Smoothened homolog

Details

Name
Smoothened homolog
Synonyms
  • Protein Gx
  • SMO
  • SMOH
Gene Name
SMO
Organism
Humans
Amino acid sequence
>lcl|BSEQ0021716|Smoothened homolog
MAAARPARGPELPLLGLLLLLLLGDPGRGAASSGNATGPGPRSAGGSARRSAAVTGPPPP
LSHCGRAAPCEPLRYNVCLGSVLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWA
VIQPLLCAVYMPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFPEGCTN
EVQNIKFNSSGQCEVPLVRTDNPKSWYEDVEGCGIQCQNPLFTEAEHQDMHSYIAAFGAV
TGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADGT
MRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYF
HLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLI
RGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEW
ERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKA
TLLIWRRTWCRLTGQSDDEPKRIKKSKMIAKAFSKRHELLQNPGQELSFSMHTVSHDGPV
AGLAFDLNEPSADVSSAWAQHVTKMVARRGAILPQDISVTPVATPVPPEEQANLWLVEAE
ISPELQKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPSTIPRLPQLPRQKCLVAAGAWG
AGDSCRQGAWTLVSNPFCPEPSPPQDPFLPSAPAPVAWAHGRRQGLGPIHSRTNLMDTEL
MDADSDF
Number of residues
787
Molecular Weight
86395.95
Theoretical pI
Not Available
GO Classification
Functions
drug binding / G-protein coupled receptor activity / patched binding / Wnt-protein binding
Processes
anterior/posterior pattern specification / astrocyte activation / atrial septum morphogenesis / cell fate specification / cellular response to cholesterol / central nervous system neuron differentiation / cerebellar cortex morphogenesis / cerebral cortex development / dentate gyrus development / detection of cell density by contact stimulus involved in contact inhibition / determination of left/right asymmetry in lateral mesoderm / dorsal/ventral neural tube patterning / epithelial-mesenchymal cell signaling / forebrain morphogenesis / hair follicle morphogenesis / heart looping / homeostasis of number of cells within a tissue / in utero embryonic development / left/right axis specification / mammary gland epithelial cell differentiation / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / midgut development / multicellular organism growth / myoblast migration / negative regulation of apoptotic process / negative regulation of DNA binding / negative regulation of epithelial cell differentiation / negative regulation of gene expression / negative regulation of hair follicle development / negative regulation of transcription from RNA polymerase II promoter / neural crest cell migration / odontogenesis of dentin-containing tooth / osteoblast differentiation / pancreas morphogenesis / positive regulation of branching involved in ureteric bud morphogenesis / positive regulation of epithelial cell proliferation / positive regulation of gene expression / positive regulation of hh target transcription factor activity / positive regulation of mesenchymal cell proliferation / positive regulation of multicellular organism growth / positive regulation of neuroblast proliferation / positive regulation of organ growth / positive regulation of protein import into nucleus / positive regulation of smoothened signaling pathway / positive regulation of transcription from RNA polymerase II promoter / protein localization to nucleus / protein stabilization / regulation of heart morphogenesis / regulation of stem cell population maintenance / renal system development / skeletal muscle fiber development / smoothened signaling pathway / smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation / smoothened signaling pathway involved in ventral spinal cord patterning / somite development / thalamus development / type B pancreatic cell development / vasculogenesis / ventral midline determination
Components
ciliary membrane / ciliary tip / endocytic vesicle membrane / extracellular exosome / integral component of membrane / intracellular membrane-bounded organelle / plasma membrane / primary cilium
General Function
Wnt-protein binding
Specific 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 and GLI3 in the cilia.
Pfam Domain Function
Transmembrane Regions
234-254 263-283 315-335 359-379 403-423 452-472 525-545
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0021717|Smoothened homolog (SMO)
ATGGCCGCTGCCCGCCCAGCGCGGGGGCCGGAGCTCCCGCTCCTGGGGCTGCTGCTGCTG
CTGCTGCTGGGGGACCCGGGCCGGGGGGCGGCCTCGAGCGGGAACGCGACCGGGCCTGGG
CCTCGGAGCGCGGGCGGGAGCGCGAGGAGGAGCGCGGCGGTGACTGGCCCTCCGCCGCCG
CTGAGCCACTGCGGCCGGGCTGCCCCCTGCGAGCCGCTGCGCTACAACGTGTGCCTGGGC
TCGGTGCTGCCCTACGGGGCCACCTCCACACTGCTGGCCGGAGACTCGGACTCCCAGGAG
GAAGCGCACGGCAAGCTCGTGCTCTGGTCGGGCCTCCGGAATGCCCCCCGCTGCTGGGCA
GTGATCCAGCCCCTGCTGTGTGCCGTATACATGCCCAAGTGTGAGAATGACCGGGTGGAG
CTGCCCAGCCGTACCCTCTGCCAGGCCACCCGAGGCCCCTGTGCCATCGTGGAGAGGGAG
CGGGGCTGGCCTGACTTCCTGCGCTGCACTCCTGACCGCTTCCCTGAAGGCTGCACGAAT
GAGGTGCAGAACATCAAGTTCAACAGTTCAGGCCAGTGCGAAGTGCCCTTGGTTCGGACA
GACAACCCCAAGAGCTGGTACGAGGACGTGGAGGGCTGCGGCATCCAGTGCCAGAACCCG
CTCTTCACAGAGGCTGAGCACCAGGACATGCACAGCTACATCGCGGCCTTCGGGGCCGTC
ACGGGCCTCTGCACGCTCTTCACCCTGGCCACATTCGTGGCTGACTGGCGGAACTCGAAT
CGCTACCCTGCTGTTATTCTCTTCTACGTCAATGCGTGCTTCTTTGTGGGCAGCATTGGC
TGGCTGGCCCAGTTCATGGATGGTGCCCGCCGAGAGATCGTCTGCCGTGCAGATGGCACC
ATGAGGCTTGGGGAGCCCACCTCCAATGAGACTCTGTCCTGCGTCATCATCTTTGTCATC
GTGTACTACGCCCTGATGGCTGGTGTGGTTTGGTTTGTGGTCCTCACCTATGCCTGGCAC
ACTTCCTTCAAAGCCCTGGGCACCACCTACCAGCCTCTCTCGGGCAAGACCTCCTACTTC
CACCTGCTCACCTGGTCACTCCCCTTTGTCCTCACTGTGGCAATCCTTGCTGTGGCGCAG
GTGGATGGGGACTCTGTGAGTGGGATTTGTTTTGTGGGCTACAAGAACTACCGATACCGT
GCGGGCTTCGTGCTGGCCCCAATCGGCCTGGTGCTCATCGTGGGAGGCTACTTCCTCATC
CGAGGAGTCATGACTCTGTTCTCCATCAAGAGCAACCACCCCGGGCTGCTGAGTGAGAAG
GCTGCCAGCAAGATCAACGAGACCATGCTGCGCCTGGGCATTTTTGGCTTCCTGGCCTTT
GGCTTTGTGCTCATTACCTTCAGCTGCCACTTCTACGACTTCTTCAACCAGGCTGAGTGG
GAGCGCAGCTTCCGGGACTATGTGCTATGTCAGGCCAATGTGACCATCGGGCTGCCCACC
AAGCAGCCCATCCCTGACTGTGAGATCAAGAATCGCCCGAGCCTTCTGGTGGAGAAGATC
AACCTGTTTGCCATGTTTGGAACTGGCATCGCCATGAGCACCTGGGTCTGGACCAAGGCC
ACGCTGCTCATCTGGAGGCGTACCTGGTGCAGGTTGACTGGGCAGAGTGACGATGAGCCA
AAGCGGATCAAGAAGAGCAAGATGATTGCCAAGGCCTTCTCTAAGCGGCACGAGCTCCTG
CAGAACCCAGGCCAGGAGCTGTCCTTCAGCATGCACACTGTGTCCCACGACGGGCCCGTG
GCGGGCTTGGCCTTTGACCTCAATGAGCCCTCAGCTGATGTCTCCTCTGCCTGGGCCCAG
CATGTCACCAAGATGGTGGCTCGGAGAGGAGCCATACTGCCCCAGGATATTTCTGTCACC
CCTGTGGCAACTCCAGTGCCCCCAGAGGAACAAGCCAACCTGTGGCTGGTTGAGGCAGAG
ATCTCCCCAGAGCTGCAGAAGCGCCTGGGCCGGAAGAAGAAGAGGAGGAAGAGGAAGAAG
GAGGTGTGCCCGCTGGCGCCGCCCCCTGAGCTTCACCCCCCTGCCCCTGCCCCCAGTACC
ATTCCTCGACTGCCTCAGCTGCCCCGGCAGAAATGCCTGGTGGCTGCAGGTGCCTGGGGA
GCTGGGGACTCTTGCCGACAGGGAGCGTGGACCCTGGTCTCCAACCCATTCTGCCCAGAG
CCCAGTCCCCCTCAGGATCCATTTCTGCCCAGTGCACCGGCCCCCGTGGCATGGGCTCAT
GGCCGCCGACAGGGCCTGGGGCCTATTCACTCCCGCACCAACCTGATGGACACAGAACTC
ATGGATGCAGACTCGGACTTCTGA
Chromosome Location
7
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ99835
UniProtKB Entry NameSMO_HUMAN
HGNC IDHGNC:11119
General References
  1. Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, Scott MP, Pennica D, Goddard A, Phillips H, Noll M, Hooper JE, de Sauvage F, Rosenthal A: The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature. 1996 Nov 14;384(6605):129-34. [PubMed:8906787]
  2. Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam CW, Hynes M, Goddard A, Rosenthal A, Epstein EH Jr, de Sauvage FJ: Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature. 1998 Jan 1;391(6662):90-2. [PubMed:9422511]
  3. Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HH, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GA, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJ, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi S, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Dohner H, Dohner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC: Human chromosome 7: DNA sequence and biology. Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10. [PubMed:12690205]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  5. Endoh-Yamagami S, Evangelista M, Wilson D, Wen X, Theunissen JW, Phamluong K, Davis M, Scales SJ, Solloway MJ, de Sauvage FJ, Peterson AS: The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development. Curr Biol. 2009 Aug 11;19(15):1320-6. doi: 10.1016/j.cub.2009.06.046. Epub 2009 Jul 9. [PubMed:19592253]
  6. Seo S, Zhang Q, Bugge K, Breslow DK, Searby CC, Nachury MV, Sheffield VC: A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened. PLoS Genet. 2011 Nov;7(11):e1002358. doi: 10.1371/journal.pgen.1002358. Epub 2011 Nov 3. [PubMed:22072986]
  7. Wang C, Wu H, Katritch V, Han GW, Huang XP, Liu W, Siu FY, Roth BL, Cherezov V, Stevens RC: Structure of the human smoothened receptor bound to an antitumour agent. Nature. 2013 May 16;497(7449):338-43. doi: 10.1038/nature12167. Epub 2013 May 1. [PubMed:23636324]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01047Fluocinonideapproved, investigationalunknownagonistDetails
DB08828Vismodegibapproved, investigationalyesantagonistDetails
DB09143Sonidegibapproved, investigationalunknownantagonistDetails
DB06786Halcinonideapproved, investigational, withdrawnunknownagonistactivatorDetails
DB11978Glasdegibapproved, investigationalyesinhibitorDetails