dentate gyrus of hippocampal formation granule cell
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
patched binding
protein binding
transmembrane signaling receptor activity
signal transducer activity
G protein-coupled receptor activity
Wnt-protein binding
Wnt-activated receptor activity
Cellular component
cytoplasm
endocytic vesicle membrane
membrane
caveola
cell projection
extracellular exosome
Golgi apparatus
intracellular membrane-bounded organelle
plasma membrane
ciliary tip
ciliary membrane
cilium
integral component of membrane
Biological process
pattern specification process
pancreas morphogenesis
negative regulation of DNA binding
smoothened signaling pathway involved in ventral spinal cord patterning
vasculogenesis
heart looping
odontogenesis of dentin-containing tooth
atrial septum morphogenesis
cell surface receptor signaling pathway
positive regulation of mesenchymal cell proliferation
cerebellar cortex morphogenesis
positive regulation of multicellular organism growth
hair follicle morphogenesis
regulation of heart morphogenesis
type B pancreatic cell development
positive regulation of neuroblast proliferation
renal system development
positive regulation of branching involved in ureteric bud morphogenesis
positive regulation of smoothened signaling pathway
ossification
embryonic organ development
dentate gyrus development
epithelial-mesenchymal cell signaling
regulation of stem cell population maintenance
in utero embryonic development
cellular response to cholesterol
negative regulation of gene expression
positive regulation of transcription, DNA-templated
forebrain morphogenesis
negative regulation of hair follicle development
central nervous system development
central nervous system neuron differentiation
positive regulation of protein import into nucleus
smoothened signaling pathway
G protein-coupled receptor signaling pathway
multicellular organism growth
thalamus development
positive regulation of epithelial cell proliferation
smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation
cell fate specification
protein stabilization
positive regulation of organ growth
negative regulation of apoptotic process
negative regulation of transcription by RNA polymerase II
developmental growth
osteoblast differentiation
determination of left/right asymmetry in lateral mesoderm
cerebral cortex development
regulation of gene expression
homeostasis of number of cells within a tissue
dorsal/ventral neural tube patterning
negative regulation of transcription, DNA-templated
dorsal/ventral pattern formation
myoblast migration
positive regulation of hh target transcription factor activity
ventral midline determination
cell development
astrocyte activation
heart morphogenesis
mesenchymal to epithelial transition involved in metanephric renal vesicle formation
somite development
mammary gland epithelial cell differentiation
multicellular organism development
positive regulation of gene expression
determination of left/right symmetry
skeletal muscle fiber development
neural crest cell migration
positive regulation of cell population proliferation
protein localization to nucleus
digestive tract development
negative regulation of epithelial cell differentiation
left/right axis specification
anterior/posterior pattern specification
positive regulation of transcription by RNA polymerase II
signal transduction
midgut development
non-canonical Wnt signaling pathway
canonical Wnt signaling pathway
Sources:Amigo / QuickGO
Orthologs
Species
Human
Mouse
Entrez
6608
319757
Ensembl
ENSG00000128602
ENSMUSG00000001761
UniProt
Q99835
P56726
RefSeq (mRNA)
NM_005631
NM_176996
RefSeq (protein)
NP_005622
NP_795970
Location (UCSC)
Chr 7: 129.19 – 129.21 Mb
Chr 6: 29.74 – 29.76 Mb
PubMed search
[3]
[4]
Wikidata
View/Edit Human
View/Edit Mouse
Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled (Class F) G protein-coupled receptor[5][6] that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecular target of the natural teratogen cyclopamine.[7] It also is the target of vismodegib, the first hedgehog pathway inhibitor to be approved by the U.S. Food and Drug Administration (FDA).[8]
Smoothened (Smo) is a key transmembrane protein that is a key component of the hedgehog signaling pathway, a cell-cell communication system critical for embryonic development and adult tissue homeostasis.[9][10] Mutations in proteins that relay Hh signals between cells cause birth defects and cancer.[11] The protein that carries the Hh signal across the membrane is the oncoprotein and G-protein coupled receptor (GPCR) Smoothened (Smo). Smo is regulated by a separate transmembrane receptor for Hh ligands called Patched (Ptc). Ptc itself is a tumor suppressor that keeps the Hh pathway off by inhibiting Smo. The excessive Hh signaling that drives human skin and brain cancer is most frequently caused by inactivating mutations in Ptc or by gain of function mutations in Smo. While direct Smo agonists and antagonists, such as SAG and vismodegib, can bind to and activate or inhibit Smo, how Ptc inhibits Smo endogenously remains a mystery in the field.
Currently, Smo is targeted and inhibited directly by a small-molecule drug, vismodegib, for the treatment of advanced basal cell cancer, however widespread resistance to this drug has become a prevalent issue.[12][13] Finding another method to target Smo activity in Hh-driven cancers would provide valuable information for novel therapeutics. Identifying these Ptc responsive sites on Smo will help solve a long-standing mystery in Hh signaling and suggest new therapeutic strategies to block Smo activity in Hh-driven cancers.
^ abcGRCh38: Ensembl release 89: ENSG00000128602 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000001761 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Ruiz-Gómez A, Molnar C, Holguín H, Mayor F, de Celis JF (April 2007). "The cell biology of Smo signalling and its relationships with GPCRs". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1768 (4): 901–12. doi:10.1016/j.bbamem.2006.09.020. hdl:10261/4737. PMID 17094938.
^Taipale J, Chen JK, Cooper MK, Wang B, Mann RK, Milenkovic L, Scott MP, Beachy PA (August 2000). "Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine". Nature. 406 (6799): 1005–9. Bibcode:2000Natur.406.1005T. doi:10.1038/35023008. PMID 10984056. S2CID 4313790.
^"Vismodegib, First Hedgehog Inhibitor, Approved for BCC Patients". OncLive. Retrieved 2017-05-26.
^Jeng KS, Chang CF, Lin SS (January 2020). "Sonic Hedgehog Signaling in Organogenesis, Tumors, and Tumor Microenvironments". Int J Mol Sci. 21 (3): 758. doi:10.3390/ijms21030758. PMC 7037908. PMID 31979397.
^Liu X, Ding C, Tan W, Zhang A (February 2020). "Medulloblastoma: Molecular understanding, treatment evolution, and new developments". Pharmacol. Ther. 210: 107516. doi:10.1016/j.pharmthera.2020.107516. PMID 32105673. S2CID 211557426.
^Laliscia C, Baldaccini D, Antonuzzo A, Paiar F (2019). "Vismodegibfor the treatment of radiation-induced basal cell carcinoma - a case report and brief literature study". Contemp Oncol (Pozn). 23 (4): 251–253. doi:10.5114/wo.2019.91540. PMC 6978755. PMID 31992959.
^Liao S, Floyd C, Verratti N, Leung L, Wu C (March 2020). "Analysis of vismodegib resistance in D473G and W535L mutants of SMO receptor and design of novel drug derivatives using molecular dynamics simulations". Life Sci. 244: 117302. doi:10.1016/j.lfs.2020.117302. PMID 31953165.
Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled (Class F) G protein-coupled receptor that is a component...
Smoothened agonist (SAG) was one of the first small-molecule agonists developed for the protein Smoothened, a key part of the hedgehog signaling pathway...
leads to increased levels of Smoothened is not clear (Step 1 in Figure 3). Following binding of Hh to Patched, Smoothened levels increase greatly over...
In statistics and image processing, to smooth a data set is to create an approximating function that attempts to capture important patterns in the data...
sterol-sensing domain in patched, which then inhibits the activity of smoothened. Smoothened is a G protein-coupled receptor, most of which is stored in membrane...
treatment. These include vismodegib and sonidegib, both inhibitors of Smoothened (SMO), which are being used for the treatment of basal cell carcinoma...
surface membrane protein smoothened may signal further cascades which impact development. Cyclopamine has a high affinity for smoothened – and upon binding...
radiation. The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the Hedgehog signaling pathway. SMO inhibition...
the "Smoothened" protein, by which the Hedgehog signal can be transduced. In the absence of Hedgehog, the Patched receptor inhibits Smoothened action...
skin together at the middle of it. This is what we call navel today. He smoothened the wrinkles and shaped the chest. But he made sure to leave a few wrinkles...
treat cancer. Sonidegib is Hedgehog signaling pathway inhibitor (via smoothened antagonism). It was approved for medical use in the United States and...
protein smoothened. Jervine binds with and inhibits smoothened, which is an integral part of the hedgehog signaling pathways. With smoothened inhibited...
Patched receptor which in the absence of SHH inhibits the Smoothened receptor. Activated smoothened in turn causes Gli1, Gli2, and Gli3 to be translocated...
"Inhibition of Hedgehog Signaling by direct binding of Cyclopamine to Smoothened". Genes Dev. 16 (21): 2743–2748. doi:10.1101/gad.1025302. PMC 187469....
focused lead performance [..] ensures that the film's rough edges are smoothened out to a certain extent." Deccan Herald reviewer Roktim Rajpal stated...
commitment regulation of transcription, DNA-templated positive regulation of smoothened signaling pathway androgen metabolic process kidney development lung development...
mellifluous flows of Shreya Ghoshal singing, the first outing "Saibo" is a smoothening surprise that extols the feel of romanticism to perfection". Later that...
S-Arrestin in humans Sagitta (optics), a measure of lens surface shape Smoothened agonist, a small bioactive molecule Lens sag, distortion of astronomical...
image. As the spatial parameter σd increases, the larger features get smoothened. The bilateral filter in its direct form can introduce several types of...
molten metal is then poured into it to obtain a cast piece which is later smoothened by filing. The casting is now coated with a strong solution of copper...
pathway activation and tumor growth associated with acquired resistance to smoothened antagonists". Cancer Cell. 23 (1): 23–34. doi:10.1016/j.ccr.2012.11.017...
position, most importantly, although more powerful, the engine delivery was smoothened to make the bike more rideable. This made the bike slower on top speed...
Global Information
