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Protein

Smoothened homolog

Gene

Smo

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  • drug binding Source: UniProtKB
  • G-protein coupled receptor activity Source: GO_Central
  • patched binding Source: MGI
  • Wnt-protein binding Source: GO_Central

GO - Biological processi

  • anterior/posterior pattern specification Source: MGI
  • astrocyte activation Source: MGI
  • atrial septum morphogenesis Source: MGI
  • cell development Source: MGI
  • cell fate specification Source: MGI
  • cellular response to cholesterol Source: BHF-UCL
  • central nervous system development Source: MGI
  • central nervous system neuron differentiation Source: MGI
  • cerebellar cortex morphogenesis Source: MGI
  • cerebral cortex development Source: MGI
  • dentate gyrus development Source: MGI
  • detection of cell density by contact stimulus involved in contact inhibition Source: UniProtKB
  • determination of left/right asymmetry in lateral mesoderm Source: BHF-UCL
  • determination of left/right symmetry Source: MGI
  • developmental growth Source: MGI
  • digestive tract development Source: MGI
  • dorsal/ventral neural tube patterning Source: MGI
  • dorsal/ventral pattern formation Source: MGI
  • embryonic organ development Source: MGI
  • epithelial-mesenchymal cell signaling Source: MGI
  • forebrain morphogenesis Source: BHF-UCL
  • hair follicle morphogenesis Source: MGI
  • heart looping Source: BHF-UCL
  • heart morphogenesis Source: MGI
  • homeostasis of number of cells within a tissue Source: MGI
  • in utero embryonic development Source: MGI
  • left/right axis specification Source: MGI
  • mammary gland epithelial cell differentiation Source: MGI
  • mesenchymal to epithelial transition involved in metanephric renal vesicle formation Source: UniProtKB
  • midgut development Source: BHF-UCL
  • multicellular organism growth Source: MGI
  • myoblast migration Source: MGI
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of DNA binding Source: UniProtKB
  • negative regulation of epithelial cell differentiation Source: MGI
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of hair follicle development Source: MGI
  • negative regulation of transcription, DNA-templated Source: CACAO
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • neural crest cell migration Source: MGI
  • odontogenesis of dentin-containing tooth Source: MGI
  • ossification Source: MGI
  • osteoblast differentiation Source: MGI
  • pancreas morphogenesis Source: MGI
  • pattern specification process Source: MGI
  • positive regulation of branching involved in ureteric bud morphogenesis Source: UniProtKB
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of epithelial cell proliferation Source: MGI
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of hh target transcription factor activity Source: BHF-UCL
  • positive regulation of mesenchymal cell proliferation Source: MGI
  • positive regulation of multicellular organism growth Source: CACAO
  • positive regulation of neuroblast proliferation Source: MGI
  • positive regulation of organ growth Source: CACAO
  • positive regulation of protein import into nucleus Source: MGI
  • positive regulation of smoothened signaling pathway Source: MGI
  • positive regulation of transcription, DNA-templated Source: CACAO
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • protein localization to nucleus Source: MGI
  • protein stabilization Source: MGI
  • regulation of gene expression Source: MGI
  • regulation of heart morphogenesis Source: BHF-UCL
  • regulation of stem cell maintenance Source: MGI
  • skeletal muscle fiber development Source: MGI
  • smoothened signaling pathway Source: UniProtKB
  • smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation Source: MGI
  • smoothened signaling pathway involved in ventral spinal cord patterning Source: BHF-UCL
  • somite development Source: BHF-UCL
  • thalamus development Source: MGI
  • type B pancreatic cell development Source: MGI
  • vasculogenesis Source: MGI
  • ventral midline determination Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_278699. Hedgehog 'off' state.
REACT_329133. Activation of SMO.
REACT_335449. Class B/2 (Secretin family receptors).

Names & Taxonomyi

Protein namesi
Recommended name:
Smoothened homolog
Short name:
SMO
Gene namesi
Name:Smo
Synonyms:Smoh
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:108075. Smo.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 237205ExtracellularSequence AnalysisAdd
BLAST
Transmembranei238 – 25821Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini259 – 2657CytoplasmicSequence Analysis
Transmembranei266 – 28621Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini287 – 31832ExtracellularSequence AnalysisAdd
BLAST
Transmembranei319 – 33921Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini340 – 36223CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei363 – 38321Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini384 – 40623ExtracellularSequence AnalysisAdd
BLAST
Transmembranei407 – 42721Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini428 – 45528CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei456 – 47621Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini477 – 52852ExtracellularSequence AnalysisAdd
BLAST
Transmembranei529 – 54921Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini550 – 793244CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • caveola Source: Ensembl
  • ciliary membrane Source: MGI
  • cilium Source: CACAO
  • cytoplasm Source: MGI
  • endocytic vesicle membrane Source: Reactome
  • extracellular exosome Source: MGI
  • Golgi apparatus Source: Ensembl
  • integral component of membrane Source: GO_Central
  • intracellular membrane-bounded organelle Source: MGI
  • plasma membrane Source: UniProtKB
  • primary cilium Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232Sequence AnalysisAdd
BLAST
Chaini33 – 793761Smoothened homologPRO_0000013016Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi38 – 381N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi74 ↔ 138PROSITE-ProRule annotation
Disulfide bondi82 ↔ 131PROSITE-ProRule annotation
Disulfide bondi122 ↔ 158PROSITE-ProRule annotation
Disulfide bondi151 ↔ 173PROSITE-ProRule annotation
Glycosylationi192 – 1921N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi197 ↔ 217PROSITE-ProRule annotation
Disulfide bondi221 ↔ 299PROSITE-ProRule annotation
Disulfide bondi318 ↔ 394PROSITE-ProRule annotation
Disulfide bondi494 ↔ 511PROSITE-ProRule annotation
Glycosylationi497 – 4971N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP56726.
PRIDEiP56726.

PTM databases

PhosphoSiteiP56726.

Expressioni

Gene expression databases

BgeeiP56726.
CleanExiMM_SMO.
ExpressionAtlasiP56726. baseline and differential.
GenevisibleiP56726. MM.

Interactioni

Subunit structurei

Homodimer (By similarity). 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.By similarity2 Publications

Protein-protein interaction databases

BioGridi235504. 1 interaction.
IntActiP56726. 4 interactions.
STRINGi10090.ENSMUSP00000001812.

Structurei

3D structure databases

ProteinModelPortaliP56726.
SMRiP56726. Positions 63-179, 194-557.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini69 – 185117FZPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni542 – 57332Interaction with BBS5 and BBS7Add
BLAST

Sequence similaritiesi

Contains 1 FZ (frizzled) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG312505.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000252964.
HOVERGENiHBG000352.
InParanoidiP56726.
KOiK06226.
OMAiKNSNRYP.
OrthoDBiEOG74J972.
TreeFamiTF106460.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
IPR026544. SMO.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF35. PTHR11309:SF35. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P56726-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAGRPVRGP ELAPRRLLQL LLLVLLGGPG RGAALSGNVT GPGPHSASGS
60 70 80 90 100
SRRDVPVTSP PPPLLSHCGR AAHCEPLRYN VCLGSALPYG ATTTLLAGDS
110 120 130 140 150
DSQEEAHGKL VLWSGLRNAP RCWAVIQPLL CAVYMPKCEN DRVELPSRTL
160 170 180 190 200
CQATRGPCAI VERERGWPDF LRCTPDHFPE GCPNEVQNIK FNSSGQCEAP
210 220 230 240 250
LVRTDNPKSW YEDVEGCGIQ CQNPLFTEAE HQDMHSYIAA FGAVTGLCTL
260 270 280 290 300
FTLATFVADW RNSNRYPAVI LFYVNACFFV GSIGWLAQFM DGARREIVCR
310 320 330 340 350
ADGTMRFGEP TSSETLSCVI IFVIVYYALM AGVVWFVVLT YAWHTSFKAL
360 370 380 390 400
GTTYQPLSGK TSYFHLLTWS LPFVLTVAIL AVAQVDGDSV SGICFVGYKN
410 420 430 440 450
YRYRAGFVLA PIGLVLIVGG YFLIRGVMTL FSIKSNHPGL LSEKAASKIN
460 470 480 490 500
ETMLRLGIFG FLAFGFVLIT FSCHFYDFFN QAEWERSFRD YVLCQANVTI
510 520 530 540 550
GLPTKKPIPD CEIKNRPSLL VEKINLFAMF GTGIAMSTWV WTKATLLIWR
560 570 580 590 600
RTWCRLTGHS DDEPKRIKKS KMIAKAFSKR RELLQNPGQE LSFSMHTVSH
610 620 630 640 650
DGPVAGLAFD LNEPSADVSS AWAQHVTKMV ARRGAILPQD VSVTPVATPV
660 670 680 690 700
PPEEQANMWL VEAEISPELE KRLGRKKKRR KRKKEVCPLR PAPELHHSAP
710 720 730 740 750
VPATSAVPRL PQLPRQKCLV AANAWGTGES CRQGAWTLVS NPFCPEPSPH
760 770 780 790
QDPFLPGASA PRVWAQGRLQ GLGSIHSRTN LMEAEILDAD SDF
Length:793
Mass (Da):87,450
Last modified:July 27, 2011 - v2
Checksum:iDEAD556A45F7C960
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti54 – 541D → N no nucleotide entry (PubMed:9196051).Curated
Sequence conflicti266 – 2661Y → L no nucleotide entry (PubMed:9196051).Curated
Sequence conflicti690 – 6901R → G no nucleotide entry (PubMed:9196051).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC069469 Genomic DNA. No translation available.
CCDSiCCDS19965.1.
PIRiJC5539.
RefSeqiNP_795970.3. NM_176996.4.
UniGeneiMm.29279.

Genome annotation databases

EnsembliENSMUST00000001812; ENSMUSP00000001812; ENSMUSG00000001761.
GeneIDi319757.
KEGGimmu:319757.
UCSCiuc009bef.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC069469 Genomic DNA. No translation available.
CCDSiCCDS19965.1.
PIRiJC5539.
RefSeqiNP_795970.3. NM_176996.4.
UniGeneiMm.29279.

3D structure databases

ProteinModelPortaliP56726.
SMRiP56726. Positions 63-179, 194-557.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi235504. 1 interaction.
IntActiP56726. 4 interactions.
STRINGi10090.ENSMUSP00000001812.

Chemistry

BindingDBiP56726.
ChEMBLiCHEMBL6080.
GuidetoPHARMACOLOGYi239.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP56726.

Proteomic databases

PaxDbiP56726.
PRIDEiP56726.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000001812; ENSMUSP00000001812; ENSMUSG00000001761.
GeneIDi319757.
KEGGimmu:319757.
UCSCiuc009bef.2. mouse.

Organism-specific databases

CTDi6608.
MGIiMGI:108075. Smo.

Phylogenomic databases

eggNOGiNOG312505.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000252964.
HOVERGENiHBG000352.
InParanoidiP56726.
KOiK06226.
OMAiKNSNRYP.
OrthoDBiEOG74J972.
TreeFamiTF106460.

Enzyme and pathway databases

ReactomeiREACT_278699. Hedgehog 'off' state.
REACT_329133. Activation of SMO.
REACT_335449. Class B/2 (Secretin family receptors).

Miscellaneous databases

ChiTaRSiSmo. mouse.
NextBioi395350.
PROiP56726.
SOURCEiSearch...

Gene expression databases

BgeeiP56726.
CleanExiMM_SMO.
ExpressionAtlasiP56726. baseline and differential.
GenevisibleiP56726. MM.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
IPR026544. SMO.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF35. PTHR11309:SF35. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiSMO_MOUSE
AccessioniPrimary (citable) accession number: P56726
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: July 22, 2015
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.