Protein smoothened

Details

Name

Protein smoothened

Kind

protein

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

Functions

cAMP-dependent protein kinase inhibitor activity / G protein-coupled receptor activity / oxysterol binding / protein kinase A catalytic subunit binding / protein sequestering activity

Processes

apoptotic 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 patterning

Components

9+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

• Fz (PF01392)
• Frizzled (PF01534)

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

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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]

Associated Data

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