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14-September-2008 18:02:44 - Smoothened Smoothened homolog Drosophila Identifiers Symbols SMO; Gx; SMOH External IDs OMIM: 601500 MGI: 108075 HomoloGene: 4115 Gene ontology Molecular function: receptor activity non-G-protein coupled 7TM receptor activity G-protein coupled receptor activity protein binding Cellular component: membrane fraction cilium membrane integral to membrane Biological process: vasculogenesis osteoblast differentiation G-protein coupled receptor protein signaling pathway smoothened signaling pathway multicellular organismal development determination of left/right symmetry central nervous system development dorsal/ventral pattern formation negative regulation of DNA binding RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 6608 319757 Ensembl ENSG00000128602 n/a Uniprot Q99835 n/a Refseq NM_005631 mRNA NP_005622 protein NM_176996 mRNA NP_795970 protein Location Chr 7: 128.62 - 128.64 Mb n/a Pubmed search 1 2 Smoothened is a G protein-coupled receptor1 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 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 Contents 1 See also 2 References 3 Further reading 4 External links See also Frizzled References ^ 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. ^ 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. ^ 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. ^ 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/S1097-27650300426-X. PMID 14636583. ^ 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 Chen Y, Struhl G 1996. Dual roles for patched in sequestering and transducing Hedgehog.. Cell 87 3: 553-63. PMID 8898207. 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. doi:10.1038/384129a0. PMID 8906787. Xie J, Murone M, Luoh SM, et al. 1998. Activating Smoothened mutations in sporadic basal-cell carcinoma.. Nature 391 6662: 90-2. doi:10.1038/34201. PMID 9422511. 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. PMID 9581815. 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. doi:10.1006/geno.1998.5227. PMID 9628830. 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. doi:10.1038/sj.onc.1202045. PMID 9764827. 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. doi:10.1006/geno.1998.5531. PMID 9799615. 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. PMID 9811851. 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. doi:10.1006/bcmd.2000.0318. PMID 11042037. 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. PMID 11748145. Incardona JP, Gruenberg J, Roelink H 2002. Sonic hedgehog induces the segregation of patched and smoothened in endosomes.. Curr. Biol. 12 12: 983-95. PMID 12123571. 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. PMID 12165511. Taipale J, Cooper MK, Maiti T, Beachy PA 2002. Patched acts catalytically to suppress the activity of Smoothened.. Nature 418 6900: 892-7. doi:10.1038/nature00989. PMID 12192414. 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. PMID 12241103. 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. doi:10.1073/pnas.242603899. PMID 12477932. 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. PMID 12499255. Scherer SW, Cheung J, MacDonald JR, et al. 2003. Human chromosome 7: DNA sequence and biology.. Science 300 5620: 767-72. doi:10.1126/science.1083423. PMID 12690205. 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. doi:10.1093/emboj/cdg271. PMID 12773389. 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. doi:10.1101/gr.2596504. PMID 15489334. 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. doi:10.1126/science.1104135. PMID 15618519. External links IUPHAR GPCR Database - Smoothened receptor MeSH SMO+protein,+human This transmembrane receptor-related article is a stub. v d e Transmembrane receptor: G protein-coupled receptors Class A: Rhodopsin like Adrenergic α1 A, B, D, α2 A, B, C, β1, β2, β3 Eicosanoid CysLT 1, 2, LTB4 1, 2, FPRL1, OXE, Prostaglandin DP, EP 1, 2, 3, 4, PGF, Prostacyclin, Thromboxane Neuropeptide B/W 1, 2, FF 1, 2, S, Y 1, 2, 4, 5 Orphan GPR 1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 79, 82, 83, 84, 85, 87, 88, 92, 101, 103, 119, 120, 132, 135, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 172, 173, 174, 176, 177, 182 Purinergics Adenosine A1, A2a, A2b, A3, P2Y, 1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14 Serotonin all but 5-HT3 5-HT1 A, B, D, E, F, 5-HT2 A, B, C, 5-HT 4, 5A, 6, 7 Other Acetylcholine M1, M2, M3, M4, M5 - Adrenomedullin - Anaphylatoxin C3a, C5a - Angiotensin 1, 2 - Apelin - Bile acid - Bombesin BRS3, GRPR, NMBR - Bradykinin B1, B2 - Cannabinoid CB1, CB2 - Chemokine - Cholecystokinin A, B - Dopamine D1, D2, D3, D4, D5 - EBI2 - Endothelin A, B - Estrogen - Formyl peptide 1, L1, L2 - Free fatty acid 1, 2, 3, 4 - FSH - Galanin 1, 2, 3 - Gonadotropin-releasing hormone 1, 2 - Ghrelin - Histamine H1, H2, H3, H4 - Kisspeptin - Luteinizing hormone/choriogonadotropin - Lysophospholipid 1, 2, 3, 4, 5, 6, 7, 8 - MAS 1, 1L, D, E, F, G, X1, X2, X3, X4 - Melanocortin 1, 2, 3, 4, 5 - MCHR 1, 2 - Melatonin 1A, 1B- Motilin - neuromedin B, U 1, 2 - Neurotensin 1, 2 - Opioid Delta, Kappa, Mu, Nociceptin, but not Sigma - Olfactory - Opsin 3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH - Orexin 1, 2 - Oxytocin - Oxoglutarate - PAF - Prokineticin 1, 2 - Prolactin-releasing peptide - Protease-activated 1, 2, 3, 4 - Relaxin 1, 2, 3, 4 - Somatostatin 1, 2, 3, 4, 5 - SREB - Succinate - TAAR 1, 2, 3, 5, 6, 8, 9 - Tachykinin 1, 2, 3 - Thyrotropin - Thyrotropin-releasing hormone - Urotensin-II - Vasopressin 1A, 1B, 2 Class B: Secretin like Brain-specific angiogenesis inhibitor 1, 2, 3 - Cadherin 1, 2, 3 - Calcitonin - CD97 - Corticotropin-releasing hormone 1, 2 - EMR 1, 2, 3 - Glucagon GR, GIPR, GLP1R, GLP2R - Growth hormone releasing hormone - PACAPR1- GPR 56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 157 - Latrophilin 1, 2, 3, ELTD1 - Parathyroid hormone 1, 2 - Secretin - Vasoactive intestinal peptide 1, 2 Class C: Metabotropic glutamate / pheromone Calcium-sensing receptor - GABA B 1, 2 - Glutamate receptor Metabotropic glutamate 1, 2, 3, 4, 5, 6, 7, 8 - GPRC6A - GPR 156, 158, 179 - RAIG 1, 2, 3, 4 - Taste receptors TAS1R 1, 2, 3 TAS2R 1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50 Frizzled / Smoothened Frizzled 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 - Smoothened v d e Signaling pathway: hedgehog signaling pathway Ligands Sonic hedgehog · Indian hedgehog · Desert hedgehog Other PTCH1 · Smoothened · GLI1 · GLI2 · GLI3 · HHIP · HHAT Retrieved from http://en..org/wiki/Smoothened Categories: Genes on chromosome 7 | Human proteins | Transmembrane receptor stubs | 7TM receptors | G protein coupled receptorsHidden category: Protein pages needing a picture Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page This page was last modified on 7 September 2008, at 22:03
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