KEGG   PATHWAY: char04340
Entry
char04340                   Pathway                                
Name
Hedgehog signaling pathway - Clupea harengus (Atlantic herring)
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
char04340  Hedgehog signaling pathway
char04340

Organism
Clupea harengus (Atlantic herring) [GN:char]
Gene
105894152  protein patched homolog 1 [KO:K06225]
116224733  ptch1; LOW QUALITY PROTEIN: protein patched homolog 1 [KO:K06225]
105898662  ptch2; protein patched homolog 1 [KO:K11101]
122130920  smo; smoothened homolog [KO:K06226]
105908991  gpr161a; G-protein coupled receptor 161 isoform X1 [KO:K08439]
105899109  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b isoform X3 [KO:K04345] [EC:2.7.11.11]
122130206  cAMP-dependent protein kinase catalytic subunit alpha-like isoform X1 [KO:K04345] [EC:2.7.11.11]
105910964  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a isoform X1 [KO:K04345] [EC:2.7.11.11]
105891269  prkacab; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105908144  csnk1a1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
105889154  csnk1g1; casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
122130445  casein kinase I isoform X1 [KO:K08958] [EC:2.7.11.1]
105910808  casein kinase I-like isoform X2 [KO:K08958] [EC:2.7.11.1]
105893926  csnk1db; casein kinase I isoform X4 [KO:K08959] [EC:2.7.11.1]
105899999  csnk1da; casein kinase I [KO:K08959] [EC:2.7.11.1]
105897698  csnk1e; casein kinase I isoform X2 [KO:K08960] [EC:2.7.11.1]
105904055  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105911913  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105912212  gli1; zinc finger protein GLI1 [KO:K16797]
105901924  gli2a; zinc finger protein GLI2a isoform X1 [KO:K16798]
105905650  LOW QUALITY PROTEIN: zinc finger protein GLI2 [KO:K16798]
105911983  gli3; transcriptional activator GLI3 [KO:K06230]
105911643  sufu; suppressor of fused homolog isoform X1 [KO:K06229]
105893028  kif7; kinesin-like protein kif7 [KO:K18806]
105903536  hedgehog-interacting protein [KO:K06231]
105911298  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
105896745  ccnd2b; G1/S-specific cyclin-D2b [KO:K10151]
105897673  ccndx; cyclin Dx [KO:K10151]
105889308  bcl2a; apoptosis regulator Bcl-2a [KO:K02161]
105891347  bcl2b; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
105905242  cul1b; cullin-1b [KO:K03347]
105907046  cul1a; cullin-1a [KO:K03347]
105893085  fbxw11a; F-box and WD repeat domain-containing 11-A isoform X2 [KO:K03362]
105905987  F-box and WD repeat domain-containing 11-B isoform X2 [KO:K03362]
105902272  hhat; protein-cysteine N-palmitoyltransferase HHAT [KO:K24678] [EC:2.3.1.-]
105900655  hhatla; hedgehog acyltransferase like, a isoform X1 [KO:K24679]
105890275  hhatlb; hedgehog acyltransferase like, b [KO:K24679]
105900478  shhb; tiggy-winkle hedgehog protein [KO:K11988]
122131833  shha; sonic hedgehog protein A isoform X1 [KO:K11988]
105903006  indian hedgehog B protein-like [KO:K11989]
105891314  indian hedgehog B protein [KO:K11989]
105897284  dhh; desert hedgehog protein [KO:K11990]
105899463  disp1; protein dispatched homolog 1 [KO:K24680]
105906533  scube2; signal peptide, CUB and EGF-like domain-containing protein 2 isoform X1 [KO:K24706]
105890221  boc; brother of CDO [KO:K20020]
105904808  cdon; cell adhesion molecule-related/down-regulated by oncogenes [KO:K20033]
105901076  gas1a; growth arrest-specific protein 1a [KO:K06232]
105907931  lrp2a; low-density lipoprotein receptor-related protein 2a isoform X1 [KO:K06233]
105905394  lrp2b; low-density lipoprotein receptor-related protein 2 isoform X1 [KO:K06233]
105898706  mosmoa; uncharacterized protein C16orf52 homolog B isoform X2 [KO:K23663]
122130086  mosmob; modulator of smoothened protein isoform X1 [KO:K23663]
105910626  megf8; multiple epidermal growth factor-like domains protein 8 [KO:K23664]
105910252  mgrn1a; probable E3 ubiquitin-protein ligase MGRN1 isoform X1 [KO:K10604] [EC:2.3.2.27]
105907877  mgrn1b; E3 ubiquitin-protein ligase MGRN1b isoform X3 [KO:K10604] [EC:2.3.2.27]
105899911  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
105891874  smurf2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
122129433  E3 ubiquitin-protein ligase SMURF2-like [KO:K04678] [EC:2.3.2.26]
105900188  E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
105890237  grk3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
105913202  efcab7; EF-hand calcium-binding domain-containing protein 7 [KO:K23852]
116219352  iqce; IQ domain-containing protein E [KO:K24677]
105904870  arrestin red cell isoform X1 [KO:K04439]
105902401  arrb2a; arrestin, beta 2a isoform X1 [KO:K04439]
105890606  arrb1; beta-arrestin-1 [KO:K04439]
105904263  kif3a; kinesin-like protein KIF3A isoform X3 [KO:K10394]
105895994  cul3b; cullin-3b [KO:K03869]
122131969  cullin-3-B-like [KO:K03869]
105898864  speckle-type POZ protein [KO:K10523]
105911847  speckle-type POZ protein-like B [KO:K10523]
105902684  spopla; speckle-type POZ protein-like A [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
char04120  Ubiquitin mediated proteolysis
KO pathway
ko04340   
LinkDB

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