala M, Barrell W, Birjandi AA, Geoghegan F, Cobourne MT
  Title
Hedgehog receptor function during craniofacial development.
  Journal
Dev Biol 415:198-215 (2016)
DOI:10.1016/j.ydbio.2016.02.009
Reference
  Authors
Briscoe J, Therond PP
  Title
The mechanisms of Hedgehog signalling and its roles in development and disease.
  Journal
Nat Rev Mol Cell Biol 14:416-29 (2013)
DOI:10.1038/nrm3598
Reference
  Authors
Alman BA
  Title
The role of hedgehog signalling in skeletal health and disease.
  Journal
Nat Rev Rheumatol 11:552-60 (2015)
DOI:10.1038/nrrheum.2015.84
Reference
  Authors
Mooney CJ, Hakimjavadi R, Fitzpatrick E, Kennedy E, Walls D, Morrow D, Redmond EM, Cahill PA
  Title
Hedgehog and Resident Vascular Stem Cell Fate.
  Journal
Stem Cells Int 2015:468428 (2015)
DOI:10.1155/2015/468428
Reference
  Authors
Sasai N, Briscoe J
  Title
Primary cilia and graded Sonic Hedgehog signaling.
  Journal
Wiley Interdiscip Rev Dev Biol 1:753-72 (2012)
DOI:10.1002/wdev.43
Reference
  Authors
Heretsch P, Tzagkaroulaki L, Giannis A
  Title
Modulators of the hedgehog signaling pathway.
  Journal
Bioorg Med Chem 18:6613-24 (2010)
DOI:10.1016/j.bmc.2010.07.038
Reference
  Authors
Anderson E, Peluso S, Lettice LA, Hill RE
  Title
Human limb abnormalities caused by disruption of hedgehog signaling.
  Journal
Trends Genet 28:364-73 (2012)
DOI:10.1016/j.tig.2012.03.012
Reference
  Authors
Rohatgi R, Scott MP
  Title
Cell biology. Arrestin' movement in cilia.
  Journal
Science 320:1726-7 (2008)
DOI:10.1126/science.1160448
Reference
  Authors
Yue S, Tang LY, Tang Y, Tang Y, Shen QH, Ding J, Chen Y, Zhang Z, Yu TT, Zhang YE, Cheng SY
  Title
Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception.
  Journal
Elife 3:e02555 (2014)
DOI:10.7554/eLife.02555
Reference
  Authors
Ok CY, Singh RR, Vega F
  Title
Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms.
  Journal
Am J Pathol 180:2-11 (2012)
DOI:10.1016/j.ajpath.2011.09.009
Reference
  Authors
Hsia EY, Gui Y, Zheng X
  Title
Regulation of Hedgehog signaling by ubiquitination.
  Journal
Front Biol (Beijing) 10:203-220 (2015)
DOI:10.1007/s11515-015-1343-5
KO pathway
ko04340   

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