P91682 (SMO_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein smoothened

Alternative name(s):
SMOH
Smooth
dSMO

Gene names

Name:	smo
ORF Names:	CG11561

Organism

Drosophila melanogaster (Fruit fly) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	1036 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	Segment polarity protein required for correct patterning of every segment. G protein-coupled receptor that associates with the patched protein (ptc) to transduce the hedgehog (hh) signal through the activation of an inhibitory G-protein. In the absence of hh, ptc represses the constitutive signaling activity of smo through fused (fu).
Subunit structure	Interacts with cos. Ref.6
Subcellular location	Membrane; Multi-pass membrane protein.
Developmental stage	Expressed at all developmental stages, though the levels vary.
Sequence similarities	Belongs to the G-protein coupled receptor Fz/Smo family. Contains 1 FZ (frizzled) domain.
Caution	It is uncertain whether Met-1, Met-9, Met-13 or Met-14 is the initiator.

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	Bolwig's organ morphogenesis Inferred from mutant phenotype PubMed 10704398. Source: FlyBase anterior/posterior lineage restriction, imaginal disc Traceable author statement PubMed 10625531. Source: FlyBase axon extension involved in axon guidance Inferred from Biological aspect of Ancestor. Source: RefGenome blastoderm segmentation Inferred from mutant phenotype Ref.2. Source: FlyBase canonical Wnt receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome cardioblast 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 determination of left/right symmetry Inferred from Biological aspect of Ancestor. Source: RefGenome eye-antennal disc morphogenesis Inferred from genetic interaction PubMed 11934850. Source: FlyBase gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome heart morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of S phase of mitotic cell cycle Inferred from mutant phenotype PubMed 15809036. Source: FlyBase negative regulation of apoptotic process 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 ovarian follicle cell development Inferred from mutant phenotype PubMed 16256740. Source: FlyBase positive regulation of neuroblast proliferation Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of smoothened signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation Inferred from Biological aspect of Ancestor. Source: RefGenome somatic stem cell maintenance Inferred from mutant phenotype PubMed 16256740. Source: FlyBase vasculogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome wing disc anterior/posterior pattern formation Traceable author statement PubMed 11253649. Source: FlyBase
Cellular_component	cilium Inferred from Biological aspect of Ancestor. Source: RefGenome endosome Traceable author statement PubMed 15104233. Source: FlyBase integral to membrane Inferred from sequence or structural similarity PubMed 10908591Ref.1. Source: FlyBase neuronal cell body Inferred from Biological aspect of Ancestor. Source: RefGenome plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	G-protein coupled receptor activity Inferred from sequence or structural similarity Ref.1. Source: FlyBase 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 hedgehog receptor activity Non-traceable author statement PubMed 11253649. Source: FlyBase
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
cos	O16844	5	EBI-142245,EBI-102069

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	Potential
	Chain	32 – 1036	1005	Protein smoothened		PRO_0000013019
Regions
	Topological domain	32 – 258	227	Extracellular Potential
	Transmembrane	259 – 279	21	Helical; Name=1; Potential
	Topological domain	280 – 287	8	Cytoplasmic Potential
	Transmembrane	288 – 308	21	Helical; Name=2; Potential
	Topological domain	309 – 339	31	Extracellular Potential
	Transmembrane	340 – 360	21	Helical; Name=3; Potential
	Topological domain	361 – 381	21	Cytoplasmic Potential
	Transmembrane	382 – 402	21	Helical; Name=4; Potential
	Topological domain	403 – 421	19	Extracellular Potential
	Transmembrane	422 – 442	21	Helical; Name=5; Potential
	Topological domain	443 – 469	27	Cytoplasmic Potential
	Transmembrane	470 – 490	21	Helical; Name=6; Potential
	Topological domain	491 – 532	42	Extracellular Potential
	Transmembrane	533 – 553	21	Helical; Name=7; Potential
	Topological domain	554 – 1036	483	Cytoplasmic Potential
	Domain	85 – 206	122	FZ
	Compositional bias	816 – 819	4	Poly-Ser
Amino acid modifications
	Modified residue	658	1	Phosphoserine Ref.7
	Modified residue	659	1	Phosphoserine Ref.7
	Modified residue	667	1	Phosphoserine Ref.7
	Modified residue	670	1	Phosphoserine Ref.7
	Modified residue	673	1	Phosphoserine Ref.7
	Modified residue	687	1	Phosphoserine Ref.7
	Modified residue	690	1	Phosphoserine Ref.7
	Modified residue	693	1	Phosphoserine Ref.7
	Glycosylation	55	1	N-linked (GlcNAc...) Potential
	Glycosylation	95	1	N-linked (GlcNAc...) Potential
	Glycosylation	184	1	N-linked (GlcNAc...) Potential
	Glycosylation	195	1	N-linked (GlcNAc...) Potential
	Glycosylation	213	1	N-linked (GlcNAc...) Potential
	Glycosylation	336	1	N-linked (GlcNAc...) Potential
	Glycosylation	419	1	N-linked (GlcNAc...) Potential
	Disulfide bond	90 ↔ 155		By similarity
	Disulfide bond	100 ↔ 148		By similarity
	Disulfide bond	139 ↔ 179		By similarity
	Disulfide bond	172 ↔ 194		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P91682 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 7797FC71A539A87A	FASTA	1,036	116,552
	10 20 30 40 50 60 MQYLNFPRMP NIMMFLEVAI LCLWVVADAS ASSAKFGSTT PASAQQSDVE LEPINGTLNY 70 80 90 100 110 120 RLYAKKGRDD KPWFDGLDSR HIQCVRRARC YPTSNATNTC FGSKLPYELS SLDLTDFHTE 130 140 150 160 170 180 KELNDKLNDY YALKHVPKCW AAIQPFLCAV FKPKCEKING EDMVYLPSYE MCRITMEPCR 190 200 210 220 230 240 ILYNTTFFPK FLRCNETLFP TKCTNGARGM KFNGTGQCLS PLVPTDTSAS YYPGIEGCGV 250 260 270 280 290 300 RCKDPLYTDD EHRQIHKLIG WAGSICLLSN LFVVSTFFID WKNANKYPAV IVFYINLCFL 310 320 330 340 350 360 IACVGWLLQF TSGSREDIVC RKDGTLRHSE PTAGENLSCI VIFVLVYYFL TAGMVWFVFL 370 380 390 400 410 420 TYAWHWRAMG HVQDRIDKKG SYFHLVAWSL PLVLTITTMA FSEVDGNSIV GICFVGYINH 430 440 450 460 470 480 SMRAGLLLGP LCGVILIGGY FITRGMVMLF GLKHFANDIK STSASNKIHL IIMRMGVCAL 490 500 510 520 530 540 LTLVFILVAI ACHVTEFRHA DEWAQSFRQF IICKISSVFE EKSSCRIENR PSVGVLQLHL 550 560 570 580 590 600 LCLFSSGIVM STWCWTPSSI ETWKRYIRKK CGKEVVEEVK MPKHKVIAQT WAKRKDFEDK 610 620 630 640 650 660 GRLSITLYNT HTDPVGLNFD VNDLNSSETN DISSTWAAYL PQCVKRRMAL TGAATGNSSS 670 680 690 700 710 720 HGPRKNSLDS EISVSVRHVS VESRRNSVDS QVSVKIAEMK TKVASRSRGK HGGSSSNRRT 730 740 750 760 770 780 QRRRDYIAAA TGKSSRRRES STSVESQVIA LKKTTYPNAS HKVGVFAHHS SKKQHNYTSS 790 800 810 820 830 840 MKRRTANAGL DPSILNEFLQ KNGDFIFPFL QNQDMSSSSE EDNSRASQKI QDLNVVVKQQ 850 860 870 880 890 900 EISEDDHDGI KIEELPNSKQ VALENFLKNI KKSNESNSNR HSRNSARSQS KKSQKRHLKN 910 920 930 940 950 960 PAADLDFRKD CVKYRSNDSL SCSSEELDVA LDVGSLLNSS FSGISMGKPH SRNSKTSCDV 970 980 990 1000 1010 1020 GIQANPFELV PSYGEDELQQ AMRLLNAASR QRTEAANEDF GGTELQGLLG HSHRHQREPT 1030 FMSESDKLKM LLLPSK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Drosophila smoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal." Alcedo J., Ayzenzon M., von Ohlen T., Noll M., Hooper J.E. Cell 86:221-232(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"smoothened encodes a receptor-like serpentine protein required for hedgehog signalling." van den Heuvel M., Ingham P.W. Nature 382:547-551(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[4]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[5]	Carlson J.W., Booth B., Frise E., Park S., Wan K.H., Yu C., Celniker S.E. Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley.
[6]	"Hedgehog-regulated Costal2-kinase complexes control phosphorylation and proteolytic processing of Cubitus interruptus." Zhang W., Zhao Y., Tong C., Wang G., Wang B., Jia J., Jiang J. Dev. Cell 8:267-278(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH COS.
[7]	"Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-658; SER-659; SER-667; SER-670; SER-673; SER-687; SER-690 AND SER-693, MASS SPECTROMETRY. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U87613 Genomic DNA. Translation: AAC33180.1. AF030334 Genomic DNA. Translation: AAB84275.1. AE014134 Genomic DNA. Translation: AAF51518.2. BT053691 mRNA. Translation: ACK77608.1.
PIR	S71804.
RefSeq	NP_523443.1. NM_078719.3.
UniGene	Dm.244.
3D structure databases
ProteinModelPortal	P91682.
SMR	P91682. Positions 88-202.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-19956N.
IntAct	P91682. 3 interactions.
MINT	MINT-811118.
Protein family/group databases
GPCRDB	Search...
Proteomic databases
PRIDE	P91682.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0078129; FBpp0077788; FBgn0003444.
GeneID	33196.
KEGG	dme:Dmel_CG11561.
UCSC	CG11561-RA. d. melanogaster.
Organism-specific databases
CTD	6608.
FlyBase	FBgn0003444. smo.
Phylogenomic databases
eggNOG	NOG312505.
GeneTree	ENSGT00560000076776.
InParanoid	P91682.
KO	K06226.
OMA	NANKYPA.
OrthoDB	EOG4PVMDP.
PhylomeDB	P91682.
Gene expression databases
Bgee	P91682.
GermOnline	CG11561. Drosophila melanogaster.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR000539. Frizzled. IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR017981. GPCR_2-like. IPR026544. SMO. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF35. PTHR11309:SF35. 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
GenomeRNAi	33196.
NextBio	782367.

Entry information

Entry name

SMO_DROME

Accession

Primary (citable) accession number: P91682
Secondary accession number(s): B7FNK1, Q9VPM8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project