Q99835 (SMO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Smoothened homolog
Short name=SMO

Alternative name(s):
Protein Gx

Gene names

Name:	SMO
Synonyms:	SMOH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	787 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. Ref.5
Subunit structure	Interacts with ARRB2 By similarity. Interacts with KIF7. Ref.5
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
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
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 electronic annotation. Source: Compara 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 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: Compara 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: Compara heart looping Inferred from sequence or structural similarity. Source: BHF-UCL in utero embryonic development Inferred from electronic annotation. Source: Compara mammary gland epithelial cell differentiation Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara negative regulation of gene expression Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of hair follicle development Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara 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: Compara protein localization to nucleus Inferred from electronic annotation. Source: Compara protein stabilization Inferred from electronic annotation. Source: Compara regulation of heart morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL regulation of stem cell maintenance Inferred from electronic annotation. Source: Compara 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 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 type B pancreatic cell development Inferred from electronic annotation. Source: Compara vasculogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome ventral midline determination Inferred from sequence or structural similarity. 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 direct assay PubMed 19304771. Source: UniProtKB primary cilium Traceable author statement PubMed 21931618. Source: BHF-UCL
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 PubMed 19304771PubMed 21177415. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 787	760	Smoothened homolog		PRO_0000013015
Regions
	Topological domain	28 – 233	206	Extracellular Potential
	Transmembrane	234 – 254	21	Helical; Name=1; Potential
	Topological domain	255 – 262	8	Cytoplasmic Potential
	Transmembrane	263 – 283	21	Helical; Name=2; Potential
	Topological domain	284 – 314	31	Extracellular Potential
	Transmembrane	315 – 335	21	Helical; Name=3; Potential
	Topological domain	336 – 358	23	Cytoplasmic Potential
	Transmembrane	359 – 379	21	Helical; Name=4; Potential
	Topological domain	380 – 402	23	Extracellular Potential
	Transmembrane	403 – 423	21	Helical; Name=5; Potential
	Topological domain	424 – 451	28	Cytoplasmic Potential
	Transmembrane	452 – 472	21	Helical; Name=6; Potential
	Topological domain	473 – 524	52	Extracellular Potential
	Transmembrane	525 – 545	21	Helical; Name=7; Potential
	Topological domain	546 – 787	242	Cytoplasmic Potential
	Domain	65 – 181	117	FZ
Amino acid modifications
	Glycosylation	35	1	N-linked (GlcNAc...) Potential
	Glycosylation	188	1	N-linked (GlcNAc...) Potential
	Glycosylation	309	1	N-linked (GlcNAc...) Potential
	Disulfide bond	70 ↔ 134		By similarity
	Disulfide bond	78 ↔ 127		By similarity
	Disulfide bond	118 ↔ 154		By similarity
	Disulfide bond	147 ↔ 169		By similarity
Natural variations
	Natural variant	473	1	D → H. Corresponds to variant rs17710891 [ dbSNP | Ensembl ].		VAR_037891
	Natural variant	535	1	W → L in basal cell carcinoma samples; somatic mutation. Ref.2		VAR_007848
	Natural variant	562	1	R → Q in basal cell carcinoma samples; somatic mutation. Ref.2		VAR_007849

Sequences

	Sequence		Length	Mass (Da)
	Q99835 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 8B4C459B34D13F83	FASTA	787	86,397
	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

References

	« Hide 'large scale' referencesShow '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.
+	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.
IPI	IPI00018471.
RefSeq	NP_005622.1. NM_005631.4.
UniGene	Hs.437846.
3D structure databases
ProteinModelPortal	Q99835.
SMR	Q99835. Positions 70-181.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-34574N.
IntAct	Q99835. 1 interaction.
STRING	9606.ENSP00000249373.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q99835.
Polymorphism databases
DMDM	6226142.
Proteomic databases
PaxDb	Q99835.
PRIDE	Q99835.
Protocols and materials databases
DNASU	6608.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000249373; ENSP00000249373; ENSG00000128602.
GeneID	6608.
KEGG	hsa:6608.
UCSC	uc003vor.3. human.
Organism-specific databases
CTD	6608.
GeneCards	GC07P128828.
HGNC	HGNC:11119. SMO.
HPA	CAB011446.
MIM	601500. gene.
neXtProt	NX_Q99835.
PharmGKB	PA35968.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG312505.
HOGENOM	HOG000252964.
HOVERGEN	HBG000352.
InParanoid	Q99835.
KO	K06226.
OMA	DRFPEGC.
OrthoDB	EOG4Q2DDX.
PhylomeDB	Q99835.
Enzyme and pathway databases
Pathway_Interaction_DB	hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins. hedgehog_2pathway. Signaling events mediated by the Hedgehog family.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q99835.
Bgee	Q99835.
CleanEx	HS_SMO.
Genevestigator	Q99835.
GermOnline	ENSG00000128602. Homo sapiens.
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
BindingDB	Q99835.
ChEMBL	CHEMBL5971.
ChiTaRS	Smo. human.
GenomeRNAi	6608.
NextBio	25725.
SOURCE	Search...

Entry information

Entry name

SMO_HUMAN

Accession

Primary (citable) accession number: Q99835

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 131 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.