Zaglađeni receptori

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Zaglađeni homolog (Drosophila)
Identifikatori
SimboliSMO; Gx; SMOH
Vanjski IDOMIM: 601500 MGI: 108075 HomoloGene: 4115 IUPHAR: SMO GeneCards: SMO Gene
Ontologija gena
Molekularna funkcija • receptorska aktivnost
• aktivnost nevezana za G-protein spregnuti receptor
• aktivnost G-protein spregnutog receptora
• proteinsko vezivanje
Celularna komponenta • membranska frakcija
• cilium
• membrana
• integralno sa membranom
Biološki proces • vaskulogeneza
• diferencijacija osteoblasta
• signalni put G-protein spregnutog receptora
• signalni put zaglađenog receptora
• razvoj više-ćelijkih organizama
• determinacija levo/desno simetrije
• razvoj centralnog nervnog sistema
• formiranje dorzalnog / ventralnog šablona
• negativna regulacija DNK vezivanja
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez6608319757
EnsemblENSG00000128602n/a
UniProtQ99835n/a
RefSeq (mRNA)NM_005631NM_176996
RefSeq (protein)NP_005622NP_795970
Lokacija (UCSC)Chr 7:
128.62 - 128.64 Mb		n/a
PubMed pretraga[1][2]

Zaglađeni (engl. Smoothened) je protein-spregnuti receptor[1] kodiran SMO genom hedgehog signalnim putem koji je konzerviran od muva do ljudi. On je molekulska meta teratogenih ciklopamina.[2]

Ćelijska lokalizacija je esencijalna za funkciju ovog receptora. Stimulacija PTCH1 receptora soničnim hedgehog ligandom dovodi do SMO translokacije u primarni cilium. SMO koji je mutiran u domenu neophodnom za cilijarnu lokalizaciju ne može da doprinese aktivaciji puta.[3] Za SMO je bilo pokazano da vezuje kinezin motorni protein Costal-2 i da učestvuje u Ci lokalizaciji (Cubitus interruptus - kompleks transkripcionog faktora).[4]

Reference

  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. 

Literatura

  • Chen Y, Struhl G (1996). „Dual roles for patched in sequestering and transducing Hedgehog.”. Cell 87 (3): 553-63. DOI:10.1016/S0092-8674(00)81374-4. 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. DOI:10.1073/pnas.95.23.13630. PMC 24870. 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. DOI:10.1016/S0960-9822(02)00895-3. 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. DOI:10.1023/A:1019660421216. 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. PMC 139241. 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. PMC 2882961. 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. PMC 156767. 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. PMC 528928. 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. 
  • „Frizzled Receptors: SMO”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2015-02-25. 

Spoljašnje veze

  • MeSH SMO+protein,+human
  • p
  • r
  • u
Klasa A: Rodopsinu slični
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(svi osim 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)
Drugi
Acetilholin (M1, M2, M3, M4, M5) • Dopamin (D1, D2, D3, D4, D5) • Histamin (H1, H2, H3, H4) • Melatonin (1A, 1B, 1C) • TAAR (1, 2, 3, 5, 6, 8, 9)
Metaboliti i
signalni molekuli
CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan
Drugi
Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat  • Lizofosfatidna kiselina (1, 2, 3, 4, 5, 6)  • Lizofosfolipid (1, 2, 3, 4, 5, 6, 7, 8) • Niacin (1, 2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1, 2, 3, 4, 5) • Sukcinat
Peptid
B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotenzin (1, 2)
Drugi
Anafilatoksin (C3a, C5a) • Angiotenzin (1, 2) • Apelin • Bombezin (BRS3, GRPR, NMBR) • Bradikinin (B1, B2) • Hemokin • Holecistokinin (A, B) • Endotelin (A, B) • Formil peptid (1, 2, 3) • FSH • Galanin (1, 2, 3) • GHB receptor • Gonadotropin-oslobađajući hormon (1, 2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanokortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Motilin • Opioidni (δ, κ, μ, Nociceptin & ζ, ali ne σ) • Oreksin (1, 2) • Oksitocin • Prokineticin (1, 2) • Prolaktin-oslobađajući peptid • Relaksin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • Tahikinin (1, 2, 3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A, 1B, 2)
Razno
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, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Drugi
Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3)
Klasa B: Sekretinu slični
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi
Klasa C: Metabotropni
glutamat / feromon
TAS1R (1, 2, 3) • TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Drugi
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni
Zaglađeni
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)