Protein detail
SMO
Protein smoothened (Protein Gx)
Entry name SMO | UniProt ID | EVMP confidence score 0.50 |
Supporting publications (n) 1 | Transmembrane count 7 | Protein classification Cancer-related genesDisease related genesFDA approved drug targetsG-protein coupled receptorsHuman disease related genesPlasma proteinsPredicted membrane proteinsTransporters |
EVMP confidence score
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40Basic Information13
Protein Names
Protein smoothened (Protein Gx)
Protein Class (8)
Cancer-related genesDisease related genesFDA approved drug targetsG-protein coupled receptorsHuman disease related genesPlasma proteinsPredicted membrane proteinsTransporters
Protein Function (8)
- Human disease related genes:Cancers:Cancers of eye, brain, and central nervous system
- Transporters
- Human disease related genes:Cancers:Skin cancers
- G-protein coupled receptors:GPCRs excl olfactory receptors
- Disease related genes
- Cancer-related genes
- G-protein coupled receptors:Family fz/smo receptors
- FDA approved drug targets:Small molecule drugs
Transmembrane
234..254; Helical; Name=1; 263..283; Helical; Name=2; 315..335; Helical; Name=3; 359..379; Helical; Name=4; 403..423; Helical; Name=5; 452..472; Helical; Name=6; 525..545; Helical; Name=7
Transmembrane Count
7
Ensembl
Entrez Gene Symbol
Gene Synonym (2)
FZD11SMOH
Gene Description
Smoothened, frizzled class receptor
Chromosome
7
Position
129188633-129213545
Supporting publications (n)
1
EVMP confidence score
0.50
Function & Pathway7
Protein Function (8)
- Human disease related genes:Cancers:Cancers of eye, brain, and central nervous system
- Transporters
- Human disease related genes:Cancers:Skin cancers
- G-protein coupled receptors:GPCRs excl olfactory receptors
- Disease related genes
- Cancer-related genes
- G-protein coupled receptors:Family fz/smo receptors
- FDA approved drug targets:Small molecule drugs
Cellular Component (15)
- GO:0005770 late endosome
- GO:0005783 endoplasmic reticulum
- GO:0005793 endoplasmic reticulum-Golgi intermediate compartment
- GO:0005794 Golgi apparatus
- GO:0005814 centriole
- GO:0005886 plasma membrane
- GO:0005901 caveola
- GO:0005929 cilium
- GO:0030425 dendrite
- GO:0030666 endocytic vesicle membrane
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Molecular Function (7)
Biological Process (3)
KEGG (5)
Reactome (11)
- R-hsa-5635838 activation of smo
- R-hsa-5620922 bbsome mediated cargo targeting to cilium
- R-hsa-5620920 cargo trafficking to the periciliary membrane
- R-hsa-5617833 cilium assembly
- R-hsa-373080 class b 2 secretin family receptors
- R-hsa-500792 gpcr ligand binding
- R-hsa-5610787 hedgehog off state
- R-hsa-5632684 hedgehog on state
- R-hsa-1852241 organelle biogenesis and maintenance
- R-hsa-372790 signaling by gpcr
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Mediation Categories (4)
Clinical-translation mediationFusion and delivery mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence109
Ligand-Receptor Signaling (54)
54 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | HPMR | No | Yes | No | Yes | No |
| receptor | receptor | CellTalkDB | No | Yes | No | Yes | No |
| receptor | receptor | Surfaceome | No | Yes | No | Yes | No |
| receptor | receptor | Ramilowski2015 | No | Yes | No | Yes | No |
| receptor | receptor | Kirouac2010 | No | Yes | No | Yes | No |
| gpcr | receptor | DGIdb | No | Yes | No | Yes | No |
| receptor | receptor | LRdb | No | Yes | No | Yes | No |
| receptor | receptor | Baccin2019 | No | Yes | No | Yes | No |
| frizzled | receptor | Almen2009 | No | Yes | No | Yes | No |
| gpcr | receptor | Almen2009 | No | Yes | No | Yes | No |
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Regulatory Interaction Network (36)
36 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| SMO | Q99835 | ARRB1 | P49407 | Yes | Yes | No | SIGNOR | SIGNOR:23074268SIGNOR:15618519 |
| KC1E | P49674 | SMO | Q99835 | Yes | Yes | No | SignaLink3 | SignaLink3:20708941SignaLink3:23331499 |
| HERC4 | Q5GLZ8 | SMO | Q99835 | Yes | No | Yes | SIGNOR | SIGNOR:30925584 |
| SMO | Q99835 | STK36 | Q9NRP7 | Yes | Yes | No | WangSIGNOR | SIGNOR:17089004 |
| SMO | Q99835 | GBG3 | P63215 | Yes | Yes | No | SIGNOR | SIGNOR:16885213SIGNOR:23074268 |
| SMO | Q99835 | GBB1 | P62873 | Yes | Yes | No | WangHINTSIGNOR | SIGNOR:16885213SIGNOR:23074268HINT:31168089HINT:32929279 |
| SMO | Q99835 | GNAT1 | P11488 | Yes | Yes | No | SIGNOR | SIGNOR:16885213SIGNOR:23074268 |
| SMO | Q99835 | KIF7 | Q2M1P5 | Yes | Yes | No | SIGNORACSN | ACSN:20956384ACSN:17688959SIGNOR:19666503ACSN:18820483ACSN:20643644ACSN:21209912ACSN:17641202ACSN:19592253ACSN:19549984ACSN:20016067ACSN:18997815 |
| SMO | Q99835 | SRC | P12931 | Yes | Yes | No | SIGNOR | SIGNOR:18455992 |
| SMO | Q99835 | GNAI3 | P08754 | Yes | Yes | No | WangSIGNOR | SIGNOR:16885213SIGNOR:23074268 |
Protein Complex Composition (18)
18 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| CDC5LCRNKL1CYP3A5EFTUD2HSPA8PRPF8SMN1SMOXSNRPASNRPA1SNRPD2SNW1 | P09012P09661P11142P20815P62316Q13573Q15029Q16637Q6P2Q9Q99459Q9BZJ0Q9NWM0 | 1:1:1:1:1:1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC9140 | ||
| DDRGK1IMMTMSMO1PDHA2YARS2 | P29803Q15800Q16891Q96HY6Q9Y2Z4 | 0:0:0:0:0 | Havugimana2012 | Havugimana2012:C_454 | ||
| EVCSMO | P57679Q99835 | 0:0 | KEGG-MEDICUS | |||
| ENTREP3HECW1SMO | P81408Q76N89Q99835 | 0:0:0 | hu.MAP2 | |||
| GPR180MSMO1 | Q15800Q86V85 | 0:0 | hu.MAP | |||
| CRBNKDM4DSMOC1TRPC4AP | Q6B0I6Q8TEL6Q96SW2Q9H4F8 | 0:0:0:0 | hu.MAP2 | |||
| KDM4DSMOC1TRPC4AP | Q6B0I6Q8TEL6Q9H4F8 | 0:0:0 | hu.MAP2 | |||
| SMO | Q99835 | 2 | PDB | PDB:5l7dPDB:5v57PDB:7zi0PDB:4jkvPDB:5v56PDB:5l7i |
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Isolation & Detection Technology (1)
1 record.
Sequence, Structure & Domains13
Sequences
Length
787
Mass
86,397
Sequence
MAAARPARGPELPLLGLLLLLLLGDPGRGAASSGNATGPGPRSAGGSARRSAAVTGPPPPLSHCGRAAPCEPLRYNVCLGSVLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFPEGCTNEVQNIKFNSSGQCEVPLVRTDNPKSWYEDVEGCGIQCQNPLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADGTMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWRRTWCRLTGQSDDEPKRIKKSKMIAKAFSKRHELLQNPGQELSFSMHTVSHDGPVAGLAFDLNEPSADVSSAWAQHVTKMVARRGAILPQDISVTPVATPVPPEEQANLWLVEAEISPELQKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPSTIPRLPQLPRQKCLVAAGAWGAGDSCRQGAWTLVSNPFCPEPSPPQDPFLPSAPAPVAWAHGRRQGLGPIHSRTNLMDTELMDADSDF
3D Structural Models
Turn
152..154; 165..167; 171..173; 182..184; 262..265; 354..356; 385..388
Helix
62..64; 99..109; 110..113; 116..130; 144..151; 155..160; 203..205; 224..254; 256..259; 266..282; 283..285; 289..294; 313..347; 361..378; 397..403; 405..432; 443..492; 515..532; 533..536; 539..548
Beta Strand
65..67; 76..78; 86..88; 90..92; 136..140; 176..178; 190..192; 197..199; 210..218; 299..301; 304..306; 308..310; 381..384; 389..395; 436..442; 496..498; 501..503; 554..558
3D Structure
Electron microscopy (5); X-ray crystallography (10)
Domain & Motif Annotations
Compositional Bias
38..53; Low complexity; 668..680; Basic residues; 685..699; Pro residues
Domain (CC)
The N-terminal extracellular domain mediates sterol-binding which is required for maximal activation of signaling (PubMed:24859340). Contains a second sterol-binding site within the seven-transmembrane pocket which is also required for activation (By similarity). The activating sterol is likely to be cholesterol (PubMed:35658032). The extracellular site is required for SHH-induced activity while the site within the transmembrane pocket regulates basal signaling in the absence of SHH (PubMed:35658032).
Domain (FT)
65..181; FZ
Region
30..60; Disordered; 538..569; Interaction with BBS5 and BBS7; 570..653; Required for interaction with PRKACA; 581..593; Interaction with DLG5; 667..704; Disordered
Protein Families
G-protein coupled receptor Fz/Smo family
Sequence Similarities
Belongs to the G-protein coupled receptor Fz/Smo family.
Clinical Relevance6
Disease Involvement (3)
Cancer-related genesDisease variantFDA approved drug targets
Related Diseases (6)
Biomarker
Approved; Phase 2; Phase 1
Drug Targets
FDA approved drug targets
Drugs (13)
Supporting Publications1
| PMID | Title | Abstract |
|---|---|---|
| 38938674 | Gestational age at birth influences protein and RNA content in human milk extracellular vesicles. | No abstract available |