KEGG   PATHWAY: rfq04340
Entry
rfq04340                    Pathway                                
Name
Hedgehog signaling pathway - Rhinolophus ferrumequinum (greater horseshoe bat)
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
rfq04340  Hedgehog signaling pathway
rfq04340

Organism
Rhinolophus ferrumequinum (greater horseshoe bat) [GN:rfq]
Gene
117011845  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
117012370  GLI3; transcriptional activator GLI3 isoform X1 [KO:K06230]
117012909  CSNK1D; casein kinase I isoform X1 [KO:K08959] [EC:2.7.11.1]
117012936  ARRB2; beta-arrestin-2 [KO:K04439]
117013506  SPOP; speckle-type POZ protein [KO:K10523]
117013738  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
117015171  GPR161; G-protein coupled receptor 161 [KO:K08439]
117015459  HHAT; protein-cysteine N-palmitoyltransferase HHAT isoform X1 [KO:K24678]
117016413  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
117016635  IQCE; IQ domain-containing protein E isoform X1 [KO:K24677]
117016648  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
117016737  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
117016830  KIF3A; kinesin-like protein KIF3A isoform X1 [KO:K10394]
117017286  GRK3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
117017596  CDON; cell adhesion molecule-related/down-regulated by oncogenes isoform X1 [KO:K20033]
117018094  CUL1; cullin-1 isoform X1 [KO:K03347]
117018290  SHH; sonic hedgehog protein isoform X1 [KO:K11988]
117018332  SMO; smoothened homolog isoform X1 [KO:K06226]
117018514  DISP1; protein dispatched homolog 1 isoform X1 [KO:K24680]
117018938  KIF7; kinesin-like protein KIF7 [KO:K18806]
117019655  MOSMO; modulator of smoothened protein [KO:K23663]
117019788  MGRN1; E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
117022009  EVC; ellis-van Creveld syndrome protein isoform X1 [KO:K19605]
117022556  EVC2; LOW QUALITY PROTEIN: limbin [KO:K19608]
117023505  CSNK1G1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
117024908  CSNK1G3; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
117025826  CUL3; cullin-3 isoform X1 [KO:K03869]
117025953  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
117026077  SPOPL; speckle-type POZ protein-like isoform X1 [KO:K10523]
117026266  GLI2; zinc finger protein GLI2 isoform X1 [KO:K16798]
117026349  IHH; indian hedgehog protein [KO:K11989]
117026578  EFCAB7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
117027001  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
117027700  PTCH2; protein patched homolog 2 isoform X1 [KO:K11101]
117028008  DHH; desert hedgehog protein [KO:K11990]
117028042  GLI1; zinc finger protein GLI1 [KO:K16797]
117028515  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
117028606  [KO:K08960] [EC:2.7.11.1]
117029970  ARRB1; beta-arrestin-1 isoform X1 [KO:K04439]
117030194  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
117030570  GRK2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
117031339  SCUBE2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
117032144  PTCH1; protein patched homolog 1 isoform X1 [KO:K06225]
117032454  GAS1; growth arrest-specific protein 1 [KO:K06232]
117033539  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
117034068  BOC; brother of CDO isoform X1 [KO:K20020]
117034412  MEGF8; LOW QUALITY PROTEIN: multiple epidermal growth factor-like domains protein 8 [KO:K23664]
117035968  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
117036059  SUFU; suppressor of fused homolog isoform X1 [KO:K06229]
117036780  HHATL; protein-cysteine N-palmitoyltransferase HHAT-like protein isoform X1 [KO:K24679]
117037772  CSNK1G2; casein kinase I [KO:K08958] [EC:2.7.11.1]
117037860  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
117038041  HHIP; hedgehog-interacting protein isoform X1 [KO:K06231]
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
Reference
  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
  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
  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
rfq04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   

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