SMO_HUMAN
ID SMO_HUMAN Reviewed; 787 AA.
AC Q99835; A4D1K5;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Smoothened homolog;
DE Short=SMO;
DE AltName: Full=Protein Gx;
DE Flags: Precursor;
GN Name=SMO; Synonyms=SMOH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryonic lung;
RX PubMed=8906787; DOI=10.1038/384129a0;
RA Stone D.M., Hynes M., Armanini M., Swanson T.A., Gu Q., Johnson R.L.,
RA Scott M.P., Pennica D., Goddard A., Phillips H., Noll M., Hooper J.E.,
RA de Sauvage F., Rosenthal A.;
RT "The tumour-suppressor gene patched encodes a candidate receptor for Sonic
RT hedgehog.";
RL Nature 384:129-134(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-535 AND GLN-562.
RX PubMed=9422511; DOI=10.1038/34201;
RA Xie J., Murone M., Luoh S.-M., Ryan A., Gu Q., Zhang C., Bonifas J.M.,
RA Lam C.-W., Hynes M., Goddard A., Rosenthal A., Epstein E.H. Jr.,
RA de Sauvage F.J.;
RT "Activating Smoothened mutations in sporadic basal-cell carcinoma.";
RL Nature 391:90-92(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Jiang N., Zeng Z.Y., Li G.Y.;
RT "Cloning and identification of Gx gene in NPC.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, AND INTERACTION WITH KIF7.
RX PubMed=19592253; DOI=10.1016/j.cub.2009.06.046;
RA Endoh-Yamagami S., Evangelista M., Wilson D., Wen X., Theunissen J.W.,
RA Phamluong K., Davis M., Scales S.J., Solloway M.J., de Sauvage F.J.,
RA Peterson A.S.;
RT "The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh
RT signal transduction during development.";
RL Curr. Biol. 19:1320-1326(2009).
RN [8]
RP INTERACTION WITH GAS8.
RX PubMed=21659505; DOI=10.1074/jbc.m111.234666;
RA Evron T., Philipp M., Lu J., Meloni A.R., Burkhalter M., Chen W.,
RA Caron M.G.;
RT "Growth arrest specific 8 (Gas8) and G protein-coupled receptor kinase 2
RT (GRK2) cooperate in the control of Smoothened signaling.";
RL J. Biol. Chem. 286:27676-27686(2011).
RN [9]
RP ASSOCIATION WITH THE BBSOME COMPLEX, INTERACTION WITH BBS5 AND BBS7, AND
RP SUBCELLULAR LOCATION.
RX PubMed=22072986; DOI=10.1371/journal.pgen.1002358;
RA Seo S., Zhang Q., Bugge K., Breslow D.K., Searby C.C., Nachury M.V.,
RA Sheffield V.C.;
RT "A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and
RT Smoothened.";
RL PLoS Genet. 7:E1002358-E1002358(2011).
RN [10]
RP INVOLVEMENT IN CRJS, AND VARIANT CRJS PHE-412.
RX PubMed=27236920; DOI=10.1016/j.ajhg.2016.04.007;
RA Twigg S.R., Hufnagel R.B., Miller K.A., Zhou Y., McGowan S.J., Taylor J.,
RA Craft J., Taylor J.C., Santoro S.L., Huang T., Hopkin R.J., Brady A.F.,
RA Clayton-Smith J., Clericuzio C.L., Grange D.K., Groesser L., Hafner C.,
RA Horn D., Temple I.K., Dobyns W.B., Curry C.J., Jones M.C., Wilkie A.O.;
RT "A recurrent mosaic mutation in SMO, encoding the hedgehog signal
RT transducer smoothened, is the major cause of Curry-Jones syndrome.";
RL Am. J. Hum. Genet. 98:1256-1265(2016).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 190-555 IN COMPLEX WITH
RP ANTAGONIST, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=23636324; DOI=10.1038/nature12167;
RA Wang C., Wu H., Katritch V., Han G.W., Huang X.P., Liu W., Siu F.Y.,
RA Roth B.L., Cherezov V., Stevens R.C.;
RT "Structure of the human smoothened receptor bound to an antitumour agent.";
RL Nature 497:338-343(2013).
RN [12]
RP VARIANT CRJS PHE-412, VARIANT LEU-535, CHARACTERIZATION OF VARIANT CRJS
RP PHE-412, AND CHARACTERIZATION OF VARIANT LEU-535.
RX PubMed=24859340; DOI=10.1038/ng.2986;
RA Sweeney R.T., McClary A.C., Myers B.R., Biscocho J., Neahring L.,
RA Kwei K.A., Qu K., Gong X., Ng T., Jones C.D., Varma S., Odegaard J.I.,
RA Sugiyama T., Koyota S., Rubin B.P., Troxell M.L., Pelham R.J.,
RA Zehnder J.L., Beachy P.A., Pollack J.R., West R.B.;
RT "Identification of recurrent SMO and BRAF mutations in ameloblastomas.";
RL Nat. Genet. 46:722-725(2014).
CC -!- FUNCTION: G protein-coupled receptor that probably associates with the
CC patched protein (PTCH) to transduce the hedgehog's proteins signal.
CC Binding of sonic hedgehog (SHH) to its receptor patched is thought to
CC prevent normal inhibition by patched of smoothened (SMO). Required for
CC the accumulation of KIF7, GLI2 and GLI3 in the cilia (PubMed:19592253).
CC Interacts with DLG5 at the ciliary base to induce the accumulation of
CC KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity).
CC {ECO:0000250|UniProtKB:P56726, ECO:0000269|PubMed:19592253}.
CC -!- SUBUNIT: Homodimer (PubMed:23636324). Interacts with ARRB2 (By
CC similarity). Interacts with KIF7 (PubMed:19592253). Interacts with BBS5
CC and BBS7; the interactions are indicative for the association of SMO
CC with the BBsome complex to facilitate ciliary localization of SMO
CC (PubMed:22072986). Interacts with DLG5 and SDCBP (By similarity).
CC Interacts with GAS8/DRC4 (PubMed:21659505).
CC {ECO:0000250|UniProtKB:P56726, ECO:0000269|PubMed:19592253,
CC ECO:0000269|PubMed:21659505, ECO:0000269|PubMed:22072986,
CC ECO:0000269|PubMed:23636324}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:22072986}; Multi-
CC pass membrane protein {ECO:0000269|PubMed:22072986}. Cell projection,
CC cilium {ECO:0000269|PubMed:22072986}.
CC -!- DISEASE: Curry-Jones syndrome (CRJS) [MIM:601707]: A multisystem
CC disorder characterized by patchy skin lesions, polysyndactyly, diverse
CC cerebral malformations, unicoronal craniosynostosis, iris colobomas,
CC microphthalmia, and intestinal malrotation with myofibromas or
CC hamartomas. {ECO:0000269|PubMed:24859340, ECO:0000269|PubMed:27236920}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry. 8 individuals have been identified with the disease-
CC causing mutation Phe-412 and all were mosaic. The mutation could not be
CC reliably detected in blood, greatest success rates were obtained with
CC affected tissues obtained by invasive procedures. It is thought that
CC the mutation has arisen postzygotically early during embryonic
CC development (PubMed:27236920). This mutation has also been identified
CC in ameloblastoma, medulloblastoma, meningioma, and basal cell
CC carcinoma, and has been reported as the oncogenic driver in some of
CC these tumors (PubMed:24859340). {ECO:0000269|PubMed:24859340,
CC ECO:0000269|PubMed:27236920}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo family.
CC {ECO:0000305}.
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DR EMBL; U84401; AAB41788.1; -; mRNA.
DR EMBL; AF114821; AAD17202.1; -; Genomic_DNA.
DR EMBL; AF114819; AAD17202.1; JOINED; Genomic_DNA.
DR EMBL; AF114820; AAD17202.1; JOINED; Genomic_DNA.
DR EMBL; AF120103; AAF31757.1; -; mRNA.
DR EMBL; AF071494; AAC24863.1; -; mRNA.
DR EMBL; CH236950; EAL24102.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83715.1; -; Genomic_DNA.
DR EMBL; BC009989; AAH09989.1; -; mRNA.
DR CCDS; CCDS5811.1; -.
DR RefSeq; NP_005622.1; NM_005631.4.
DR PDB; 4JKV; X-ray; 2.45 A; A/B=190-555.
DR PDB; 4N4W; X-ray; 2.80 A; A=190-555.
DR PDB; 4O9R; X-ray; 3.20 A; A=190-433, A=441-555.
DR PDB; 4QIM; X-ray; 2.61 A; A=190-433, A=441-555.
DR PDB; 4QIN; X-ray; 2.60 A; A=190-433, A=441-555.
DR PDB; 5L7D; X-ray; 3.20 A; A/B=32-428, A/B=443-555.
DR PDB; 5L7I; X-ray; 3.30 A; A/B=32-428, A/B=443-555.
DR PDB; 5V56; X-ray; 2.90 A; A/B=53-437, A/B=444-558.
DR PDB; 5V57; X-ray; 3.00 A; A/B=58-437, A/B=444-558.
DR PDB; 6OT0; EM; 3.90 A; R=1-555.
DR PDB; 6XBJ; EM; 3.88 A; R=1-644.
DR PDB; 6XBK; EM; 3.24 A; R=1-644.
DR PDB; 6XBL; EM; 3.90 A; R=1-644.
DR PDB; 6XBM; EM; 3.15 A; R=1-644.
DR PDBsum; 4JKV; -.
DR PDBsum; 4N4W; -.
DR PDBsum; 4O9R; -.
DR PDBsum; 4QIM; -.
DR PDBsum; 4QIN; -.
DR PDBsum; 5L7D; -.
DR PDBsum; 5L7I; -.
DR PDBsum; 5V56; -.
DR PDBsum; 5V57; -.
DR PDBsum; 6OT0; -.
DR PDBsum; 6XBJ; -.
DR PDBsum; 6XBK; -.
DR PDBsum; 6XBL; -.
DR PDBsum; 6XBM; -.
DR AlphaFoldDB; Q99835; -.
DR SMR; Q99835; -.
DR BioGRID; 112492; 52.
DR DIP; DIP-34574N; -.
DR IntAct; Q99835; 35.
DR MINT; Q99835; -.
DR STRING; 9606.ENSP00000249373; -.
DR BindingDB; Q99835; -.
DR ChEMBL; CHEMBL5971; -.
DR DrugBank; DB01047; Fluocinonide.
DR DrugBank; DB11978; Glasdegib.
DR DrugBank; DB06786; Halcinonide.
DR DrugBank; DB09143; Sonidegib.
DR DrugBank; DB08828; Vismodegib.
DR DrugCentral; Q99835; -.
DR GuidetoPHARMACOLOGY; 239; -.
DR TCDB; 9.A.14.16.4; the g-protein-coupled receptor (gpcr) family.
DR GlyConnect; 2079; 1 N-Linked glycan (1 site).
DR GlyGen; Q99835; 5 sites, 2 N-linked glycans (1 site), 2 O-linked glycans (2 sites).
DR iPTMnet; Q99835; -.
DR PhosphoSitePlus; Q99835; -.
DR BioMuta; SMO; -.
DR DMDM; 6226142; -.
DR EPD; Q99835; -.
DR jPOST; Q99835; -.
DR MassIVE; Q99835; -.
DR PaxDb; Q99835; -.
DR PeptideAtlas; Q99835; -.
DR PRIDE; Q99835; -.
DR ProteomicsDB; 78499; -.
DR Antibodypedia; 31982; 605 antibodies from 38 providers.
DR DNASU; 6608; -.
DR Ensembl; ENST00000249373.8; ENSP00000249373.3; ENSG00000128602.11.
DR GeneID; 6608; -.
DR KEGG; hsa:6608; -.
DR MANE-Select; ENST00000249373.8; ENSP00000249373.3; NM_005631.5; NP_005622.1.
DR UCSC; uc003vor.4; human.
DR CTD; 6608; -.
DR DisGeNET; 6608; -.
DR GeneCards; SMO; -.
DR HGNC; HGNC:11119; SMO.
DR HPA; ENSG00000128602; Low tissue specificity.
DR MalaCards; SMO; -.
DR MIM; 601500; gene.
DR MIM; 601707; phenotype.
DR neXtProt; NX_Q99835; -.
DR OpenTargets; ENSG00000128602; -.
DR Orphanet; 1553; Curry-Jones syndrome.
DR Orphanet; 388; Hirschsprung disease.
DR Orphanet; 2495; Meningioma.
DR PharmGKB; PA35968; -.
DR VEuPathDB; HostDB:ENSG00000128602; -.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000157206; -.
DR HOGENOM; CLU_007873_3_1_1; -.
DR InParanoid; Q99835; -.
DR OMA; FLKCTPD; -.
DR OrthoDB; 385042at2759; -.
DR PhylomeDB; Q99835; -.
DR TreeFam; TF106460; -.
DR PathwayCommons; Q99835; -.
DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR Reactome; R-HSA-5620922; BBSome-mediated cargo-targeting to cilium.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR Reactome; R-HSA-5635838; Activation of SMO.
DR SignaLink; Q99835; -.
DR SIGNOR; Q99835; -.
DR BioGRID-ORCS; 6608; 15 hits in 1070 CRISPR screens.
DR ChiTaRS; SMO; human.
DR GeneWiki; Smoothened; -.
DR GenomeRNAi; 6608; -.
DR Pharos; Q99835; Tclin.
DR PRO; PR:Q99835; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q99835; protein.
DR Bgee; ENSG00000128602; Expressed in ventricular zone and 141 other tissues.
DR ExpressionAtlas; Q99835; baseline and differential.
DR Genevisible; Q99835; HS.
DR GO; GO:0097731; C:9+0 non-motile cilium; IEA:Ensembl.
DR GO; GO:0005814; C:centriole; IEA:Ensembl.
DR GO; GO:0060170; C:ciliary membrane; TAS:Reactome.
DR GO; GO:0097542; C:ciliary tip; TAS:Reactome.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0005113; F:patched binding; IPI:BHF-UCL.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl.
DR GO; GO:0048143; P:astrocyte activation; IEA:Ensembl.
DR GO; GO:0060413; P:atrial septum morphogenesis; IEA:Ensembl.
DR GO; GO:0001708; P:cell fate specification; IEA:Ensembl.
DR GO; GO:0071397; P:cellular response to cholesterol; ISS:BHF-UCL.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0021953; P:central nervous system neuron differentiation; IEA:Ensembl.
DR GO; GO:0021696; P:cerebellar cortex morphogenesis; IEA:Ensembl.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR GO; GO:0071679; P:commissural neuron axon guidance; IBA:GO_Central.
DR GO; GO:0060242; P:contact inhibition; IMP:BHF-UCL.
DR GO; GO:0021542; P:dentate gyrus development; IEA:Ensembl.
DR GO; GO:0003140; P:determination of left/right asymmetry in lateral mesoderm; ISS:BHF-UCL.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IEA:Ensembl.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0060684; P:epithelial-mesenchymal cell signaling; IEA:Ensembl.
DR GO; GO:0048853; P:forebrain morphogenesis; ISS:BHF-UCL.
DR GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0070986; P:left/right axis specification; IEA:Ensembl.
DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0072285; P:mesenchymal to epithelial transition involved in metanephric renal vesicle formation; ISS:UniProtKB.
DR GO; GO:0007494; P:midgut development; ISS:BHF-UCL.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0051451; P:myoblast migration; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0043392; P:negative regulation of DNA binding; ISS:UniProtKB.
DR GO; GO:0030857; P:negative regulation of epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0051799; P:negative regulation of hair follicle development; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0001755; P:neural crest cell migration; IEA:Ensembl.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0061113; P:pancreas morphogenesis; IEA:Ensembl.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:ARUK-UCL.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0007228; P:positive regulation of hh target transcription factor activity; ISS:BHF-UCL.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0046622; P:positive regulation of organ growth; IEA:Ensembl.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0050821; P:protein stabilization; IEA:Ensembl.
DR GO; GO:2000826; P:regulation of heart morphogenesis; ISS:BHF-UCL.
DR GO; GO:1904672; P:regulation of somatic stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0048741; P:skeletal muscle fiber development; IEA:Ensembl.
DR GO; GO:0048745; P:smooth muscle tissue development; IEP:UniProtKB.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:UniProtKB.
DR GO; GO:0021938; P:smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation; IEA:Ensembl.
DR GO; GO:0021910; P:smoothened signaling pathway involved in ventral spinal cord patterning; IEA:Ensembl.
DR GO; GO:0061053; P:somite development; ISS:BHF-UCL.
DR GO; GO:0021794; P:thalamus development; IEA:Ensembl.
DR GO; GO:0003323; P:type B pancreatic cell development; IEA:Ensembl.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
DR GO; GO:0007371; P:ventral midline determination; ISS:BHF-UCL.
DR CDD; cd15030; 7tmF_SMO_homolog; 1.
DR CDD; cd07451; CRD_SMO; 1.
DR Gene3D; 1.10.2000.10; -; 1.
DR InterPro; IPR015526; Frizzled/SFRP.
DR InterPro; IPR000539; Frizzled/Smoothened_TM.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR017981; GPCR_2-like.
DR InterPro; IPR026544; SMO.
DR InterPro; IPR035683; SMO_7TM.
DR InterPro; IPR041771; SMO_CRD.
DR PANTHER; PTHR11309; PTHR11309; 1.
DR PANTHER; PTHR11309:SF35; PTHR11309:SF35; 1.
DR Pfam; PF01534; Frizzled; 1.
DR Pfam; PF01392; Fz; 1.
DR PRINTS; PR00489; FRIZZLED.
DR SMART; SM00063; FRI; 1.
DR SMART; SM01330; Frizzled; 1.
DR SUPFAM; SSF63501; SSF63501; 1.
DR PROSITE; PS50038; FZ; 1.
DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell projection; Developmental protein; Disease variant;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane;
KW Receptor; Reference proteome; Signal; Transducer; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..787
FT /note="Smoothened homolog"
FT /id="PRO_0000013015"
FT TOPO_DOM 28..233
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 234..254
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 255..262
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 263..283
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 284..314
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 315..335
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 336..358
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 359..379
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 380..402
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 403..423
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 424..451
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 452..472
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 473..524
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 525..545
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 546..787
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 65..181
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT REGION 30..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 538..569
FT /note="Interaction with BBS5 and BBS7"
FT /evidence="ECO:0000269|PubMed:22072986"
FT REGION 581..593
FT /note="Interaction with DLG5"
FT /evidence="ECO:0000250|UniProtKB:P56726"
FT REGION 667..704
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 686..703
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 70..134
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 78..127
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 118..154
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 147..169
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 193..213
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090,
FT ECO:0000269|PubMed:23636324"
FT DISULFID 217..295
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090,
FT ECO:0000269|PubMed:23636324"
FT DISULFID 314..390
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090,
FT ECO:0000269|PubMed:23636324"
FT DISULFID 490..507
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090,
FT ECO:0000269|PubMed:23636324"
FT VARIANT 412
FT /note="L -> F (in CRJS; constitutive activation of the
FT smoothened signaling pathway; dbSNP:rs879255280)"
FT /evidence="ECO:0000269|PubMed:24859340,
FT ECO:0000269|PubMed:27236920"
FT /id="VAR_077087"
FT VARIANT 473
FT /note="D -> H (in dbSNP:rs17710891)"
FT /id="VAR_037891"
FT VARIANT 535
FT /note="W -> L (in basal cell carcinoma and ameloblastoma
FT samples; somatic mutation; constitutive activation of the
FT smoothened signaling pathway; dbSNP:rs121918347)"
FT /evidence="ECO:0000269|PubMed:24859340,
FT ECO:0000269|PubMed:9422511"
FT /id="VAR_007848"
FT VARIANT 562
FT /note="R -> Q (in basal cell carcinoma samples; somatic
FT mutation; dbSNP:rs121918348)"
FT /evidence="ECO:0000269|PubMed:9422511"
FT /id="VAR_007849"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:5V56"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:5V56"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:5V56"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:5V56"
FT HELIX 99..109
FT /evidence="ECO:0007829|PDB:5V56"
FT HELIX 110..113
FT /evidence="ECO:0007829|PDB:5V56"
FT HELIX 116..130
FT /evidence="ECO:0007829|PDB:5V56"
FT STRAND 136..140
FT /evidence="ECO:0007829|PDB:5V56"
FT HELIX 144..151
FT /evidence="ECO:0007829|PDB:5V56"
FT TURN 152..154
FT /evidence="ECO:0007829|PDB:5V56"
FT HELIX 155..160
FT /evidence="ECO:0007829|PDB:5V56"
FT TURN 165..167
FT /evidence="ECO:0007829|PDB:5V56"
FT TURN 171..173
FT /evidence="ECO:0007829|PDB:5V56"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:6XBK"
FT TURN 182..184
FT /evidence="ECO:0007829|PDB:5V56"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:4JKV"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:4JKV"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:4JKV"
FT STRAND 210..218
FT /evidence="ECO:0007829|PDB:4JKV"
FT HELIX 224..254
FT /evidence="ECO:0007829|PDB:4JKV"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:4JKV"
FT TURN 262..265
FT /evidence="ECO:0007829|PDB:4JKV"
FT HELIX 266..282
FT /evidence="ECO:0007829|PDB:4JKV"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:4JKV"
FT HELIX 289..294
FT /evidence="ECO:0007829|PDB:4JKV"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:4JKV"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:4JKV"
FT STRAND 308..310
FT /evidence="ECO:0007829|PDB:5L7D"
FT HELIX 313..347
FT /evidence="ECO:0007829|PDB:4JKV"
FT TURN 354..356
FT /evidence="ECO:0007829|PDB:4QIM"
FT HELIX 361..378
FT /evidence="ECO:0007829|PDB:4JKV"
FT STRAND 381..384
FT /evidence="ECO:0007829|PDB:4JKV"
FT TURN 385..388
FT /evidence="ECO:0007829|PDB:4JKV"
FT STRAND 389..395
FT /evidence="ECO:0007829|PDB:4JKV"
FT HELIX 397..403
FT /evidence="ECO:0007829|PDB:4JKV"
FT HELIX 405..432
FT /evidence="ECO:0007829|PDB:4JKV"
FT STRAND 436..442
FT /evidence="ECO:0007829|PDB:4JKV"
FT HELIX 443..492
FT /evidence="ECO:0007829|PDB:4JKV"
FT STRAND 501..503
FT /evidence="ECO:0007829|PDB:5V56"
FT HELIX 515..532
FT /evidence="ECO:0007829|PDB:4JKV"
FT HELIX 533..536
FT /evidence="ECO:0007829|PDB:4JKV"
FT HELIX 539..548
FT /evidence="ECO:0007829|PDB:4JKV"
FT STRAND 554..558
FT /evidence="ECO:0007829|PDB:5V57"
SQ SEQUENCE 787 AA; 86397 MW; 8B4C459B34D13F83 CRC64;
MAAARPARGP ELPLLGLLLL LLLGDPGRGA ASSGNATGPG PRSAGGSARR SAAVTGPPPP
LSHCGRAAPC EPLRYNVCLG SVLPYGATST LLAGDSDSQE EAHGKLVLWS GLRNAPRCWA
VIQPLLCAVY MPKCENDRVE LPSRTLCQAT RGPCAIVERE RGWPDFLRCT PDRFPEGCTN
EVQNIKFNSS GQCEVPLVRT DNPKSWYEDV EGCGIQCQNP LFTEAEHQDM HSYIAAFGAV
TGLCTLFTLA TFVADWRNSN RYPAVILFYV NACFFVGSIG WLAQFMDGAR REIVCRADGT
MRLGEPTSNE TLSCVIIFVI VYYALMAGVV WFVVLTYAWH TSFKALGTTY QPLSGKTSYF
HLLTWSLPFV LTVAILAVAQ VDGDSVSGIC FVGYKNYRYR AGFVLAPIGL VLIVGGYFLI
RGVMTLFSIK SNHPGLLSEK AASKINETML RLGIFGFLAF GFVLITFSCH FYDFFNQAEW
ERSFRDYVLC QANVTIGLPT KQPIPDCEIK NRPSLLVEKI NLFAMFGTGI AMSTWVWTKA
TLLIWRRTWC RLTGQSDDEP KRIKKSKMIA KAFSKRHELL QNPGQELSFS MHTVSHDGPV
AGLAFDLNEP SADVSSAWAQ HVTKMVARRG AILPQDISVT PVATPVPPEE QANLWLVEAE
ISPELQKRLG RKKKRRKRKK EVCPLAPPPE LHPPAPAPST IPRLPQLPRQ KCLVAAGAWG
AGDSCRQGAW TLVSNPFCPE PSPPQDPFLP SAPAPVAWAH GRRQGLGPIH SRTNLMDTEL
MDADSDF
