Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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smoothened, frizzled class receptor(SMO) smoothened, frizzled class receptor(SMO) Related Genes Homo sapiens
CHROMOSOME 7,
CYTOBAND 7q32.3,
ENSEMBL_GENE_ID ENSG00000128602,
GENERIF_SUMMARY results suggest that the Ptc tumour suppressor functions normally as a transmembrane molecular transporter, which acts indirectly to inhibit Smo activity, smoothened expression in human astrocytic tumors inversely correlates with histological malignancy, Significantly high levels of ultraviolet-specific mutations in the smoothened gene are found in basal cell carcinomas from DNA repair-deficient xeroderma pigmentosum patients., role of the human M2SMO mutant in BCC development in adult transgenic mice, beta-Arrestin 2 and GRK2 are potential mediators of signaling by activated Smoothened, overexpression and/or tumorigenic activation of the Smo proto-oncogene mediates c-myc overexpression which plays a critical role in hepatocarcinogenesis; study suggests that Smo is a prognostic factor in HCC tumorigenesis, aberrant expressions of PTCH and Smo were common in pancreatic carcinoma tissues & were associated with low-level differentiation of tumor tissue & hyperglycemia; this indicated that these molecules played a fundamental role in pancreas tumorigenesis, the upstream part of the Hedgehog pathway involving Hedgehog interaction with Patched, regulation of Smoothened by Patched, and Smoothened enrichment at the plasma membrane is highly conserved between Drosophila and humans, analysis of Hedgehog modulator properties after functional coupling of Smoothened to G15, Specific siRNA can significantly decrease Smo mRNA expression and inhibit the proliferation while inducing apoptosis of LoVo cells., Smo mutants augment p53 binding to the E3 ubiquitin-protein ligase Mdm2 and promote p53 ubiquitination., mutations are rare in SMO in sporadic and nevoid basal cell carcinoma syndrome-associated keratocystic odontogenic tumors, Constitutive activation of the hedgehog signaling pathway in chondrosarcoma is rarely caused by SMO protein mutation., The interactions of small molecule agonists and antagonists with SMO were characterized., the expression of Smoothened was very low or almost absent In the normal endometrium and significantly highly expressed in complex and atypical hyperplasia, investigated immunohistochemical expression of sonic hedgehog signaling pathway-related proteins, PTCH, smoothened (SMO) and GLI-1 in a series of primary OKC, recurrent OKC (rOKC) and nevoid basal cell carcinoma syndrome-associated OKCs, Studies suggest that Hh binding to Ptc leads to the de-repression of the GPCR-related protein Smo., study identified an amino acid substitution at a conserved aspartic acid residue of SMO that had no effect on Hh signaling but disrupted the ability of GDC-0449 to bind SMO and suppress this pathway, SMO is preferentially expressed by human bulge cells, compared to differentiated hair follicle keratinocytes, Knockdown of SMO by SMO shRNA prevents osteosarcoma growth in vitro and in vivo., Overexpression of SMO activates the sonic hedgehog signaling pathway and is associated with pancreatic cancer., proteins of the SHH signaling pathway are predominantly located within the epithelial components of GOCs and DCs. SHH signaling pathway may play a role in epithelial lining formation., functional role of SMOH and GLI in cell survival, The expression level of SMO in NPC is generally high, but the expression level of PTCH-1 was relatively low., We found that hedgehog-interacting protein, PDGFRalpha, SMO and Su(Fu) gene highly expressed in the primary esophageal squamous cell carcinomas, hypoxia induces upregulation of Smo transcription, consequently increasing Hh pathway activation in a ligand-independent manner and enhancing the invasiveness of pancreatic cancer., alpha subunit of the G protein G13 regulates activity of one or more Gli transcription factors independently of smoothened, Sonic Hedgehog activates the GTPases Rac1 and RhoA in a Gli-independent manner through coupling of smoothened to Gi proteins., the effects of oxysterols on Hedgehog signaling are exquisitely stereoselective, consistent with the hypothesis that they function through a specific protein target., USP8 is a positive regulator in Hh signaling by down-regulating Smo ubiquitination and thereby mediating Smo intracellular trafficking., Results suggest that hypoxia-induced increase of Smo directly contributes to the proliferation of pancreatic ductal adenocarcinoma (PDAC) cells through a hedgehog/Gli1-independent pathway., The immunoexpression of Shh, Smo and Gli2 proteins was lower in Helicobacter pylori-positive group compared to Helicobacter pylori-negative group, different pools of Smo move into cilia through distinct mechanisms, High SMO expression is associated with colorectal cancer., Study shows that hedgehog signaling rewires cellular metabolism; Smo-dependent noncanonical signal rewires metabolism in vitro and in vivo., High SMO expression is asociated with postoperative liver metastasis in colon cancer., A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways., downregulation of miR-326 may be a possible mechanism for unrestricted activation of Smo signal transducer of the oncogenic Hedgehog pathway in chronic myeloid leukemia, 5% of non-NF2 mutant meningiomas, SMO and/or PTCH1 mutations are present at low frequency in different histologic subtypes of gastric tumors and these do not appear to be driver mutations., We observed strong correlation between higher SMO and SHH expression levels with poorer overall survival., GSA-10 allows the pharmacological characterization of a novel Smo active site., Nonclassical activation of Hedgehog signaling enhances multidrug resistance and makes cancer cells refractory to Smoothened-targeting Hedgehog inhibition, miR-338-3p could suppress colorectal carcinoma growth by inhibiting SMO protein expression., crystal structure of the transmembrane domain of the human SMO receptor bound to the small-molecule antagonist LY2940680 at 2.5 A resolution, Smo antagonism led to reduced Hedgehog pathway activity, resulting in decreased cell proliferation and induction of apoptosis via the intrinsic pathway in the esophageal cancer cells, The structure of the Smo receptor will promote the development of small molecules interacting with a key therapeutic target with interests in regenerative medicine and cancer.[review], MicroRNA-338-3p could inhibit colorectal carcinoma cell invasion and migration by inhibiting smoothened expression., signaling mediated by Smo contributes to acquired chemoresistance through activating the transcriptional factor Gli, Studies indicate that Smoothened (Smo) inhibitor was beneficial for the treatment of advanced basal cell carcinoma (BCC)., SMO mutation is asociated with ameloblastoma., The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis., SMO expression was significantly associated with better colorectal cancer-specific survival., SMO was upregulated in gliomas and was associated with tumor grade and survival period. SMO inhibition suppressed the biological behaviors of glioma cells. SMO expression was inversely correlated with miR-326 and is a novel direct target of miR-326., report discussed two different SMO mutations representing examples of primary or secondary resistance respectively to vismodegib in two distinct basal cell carcinoma cases, SMO mutations are implicated in drug resistance in basal cell carcinoma., Mutations within the SMO protein are implicated in drug resistance in basal cell carcinoma., analysis of small-molecule regulation of SMO and discussion of potential mechanisms for its endogenous regulation [review], The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E-activating mutation is a common event in ameloblastomas, occurring regardless of site or histological type. This mutation is also detected in odontogenic carcinomas., Recipient SMO rs3824 polymorphism is associated with an increased risk of hepatocellular carcinoma recurrence following orthotopic liver transplantation., The combined inhibition of SMO and EGFR exerted a strong antiproliferative activity., Calcitriol represents a possible endogenous transmitter of Ptch/Smo interaction., Strikingly, in basal cell carcinoma patients treated with Smo inhibitor, squamous cell cancers with RAS/MAPK activation emerged from the antecedent basal cell carcinoma tumors., These findings suggest that miR-218 inhibits multidrug resistance of gastric cancer cells by down-regulating smoothened expression., Crocetinic acid inhibited the expression of both Shh and smoothened in pancreatic cancer stem cells, thereby inhibiting pancreatic tumorigenesis, Suggest that hypoxia promotes SMO transcription through upregulation of MAML3 and RBPJ to induce proliferation, invasiveness and tumorigenesis in pancreatic cancer., Smoothened determines beta-arrestin-mediated removal of the G protein-coupled receptor Gpr161 from the primary cilium., crystal structures of the Hh signal transducer and oncoprotein Smoothened, a GPCR that contains two distinct ligand-binding sites,
OMIM_DISEASE Basal cell carcinoma, somatic,
SP_COMMENT disease:Defects in SMO are involved in basal cell carcinoma (BCC)., function:G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO)., similarity:Belongs to the G-protein coupled receptor Fz/Smo family., similarity:Contains 1 FZ (frizzled) domain.,