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P56726

- SMO_MOUSE

UniProt

P56726 - SMO_MOUSE

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Protein

Smoothened homolog

Gene

Smo

Organism
Mus musculus (Mouse)
Status
Reviewed - 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

  1. drug binding Source: UniProtKB
  2. G-protein coupled receptor activity Source: UniProtKB-KW
  3. PDZ domain binding Source: RefGenome
  4. Wnt-activated receptor activity Source: RefGenome
  5. Wnt-protein binding Source: RefGenome

GO - Biological processi

  1. adenohypophysis development Source: RefGenome
  2. anterior/posterior pattern specification Source: MGI
  3. astrocyte activation Source: MGI
  4. atrial septum morphogenesis Source: MGI
  5. axon extension involved in axon guidance Source: RefGenome
  6. canonical Wnt signaling pathway Source: RefGenome
  7. cardioblast differentiation Source: RefGenome
  8. cell development Source: MGI
  9. cell fate specification Source: MGI
  10. cellular response to cholesterol Source: BHF-UCL
  11. central nervous system development Source: MGI
  12. central nervous system neuron differentiation Source: MGI
  13. cerebellar cortex morphogenesis Source: MGI
  14. cerebral cortex development Source: MGI
  15. ciliary receptor clustering involved in smoothened signaling pathway Source: RefGenome
  16. detection of cell density by contact stimulus involved in contact inhibition Source: UniProtKB
  17. determination of left/right asymmetry in lateral mesoderm Source: BHF-UCL
  18. determination of left/right symmetry Source: MGI
  19. developmental growth Source: MGI
  20. digestive tract development Source: MGI
  21. dorsal/ventral neural tube patterning Source: MGI
  22. dorsal/ventral pattern formation Source: MGI
  23. embryonic camera-type eye development Source: RefGenome
  24. embryonic digestive tract morphogenesis Source: RefGenome
  25. embryonic neurocranium morphogenesis Source: RefGenome
  26. embryonic organ development Source: MGI
  27. embryonic viscerocranium morphogenesis Source: RefGenome
  28. epithelial-mesenchymal cell signaling Source: MGI
  29. exocrine pancreas development Source: RefGenome
  30. facial nerve development Source: RefGenome
  31. floor plate formation Source: RefGenome
  32. forebrain morphogenesis Source: BHF-UCL
  33. gonad development Source: RefGenome
  34. hair follicle morphogenesis Source: MGI
  35. heart looping Source: BHF-UCL
  36. heart morphogenesis Source: MGI
  37. homeostasis of number of cells within a tissue Source: MGI
  38. in utero embryonic development Source: MGI
  39. mammary gland epithelial cell differentiation Source: MGI
  40. mesenchymal to epithelial transition involved in metanephric renal vesicle formation Source: UniProtKB
  41. midgut development Source: BHF-UCL
  42. multicellular organism growth Source: MGI
  43. muscle cell fate commitment Source: RefGenome
  44. myoblast migration Source: MGI
  45. negative regulation of apoptotic process Source: MGI
  46. negative regulation of DNA binding Source: UniProtKB
  47. negative regulation of epithelial cell differentiation Source: MGI
  48. negative regulation of gene expression Source: UniProtKB
  49. negative regulation of hair follicle development Source: MGI
  50. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  51. neural crest cell migration Source: MGI
  52. neuron fate commitment Source: RefGenome
  53. neuron projection regeneration Source: RefGenome
  54. odontogenesis of dentin-containing tooth Source: MGI
  55. ossification Source: MGI
  56. osteoblast differentiation Source: MGI
  57. otolith morphogenesis Source: RefGenome
  58. pancreas morphogenesis Source: MGI
  59. pattern specification process Source: MGI
  60. positive regulation of branching involved in ureteric bud morphogenesis Source: UniProtKB
  61. positive regulation of cell proliferation Source: MGI
  62. positive regulation of epithelial cell proliferation Source: MGI
  63. positive regulation of gene expression Source: UniProtKB
  64. positive regulation of hh target transcription factor activity Source: BHF-UCL
  65. positive regulation of mesenchymal cell proliferation Source: MGI
  66. positive regulation of neuroblast proliferation Source: MGI
  67. positive regulation of protein import into nucleus Source: MGI
  68. positive regulation of smoothened signaling pathway Source: MGI
  69. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  70. protein localization to nucleus Source: MGI
  71. protein stabilization Source: MGI
  72. regulation of gene expression Source: MGI
  73. regulation of heart morphogenesis Source: BHF-UCL
  74. regulation of stem cell maintenance Source: MGI
  75. semicircular canal morphogenesis Source: RefGenome
  76. skeletal muscle fiber development Source: MGI
  77. smoothened signaling pathway Source: UniProtKB
  78. smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation Source: MGI
  79. smoothened signaling pathway involved in ventral spinal cord patterning Source: BHF-UCL
  80. somite development Source: BHF-UCL
  81. spermatogenesis Source: RefGenome
  82. thalamus development Source: MGI
  83. type B pancreatic cell development Source: MGI
  84. vasculogenesis Source: MGI
  85. 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_250061. Class B/2 (Secretin family receptors).
REACT_269412. Hedgehog 'off' state.

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: 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

  1. caveola Source: Ensembl
  2. ciliary membrane Source: MGI
  3. cilium Source: MGI
  4. cytoplasm Source: MGI
  5. extracellular vesicular exosome Source: Ensembl
  6. Golgi apparatus Source: Ensembl
  7. integral component of membrane Source: UniProtKB-KW
  8. neuronal cell body Source: RefGenome
  9. plasma membrane Source: UniProtKB
  10. 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.
GenevestigatoriP56726.

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.

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.
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.
CCDSi CCDS19965.1.
PIRi JC5539.
RefSeqi NP_795970.3. NM_176996.4.
UniGenei Mm.29279.

3D structure databases

ProteinModelPortali P56726.
SMRi P56726. Positions 63-179, 194-557.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 235504. 1 interaction.
IntActi P56726. 4 interactions.

Chemistry

BindingDBi P56726.
ChEMBLi CHEMBL6080.
GuidetoPHARMACOLOGYi 239.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei P56726.

Proteomic databases

PaxDbi P56726.
PRIDEi P56726.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000001812 ; ENSMUSP00000001812 ; ENSMUSG00000001761 .
GeneIDi 319757.
KEGGi mmu:319757.
UCSCi uc009bef.2. mouse.

Organism-specific databases

CTDi 6608.
MGIi MGI:108075. Smo.

Phylogenomic databases

eggNOGi NOG312505.
HOGENOMi HOG000252964.
HOVERGENi HBG000352.
InParanoidi P56726.
KOi K06226.
OMAi KNSNRYP.
OrthoDBi EOG74J972.
TreeFami TF106460.

Enzyme and pathway databases

Reactomei REACT_250061. Class B/2 (Secretin family receptors).
REACT_269412. Hedgehog 'off' state.

Miscellaneous databases

ChiTaRSi Smo. mouse.
NextBioi 395350.
PROi P56726.
SOURCEi Search...

Gene expression databases

Bgeei P56726.
CleanExi MM_SMO.
ExpressionAtlasi P56726. baseline and differential.
Genevestigatori P56726.

Family and domain databases

Gene3Di 1.10.2000.10. 1 hit.
InterProi IPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
IPR026544. SMO.
[Graphical view ]
PANTHERi PTHR11309. PTHR11309. 1 hit.
PTHR11309:SF35. PTHR11309:SF35. 1 hit.
Pfami PF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view ]
PRINTSi PR00489. FRIZZLED.
SMARTi SM00063. FRI. 1 hit.
[Graphical view ]
SUPFAMi SSF63501. SSF63501. 1 hit.
PROSITEi PS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: January 7, 2015
This is version 115 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.