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Q99835 (SMO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Smoothened homolog

Short name=SMO
Alternative name(s):
Protein Gx
Gene names
Name:SMO
Synonyms:SMOH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length787 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.5

Subunit structure

Interacts with ARRB2. Interacts with KIF7. Interacts with BBS5 and BBS7; the interactions are indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO. Ref.5 Ref.6

Subcellular location

Membrane; Multi-pass membrane protein. Cell projectioncilium Ref.6.

Sequence similarities

Belongs to the G-protein coupled receptor Fz/Smo family.

Contains 1 FZ (frizzled) domain.

Ontologies

Keywords
   Cellular componentCell projection
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenohypophysis development

Inferred from Biological aspect of Ancestor. Source: RefGenome

atrial septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

axon extension involved in axon guidance

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

cardioblast differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell fate specification

Inferred from electronic annotation. Source: Ensembl

cellular response to cholesterol

Inferred from sequence or structural similarity. Source: BHF-UCL

central nervous system neuron differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

cerebellar cortex morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

ciliary receptor clustering involved in smoothened signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

detection of cell density by contact stimulus involved in contact inhibition

Inferred from mutant phenotype Ref.2. Source: BHF-UCL

determination of left/right asymmetry in lateral mesoderm

Inferred from sequence or structural similarity. Source: BHF-UCL

determination of left/right symmetry

Inferred from Biological aspect of Ancestor. Source: RefGenome

dorsal/ventral neural tube patterning

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic camera-type eye development

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic digestive tract morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic neurocranium morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic viscerocranium morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

epithelial-mesenchymal cell signaling

Inferred from electronic annotation. Source: Ensembl

exocrine pancreas development

Inferred from Biological aspect of Ancestor. Source: RefGenome

facial nerve development

Inferred from Biological aspect of Ancestor. Source: RefGenome

floor plate formation

Inferred from Biological aspect of Ancestor. Source: RefGenome

forebrain morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

hair follicle morphogenesis

Inferred from electronic annotation. Source: Ensembl

heart looping

Inferred from sequence or structural similarity. Source: BHF-UCL

heart morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

mammary gland epithelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

mesenchymal to epithelial transition involved in metanephric renal vesicle formation

Inferred from sequence or structural similarity. Source: UniProtKB

midgut development

Inferred from sequence or structural similarity. Source: BHF-UCL

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

muscle cell fate commitment

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of epithelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of hair follicle development

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

neural crest cell migration

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuron fate commitment

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuron projection regeneration

Inferred from Biological aspect of Ancestor. Source: RefGenome

odontogenesis of dentin-containing tooth

Inferred from Biological aspect of Ancestor. Source: RefGenome

osteoblast differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

otolith morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

pancreas morphogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of branching involved in ureteric bud morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of epithelial cell proliferation

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of hh target transcription factor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of mesenchymal cell proliferation

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of neuroblast proliferation

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of smoothened signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein localization to nucleus

Inferred from electronic annotation. Source: Ensembl

protein stabilization

Inferred from electronic annotation. Source: Ensembl

regulation of heart morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of stem cell maintenance

Inferred from electronic annotation. Source: Ensembl

renal system development

Inferred from expression pattern PubMed 17850284. Source: UniProtKB

semicircular canal morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

smoothened signaling pathway

Inferred from mutant phenotype PubMed 19304771PubMed 21177415. Source: UniProtKB

smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation

Inferred from Biological aspect of Ancestor. Source: RefGenome

smoothened signaling pathway involved in ventral spinal cord patterning

Inferred from Biological aspect of Ancestor. Source: RefGenome

somite development

Inferred from sequence or structural similarity. Source: BHF-UCL

spermatogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

thalamus development

Inferred from electronic annotation. Source: Ensembl

type B pancreatic cell development

Inferred from electronic annotation. Source: Ensembl

vasculogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

ventral midline determination

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentciliary membrane

Inferred from electronic annotation. Source: Ensembl

cilium

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular membrane-bounded organelle

Inferred from direct assay PubMed 11278759. Source: BHF-UCL

neuronal cell body

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Inferred from direct assay PubMed 19304771. Source: UniProtKB

primary cilium

Traceable author statement PubMed 21931618. Source: BHF-UCL

   Molecular_functionG-protein coupled receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

PDZ domain binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-activated receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-protein binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

drug binding

Inferred from direct assay PubMed 19304771PubMed 21177415. Source: UniProtKB

patched binding

Inferred from physical interaction PubMed 9811851. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 787760Smoothened homolog
PRO_0000013015

Regions

Topological domain28 – 233206Extracellular Potential
Transmembrane234 – 25421Helical; Name=1; Potential
Topological domain255 – 2628Cytoplasmic Potential
Transmembrane263 – 28321Helical; Name=2; Potential
Topological domain284 – 31431Extracellular Potential
Transmembrane315 – 33521Helical; Name=3; Potential
Topological domain336 – 35823Cytoplasmic Potential
Transmembrane359 – 37921Helical; Name=4; Potential
Topological domain380 – 40223Extracellular Potential
Transmembrane403 – 42321Helical; Name=5; Potential
Topological domain424 – 45128Cytoplasmic Potential
Transmembrane452 – 47221Helical; Name=6; Potential
Topological domain473 – 52452Extracellular Potential
Transmembrane525 – 54521Helical; Name=7; Potential
Topological domain546 – 787242Cytoplasmic Potential
Domain65 – 181117FZ
Region538 – 56932Interaction with BBS5 and BBS7

Amino acid modifications

Glycosylation351N-linked (GlcNAc...) Potential
Glycosylation1881N-linked (GlcNAc...) Potential
Glycosylation3091N-linked (GlcNAc...) Potential
Disulfide bond70 ↔ 134 By similarity
Disulfide bond78 ↔ 127 By similarity
Disulfide bond118 ↔ 154 By similarity
Disulfide bond147 ↔ 169 By similarity

Natural variations

Natural variant4731D → H.
Corresponds to variant rs17710891 [ dbSNP | Ensembl ].
VAR_037891
Natural variant5351W → L in basal cell carcinoma samples; somatic mutation. Ref.2
VAR_007848
Natural variant5621R → Q in basal cell carcinoma samples; somatic mutation. Ref.2
VAR_007849

Secondary structure

............................................. 787
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q99835 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 8B4C459B34D13F83

FASTA78786,397
        10         20         30         40         50         60 
MAAARPARGP ELPLLGLLLL LLLGDPGRGA ASSGNATGPG PRSAGGSARR SAAVTGPPPP 

        70         80         90        100        110        120 
LSHCGRAAPC EPLRYNVCLG SVLPYGATST LLAGDSDSQE EAHGKLVLWS GLRNAPRCWA 

       130        140        150        160        170        180 
VIQPLLCAVY MPKCENDRVE LPSRTLCQAT RGPCAIVERE RGWPDFLRCT PDRFPEGCTN 

       190        200        210        220        230        240 
EVQNIKFNSS GQCEVPLVRT DNPKSWYEDV EGCGIQCQNP LFTEAEHQDM HSYIAAFGAV 

       250        260        270        280        290        300 
TGLCTLFTLA TFVADWRNSN RYPAVILFYV NACFFVGSIG WLAQFMDGAR REIVCRADGT 

       310        320        330        340        350        360 
MRLGEPTSNE TLSCVIIFVI VYYALMAGVV WFVVLTYAWH TSFKALGTTY QPLSGKTSYF 

       370        380        390        400        410        420 
HLLTWSLPFV LTVAILAVAQ VDGDSVSGIC FVGYKNYRYR AGFVLAPIGL VLIVGGYFLI 

       430        440        450        460        470        480 
RGVMTLFSIK SNHPGLLSEK AASKINETML RLGIFGFLAF GFVLITFSCH FYDFFNQAEW 

       490        500        510        520        530        540 
ERSFRDYVLC QANVTIGLPT KQPIPDCEIK NRPSLLVEKI NLFAMFGTGI AMSTWVWTKA 

       550        560        570        580        590        600 
TLLIWRRTWC RLTGQSDDEP KRIKKSKMIA KAFSKRHELL QNPGQELSFS MHTVSHDGPV 

       610        620        630        640        650        660 
AGLAFDLNEP SADVSSAWAQ HVTKMVARRG AILPQDISVT PVATPVPPEE QANLWLVEAE 

       670        680        690        700        710        720 
ISPELQKRLG RKKKRRKRKK EVCPLAPPPE LHPPAPAPST IPRLPQLPRQ KCLVAAGAWG 

       730        740        750        760        770        780 
AGDSCRQGAW TLVSNPFCPE PSPPQDPFLP SAPAPVAWAH GRRQGLGPIH SRTNLMDTEL 


MDADSDF 

« Hide

References

« Hide 'large scale' references
[1]"The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog."
Stone D.M., Hynes M., Armanini M., Swanson T.A., Gu Q., Johnson R.L., Scott M.P., Pennica D., Goddard A., Phillips H., Noll M., Hooper J.E., de Sauvage F., Rosenthal A.
Nature 384:129-134(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Embryonic lung.
[2]"Activating Smoothened mutations in sporadic basal-cell carcinoma."
Xie J., Murone M., Luoh S.-M., Ryan A., Gu Q., Zhang C., Bonifas J.M., Lam C.-W., Hynes M., Goddard A., Rosenthal A., Epstein E.H. Jr., de Sauvage F.J.
Nature 391:90-92(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-535 AND GLN-562.
[3]"Cloning and identification of Gx gene in NPC."
Jiang N., Zeng Z.Y., Li G.Y.
Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development."
Endoh-Yamagami S., Evangelista M., Wilson D., Wen X., Theunissen J.W., Phamluong K., Davis M., Scales S.J., Solloway M.J., de Sauvage F.J., Peterson A.S.
Curr. Biol. 19:1320-1326(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH KIF7.
[6]"A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened."
Seo S., Zhang Q., Bugge K., Breslow D.K., Searby C.C., Nachury M.V., Sheffield V.C.
PLoS Genet. 7:E1002358-E1002358(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH THE BBSOME COMPLEX, INTERACTION WITH BBS5 AND BBS7, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U84401 mRNA. Translation: AAB41788.1.
AF114821, AF114819, AF114820 Genomic DNA. Translation: AAD17202.1.
AF120103 mRNA. Translation: AAF31757.1.
AF071494 mRNA. Translation: AAC24863.1.
BC009989 mRNA. Translation: AAH09989.1.
RefSeqNP_005622.1. NM_005631.4.
UniGeneHs.437846.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4JKVX-ray2.45A/B190-555[»]
4N4WX-ray2.80A128-190[»]
4O9RX-ray3.20A190-433[»]
A441-555[»]
ProteinModelPortalQ99835.
SMRQ99835. Positions 63-179, 190-550.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112492. 3 interactions.
DIPDIP-34574N.
IntActQ99835. 5 interactions.
STRING9606.ENSP00000249373.

Chemistry

BindingDBQ99835.
ChEMBLCHEMBL5971.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ99835.

Polymorphism databases

DMDM6226142.

Proteomic databases

PaxDbQ99835.
PRIDEQ99835.

Protocols and materials databases

DNASU6608.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000249373; ENSP00000249373; ENSG00000128602.
GeneID6608.
KEGGhsa:6608.
UCSCuc003vor.3. human.

Organism-specific databases

CTD6608.
GeneCardsGC07P128828.
HGNCHGNC:11119. SMO.
HPACAB011446.
MIM601500. gene.
neXtProtNX_Q99835.
PharmGKBPA35968.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG312505.
HOGENOMHOG000252964.
HOVERGENHBG000352.
InParanoidQ99835.
KOK06226.
OMADRFPEGC.
OrthoDBEOG74J972.
PhylomeDBQ99835.
TreeFamTF106460.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ99835.

Gene expression databases

ArrayExpressQ99835.
BgeeQ99835.
CleanExHS_SMO.
GenevestigatorQ99835.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
IPR026544. SMO.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF35. PTHR11309:SF35. 1 hit.
PfamPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSPR00489. FRIZZLED.
SMARTSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMSSF63501. SSF63501. 1 hit.
PROSITEPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSmo. human.
GeneWikiSmoothened.
GenomeRNAi6608.
NextBio25725.
PROQ99835.
SOURCESearch...

Entry information

Entry nameSMO_HUMAN
AccessionPrimary (citable) accession number: Q99835
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries