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P56726 (SMO_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Smoothened homolog

Short name=SMO
Gene names
Name:Smo
Synonyms:Smoh
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length793 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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). Required for the accumulation of KIF7 and GLI3 in the cilia By similarity.

Subunit structure

Interacts with ARRB2. Interacts with KIF7. Interacts with BBS5 and BBS7; the interactions are indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO. Ref.3 Ref.4

Subcellular location

Membrane; Multi-pass membrane protein. Cell projectioncilium By similarity.

Sequence similarities

Belongs to the G-protein coupled receptor Fz/Smo family.

Contains 1 FZ (frizzled) domain.

Ontologies

Keywords
   Cellular componentCell projection
Membrane
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenohypophysis development

Inferred from Biological aspect of Ancestor. Source: RefGenome

atrial septum morphogenesis

Inferred from genetic interaction PubMed 22898775. Source: MGI

axon extension involved in axon guidance

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

cardioblast differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell development

Inferred from mutant phenotype PubMed 12403705. Source: MGI

cell fate specification

Inferred from mutant phenotype PubMed 18590716. Source: MGI

cellular response to cholesterol

Inferred from expression pattern PubMed 21931618. Source: BHF-UCL

central nervous system development

Inferred from genetic interaction PubMed 12435628. Source: MGI

central nervous system neuron differentiation

Inferred from mutant phenotype PubMed 16571630. Source: MGI

cerebellar cortex morphogenesis

Inferred from mutant phenotype PubMed 16571625. Source: MGI

ciliary receptor clustering involved in smoothened signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

detection of cell density by contact stimulus involved in contact inhibition

Inferred from sequence or structural similarity. Source: UniProtKB

determination of left/right asymmetry in lateral mesoderm

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

determination of left/right symmetry

Inferred from mutant phenotype PubMed 12421714PubMed 15755804. Source: MGI

developmental growth

Inferred from mutant phenotype PubMed 16571630. Source: MGI

digestive tract development

Inferred from mutant phenotype PubMed 19619492. Source: MGI

dorsal/ventral neural tube patterning

Inferred from mutant phenotype PubMed 18590716. Source: MGI

dorsal/ventral pattern formation

Inferred from mutant phenotype PubMed 15755804PubMed 16571630. Source: MGI

embryonic camera-type eye development

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic digestive tract morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic neurocranium morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic viscerocranium morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

epithelial-mesenchymal cell signaling

Inferred from mutant phenotype PubMed 19304890. Source: MGI

exocrine pancreas development

Inferred from Biological aspect of Ancestor. Source: RefGenome

facial nerve development

Inferred from Biological aspect of Ancestor. Source: RefGenome

floor plate formation

Inferred from Biological aspect of Ancestor. Source: RefGenome

forebrain morphogenesis

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

hair follicle morphogenesis

Inferred from mutant phenotype PubMed 17199044. Source: MGI

heart looping

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

heart morphogenesis

Inferred from genetic interaction PubMed 16687132. Source: MGI

in utero embryonic development

Inferred from mutant phenotype PubMed 17881493. Source: MGI

mammary gland epithelial cell differentiation

Inferred from mutant phenotype PubMed 17199044. Source: MGI

mesenchymal to epithelial transition involved in metanephric renal vesicle formation

Inferred from mutant phenotype PubMed 16396903. Source: UniProtKB

midgut development

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

multicellular organism growth

Inferred from mutant phenotype PubMed 18590716. Source: MGI

muscle cell fate commitment

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of DNA binding

Inferred from mutant phenotype PubMed 16396903. Source: UniProtKB

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 16571630. Source: MGI

negative regulation of epithelial cell differentiation

Inferred from mutant phenotype PubMed 17199044. Source: MGI

negative regulation of gene expression

Inferred from mutant phenotype PubMed 16396903. Source: UniProtKB

negative regulation of hair follicle development

Inferred from mutant phenotype PubMed 17199044. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 19304890. Source: MGI

neural crest cell migration

Inferred from genetic interaction PubMed 16687132. Source: MGI

neuron fate commitment

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuron projection regeneration

Inferred from Biological aspect of Ancestor. Source: RefGenome

odontogenesis of dentin-containing tooth

Inferred from mutant phenotype PubMed 12403705PubMed 17199044. Source: MGI

ossification

Inferred from mutant phenotype PubMed 11748145. Source: MGI

osteoblast differentiation

Inferred from mutant phenotype PubMed 14973297. Source: MGI

otolith morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

pancreas morphogenesis

Inferred from mutant phenotype PubMed 20185815. Source: MGI

pattern specification process

Inferred from mutant phenotype PubMed 15107405. Source: MGI

positive regulation of branching involved in ureteric bud morphogenesis

Inferred from mutant phenotype PubMed 16396903. Source: UniProtKB

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 12403705PubMed 19124651. Source: MGI

positive regulation of epithelial cell proliferation

Inferred from mutant phenotype PubMed 19304890. Source: MGI

positive regulation of gene expression

Inferred from mutant phenotype PubMed 16396903. Source: UniProtKB

positive regulation of hh target transcription factor activity

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

positive regulation of mesenchymal cell proliferation

Inferred from mutant phenotype PubMed 19304890. Source: MGI

positive regulation of neuroblast proliferation

Inferred from genetic interaction PubMed 16543460. Source: MGI

positive regulation of protein import into nucleus

Inferred from genetic interaction PubMed 17043310. Source: MGI

positive regulation of smoothened signaling pathway

Inferred from mutant phenotype PubMed 16459297. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 15906375PubMed 19304890. Source: MGI

protein localization to nucleus

Inferred from mutant phenotype PubMed 19952108. Source: MGI

protein stabilization

Inferred from direct assay PubMed 19124651. Source: MGI

regulation of gene expression

Inferred from genetic interaction PubMed 18590716. Source: MGI

regulation of heart morphogenesis

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

regulation of stem cell maintenance

Inferred from mutant phenotype PubMed 17199044. Source: MGI

semicircular canal morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

smoothened signaling pathway

Inferred from mutant phenotype PubMed 21177415. Source: UniProtKB

smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation

Inferred from mutant phenotype PubMed 16571625. Source: MGI

smoothened signaling pathway involved in ventral spinal cord patterning

Inferred from mutant phenotype PubMed 19286674. Source: MGI

somite development

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

spermatogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

thalamus development

Inferred from mutant phenotype PubMed 19357274. Source: MGI

type B pancreatic cell development

Inferred from mutant phenotype PubMed 20185815. Source: MGI

vasculogenesis

Inferred from mutant phenotype PubMed 15294868PubMed 17881493. Source: MGI

ventral midline determination

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

caveola

Inferred from electronic annotation. Source: Ensembl

ciliary membrane

Inferred from direct assay PubMed 22179047. Source: MGI

cilium

Inferred from direct assay PubMed 16229832PubMed 22689656. Source: MGI

cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

neuronal cell body

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

primary cilium

Inferred from direct assay PubMed 16136078PubMed 19654211PubMed 19684112. Source: MGI

   Molecular_functionG-protein coupled receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

PDZ domain binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-activated receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-protein binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

drug binding

Inferred from direct assay PubMed 21177415. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232 Potential
Chain33 – 793761Smoothened homolog
PRO_0000013016

Regions

Topological domain33 – 237205Extracellular Potential
Transmembrane238 – 25821Helical; Name=1; Potential
Topological domain259 – 2657Cytoplasmic Potential
Transmembrane266 – 28621Helical; Name=2; Potential
Topological domain287 – 31832Extracellular Potential
Transmembrane319 – 33921Helical; Name=3; Potential
Topological domain340 – 36223Cytoplasmic Potential
Transmembrane363 – 38321Helical; Name=4; Potential
Topological domain384 – 40623Extracellular Potential
Transmembrane407 – 42721Helical; Name=5; Potential
Topological domain428 – 45528Cytoplasmic Potential
Transmembrane456 – 47621Helical; Name=6; Potential
Topological domain477 – 52852Extracellular Potential
Transmembrane529 – 54921Helical; Name=7; Potential
Topological domain550 – 793244Cytoplasmic Potential
Domain69 – 185117FZ
Region542 – 57332Interaction with BBS5 and BBS7

Amino acid modifications

Glycosylation381N-linked (GlcNAc...) Potential
Glycosylation1921N-linked (GlcNAc...) Potential
Glycosylation4971N-linked (GlcNAc...) Potential
Disulfide bond74 ↔ 138 By similarity
Disulfide bond82 ↔ 131 By similarity
Disulfide bond122 ↔ 158 By similarity
Disulfide bond151 ↔ 173 By similarity

Experimental info

Sequence conflict541D → N no nucleotide entry Ref.1
Sequence conflict2661Y → L no nucleotide entry Ref.1
Sequence conflict6901R → G no nucleotide entry Ref.1

Sequences

Sequence LengthMass (Da)Tools
P56726 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: DEAD556A45F7C960

FASTA79387,450
        10         20         30         40         50         60 
MAAGRPVRGP ELAPRRLLQL LLLVLLGGPG RGAALSGNVT GPGPHSASGS SRRDVPVTSP 

        70         80         90        100        110        120 
PPPLLSHCGR AAHCEPLRYN VCLGSALPYG ATTTLLAGDS DSQEEAHGKL VLWSGLRNAP 

       130        140        150        160        170        180 
RCWAVIQPLL CAVYMPKCEN DRVELPSRTL CQATRGPCAI VERERGWPDF LRCTPDHFPE 

       190        200        210        220        230        240 
GCPNEVQNIK FNSSGQCEAP LVRTDNPKSW YEDVEGCGIQ CQNPLFTEAE HQDMHSYIAA 

       250        260        270        280        290        300 
FGAVTGLCTL FTLATFVADW RNSNRYPAVI LFYVNACFFV GSIGWLAQFM DGARREIVCR 

       310        320        330        340        350        360 
ADGTMRFGEP TSSETLSCVI IFVIVYYALM AGVVWFVVLT YAWHTSFKAL GTTYQPLSGK 

       370        380        390        400        410        420 
TSYFHLLTWS LPFVLTVAIL AVAQVDGDSV SGICFVGYKN YRYRAGFVLA PIGLVLIVGG 

       430        440        450        460        470        480 
YFLIRGVMTL FSIKSNHPGL LSEKAASKIN ETMLRLGIFG FLAFGFVLIT FSCHFYDFFN 

       490        500        510        520        530        540 
QAEWERSFRD YVLCQANVTI GLPTKKPIPD CEIKNRPSLL VEKINLFAMF GTGIAMSTWV 

       550        560        570        580        590        600 
WTKATLLIWR RTWCRLTGHS DDEPKRIKKS KMIAKAFSKR RELLQNPGQE LSFSMHTVSH 

       610        620        630        640        650        660 
DGPVAGLAFD LNEPSADVSS AWAQHVTKMV ARRGAILPQD VSVTPVATPV PPEEQANMWL 

       670        680        690        700        710        720 
VEAEISPELE KRLGRKKKRR KRKKEVCPLR PAPELHHSAP VPATSAVPRL PQLPRQKCLV 

       730        740        750        760        770        780 
AANAWGTGES CRQGAWTLVS NPFCPEPSPH QDPFLPGASA PRVWAQGRLQ GLGSIHSRTN 

       790 
LMEAEILDAD SDF 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of a mouse Smoothened cDNA and expression patterns of hedgehog signalling molecules during chondrogenesis and cartilage differentiation in clonal mouse EC cells, ATDC5."
Akiyama H., Shigeno C., Hiraki Y., Shukunami C., Kohno H., Akagi M., Konishi J., Nakamura T.
Biochem. Biophys. Res. Commun. 235:142-147(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2."
Chen W., Ren X.R., Nelson C.D., Barak L.S., Chen J.K., Beachy P.A., de Sauvage F., Lefkowitz R.J.
Science 306:2257-2260(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB2.
[4]"A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened."
Seo S., Zhang Q., Bugge K., Breslow D.K., Searby C.C., Nachury M.V., Sheffield V.C.
PLoS Genet. 7:E1002358-E1002358(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH THE BBSOME COMPLEX, INTERACTION WITH BBS5 AND BBS7.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC069469 Genomic DNA. No translation available.
PIRJC5539.
RefSeqNP_795970.3. NM_176996.4.
UniGeneMm.29279.

3D structure databases

ProteinModelPortalP56726.
SMRP56726. Positions 72-181, 194-554.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid235504. 1 interaction.
IntActP56726. 4 interactions.

Chemistry

BindingDBP56726.
ChEMBLCHEMBL6080.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP56726.

Proteomic databases

PaxDbP56726.
PRIDEP56726.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000001812; ENSMUSP00000001812; ENSMUSG00000001761.
GeneID319757.
KEGGmmu:319757.
UCSCuc009bef.2. mouse.

Organism-specific databases

CTD6608.
MGIMGI:108075. Smo.

Phylogenomic databases

eggNOGNOG312505.
HOGENOMHOG000252964.
HOVERGENHBG000352.
InParanoidP56726.
KOK06226.
OMADRFPEGC.
OrthoDBEOG74J972.
TreeFamTF106460.

Gene expression databases

ArrayExpressP56726.
BgeeP56726.
CleanExMM_SMO.
GenevestigatorP56726.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
IPR026544. SMO.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF35. PTHR11309:SF35. 1 hit.
PfamPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSPR00489. FRIZZLED.
SMARTSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMSSF63501. SSF63501. 1 hit.
PROSITEPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSmo. mouse.
NextBio395350.
PROP56726.
SOURCESearch...

Entry information

Entry nameSMO_MOUSE
AccessionPrimary (citable) accession number: P56726
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries