Protein smoothened
Details
- Name
- Protein smoothened
- Synonyms
- Protein Gx
- SMOH
- Gene Name
- SMO
- UniProtKB Entry
- Q99835Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0021716|Protein smoothened 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
- FunctionscAMP-dependent protein kinase inhibitor activity / G protein-coupled receptor activity / oxysterol binding / protein kinase A catalytic subunit binding / protein sequestering activityProcessesapoptotic process / central nervous system development / commissural neuron axon guidance / contact inhibition / dopaminergic neuron differentiation / epithelial cell proliferation / gene expression / negative regulation of protein phosphorylation / negative regulation of transcription by RNA polymerase II / neuroblast proliferation / pattern specification process / positive regulation of cell migration / positive regulation of transcription by RNA polymerase II / protein import into nucleus / regulation of somatic stem cell population maintenance / smooth muscle tissue development / spinal cord dorsal/ventral patterningComponents9+0 non-motile cilium / centriole / cilium / dendrite / endoplasmic reticulum / endoplasmic reticulum-Golgi intermediate compartment / Golgi apparatus / late endosome
- General Function
- G protein-coupled receptor which associates with the patched protein (PTCH) to transduce hedgehog protein signaling. Binding of sonic hedgehog (SHH) to its receptor patched prevents inhibition of smoothened (SMO) by patched. When active, SMO binds to and sequesters protein kinase A catalytic subunit PRKACA at the cell membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors which releases the GLI proteins from PRKACA-mediated inhibition and allows for transcriptional activation of hedgehog pathway target genes (By similarity). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia (PubMed:19592253). Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity)
- Specific Function
- cAMP-dependent protein kinase inhibitor activity
- Pfam Domain Function
- Signal Regions
- 1-27
- Transmembrane Regions
- 234-254 263-283 315-335 359-379 403-423 452-472 525-545
- Cellular Location
- Cell 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
- 7q32.1
- External Identifiers
Resource Link UniProtKB ID Q99835 UniProtKB Entry Name SMO_HUMAN GeneCard ID SMO HGNC ID HGNC:11119 PDB ID(s) 4JKV, 4N4W, 4O9R, 4QIM, 4QIN, 5L7D, 5L7I, 5V56, 5V57, 6OT0, 6XBJ, 6XBK, 6XBL, 6XBM, 7ZI0 KEGG ID hsa:6608 IUPHAR/Guide To Pharmacology ID 239 NCBI Gene ID 6608 - General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Associated Data
- Bio-Entities
Bio-Entity Type Protein smoothened (Humans) protein primary- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Fluocinonide approved, investigational unknown target agonist Details Vismodegib approved, investigational yes target antagonistinhibitor Details Sonidegib approved, investigational yes target antagonist Details Halcinonide approved, investigational, withdrawn unknown target agonistactivator Details Glasdegib approved, investigational yes target inhibitor Details NVP-LEQ-506 investigational yes target inhibitor Details BMS-833923 investigational yes target inhibitor Details Taladegib investigational yes target modulator Details