Molecule Information

General Information of the Molecule (ID: Mol00635)
Name
Smoothened homolog (SMO) ,Homo sapiens
Synonyms
SMO; Protein Gx; SMOH
    Click to Show/Hide
Molecule Type
Protein
Gene Name
SMO
Gene ID
6608
Location
chr7:129188633-129213545[+]
Sequence
MAAARPARGPELPLLGLLLLLLLGDPGRGAASSGNATGPGPRSAGGSARRSAAVTGPPPP
LSHCGRAAPCEPLRYNVCLGSVLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWA
VIQPLLCAVYMPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFPEGCTN
EVQNIKFNSSGQCEVPLVRTDNPKSWYEDVEGCGIQCQNPLFTEAEHQDMHSYIAAFGAV
TGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADGT
MRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYF
HLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLI
RGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEW
ERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKA
TLLIWRRTWCRLTGQSDDEPKRIKKSKMIAKAFSKRHELLQNPGQELSFSMHTVSHDGPV
AGLAFDLNEPSADVSSAWAQHVTKMVARRGAILPQDISVTPVATPVPPEEQANLWLVEAE
ISPELQKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPSTIPRLPQLPRQKCLVAAGAWG
AGDSCRQGAWTLVSNPFCPEPSPPQDPFLPSAPAPVAWAHGRRQGLGPIHSRTNLMDTEL
MDADSDF
    Click to Show/Hide
3D-structure
PDB ID
6XBM
Classification
Membrane protein
Method
Electron microscopy
Resolution
3.14  Å
Function
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, GLI2 and GLI3 in the cilia. Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation.
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Uniprot ID
SMO_HUMAN
Ensembl ID
ENSG00000128602
HGNC ID
HGNC:11119
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule with Structure Alteration
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Preclinical Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
MRT-92
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug MRT-92
 Drug Info 
Molecule Alteration Missense mutation
p.V329F (c.985_987delGTGinsTTT)
Wild Type Structure Method: Electron microscopy Resolution: 3.14  Å
PDB: 6XBM
Mutant Type Structure Method: X-ray diffraction Resolution: 3.00  Å
PDB: 7ZI0
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.44
TM score: 0.90019
Amino acid change:
V329F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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600
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Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay
References
Ref 1 MRT-92 inhibits Hedgehog signaling by blocking overlapping binding sites in the transmembrane domain of the Smoothened receptorFASEB J. 2015 May;29(5):1817-29. doi: 10.1096/fj.14-267849. Epub 2015 Jan 30.

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