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P56726

- SMO_MOUSE

UniProt

P56726 - SMO_MOUSE

Protein

Smoothened homolog

Gene

Smo

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 112 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    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. atrial septum morphogenesis Source: MGI
    4. axon extension involved in axon guidance Source: RefGenome
    5. canonical Wnt signaling pathway Source: RefGenome
    6. cardioblast differentiation Source: RefGenome
    7. cell development Source: MGI
    8. cell fate specification Source: MGI
    9. cellular response to cholesterol Source: BHF-UCL
    10. central nervous system development Source: MGI
    11. central nervous system neuron differentiation Source: MGI
    12. cerebellar cortex morphogenesis Source: MGI
    13. ciliary receptor clustering involved in smoothened signaling pathway Source: RefGenome
    14. detection of cell density by contact stimulus involved in contact inhibition Source: UniProtKB
    15. determination of left/right asymmetry in lateral mesoderm Source: BHF-UCL
    16. determination of left/right symmetry Source: MGI
    17. developmental growth Source: MGI
    18. digestive tract development Source: MGI
    19. dorsal/ventral neural tube patterning Source: MGI
    20. dorsal/ventral pattern formation Source: MGI
    21. embryonic camera-type eye development Source: RefGenome
    22. embryonic digestive tract morphogenesis Source: RefGenome
    23. embryonic neurocranium morphogenesis Source: RefGenome
    24. embryonic organ development Source: MGI
    25. embryonic viscerocranium morphogenesis Source: RefGenome
    26. epithelial-mesenchymal cell signaling Source: MGI
    27. exocrine pancreas development Source: RefGenome
    28. facial nerve development Source: RefGenome
    29. floor plate formation Source: RefGenome
    30. forebrain morphogenesis Source: BHF-UCL
    31. gonad development Source: RefGenome
    32. hair follicle morphogenesis Source: MGI
    33. heart looping Source: BHF-UCL
    34. heart morphogenesis Source: MGI
    35. in utero embryonic development Source: MGI
    36. mammary gland epithelial cell differentiation Source: MGI
    37. mesenchymal to epithelial transition involved in metanephric renal vesicle formation Source: UniProtKB
    38. midgut development Source: BHF-UCL
    39. multicellular organism growth Source: MGI
    40. muscle cell fate commitment Source: RefGenome
    41. myoblast migration Source: MGI
    42. negative regulation of apoptotic process Source: MGI
    43. negative regulation of DNA binding Source: UniProtKB
    44. negative regulation of epithelial cell differentiation Source: MGI
    45. negative regulation of gene expression Source: UniProtKB
    46. negative regulation of hair follicle development Source: MGI
    47. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    48. neural crest cell migration Source: MGI
    49. neuron fate commitment Source: RefGenome
    50. neuron projection regeneration Source: RefGenome
    51. odontogenesis of dentin-containing tooth Source: MGI
    52. ossification Source: MGI
    53. osteoblast differentiation Source: MGI
    54. otolith morphogenesis Source: RefGenome
    55. pancreas morphogenesis Source: MGI
    56. pattern specification process Source: MGI
    57. positive regulation of branching involved in ureteric bud morphogenesis Source: UniProtKB
    58. positive regulation of cell proliferation Source: MGI
    59. positive regulation of epithelial cell proliferation Source: MGI
    60. positive regulation of gene expression Source: UniProtKB
    61. positive regulation of hh target transcription factor activity Source: BHF-UCL
    62. positive regulation of mesenchymal cell proliferation Source: MGI
    63. positive regulation of neuroblast proliferation Source: MGI
    64. positive regulation of protein import into nucleus Source: MGI
    65. positive regulation of smoothened signaling pathway Source: MGI
    66. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    67. protein localization to nucleus Source: MGI
    68. protein stabilization Source: MGI
    69. regulation of gene expression Source: MGI
    70. regulation of heart morphogenesis Source: BHF-UCL
    71. regulation of stem cell maintenance Source: MGI
    72. semicircular canal morphogenesis Source: RefGenome
    73. skeletal muscle fiber development Source: MGI
    74. smoothened signaling pathway Source: UniProtKB
    75. smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation Source: MGI
    76. smoothened signaling pathway involved in ventral spinal cord patterning Source: BHF-UCL
    77. somite development Source: BHF-UCL
    78. spermatogenesis Source: RefGenome
    79. thalamus development Source: MGI
    80. type B pancreatic cell development Source: MGI
    81. vasculogenesis Source: MGI
    82. ventral midline determination Source: BHF-UCL

    Keywords - Molecular functioni

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

    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

    GO - Cellular componenti

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

    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

    ArrayExpressiP56726.
    BgeeiP56726.
    CleanExiMM_SMO.
    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini33 – 237205ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini259 – 2657CytoplasmicSequence Analysis
    Topological domaini287 – 31832ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini340 – 36223CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini384 – 40623ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini428 – 45528CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini477 – 52852ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini550 – 793244CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei238 – 25821Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei266 – 28621Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei319 – 33921Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei363 – 38321Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei407 – 42721Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei456 – 47621Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei529 – 54921Helical; Name=7Sequence AnalysisAdd
    BLAST

    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.
    OMAiEVCPLAP.
    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

    MAAGRPVRGP ELAPRRLLQL LLLVLLGGPG RGAALSGNVT GPGPHSASGS    50
    SRRDVPVTSP PPPLLSHCGR AAHCEPLRYN VCLGSALPYG ATTTLLAGDS 100
    DSQEEAHGKL VLWSGLRNAP RCWAVIQPLL CAVYMPKCEN DRVELPSRTL 150
    CQATRGPCAI VERERGWPDF LRCTPDHFPE GCPNEVQNIK FNSSGQCEAP 200
    LVRTDNPKSW YEDVEGCGIQ CQNPLFTEAE HQDMHSYIAA FGAVTGLCTL 250
    FTLATFVADW RNSNRYPAVI LFYVNACFFV GSIGWLAQFM DGARREIVCR 300
    ADGTMRFGEP TSSETLSCVI IFVIVYYALM AGVVWFVVLT YAWHTSFKAL 350
    GTTYQPLSGK TSYFHLLTWS LPFVLTVAIL AVAQVDGDSV SGICFVGYKN 400
    YRYRAGFVLA PIGLVLIVGG YFLIRGVMTL FSIKSNHPGL LSEKAASKIN 450
    ETMLRLGIFG FLAFGFVLIT FSCHFYDFFN QAEWERSFRD YVLCQANVTI 500
    GLPTKKPIPD CEIKNRPSLL VEKINLFAMF GTGIAMSTWV WTKATLLIWR 550
    RTWCRLTGHS DDEPKRIKKS KMIAKAFSKR RELLQNPGQE LSFSMHTVSH 600
    DGPVAGLAFD LNEPSADVSS AWAQHVTKMV ARRGAILPQD VSVTPVATPV 650
    PPEEQANMWL VEAEISPELE KRLGRKKKRR KRKKEVCPLR PAPELHHSAP 700
    VPATSAVPRL PQLPRQKCLV AANAWGTGES CRQGAWTLVS NPFCPEPSPH 750
    QDPFLPGASA PRVWAQGRLQ GLGSIHSRTN LMEAEILDAD SDF 793
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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.

    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 EVCPLAP.
    OrthoDBi EOG74J972.
    TreeFami TF106460.

    Miscellaneous databases

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

    Gene expression databases

    ArrayExpressi P56726.
    Bgeei P56726.
    CleanExi MM_SMO.
    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

    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: October 1, 2014
    This is version 112 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