KEGG   PATHWAY: tfs04340
Entry
tfs04340                    Pathway                                
Name
Hedgehog signaling pathway - Takifugu flavidus (sansaifugu)
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
Pathway map
tfs04340  Hedgehog signaling pathway
tfs04340

Organism
Takifugu flavidus (sansaifugu) [GN:tfs]
Gene
130525821  ptch1; protein patched homolog 1 [KO:K06225]
130539525  ptch2; protein patched homolog 1 [KO:K11101]
130519485  smo; protein smoothened [KO:K06226]
130532306  gpr161a; G-protein coupled receptor 161 [KO:K08439]
130527227  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
130539508  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b isoform X1 [KO:K04345] [EC:2.7.11.11]
130528158  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
130531093  csnk1a1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
130521628  csnk1g1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
130529320  csnk1g2b; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
130538620  casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
130515460  csnk1da; casein kinase I [KO:K08959] [EC:2.7.11.1]
130514707  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
130515231  csnk1e; casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
130527385  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
130524421  gli1; zinc finger protein GLI1 [KO:K16797]
130522992  LOW QUALITY PROTEIN: zinc finger protein GLI2-like [KO:K16798]
130530104  gli2a; LOW QUALITY PROTEIN: zinc finger protein GLI2a [KO:K16798]
130514088  gli3; LOW QUALITY PROTEIN: transcriptional activator GLI3 [KO:K06230]
130533689  sufu; suppressor of fused homolog isoform X1 [KO:K06229]
130518153  kif7; kinesin-like protein kif7 [KO:K18806]
130527716  hhip; hedgehog-interacting protein [KO:K06231]
130536034  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
130519149  G1/S-specific cyclin-D2-like [KO:K10151]
130515110  ccndx; cyclin Dx [KO:K10151]
130536644  G1/S-specific cyclin-D2-like isoform X1 [KO:K10151]
130539428  bcl2b; apoptosis regulator Bcl-2 [KO:K02161]
130513650  cullin-1 [KO:K03347]
130531069  fbxw11a; F-box and WD repeat domain-containing 11-A isoform X1 [KO:K03362]
130533603  hhat; protein-cysteine N-palmitoyltransferase HHAT [KO:K24678] [EC:2.3.1.-]
130539570  hhatla; hedgehog acyltransferase like, a isoform X1 [KO:K24679]
130514303  hhatlb; hedgehog acyltransferase like, b [KO:K24679]
130514035  shha; sonic hedgehog protein [KO:K11988]
130533666  indian hedgehog B protein-like [KO:K11989]
130522042  indian hedgehog B protein-like [KO:K11989]
130529887  dhh; desert hedgehog protein [KO:K11990]
130520790  LOW QUALITY PROTEIN: protein dispatched homolog 1-like [KO:K24680]
130515867  disp1; protein dispatched homolog 1 [KO:K24680]
130521076  scube2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
130514153  boc; brother of CDO [KO:K20020]
130535102  cdon; cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
130521736  si:ch1073-459b3.2; growth arrest-specific protein 1 [KO:K06232]
130517012  gas1b; growth arrest-specific protein 1b [KO:K06232]
130526229  gas1a; growth arrest-specific protein 1a [KO:K06232]
130527319  lrp2a; low-density lipoprotein receptor-related protein 2a isoform X1 [KO:K06233]
130523466  lrp2b; low-density lipoprotein receptor-related protein 2 [KO:K06233]
130528011  uncharacterized protein C16orf52 homolog B-like [KO:K23663]
130514926  mosmoa; uncharacterized protein C16orf52 homolog B [KO:K23663]
130532890  megf8; LOW QUALITY PROTEIN: multiple epidermal growth factor-like domains protein 8 [KO:K23664]
130515249  mgrn1b; E3 ubiquitin-protein ligase MGRN1b isoform X1 [KO:K10604] [EC:2.3.2.27]
130527882  E3 ubiquitin-protein ligase SMURF2-like isoform X1 [KO:K04678] [EC:2.3.2.26]
130514654  smurf2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
130514815  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
130517213  grk3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
130524194  evC complex member EVC-like isoform X1 [KO:K19605]
130524193  limbin-like [KO:K19608]
130528495  efcab7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
130526827  iqce; IQ domain-containing protein E [KO:K24677]
130534442  beta-arrestin-1-like isoform X1 [KO:K04439]
130522952  arrb2b; arrestin, beta 2b [KO:K04439]
130538043  arrestin red cell isoform X1 [KO:K04439]
130530930  kinesin-like protein KIF3A [KO:K10394]
130530931  kinesin-like protein KIF3A [KO:K10394]
130535031  cullin-3 [KO:K03869]
130539000  cullin-3-like [KO:K03869]
130530807  spopla; speckle-type POZ protein-like A isoform X1 [KO:K10523]
130530864  speckle-type POZ protein [KO:K10523]
Compound
C00575  3',5'-Cyclic AMP
Reference
PMID:26875496
  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
PMID:23719536
  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
PMID:26077918
  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
PMID:26064136
  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
PMID:23799571
  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
PMID:20708941
  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
PMID:22534646
  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
PMID:18583599
  Authors
Rohatgi R, Scott MP
  Title
Cell biology. Arrestin' movement in cilia.
  Journal
Science 320:1726-7 (2008)
DOI:10.1126/science.1160448
Reference
PMID:24925320
  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
PMID:22056910
  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
PMID:26366162
  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
Reference
PMID:29290584
  Authors
Pusapati GV, Kong JH, Patel BB, Krishnan A, Sagner A, Kinnebrew M, Briscoe J, Aravind L, Rohatgi R
  Title
CRISPR Screens Uncover Genes that Regulate Target Cell Sensitivity to the Morphogen Sonic Hedgehog.
  Journal
Dev Cell 44:113-129.e8 (2018)
DOI:10.1016/j.devcel.2017.12.003
Reference
PMID:24582806
  Authors
Pusapati GV, Hughes CE, Dorn KV, Zhang D, Sugianto P, Aravind L, Rohatgi R
  Title
EFCAB7 and IQCE regulate hedgehog signaling by tethering the EVC-EVC2 complex to the base of primary cilia.
  Journal
Dev Cell 28:483-96 (2014)
DOI:10.1016/j.devcel.2014.01.021
Reference
PMID:27779865
  Authors
Rodgers UR, Lanyon-Hogg T, Masumoto N, Ritzefeld M, Burke R, Blagg J, Magee AI, Tate EW
  Title
Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells.
  Journal
ACS Chem Biol 11:3256-3262 (2016)
DOI:10.1021/acschembio.6b00896
Related
pathway
tfs04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
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