Smo smoothened, frizzled class receptor [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Smoprovided by MGI
Official Full Name: smoothened, frizzled class receptorprovided by MGI
Primary source: MGI:MGI:108075
See related: Ensembl:ENSMUSG00000001761
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: bnb; Smoh; smoothened; E130215L21Rik
Expression: Broad expression in ovary adult (RPKM 53.2), limb E14.5 (RPKM 37.8) and 25 other tissues See more
Orthologs: human all

Genomic context

Location:: 6 A3.3; 6 12.36 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
106	current	GRCm38.p4 (GCF_000001635.24)	6	NC_000072.6 (29735497..29761366)
Build 37.2	previous assembly	MGSCv37 (GCF_000001635.18)	6	NC_000072.5 (29685497..29711366)

Chromosome 6 - NC_000072.6 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Identify SMO-dependent Shh signalling as a specific process for the activation of adventitial fibroblasts and the subsequent proliferation of smooth muscle cells and neointima formation.
Title: Sonic hedgehog-dependent activation of adventitial fibroblasts promotes neointima formation.
cholesterol within the bilayer is sufficient for constitutive Smoothened activation. Cholesterol effects occur independently of the lipid-binding Smoothened extracellular domain, a region that is dispensable for Patched1-Smoothened coupling.
Title: Rapid, direct activity assays for Smoothened reveal Hedgehog pathway regulation by membrane cholesterol and extracellular sodium.
Highest levels of vertebrate Hedgehog signaling activity require efficient Smo ciliary enrichment.
Title: Hypomorphic Smo mutant with inefficient ciliary enrichment disrupts the highest level of vertebrate Hedgehog response.
This study showed for the first time that sustained Smo inhibits postnatal kidney development by suppressing the proliferation of the mesenchyme and medullary collecting ducts in mice.
Title: Constitutive Activation of Smoothened in the Renal Collecting Ducts Leads to Renal Hypoplasia, Hydronephrosis, and Hydroureter.
the cytosolic phospholipase cPLA2alpha is activated through Gbetagamma downstream of Smo to release arachidonic acid. Arachidonic acid binds Smo and synergizes with CRD-binding agonists, promoting Smo ciliary trafficking and high-level signaling.
Title: Sonic Hedgehog Activates Phospholipase A2 to Enhance Smoothened Ciliary Translocation.
The authors find that cholesterol, an important component of the cell membrane, directly binds to Smoothened and changes its shape so that it can activate Hedgehog signaling components inside cells.
Title: Cholesterol activates the G-protein coupled receptor Smoothened to promote Hedgehog signaling.
Depletion of SMO mRNA in Jurkat cells facilitated HIV-1 vector infection, suggesting that endogenous SMO plays a role in limiting lentiviral infection. These results suggest that SMO inhibits HIV-1 replication after completion of reverse transcription but before integration.
Title: Human SMOOTHENED inhibits human immunodeficiency virus type 1 infection.
These findings support a model in which Ptch1/2 mediate secretion of a Smo-inhibitory cholesterol precursor.
Title: Patched1 and Patched2 inhibit Smoothened non-cell autonomously.
the data suggest that CCRK positively regulates the kinetics by which ciliary proteins such as Smoothened and Gli2 are imported into the cilium, and that the efficiency of ciliary recruitment allows for potent responses to Hedgehog signaling over long time periods.
Title: Cell Cycle-Related Kinase (CCRK) regulates ciliogenesis and Hedgehog signaling in mice.
SMO is covalently modified by cholesterol. This modification is regulated by Ptch1 and Hh and is essential for Hh signaling.
Title: Cholesterol Modification of Smoothened Is Required for Hedgehog Signaling.

Submit: New GeneRIF Correction See all GeneRIFs (81)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (6) 1 citation
Chemically induced (ENU) (3) 1 citation

Pathways from BioSystems

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Activation of SMO, organism-specific biosystem (from REACTOME)
Activation of SMO, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Axon guidance, organism-specific biosystem (from KEGG)
Axon guidance, organism-specific biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
Axon guidance, conserved biosystem (from KEGG)
Axon guidance, conserved biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
Basal cell carcinoma, organism-specific biosystem (from KEGG)
Basal cell carcinoma, organism-specific biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
Basal cell carcinoma, conserved biosystem (from KEGG)
Basal cell carcinoma, conserved biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
GPCRs, Other, organism-specific biosystem (from WikiPathways)
GPCRs, Other, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.cmbi.kun.nl/7tm/. The groupings are based on the GPCR phylogenetic tree available from the GPCRDB and the training sets used ...
Hedgehog 'off' state, organism-specific biosystem (from REACTOME)
Hedgehog 'off' state, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Hedgehog 'on' state, organism-specific biosystem (from REACTOME)
Hedgehog 'on' state, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Hedgehog Signaling Pathway, organism-specific biosystem (from WikiPathways)
Hedgehog Signaling Pathway, organism-specific biosystemThe Hedgehog proteins are a family of secreted ligands that include sonic hedgehog, Indian hedgehog and desert hedgehog in humans. Binding of Hedgehog ligands to their receptors, Patched 1 and 2, pre...
Hedgehog signaling, organism-specific biosystem (from KEGG)
Hedgehog signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
Hedgehog signaling, conserved biosystem (from KEGG)
Hedgehog signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
Hedgehog signaling pathway, organism-specific biosystem (from KEGG)
Hedgehog signaling pathway, organism-specific biosystemThe Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for tr...
Hedgehog signaling pathway, conserved biosystem (from KEGG)
Hedgehog signaling pathway, conserved biosystemThe Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for tr...
Non-odorant GPCRs, organism-specific biosystem (from WikiPathways)
Non-odorant GPCRs, organism-specific biosystemListing of non-odorant Mouse GCPRs by coupling.
Pathways in cancer, organism-specific biosystem (from KEGG)
Pathways in cancer, organism-specific biosystem
Pathways in cancer
PluriNetWork, organism-specific biosystem (from WikiPathways)
PluriNetWork, organism-specific biosystemThe aim of the PluriNetWork is to give an overview of specific mechanisms associated with pluripotency in mouse. Each node represents a gene and its corresponding protein product. As stated, we inten...
Proteoglycans in cancer, organism-specific biosystem (from KEGG)
Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
Proteoglycans in cancer, conserved biosystem (from KEGG)
Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Signaling by Hedgehog, organism-specific biosystem (from REACTOME)
Signaling by Hedgehog, organism-specific biosystemcomputationally inferred pathway (not manually curated)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:237068

Smoh (e-PCR), detects polymorphism
- UniSTS:144443

AU041277 (e-PCR)
- UniSTS:160324

Smo (e-PCR), detects polymorphism
- UniSTS:465497

D6Mit159 (e-PCR), detects polymorphism
- UniSTS:116597

NoName (e-PCR)
- UniSTS:548507

Smo (e-PCR), detects polymorphism
- UniSTS:546036

Homology

Homologs of the Smo gene: The Smo gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 239 organisms have orthologs with human gene Smo
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
G protein-coupled receptor activity	IEA Inferred from Electronic Annotation more info
drug binding	IDA Inferred from Direct Assay more info	PubMed
drug binding	ISO Inferred from Sequence Orthology more info
patched binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
patched binding	ISO Inferred from Sequence Orthology more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
transmembrane signaling receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
anterior/posterior pattern specification	IMP Inferred from Mutant Phenotype more info	PubMed
astrocyte activation	IMP Inferred from Mutant Phenotype more info	PubMed
atrial septum morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
axon extension involved in axon guidance	ISO Inferred from Sequence Orthology more info
cell development	IMP Inferred from Mutant Phenotype more info	PubMed
cell fate specification	IMP Inferred from Mutant Phenotype more info	PubMed
cell surface receptor signaling pathway	IEA Inferred from Electronic Annotation more info
cellular response to cholesterol	IEP Inferred from Expression Pattern more info	PubMed
central nervous system development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
central nervous system development	IGI Inferred from Genetic Interaction more info	PubMed
central nervous system neuron differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
cerebellar cortex morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
cerebral cortex development	IMP Inferred from Mutant Phenotype more info	PubMed
commissural neuron axon guidance	IBA Inferred from Biological aspect of Ancestor more info	PubMed
commissural neuron axon guidance	ISO Inferred from Sequence Orthology more info
dentate gyrus development	IMP Inferred from Mutant Phenotype more info	PubMed
detection of cell density by contact stimulus involved in contact inhibition	ISO Inferred from Sequence Orthology more info
determination of left/right asymmetry in lateral mesoderm	IMP Inferred from Mutant Phenotype more info	PubMed
determination of left/right symmetry	IMP Inferred from Mutant Phenotype more info	PubMed
developmental growth	IMP Inferred from Mutant Phenotype more info	PubMed
digestive tract development	IMP Inferred from Mutant Phenotype more info	PubMed
dorsal/ventral neural tube patterning	IMP Inferred from Mutant Phenotype more info	PubMed
dorsal/ventral pattern formation	IMP Inferred from Mutant Phenotype more info	PubMed
embryonic organ development	IGI Inferred from Genetic Interaction more info	PubMed
epithelial-mesenchymal cell signaling	IMP Inferred from Mutant Phenotype more info	PubMed
forebrain morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
hair follicle morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
heart looping	IMP Inferred from Mutant Phenotype more info	PubMed
heart morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
homeostasis of number of cells within a tissue	IDA Inferred from Direct Assay more info	PubMed
in utero embryonic development	IMP Inferred from Mutant Phenotype more info	PubMed
left/right axis specification	IMP Inferred from Mutant Phenotype more info	PubMed
mammary gland epithelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
mesenchymal to epithelial transition involved in metanephric renal vesicle formation	IMP Inferred from Mutant Phenotype more info	PubMed
midgut development	IMP Inferred from Mutant Phenotype more info	PubMed
multicellular organism development	IEA Inferred from Electronic Annotation more info
multicellular organism growth	IGI Inferred from Genetic Interaction more info	PubMed
multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
myoblast migration	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of DNA binding	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of epithelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of hair follicle development	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
negative regulation of neuron death	ISO Inferred from Sequence Orthology more info
negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
neural crest cell migration	IGI Inferred from Genetic Interaction more info	PubMed
odontogenesis of dentin-containing tooth	IMP Inferred from Mutant Phenotype more info	PubMed
ossification	IMP Inferred from Mutant Phenotype more info	PubMed
osteoblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
pancreas morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
pattern specification process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of branching involved in ureteric bud morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of hh target transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of mesenchymal cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of neural precursor cell proliferation	ISO Inferred from Sequence Orthology more info
positive regulation of neuroblast proliferation	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of organ growth	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein import into nucleus	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of smoothened signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of smoothened signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of vascular associated smooth muscle cell migration	ISO Inferred from Sequence Orthology more info
protein localization to nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
protein stabilization	IDA Inferred from Direct Assay more info	PubMed
regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
regulation of heart morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of stem cell population maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
signal transduction	IEA Inferred from Electronic Annotation more info
skeletal muscle fiber development	IMP Inferred from Mutant Phenotype more info	PubMed
smoothened signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
smoothened signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
smoothened signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
smoothened signaling pathway	ISO Inferred from Sequence Orthology more info
smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
smoothened signaling pathway involved in ventral spinal cord patterning	IMP Inferred from Mutant Phenotype more info	PubMed
somite development	IMP Inferred from Mutant Phenotype more info	PubMed
thalamus development	IMP Inferred from Mutant Phenotype more info	PubMed
type B pancreatic cell development	IMP Inferred from Mutant Phenotype more info	PubMed
vasculogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
ventral midline determination	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
colocalizes_with Golgi apparatus	ISO Inferred from Sequence Orthology more info
axonal growth cone	ISO Inferred from Sequence Orthology more info
colocalizes_with caveola	ISO Inferred from Sequence Orthology more info
cell projection	IEA Inferred from Electronic Annotation more info
ciliary membrane	IDA Inferred from Direct Assay more info	PubMed
cilium	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cilium	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	ISO Inferred from Sequence Orthology more info
dendrite	IBA Inferred from Biological aspect of Ancestor more info	PubMed
dendrite	ISO Inferred from Sequence Orthology more info
dendritic growth cone	ISO Inferred from Sequence Orthology more info
integral component of membrane	IEA Inferred from Electronic Annotation more info
intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
membrane	IEA Inferred from Electronic Annotation more info
neuronal cell body	ISO Inferred from Sequence Orthology more info
nucleus	ISO Inferred from Sequence Orthology more info
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	ISO Inferred from Sequence Orthology more info
postsynaptic density	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: smoothened homolog

Names: bent body

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_176996.4 → NP_795970.3 smoothened homolog precursor

See identical proteins and their annotated locations for NP_795970.3

Status: VALIDATED

Source sequence(s)

AC069469, AK081050, AW555326, BB659739, CA749812, CN665198

Consensus CDS

CCDS19965.1

UniProtKB/Swiss-Prot

P56726

UniProtKB/TrEMBL

Q4VBD5, Q8BJN8

Related

ENSMUSP00000001812.4, ENSMUST00000001812.4

Conserved Domains (2) summary

cd07451
Location:70 → 200

CRD_SMO; Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein

pfam01534
Location:225 → 554

Frizzled; Frizzled/Smoothened family membrane region

RefSeqs of Annotated Genomes: Mus musculus Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm38.p4 C57BL/6J

Genomic

NC_000072.6 Reference GRCm38.p4 C57BL/6J

Range

29735497..29761366

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006505106.3 → XP_006505169.1 smoothened homolog isoform X1

Conserved Domains (2) summary

pfam01534
Location:91 → 420

Frizzled; Frizzled/Smoothened family membrane region

cl02447
Location:1 → 66

CRD_FZ; CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain