Smoothened homolog

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• drug binding Source: UniProtKB <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Identification and mechanism of action of the acylguanidine MRT-83, a novel potent Smoothened antagonist."
    Roudaut H., Traiffort E., Gorojankina T., Vincent L., Faure H., Schoenfelder A., Mann A., Manetti F., Solinas A., Taddei M., Ruat M.
    Mol. Pharmacol. 79:453-460(2011) [PubMed] [Europe PMC] [Abstract]
• G protein-coupled receptor activity Source: UniProtKB-KW
• patched binding Source: BHF-UCL <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Characterization of two patched receptors for the vertebrate hedgehog protein family."
    Carpenter D., Stone D.M., Brush J., Ryan A., Armanini M., Frantz G., Rosenthal A., de Sauvage F.J.
    Proc. Natl. Acad. Sci. U.S.A. 95:13630-13634(1998) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• anterior/posterior pattern specification Source: Ensembl
• astrocyte activation Source: Ensembl
• atrial septum morphogenesis Source: Ensembl
• cell fate specification Source: Ensembl
• cellular response to cholesterol Source: BHF-UCL
• central nervous system development Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• central nervous system neuron differentiation Source: Ensembl
• cerebellar cortex morphogenesis Source: Ensembl
• cerebral cortex development Source: Ensembl
• commissural neuron axon guidance Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• contact inhibition Source: BHF-UCL <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • Ref.2

    "Activating Smoothened mutations in sporadic basal-cell carcinoma."
    Xie J., Murone M., Luoh S.-M., Ryan A., Gu Q., Zhang C., Bonifas J.M., Lam C.-W., Hynes M., Goddard A., Rosenthal A., Epstein E.H. Jr., de Sauvage F.J.
    Nature 391:90-92(1998) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-535 AND GLN-562.
• dentate gyrus development Source: Ensembl
• determination of left/right asymmetry in lateral mesoderm Source: BHF-UCL
• dorsal/ventral neural tube patterning Source: Ensembl
• epithelial-mesenchymal cell signaling Source: Ensembl
• forebrain morphogenesis Source: BHF-UCL
• hair follicle morphogenesis Source: Ensembl
• heart looping Source: BHF-UCL
• homeostasis of number of cells within a tissue Source: Ensembl
• in utero embryonic development Source: Ensembl
• left/right axis specification Source: Ensembl
• mammary gland epithelial cell differentiation Source: Ensembl
• mesenchymal to epithelial transition involved in metanephric renal vesicle formation Source: UniProtKB
• midgut development Source: BHF-UCL
• multicellular organism growth Source: Ensembl
• myoblast migration Source: Ensembl
• negative regulation of apoptotic process Source: Ensembl
• negative regulation of DNA binding Source: UniProtKB
• negative regulation of epithelial cell differentiation Source: Ensembl
• negative regulation of gene expression Source: UniProtKB
• negative regulation of hair follicle development Source: Ensembl
• negative regulation of transcription by RNA polymerase II Source: Ensembl
• neural crest cell migration Source: Ensembl
• odontogenesis of dentin-containing tooth Source: Ensembl
• osteoblast differentiation Source: Ensembl
• pancreas morphogenesis Source: Ensembl
• positive regulation of branching involved in ureteric bud morphogenesis Source: UniProtKB
• positive regulation of cell migration Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "miR-338-3p suppresses invasion of liver cancer cell by targeting smoothened."
    Huang X.H., Chen J.S., Wang Q., Chen X.L., Wen L., Chen L.Z., Bi J., Zhang L.J., Su Q., Zeng W.T.
    J. Pathol. 225:463-472(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of epithelial cell proliferation Source: Ensembl
• positive regulation of gene expression Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "miR-338-3p suppresses invasion of liver cancer cell by targeting smoothened."
    Huang X.H., Chen J.S., Wang Q., Chen X.L., Wen L., Chen L.Z., Bi J., Zhang L.J., Su Q., Zeng W.T.
    J. Pathol. 225:463-472(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of hh target transcription factor activity Source: BHF-UCL
• positive regulation of mesenchymal cell proliferation Source: Ensembl
• positive regulation of multicellular organism growth Source: Ensembl
• positive regulation of neuroblast proliferation Source: Ensembl
• positive regulation of organ growth Source: Ensembl
• positive regulation of protein import into nucleus Source: Ensembl
• positive regulation of smoothened signaling pathway Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription by RNA polymerase II Source: Ensembl
• protein localization to nucleus Source: Ensembl
• protein stabilization Source: Ensembl
• regulation of heart morphogenesis Source: BHF-UCL
• regulation of stem cell population maintenance Source: Ensembl
• skeletal muscle fiber development Source: Ensembl
• smoothened signaling pathway Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Evidence for allosteric interactions of antagonist binding to the smoothened receptor."
    Rominger C.M., Bee W.L., Copeland R.A., Davenport E.A., Gilmartin A., Gontarek R., Hornberger K.R., Kallal L.A., Lai Z., Lawrie K., Lu Q., McMillan L., Truong M., Tummino P.J., Turunen B., Will M., Zuercher W.J., Rominger D.H.
    J. Pharmacol. Exp. Ther. 329:995-1005(2009) [PubMed] [Europe PMC] [Abstract]
  • "Identification and mechanism of action of the acylguanidine MRT-83, a novel potent Smoothened antagonist."
    Roudaut H., Traiffort E., Gorojankina T., Vincent L., Faure H., Schoenfelder A., Mann A., Manetti F., Solinas A., Taddei M., Ruat M.
    Mol. Pharmacol. 79:453-460(2011) [PubMed] [Europe PMC] [Abstract]
• smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation Source: Ensembl
• smoothened signaling pathway involved in ventral spinal cord patterning Source: Ensembl
• smooth muscle tissue development Source: UniProtKB <p>Inferred from Expression Pattern</p> <p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "Immunohistochemical analysis of Sonic hedgehog signalling in normal human urinary tract development."
    Jenkins D., Winyard P.J., Woolf A.S.
    J. Anat. 211:620-629(2007) [PubMed] [Europe PMC] [Abstract]
• somite development Source: BHF-UCL
• thalamus development Source: Ensembl
• type B pancreatic cell development Source: Ensembl
• vasculogenesis Source: Ensembl
• ventral midline determination Source: BHF-UCL

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Topology

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

Keywords - Diseaseⁱ

Organism-specific databases

Miscellaneous databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

GO - Molecular functionⁱ

• patched binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Characterization of two patched receptors for the vertebrate hedgehog protein family."
    Carpenter D., Stone D.M., Brush J., Ryan A., Armanini M., Frantz G., Rosenthal A., de Sauvage F.J.
    Proc. Natl. Acad. Sci. U.S.A. 95:13630-13634(1998) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

Chemistry databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Region

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

        10         20         30         40         50
MAAARPARGP ELPLLGLLLL LLLGDPGRGA ASSGNATGPG PRSAGGSARR 
        60         70         80         90        100
SAAVTGPPPP LSHCGRAAPC EPLRYNVCLG SVLPYGATST LLAGDSDSQE 
       110        120        130        140        150
EAHGKLVLWS GLRNAPRCWA VIQPLLCAVY MPKCENDRVE LPSRTLCQAT 
       160        170        180        190        200
RGPCAIVERE RGWPDFLRCT PDRFPEGCTN EVQNIKFNSS GQCEVPLVRT 
       210        220        230        240        250
DNPKSWYEDV EGCGIQCQNP LFTEAEHQDM HSYIAAFGAV TGLCTLFTLA 
       260        270        280        290        300
TFVADWRNSN RYPAVILFYV NACFFVGSIG WLAQFMDGAR REIVCRADGT 
       310        320        330        340        350
MRLGEPTSNE TLSCVIIFVI VYYALMAGVV WFVVLTYAWH TSFKALGTTY 
       360        370        380        390        400
QPLSGKTSYF HLLTWSLPFV LTVAILAVAQ VDGDSVSGIC FVGYKNYRYR 
       410        420        430        440        450
AGFVLAPIGL VLIVGGYFLI RGVMTLFSIK SNHPGLLSEK AASKINETML 
       460        470        480        490        500
RLGIFGFLAF GFVLITFSCH FYDFFNQAEW ERSFRDYVLC QANVTIGLPT 
       510        520        530        540        550
KQPIPDCEIK NRPSLLVEKI NLFAMFGTGI AMSTWVWTKA TLLIWRRTWC 
       560        570        580        590        600
RLTGQSDDEP KRIKKSKMIA KAFSKRHELL QNPGQELSFS MHTVSHDGPV 
       610        620        630        640        650
AGLAFDLNEP SADVSSAWAQ HVTKMVARRG AILPQDISVT PVATPVPPEE 
       660        670        680        690        700
QANLWLVEAE ISPELQKRLG RKKKRRKRKK EVCPLAPPPE LHPPAPAPST 
       710        720        730        740        750
IPRLPQLPRQ KCLVAAGAWG AGDSCRQGAW TLVSNPFCPE PSPPQDPFLP 
       760        770        780 
SAPAPVAWAH GRRQGLGPIH SRTNLMDTEL MDADSDF               

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityⁱ

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. Human chromosome 7
   Human chromosome 7: entries, gene names and cross-references to MIM
2. Human entries with polymorphisms or disease mutations
   List of human entries with polymorphisms or disease mutations
3. Human polymorphisms and disease mutations
   Index of human polymorphisms and disease mutations
4. MIM cross-references
   Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
5. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references
6. SIMILARITY comments
   Index of protein domains and families
7. 7-transmembrane G-linked receptors
   List of 7-transmembrane G-linked receptor entries