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Smoothened

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Smoothened homolog (Drosophila)
Identifiers
Symbol(s) SMO; Gx; SMOH
External IDs OMIM: 601500 MGI108075 Homologene4115
RNA expression pattern

250px

More reference expression data

Orthologs
Human Mouse Entrez 6608 319757 Ensembl ENSG00000128602 na Uniprot Q99835 na Refseq NM_005631 (mRNA)
NP_005622 (protein)
NM_176996 (mRNA)
NP_795970 (protein)
Location Chr 7: 128.62 - 128.64 Mb na
Pubmed search [1] [2]

Smoothened is a G protein-coupled receptor[1] protein encoded by the SMO gene of the hedgehog 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 Sonic hedgehog 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 Costal-2 and play a role in the localization of the Ci cytoplasmic complex.

SMO can function as an oncogene. Activating SMO mutations can lead to unregulated activation of the hedgehog pathway and cancer.[4]

See alsoEdit

ReferencesEdit

  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.
  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.
  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.
  4. 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.

Further readingEdit


  • Chen Y, Struhl G (1996). Dual roles for patched in sequestering and transducing Hedgehog.. Cell 87 (3): 553-63.
  • Stone DM, Hynes M, Armanini M, et al. (1996). The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.. Nature 384 (6605): 129-34.
  • Xie J, Murone M, Luoh SM, et al. (1998). Activating Smoothened mutations in sporadic basal-cell carcinoma.. Nature 391 (6662): 90-2.
  • Reifenberger J, Wolter M, Weber RG, et al. (1998). Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system.. Cancer Res. 58 (9): 1798-803.
  • Sublett JE, Entrekin RE, Look AT, Reardon DA (1999). Chromosomal localization of the human smoothened gene (SMOH) to 7q32. 3 by fluorescence in situ hybridization and radiation hybrid mapping.. Genomics 50 (1): 112-4.
  • McGarvey TW, Maruta Y, Tomaszewski JE, et al. (1998). PTCH gene mutations in invasive transitional cell carcinoma of the bladder.. Oncogene 17 (9): 1167-72.
  • Chidambaram A, Gerrard B, Hanson M, Dean M (1998). Chromosomal localization of the human and murine orthologues of the Drosophila smoothened gene.. Genomics 53 (3): 416-7.
  • Carpenter D, Stone DM, Brush J, et al. (1998). Characterization of two patched receptors for the vertebrate hedgehog protein family.. Proc. Natl. Acad. Sci. U.S.A. 95 (23): 13630-4.
  • Detmer K, Walker AN, Jenkins TM, et al. (2000). Erythroid differentiation in vitro is blocked by cyclopamine, an inhibitor of hedgehog signaling.. Blood Cells Mol. Dis. 26 (4): 360-72.
  • Long F, Zhang XM, Karp S, et al. (2002). Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation.. Development 128 (24): 5099-108.
  • Incardona JP, Gruenberg J, Roelink H (2002). Sonic hedgehog induces the segregation of patched and smoothened in endosomes.. Curr. Biol. 12 (12): 983-95.
  • Lowrey JA, Stewart GA, Lindey S, et al. (2002). Sonic hedgehog promotes cell cycle progression in activated peripheral CD4(+) T lymphocytes.. J. Immunol. 169 (4): 1869-75.
  • Taipale J, Cooper MK, Maiti T, Beachy PA (2002). Patched acts catalytically to suppress the activity of Smoothened.. Nature 418 (6900): 892-7.
  • Katayam M, Yoshida K, Ishimori H, et al. (2003). Patched and smoothened mRNA expression in human astrocytic tumors inversely correlates with histological malignancy.. J. Neurooncol. 59 (2): 107-15.
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899-903.
  • Couvé-Privat S, Bouadjar B, Avril MF, et al. (2003). Significantly high levels of ultraviolet-specific mutations in the smoothened gene in basal cell carcinomas from DNA repair-deficient xeroderma pigmentosum patients.. Cancer Res. 62 (24): 7186-9.
  • Scherer SW, Cheung J, MacDonald JR, et al. (2003). Human chromosome 7: DNA sequence and biology.. Science 300 (5620): 767-72.
  • Grachtchouk V, Grachtchouk M, Lowe L, et al. (2003). The magnitude of hedgehog signaling activity defines skin tumor phenotype.. EMBO J. 22 (11): 2741-51.
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).. Genome Res. 14 (10B): 2121-7.
  • Chen W, Ren XR, Nelson CD, et al. (2005). Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2.. Science 306 (5705): 2257-60.




External linksEdit

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