Property Summary

NCBI Gene PubMed Count 97
PubMed Score 12.47
PubTator Score 331.28

Knowledge Summary

Patent (70,141)

Expression

  Differential Expression (8)

Disease log2 FC p
posterior fossa group A ependymoma 1.500 1.9e-12
cutaneous lupus erythematosus -1.200 6.9e-03
osteosarcoma 1.529 7.7e-05
atypical teratoid / rhabdoid tumor 1.900 4.3e-10
glioblastoma 1.300 2.4e-06
sonic hedgehog group medulloblastoma 1.400 5.0e-07
medulloblastoma, large-cell 1.100 6.0e-03
lung cancer 1.200 9.7e-03

Protein-protein Interaction (2)

Gene RIF (74)

PMID Text
27437577 crystal structures of the Hh signal transducer and oncoprotein Smoothened, a GPCR that contains two distinct ligand-binding sites: one in its transmembrane domain and one in the cysteine-rich domain
27002170 Smoothened determines beta-arrestin-mediated removal of the G protein-coupled receptor Gpr161 from the primary cilium.
26655998 Suggest that hypoxia promotes SMO transcription through upregulation of MAML3 and RBPJ to induce proliferation, invasiveness and tumorigenesis in pancreatic cancer.
26317547 Crocetinic acid inhibited the expression of both Shh and smoothened in pancreatic cancer stem cells, thereby inhibiting pancreatic tumorigenesis
26261515 These findings suggest that miR-218 inhibits multidrug resistance of gastric cancer cells by down-regulating smoothened expression.
26130651 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.
26126827 Calcitriol represents a possible endogenous transmitter of Ptch/Smo interaction.
26124204 The combined inhibition of SMO and EGFR exerted a strong antiproliferative activity.
25944162 Recipient SMO rs3824 polymorphism is associated with an increased risk of hepatocellular carcinoma recurrence following orthotopic liver transplantation.
25854168 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.
25785427 analysis of small-molecule regulation of SMO and discussion of potential mechanisms for its endogenous regulation [review]
25759020 Mutations within the SMO protein are implicated in drug resistance in basal cell carcinoma.
25759019 SMO mutations are implicated in drug resistance in basal cell carcinoma.
25306392 report discussed two different SMO mutations representing examples of primary or secondary resistance respectively to vismodegib in two distinct basal cell carcinoma cases
25173582 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.
25023548 SMO expression was significantly associated with better colorectal cancer-specific survival.
25008467 The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis.
24859340 SMO mutation is asociated with ameloblastoma.
24469022 Studies indicate that Smoothened (Smo) inhibitor was beneficial for the treatment of advanced basal cell carcinoma (BCC).
24393163 signaling mediated by Smo contributes to acquired chemoresistance through activating the transcriptional factor Gli
24277750 MicroRNA-338-3p could inhibit colorectal carcinoma cell invasion and migration by inhibiting smoothened expression.
24148123 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]
23915072 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
23636324 crystal structure of the transmembrane domain of the human SMO receptor bound to the small-molecule antagonist LY2940680 at 2.5 A resolution
23599646 miR-338-3p could suppress colorectal carcinoma growth by inhibiting SMO protein expression.
23508962 Nonclassical activation of Hedgehog signaling enhances multidrug resistance and makes cancer cells refractory to Smoothened-targeting Hedgehog inhibition
23448715 GSA-10 allows the pharmacological characterization of a novel Smo active site.
23379358 We observed strong correlation between higher SMO and SHH expression levels with poorer overall survival.
23349881 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.
23348505 SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas
23341351 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
23334667 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.
23098507 High SMO expression is asociated with postoperative liver metastasis in colon cancer.
23063129 Study shows that hedgehog signaling rewires cellular metabolism; Smo-dependent noncanonical signal rewires metabolism in vitro and in vivo.
22901214 High SMO expression is associated with colorectal cancer.
22864913 different pools of Smo move into cilia through distinct mechanisms
22535603 The immunoexpression of Shh, Smo and Gli2 proteins was lower in Helicobacter pylori-positive group compared to Helicobacter pylori-negative group
22486854 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.
22253573 USP8 is a positive regulator in Hh signaling by down-regulating Smo ubiquitination and thereby mediating Smo intracellular trafficking.
22231273 the effects of oxysterols on Hedgehog signaling are exquisitely stereoselective, consistent with the hypothesis that they function through a specific protein target.
22114142 Sonic Hedgehog activates the GTPases Rac1 and RhoA in a Gli-independent manner through coupling of smoothened to Gi proteins.
21757753 alpha subunit of the G protein G13 regulates activity of one or more Gli transcription factors independently of smoothened
21338440 hypoxia induces upregulation of Smo transcription, consequently increasing Hh pathway activation in a ligand-independent manner and enhancing the invasiveness of pancreatic cancer.
21210262 We found that hedgehog-interacting protein, PDGFRalpha, SMO and Su(Fu) gene highly expressed in the primary esophageal squamous cell carcinomas
20937227 The expression level of SMO in NPC is generally high, but the expression level of PTCH-1 was relatively low.
20819778 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20603613 functional role of SMOH and GLI in cell survival
20561215 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.
20215540 Overexpression of SMO activates the sonic hedgehog signaling pathway and is associated with pancreatic cancer.
20067614 Knockdown of SMO by SMO shRNA prevents osteosarcoma growth in vitro and in vivo.
20050020 SMO is preferentially expressed by human bulge cells, compared to differentiated hair follicle keratinocytes
19730683 Observational study of gene-disease association. (HuGE Navigator)
19726788 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
19564910 Studies suggest that Hh binding to Ptc leads to the de-repression of the GPCR-related protein Smo.
19473442 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
19453261 Observational study of gene-disease association. (HuGE Navigator)
19432668 the expression of Smoothened was very low or almost absent In the normal endometrium and significantly highly expressed in complex and atypical hyperplasia
19401682 Observational study of gene-disease association. (HuGE Navigator)
19351817 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19304771 The interactions of small molecule agonists and antagonists with SMO were characterized.
19237606 Observational study of gene-disease association, gene-gene interaction, and gene-environment interaction. (HuGE Navigator)
18543049 Constitutive activation of the hedgehog signaling pathway in chondrosarcoma is rarely caused by SMO protein mutation.
18502968 mutations are rare in SMO in sporadic and nevoid basal cell carcinoma syndrome-associated keratocystic odontogenic tumors
18359851 Smo mutants augment p53 binding to the E3 ubiquitin-protein ligase Mdm2 and promote p53 ubiquitination.
17884791 Specific siRNA can significantly decrease Smo mRNA expression and inhibit the proliferation while inducing apoptosis of LoVo cells.
16945339 analysis of Hedgehog modulator properties after functional coupling of Smoothened to G15
16867986 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
16804411 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
16339184 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
15618519 beta-Arrestin 2 and GRK2 are potential mediators of signaling by activated Smoothened
12773389 role of the human M2SMO mutant in BCC development in adult transgenic mice
12499255 Significantly high levels of ultraviolet-specific mutations in the smoothened gene are found in basal cell carcinomas from DNA repair-deficient xeroderma pigmentosum patients.
12241103 smoothened expression in human astrocytic tumors inversely correlates with histological malignancy
12192414 results suggest that the Ptc tumour suppressor functions normally as a transmembrane molecular transporter, which acts indirectly to inhibit Smo activity

AA Sequence

MAAARPARGPELPLLGLLLLLLLGDPGRGAASSGNATGPGPRSAGGSARRSAAVTGPPPPLSHCGRAAPC      1 - 70
EPLRYNVCLGSVLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVE     71 - 140
LPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFPEGCTNEVQNIKFNSSGQCEVPLVRTDNPKSWYEDV    141 - 210
EGCGIQCQNPLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIG    211 - 280
WLAQFMDGARREIVCRADGTMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTY    281 - 350
QPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLI    351 - 420
RGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLC    421 - 490
QANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWRRTWCRLTGQSDDEP    491 - 560
KRIKKSKMIAKAFSKRHELLQNPGQELSFSMHTVSHDGPVAGLAFDLNEPSADVSSAWAQHVTKMVARRG    561 - 630
AILPQDISVTPVATPVPPEEQANLWLVEAEISPELQKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPST    631 - 700
IPRLPQLPRQKCLVAAGAWGAGDSCRQGAWTLVSNPFCPEPSPPQDPFLPSAPAPVAWAHGRRQGLGPIH    701 - 770
SRTNLMDTELMDADSDF                                                         771 - 787
//

Text Mined References (98)

PMID Year Title
27437577 2016 Structural basis of Smoothened regulation by its extracellular domains.
27002170 2016 Smoothened determines ?-arrestin-mediated removal of the G protein-coupled receptor Gpr161 from the primary cilium.
26655998 2016 Hypoxia but not normoxia promotes Smoothened transcription through upregulation of RBPJ and Mastermind-like 3 in pancreatic cancer.
26317547 2015 Crocetinic acid inhibits hedgehog signaling to inhibit pancreatic cancer stem cells.
26261515 2015 MiR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened.
26130651 2015 RAS/MAPK Activation Drives Resistance to Smo Inhibition, Metastasis, and Tumor Evolution in Shh Pathway-Dependent Tumors.
26126827 2015 A Functional and Putative Physiological Role of Calcitriol in Patched1/Smoothened Interaction.
26124204 2015 SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer.
25944162 2015 Association between donor and recipient smoothened gene polymorphisms and the risk of hepatocellular carcinoma recurrence following orthotopic liver transplantation in a Han Chinese population.
25854168 2015 Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours.
25785427 2015 Regulation of the oncoprotein Smoothened by small molecules.
25759020 2015 Smoothened variants explain the majority of drug resistance in basal cell carcinoma.
25759019 2015 Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma.
25306392 2015 Smoothened (SMO) receptor mutations dictate resistance to vismodegib in basal cell carcinoma.
25173582 2015 Targeting the SMO oncogene by miR-326 inhibits glioma biological behaviors and stemness.
25023548 2014 SMO expression in colorectal cancer: associations with clinical, pathological, and molecular features.
25008467 2014 Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs.
24859340 2014 Identification of recurrent SMO and BRAF mutations in ameloblastomas.
24469022 2014 Smoothened inhibitors in the treatment of advanced basal cell carcinomas.
24393163 2014 GPCR-like signaling mediated by smoothened contributes to acquired chemoresistance through activating Gli.
24277750 2014 MicroRNA-338-3p inhibits colorectal carcinoma cell invasion and migration by targeting smoothened.
24148123 2013 [Structure of the Smoothened receptor].
23915072 2013 Smoothened inhibition leads to decreased proliferation and induces apoptosis in esophageal adenocarcinoma cells.
23636324 2013 Structure of the human smoothened receptor bound to an antitumour agent.
23599646 2013 miRNA-338-3p suppresses cell growth of human colorectal carcinoma by targeting smoothened.
23533145 2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
23508962 2013 Nonclassical activation of Hedgehog signaling enhances multidrug resistance and makes cancer cells refractory to Smoothened-targeting Hedgehog inhibition.
23448715 2013 Discovery, molecular and pharmacological characterization of GSA-10, a novel small-molecule positive modulator of Smoothened.
23379358 2013 SMO expression level correlates with overall survival in patients with malignant pleural mesothelioma.
23349881 2013 Mutations in the hedgehog pathway genes SMO and PTCH1 in human gastric tumors.
23348505 2013 Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.
23341351 2013 Targeting of the signal transducer Smo links microRNA-326 to the oncogenic Hedgehog pathway in CD34+ CML stem/progenitor cells.
23334667 2013 Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations.
23098507 2012 Expression of smoothened protein in colon cancer and its prognostic value for postoperative liver metastasis.
23063129 2012 Hedgehog partial agonism drives Warburg-like metabolism in muscle and brown fat.
22901214 2012 Expression and clinical significance of hedgehog signaling pathway related components in colorectal cancer.
22864913 2012 Small molecule inhibitors of Smoothened ciliary localization and ciliogenesis.
22535603 2012 The immunoexpression of Shh, Smo and Gli2 in Helicobacter pylori positive and negative gastric biopsies.
22486854 2012 Hedgehog inhibitor decreases chemosensitivity to 5-fluorouracil and gemcitabine under hypoxic conditions in pancreatic cancer.
22253573 2012 USP8 promotes smoothened signaling by preventing its ubiquitination and changing its subcellular localization.
22231273 2012 Oxysterols are allosteric activators of the oncoprotein Smoothened.
22114142 2011 Sonic Hedgehog activates the GTPases Rac1 and RhoA in a Gli-independent manner through coupling of smoothened to Gi proteins.
22072986 2011 A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.
21931618 2011 The hedgehog receptor patched is involved in cholesterol transport.
21757753 2011 The alpha subunit of the G protein G13 regulates activity of one or more Gli transcription factors independently of smoothened.
21338440 2011 Hypoxia activates the hedgehog signaling pathway in a ligand-independent manner by upregulation of Smo transcription in pancreatic cancer.
21210262 2011 Identification of signature genes for detecting hedgehog pathway activation in esophageal cancer.
21177415 2011 Identification and mechanism of action of the acylguanidine MRT-83, a novel potent Smoothened antagonist.
20937227 2010 [Expression of PTCH-1 and SMO mRNA in nasopharyngeal carcinoma].
20819778 2010 MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer.
20603613 2010 Inhibition of GLI, but not Smoothened, induces apoptosis in chronic lymphocytic leukemia cells.
20561215 2010 Immunohistochemical expression of SHH, PTC, SMO and GLI1 in glandular odontogenic cysts and dentigerous cysts.
20215540 2010 Overexpression of smoothened activates the sonic hedgehog signaling pathway in pancreatic cancer-associated fibroblasts.
20067614 2010 Smoothened as a new therapeutic target for human osteosarcoma.
20050020 2009 Hedgehog signaling maintains hair follicle stem cell phenotype in young and aged human skin.
19730683 2009 The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors.
19726788 2009 Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma.
19592253 2009 The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development.
19564910 2009 The hedgehog signaling pathway: where did it come from?
19473442 2009 The immunoprofile of odontogenic keratocyst (keratocystic odontogenic tumor) that includes expression of PTCH, SMO, GLI-1 and bcl-2 is similar to ameloblastoma but different from odontogenic cysts.
19453261 2009 High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men.
19432668 2009 Expression of sonic hedgehog signaling molecules in normal, hyperplastic and carcinomatous endometrium.
19401682 2010 High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility.
19351817 2009 Genetic mutations associated with cigarette smoking in pancreatic cancer.
19304771 2009 Evidence for allosteric interactions of antagonist binding to the smoothened receptor.
19237606 2009 Genetic polymorphisms in 85 DNA repair genes and bladder cancer risk.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18543049 2008 Patched-one or smoothened gene mutations are infrequent in chondrosarcoma.
18502968 2008 PTCH1 and SMO gene alterations in keratocystic odontogenic tumors.
18359851 2008 Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2.
17884791 2007 [Effects of specific small interfering RNA on Smoothened expression and LoVo cell proliferation and apoptosis].
17850284 2007 Immunohistochemical analysis of Sonic hedgehog signalling in normal human urinary tract development.
16945339 2006 Identification and characterization of Hedgehog modulator properties after functional coupling of Smoothened to G15.
16867986 2006 Human receptors patched and smoothened partially transduce hedgehog signal when expressed in Drosophila cells.
16804411 2006 Aberrant expression of PTCH (patched gene) and Smo (smoothened gene) in human pancreatic cancerous tissues and its association with hyperglycemia.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16339184 2006 Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis.
15618519 2004 Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
12773389 2003 The magnitude of hedgehog signaling activity defines skin tumor phenotype.
12690205 2003 Human chromosome 7: DNA sequence and biology.
12499255 2002 Significantly high levels of ultraviolet-specific mutations in the smoothened gene in basal cell carcinomas from DNA repair-deficient xeroderma pigmentosum patients.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12241103 2002 Patched and smoothened mRNA expression in human astrocytic tumors inversely correlates with histological malignancy.
12192414 2002 Patched acts catalytically to suppress the activity of Smoothened.
12165511 2002 Sonic hedgehog promotes cell cycle progression in activated peripheral CD4(+) T lymphocytes.
12123571 2002 Sonic hedgehog induces the segregation of patched and smoothened in endosomes.
11748145 2001 Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation.
11278759 2001 The sonic hedgehog receptor patched associates with caveolin-1 in cholesterol-rich microdomains of the plasma membrane.
11042037 2000 Erythroid differentiation in vitro is blocked by cyclopamine, an inhibitor of hedgehog signaling.
9811851 1998 Characterization of two patched receptors for the vertebrate hedgehog protein family.
9799615 1998 Chromosomal localization of the human and murine orthologues of the Drosophila smoothened gene.
9764827 1998 PTCH gene mutations in invasive transitional cell carcinoma of the bladder.
9628830 1998 Chromosomal localization of the human smoothened gene (SMOH) to 7q32. 3 by fluorescence in situ hybridization and radiation hybrid mapping.
9581815 1998 Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system.
9422511 1998 Activating Smoothened mutations in sporadic basal-cell carcinoma.
8906787 1996 The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.
8898207 1996 Dual roles for patched in sequestering and transducing Hedgehog.