P56726 (SMO_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Smoothened homolog
Short name=SMO

Gene names

Name:	Smo
Synonyms:	Smoh

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	793 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 By similarity.
Subunit structure	Interacts with ARRB2. Interacts with KIF7 By similarity. Ref.3
Subcellular location	Membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the G-protein coupled receptor Fz/Smo family. Contains 1 FZ (frizzled) domain.

Ontologies

Keywords
Cellular component	Membrane
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	adenohypophysis development Inferred from Biological aspect of Ancestor. Source: RefGenome axon extension involved in axon guidance Inferred from Biological aspect of Ancestor. Source: RefGenome canonical Wnt receptor 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 mutant phenotype. Source: MGI central nervous system neuron differentiation Inferred from mutant phenotype. Source: MGI cerebellar cortex morphogenesis Inferred from mutant phenotype. Source: MGI 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 sequence or structural similarity. Source: UniProtKB determination of left/right asymmetry in lateral mesoderm Inferred from mutant phenotype. Source: BHF-UCL dorsal/ventral neural tube patterning Inferred from mutant phenotype. Source: MGI 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 mutant phenotype. Source: MGI 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 mutant phenotype. Source: BHF-UCL gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome hair follicle morphogenesis Inferred from mutant phenotype. Source: MGI heart looping Inferred from mutant phenotype. Source: BHF-UCL in utero embryonic development Inferred from mutant phenotype. Source: MGI mammary gland epithelial cell differentiation Inferred from mutant phenotype. Source: MGI mesenchymal to epithelial transition involved in metanephric renal vesicle formation Inferred from mutant phenotype. Source: UniProtKB midgut development Inferred from mutant phenotype. Source: BHF-UCL multicellular organism growth Inferred from mutant phenotype. Source: MGI muscle cell fate commitment Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of DNA binding Inferred from mutant phenotype. Source: UniProtKB negative regulation of apoptotic process Inferred from mutant phenotype. Source: MGI negative regulation of epithelial cell differentiation Inferred from mutant phenotype. Source: MGI negative regulation of hair follicle development Inferred from mutant phenotype. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: MGI neural crest cell migration Inferred from genetic interaction. Source: MGI 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 mutant phenotype. Source: MGI osteoblast differentiation Inferred from mutant phenotype. Source: MGI otolith morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome pancreas morphogenesis Inferred from mutant phenotype. Source: MGI positive regulation of branching involved in ureteric bud morphogenesis Inferred from mutant phenotype. Source: UniProtKB positive regulation of epithelial cell proliferation Inferred from mutant phenotype. Source: MGI positive regulation of hh target transcription factor activity Inferred from mutant phenotype. Source: BHF-UCL positive regulation of mesenchymal cell proliferation Inferred from mutant phenotype. Source: MGI positive regulation of neuroblast proliferation Inferred from genetic interaction. Source: MGI positive regulation of smoothened signaling pathway Inferred from mutant phenotype. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: MGI protein localization to nucleus Inferred from mutant phenotype. Source: MGI protein stabilization Inferred from direct assay. Source: MGI regulation of heart morphogenesis Inferred from mutant phenotype. Source: BHF-UCL regulation of stem cell maintenance Inferred from mutant phenotype. Source: MGI semicircular canal morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation Inferred from mutant phenotype. Source: MGI smoothened signaling pathway involved in ventral spinal cord patterning Inferred from mutant phenotype. Source: MGI somite development Inferred from mutant phenotype. Source: BHF-UCL spermatogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome type B pancreatic cell development Inferred from mutant phenotype. Source: MGI vasculogenesis Inferred from mutant phenotype. Source: MGI ventral midline determination Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuronal cell body Inferred from Biological aspect of Ancestor. Source: RefGenome plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB primary cilium Inferred from direct assay. Source: MGI
Molecular function	G-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. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 32	32	Potential
	Chain	33 – 793	761	Smoothened homolog		PRO_0000013016
Regions
	Topological domain	33 – 237	205	Extracellular Potential
	Transmembrane	238 – 258	21	Helical; Name=1; Potential
	Topological domain	259 – 265	7	Cytoplasmic Potential
	Transmembrane	266 – 286	21	Helical; Name=2; Potential
	Topological domain	287 – 318	32	Extracellular Potential
	Transmembrane	319 – 339	21	Helical; Name=3; Potential
	Topological domain	340 – 362	23	Cytoplasmic Potential
	Transmembrane	363 – 383	21	Helical; Name=4; Potential
	Topological domain	384 – 406	23	Extracellular Potential
	Transmembrane	407 – 427	21	Helical; Name=5; Potential
	Topological domain	428 – 455	28	Cytoplasmic Potential
	Transmembrane	456 – 476	21	Helical; Name=6; Potential
	Topological domain	477 – 528	52	Extracellular Potential
	Transmembrane	529 – 549	21	Helical; Name=7; Potential
	Topological domain	550 – 793	244	Cytoplasmic Potential
	Domain	69 – 185	117	FZ
Amino acid modifications
	Modified residue	791	1	Phosphoserine By similarity
	Glycosylation	38	1	N-linked (GlcNAc...) Potential
	Glycosylation	192	1	N-linked (GlcNAc...) Potential
	Glycosylation	497	1	N-linked (GlcNAc...) Potential
	Disulfide bond	74 ↔ 138		By similarity
	Disulfide bond	82 ↔ 131		By similarity
	Disulfide bond	122 ↔ 158		By similarity
	Disulfide bond	151 ↔ 173		By similarity
Experimental info
	Sequence conflict	54	1	D → N no nucleotide entry Ref.1
	Sequence conflict	266	1	Y → L no nucleotide entry Ref.1
	Sequence conflict	690	1	R → G no nucleotide entry Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P56726 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: DEAD556A45F7C960	FASTA	793	87,450
	10 20 30 40 50 60 MAAGRPVRGP ELAPRRLLQL LLLVLLGGPG RGAALSGNVT GPGPHSASGS SRRDVPVTSP 70 80 90 100 110 120 PPPLLSHCGR AAHCEPLRYN VCLGSALPYG ATTTLLAGDS DSQEEAHGKL VLWSGLRNAP 130 140 150 160 170 180 RCWAVIQPLL CAVYMPKCEN DRVELPSRTL CQATRGPCAI VERERGWPDF LRCTPDHFPE 190 200 210 220 230 240 GCPNEVQNIK FNSSGQCEAP LVRTDNPKSW YEDVEGCGIQ CQNPLFTEAE HQDMHSYIAA 250 260 270 280 290 300 FGAVTGLCTL FTLATFVADW RNSNRYPAVI LFYVNACFFV GSIGWLAQFM DGARREIVCR 310 320 330 340 350 360 ADGTMRFGEP TSSETLSCVI IFVIVYYALM AGVVWFVVLT YAWHTSFKAL GTTYQPLSGK 370 380 390 400 410 420 TSYFHLLTWS LPFVLTVAIL AVAQVDGDSV SGICFVGYKN YRYRAGFVLA PIGLVLIVGG 430 440 450 460 470 480 YFLIRGVMTL FSIKSNHPGL LSEKAASKIN ETMLRLGIFG FLAFGFVLIT FSCHFYDFFN 490 500 510 520 530 540 QAEWERSFRD YVLCQANVTI GLPTKKPIPD CEIKNRPSLL VEKINLFAMF GTGIAMSTWV 550 560 570 580 590 600 WTKATLLIWR RTWCRLTGHS DDEPKRIKKS KMIAKAFSKR RELLQNPGQE LSFSMHTVSH 610 620 630 640 650 660 DGPVAGLAFD LNEPSADVSS AWAQHVTKMV ARRGAILPQD VSVTPVATPV PPEEQANMWL 670 680 690 700 710 720 VEAEISPELE KRLGRKKKRR KRKKEVCPLR PAPELHHSAP VPATSAVPRL PQLPRQKCLV 730 740 750 760 770 780 AANAWGTGES CRQGAWTLVS NPFCPEPSPH QDPFLPGASA PRVWAQGRLQ GLGSIHSRTN 790 LMEAEILDAD SDF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a mouse Smoothened cDNA and expression patterns of hedgehog signalling molecules during chondrogenesis and cartilage differentiation in clonal mouse EC cells, ATDC5." Akiyama H., Shigeno C., Hiraki Y., Shukunami C., Kohno H., Akagi M., Konishi J., Nakamura T. Biochem. Biophys. Res. Commun. 235:142-147(1997) [PubMed: 9196051] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[3]	"Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2." Chen W., Ren X.R., Nelson C.D., Barak L.S., Chen J.K., Beachy P.A., de Sauvage F., Lefkowitz R.J. Science 306:2257-2260(2004) [PubMed: 15618519] [Abstract] Cited for: INTERACTION WITH ARRB2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC069469 Genomic DNA. No translation available.
IPI	IPI00341032.
PIR	JC5539.
RefSeq	NP_795970.3. NM_176996.4.
UniGene	Mm.29279.
3D structure databases
ProteinModelPortal	P56726.
SMR	P56726. Positions 72-181.
ModBase	Search...
Protein-protein interaction databases
STRING	P56726.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P56726.
Proteomic databases
PRIDE	P56726.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000001812; ENSMUSP00000001812; ENSMUSG00000001761.
GeneID	319757.
KEGG	mmu:319757.
Organism-specific databases
CTD	6608.
MGI	MGI:108075. Smo.
Phylogenomic databases
eggNOG	roNOG05761.
HOGENOM	HBG714469.
HOVERGEN	HBG000352.
InParanoid	P56726.
OrthoDB	EOG4Q2DDX.
Gene expression databases
ArrayExpress	P56726.
Bgee	P56726.
CleanEx	MM_SMO.
Genevestigator	P56726.
GermOnline	ENSMUSG00000001761. Mus musculus.
Family and domain databases
InterPro	IPR000539. Frizzled. IPR015526. Frizzled-related. IPR020067. Frizzled_dom. IPR017981. GPCR_2-like. [Graphical view]
Gene3D	G3DSA:1.10.2000.10. Frizzled_Cys-rich. 1 hit.
KO	K06226.
PANTHER	PTHR11309. Fz_related. 1 hit.
Pfam	PF01534. Frizzled. 1 hit. PF01392. Fz. 1 hit. [Graphical view]
PRINTS	PR00489. FRIZZLED.
SMART	SM00063. FRI. 1 hit. [Graphical view]
SUPFAM	SSF63501. Frizzled_Cys-rich. 1 hit.
PROSITE	PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

SMO_MOUSE

Accession

Primary (citable) accession number: P56726

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 27, 2011
Last modified:	January 25, 2012
This is version 88 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program