Smoothened

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Smoothened, frizzled family receptor
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SMO ; FZD11; Gx; SMOH
External IDs OMIM601500 MGI108075 HomoloGene4115 IUPHAR: SMO ChEMBL: 5971 GeneCards: SMO Gene
RNA expression pattern
PBB GE SMO 218629 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6608 319757
Ensembl ENSG00000128602 ENSMUSG00000001761
UniProt Q99835 P56726
RefSeq (mRNA) NM_005631 NM_176996
RefSeq (protein) NP_005622 NP_795970
Location (UCSC) Chr 7:
128.83 – 128.85 Mb
Chr 6:
29.74 – 29.76 Mb
PubMed search [1] [2]

Smoothened is a G protein-coupled receptor[1] protein encoded by the SMO gene of the hedgehog signaling pathway conserved from flies to humans. It is the molecular target of the teratogen cyclopamine.[2]

Cellular localization plays an essential role in the function of SMO. Stimulation of the patched receptor by the sonic hedgehog ligand leads to translocation of SMO to the primary cilium. Furthermore, SMO that is mutated in the domain required for ciliary localisation cannot contribute to pathway activation.[3] SMO has also been shown to bind the kinesin motor protein Costal-2 and play a role in the localization of the Ci (Cubitus interruptus transcription factor) complex.[4]

SMO can function as an oncogene. Activating SMO mutations can lead to unregulated activation of the hedgehog pathway and cancer.[5]

Overview of signal transduction pathways involved in apoptosis.

Agonists[edit]

Antagonists[edit]

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References[edit]

  1. ^ Ruiz-Gómez A, Molnar C, Holguín H, Mayor F, de Celis JF (2007). "The cell biology of Smo signalling and its relationships with GPCRs". Biochim. Biophys. Acta 1768 (4): 901–12. doi:10.1016/j.bbamem.2006.09.020. PMID 17094938. 
  2. ^ Taipale J, Chen JK, Cooper MK, Wang B, Mann RK, Milenkovic L, Scott MP, Beachy PA (2000). "Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine". Nature 406 (6799): 1005–9. doi:10.1038/35023008. PMID 10984056. 
  3. ^ Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DY, Reiter JF (2005). "Vertebrate Smoothened functions at the primary cilium". Nature 437 (7061): 1018–21. doi:10.1038/nature04117. PMID 16136078. 
  4. ^ Lum L, Zhang C, Oh S, Mann RK, von Kessler DP, Taipale J, Weis-Garcia F, Gong R, Wang B, Beachy PA (November 2003). "Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2". Mol. Cell 12 (5): 1261–74. doi:10.1016/S1097-2765(03)00426-X. PMID 14636583. 
  5. ^ Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam CW, Hynes M, Goddard A, Rosenthal A, Epstein EH, de Sauvage FJ (1998). "Activating Smoothened mutations in sporadic basal-cell carcinoma". Nature 391 (6662): 90–2. doi:10.1038/34201. PMID 9422511. 

Further reading[edit]

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