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
Hedgehog signaling pathway
hsa04340

All organismsOrtholog table
Module
Hedgehog signaling [PATH:hsa04340]
Disease
H00263  
Acrocallosal syndrome
H00267  
Holoprosencephaly (HPE)
H00482  
Brachydactyly
H00502  
Pallister-Hall syndrome
H00607  
46,XY disorders of sex development (Disorders of gonadal development)
H00646  
Odontoonychodermal dysplasia
H00652  
Solitary median maxillary central incisor syndrome
H00675  
Acrocapitofemoral dysplasia
H00855  
Triphalangeal thumb
H00886  
Donnai-Barrow syndrome
H00895  
Basal cell nevus syndrome
H01027  
Anophthalmia and microphthalmia (A/M)
H01160  
Schizencephaly
H01226  
GLI3 morphopathies
H01667  
Medulloblastoma
Drug
D09992  
Vismodegib (USAN/INN)
D10119  
Sonidegib (USAN/INN)
D10324  
Saridegib (USAN)
D10325  
Saridegib hydrochloride (USAN)
D10636  
Glasdegib (USAN/INN)
D10729  
Sonidegib phosphate (USAN)
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]
LOC400927-CSNK1E readthrough; K08960 casein kinase 1, epsilon [EC:2.7.11.1] [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 (2016)
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)
Reference
  Authors
Alman BA
  Title
The role of hedgehog signalling in skeletal health and disease.
  Journal
Nat Rev Rheumatol 11:552-60 (2015)
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)
Reference
  Authors
Sasai N, Briscoe J
  Title
Primary cilia and graded Sonic Hedgehog signaling.
  Journal
Wiley Interdiscip Rev Dev Biol 1:753-72 (2012)
Reference
  Authors
Heretsch P, Tzagkaroulaki L, Giannis A
  Title
Modulators of the hedgehog signaling pathway.
  Journal
Bioorg Med Chem 18:6613-24 (2010)
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)
Reference
  Authors
Rohatgi R, Scott MP
  Title
Cell biology. Arrestin' movement in cilia.
  Journal
Science 320:1726-7 (2008)
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 (2014)
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)
Reference
  Authors
Hsia EY, Gui Y, Zheng X
  Title
Regulation of Hedgehog signaling by ubiquitination.
  Journal
Front Biol (Beijing) 10:203-220 (2015)
KO pathway
 

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