CleftGeneDB-Search

Gene: Smo

Basic information

Tag	Content
Uniprot ID	P56726
Entrez ID	319757
Genbank protein ID
Genbank nucleotide ID	NM_176996.4
Ensembl protein ID	ENSMUSP00000001812
Ensembl nucleotide ID	ENSMUSG00000001761
Gene name	Smoothened homolog
Gene symbol	Smo
Organism	Mus musculus
NCBI taxa ID	10090
Cleft type	CPO
Developmental stage	E13.0, E14.5
Data sources	Manually collected
Reference	29981310; 19304890;
Functional description	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) (By similarity). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia. Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (PubMed:25644602).
Sequence	MAAGRPVRGP ELAPRRLLQL LLLVLLGGPG RGAALSGNVT GPGPHSASGS SRRDVPVTSP 60 PPPLLSHCGR AAHCEPLRYN VCLGSALPYG ATTTLLAGDS DSQEEAHGKL VLWSGLRNAP 120 RCWAVIQPLL CAVYMPKCEN DRVELPSRTL CQATRGPCAI VERERGWPDF LRCTPDHFPE 180 GCPNEVQNIK FNSSGQCEAP LVRTDNPKSW YEDVEGCGIQ CQNPLFTEAE HQDMHSYIAA 240 FGAVTGLCTL FTLATFVADW RNSNRYPAVI LFYVNACFFV GSIGWLAQFM DGARREIVCR 300 ADGTMRFGEP TSSETLSCVI IFVIVYYALM AGVVWFVVLT YAWHTSFKAL GTTYQPLSGK 360 TSYFHLLTWS LPFVLTVAIL AVAQVDGDSV SGICFVGYKN YRYRAGFVLA PIGLVLIVGG 420 YFLIRGVMTL FSIKSNHPGL LSEKAASKIN ETMLRLGIFG FLAFGFVLIT FSCHFYDFFN 480 QAEWERSFRD YVLCQANVTI GLPTKKPIPD CEIKNRPSLL VEKINLFAMF GTGIAMSTWV 540 WTKATLLIWR RTWCRLTGHS DDEPKRIKKS KMIAKAFSKR RELLQNPGQE LSFSMHTVSH 600 DGPVAGLAFD LNEPSADVSS AWAQHVTKMV ARRGAILPQD VSVTPVATPV PPEEQANMWL 660 VEAEISPELE KRLGRKKKRR KRKKEVCPLR PAPELHHSAP VPATSAVPRL PQLPRQKCLV 720 AANAWGTGES CRQGAWTLVS NPFCPEPSPH QDPFLPGASA PRVWAQGRLQ GLGSIHSRTN 780 LMEAEILDAD SDF 793

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression during embryonic days (E11.5~E18.5) ~ adult days (Ps) in the lip and palate tissues. (X-axis: days, Y-axis: tissues)

Protein structural annotations

3D structure in PDB database

PDB ID
6O3C

Protein disorder information

Orthologous information

Relation	Gene symbol	Entrez ID	UniProt ID	Cleft type	Developmental stage	Species	Evidence	Details
1:1 ortholog	SMO	539308	E1BE57			Bos taurus	Prediction	More>>
1:1 ortholog	SMO	102171572	A0A452FRY0			Capra hircus	Prediction	More>>
1:1 ortholog	SMO	6608	Q99835			Homo sapiens	Prediction	More>>
1:1 ortholog	Smo	319757	P56726	CPO	E13.0, E14.5	Mus musculus	Publication	More>>
1:1 ortholog	SMO	100515110	F1SMQ3			Sus scrofa	Prediction	More>>
1:1 ortholog	Smo		G3V736			Rattus norvegicus	Prediction	More>>
1:1 ortholog	smo	30225	Q5RH73			Danio rerio	Prediction	More>>

Other genetic variants/mutations

ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
rs213534114	p.Val39Ala	missense variant	-	NC_000072.6:g.29736126T>C	UniProt
rs230479111	p.His45Arg	missense variant	-	NC_000072.6:g.29736144A>G	UniProt
rs256495993	p.Ser51Ala	missense variant	-	NC_000072.6:g.29736161T>G	UniProt
rs30765548	p.Asp54Asn	missense variant	-	NC_000072.6:g.29736170G>A	UniProt
rs263803957	p.Ala71Val	missense variant	-	NC_000072.6:g.29736222C>T	UniProt
rs30156064	p.Arg690Gly	missense variant	-	NC_000072.6:g.29759971A>G	UniProt
rs29618938	p.Ter794AlaArgGlyGluUnkThrThrGluArgUnkUnk	stop lost	-	NC_000072.6:g.29760283T>A	UniProt

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID	GO Term	Evidence
GO:0004930	G protein-coupled receptor activity	IEA
GO:0005113	patched binding	ISO
GO:0005113	patched binding	IBA
GO:0005515	protein binding	IPI
GO:0008144	drug binding	ISO
GO:0008144	drug binding	IDA

GO:Biological Process

GO ID	GO Term	Evidence
GO:0000122	negative regulation of transcription by RNA polymerase II	IMP
GO:0001503	ossification	IMP
GO:0001570	vasculogenesis	IMP
GO:0001649	osteoblast differentiation	IMP
GO:0001701	in utero embryonic development	IMP
GO:0001708	cell fate specification	IMP
GO:0001755	neural crest cell migration	IGI
GO:0001947	heart looping	IMP
GO:0002052	positive regulation of neuroblast proliferation	IGI
GO:0002053	positive regulation of mesenchymal cell proliferation	IMP
GO:0003007	heart morphogenesis	IGI
GO:0003140	determination of left/right asymmetry in lateral mesoderm	IMP
GO:0003323	type B pancreatic cell development	IMP
GO:0007186	G protein-coupled receptor signaling pathway	IEA
GO:0007224	smoothened signaling pathway	ISO
GO:0007224	smoothened signaling pathway	IMP
GO:0007224	smoothened signaling pathway	IGI
GO:0007224	smoothened signaling pathway	IBA
GO:0007228	positive regulation of hh target transcription factor activity	IMP
GO:0007368	determination of left/right symmetry	IMP
GO:0007371	ventral midline determination	IMP
GO:0007389	pattern specification process	IMP
GO:0007417	central nervous system development	IGI
GO:0007417	central nervous system development	IBA
GO:0007494	midgut development	IMP
GO:0008284	positive regulation of cell population proliferation	IMP
GO:0009952	anterior/posterior pattern specification	IMP
GO:0009953	dorsal/ventral pattern formation	IMP
GO:0010468	regulation of gene expression	IGI
GO:0010628	positive regulation of gene expression	ISO
GO:0010628	positive regulation of gene expression	IMP
GO:0010629	negative regulation of gene expression	IMP
GO:0021542	dentate gyrus development	IMP
GO:0021696	cerebellar cortex morphogenesis	IMP
GO:0021794	thalamus development	IMP
GO:0021904	dorsal/ventral neural tube patterning	IMP
GO:0021910	smoothened signaling pathway involved in ventral spinal cord patterning	IMP
GO:0021938	smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation	IMP
GO:0021953	central nervous system neuron differentiation	IMP
GO:0021987	cerebral cortex development	IMP
GO:0030335	positive regulation of cell migration	ISO
GO:0030857	negative regulation of epithelial cell differentiation	IMP
GO:0031069	hair follicle morphogenesis	IMP
GO:0034504	protein localization to nucleus	IMP
GO:0035264	multicellular organism growth	IGI
GO:0035264	multicellular organism growth	IMP
GO:0040018	positive regulation of multicellular organism growth	IMP
GO:0042307	positive regulation of protein import into nucleus	IGI
GO:0042475	odontogenesis of dentin-containing tooth	IMP
GO:0043066	negative regulation of apoptotic process	IMP
GO:0043392	negative regulation of DNA binding	IGI
GO:0043392	negative regulation of DNA binding	IMP
GO:0043524	negative regulation of neuron apoptotic process	ISO
GO:0045880	positive regulation of smoothened signaling pathway	IMP
GO:0045880	positive regulation of smoothened signaling pathway	IBA
GO:0045892	negative regulation of transcription, DNA-templated	IMP
GO:0045893	positive regulation of transcription, DNA-templated	IMP
GO:0045944	positive regulation of transcription by RNA polymerase II	IMP
GO:0046622	positive regulation of organ growth	IMP
GO:0048143	astrocyte activation	IMP
GO:0048468	cell development	IMP
GO:0048565	digestive tract development	IMP
GO:0048568	embryonic organ development	IGI
GO:0048589	developmental growth	IMP
GO:0048741	skeletal muscle fiber development	IMP
GO:0048745	smooth muscle tissue development	IEA
GO:0048846	axon extension involved in axon guidance	ISO
GO:0048853	forebrain morphogenesis	IMP
GO:0048873	homeostasis of number of cells within a tissue	IDA
GO:0050679	positive regulation of epithelial cell proliferation	IMP
GO:0050821	protein stabilization	IDA
GO:0051451	myoblast migration	IGI
GO:0051799	negative regulation of hair follicle development	IMP
GO:0060242	contact inhibition	ISS
GO:0060242	contact inhibition	ISO
GO:0060413	atrial septum morphogenesis	IGI
GO:0060644	mammary gland epithelial cell differentiation	IMP
GO:0060684	epithelial-mesenchymal cell signaling	IMP
GO:0061053	somite development	IMP
GO:0061113	pancreas morphogenesis	IMP
GO:0070986	left/right axis specification	IMP
GO:0071397	cellular response to cholesterol	IEP
GO:0071679	commissural neuron axon guidance	ISO
GO:0071679	commissural neuron axon guidance	IBA
GO:0072285	mesenchymal to epithelial transition involved in metanephric renal vesicle formation	IMP
GO:0090190	positive regulation of branching involved in ureteric bud morphogenesis	IMP
GO:1901215	negative regulation of neuron death	ISO
GO:1904754	positive regulation of vascular associated smooth muscle cell migration	ISO
GO:2000036	regulation of stem cell population maintenance	IMP
GO:2000179	positive regulation of neural precursor cell proliferation	ISO
GO:2000826	regulation of heart morphogenesis	IMP

GO:Cellular Component

GO ID	GO Term	Evidence
GO:0005634	nucleus	ISO
GO:0005737	cytoplasm	ISO
GO:0005737	cytoplasm	IDA
GO:0005886	plasma membrane	ISS
GO:0005886	plasma membrane	ISO
GO:0005886	plasma membrane	IBA
GO:0005886	plasma membrane	IDA
GO:0005929	cilium	IDA
GO:0005929	cilium	IBA
GO:0014069	postsynaptic density	ISO
GO:0016021	integral component of membrane	IBA
GO:0030425	dendrite	ISO
GO:0030425	dendrite	IBA
GO:0030666	endocytic vesicle membrane	TAS
GO:0043025	neuronal cell body	ISO
GO:0043231	intracellular membrane-bounded organelle	ISO
GO:0044294	dendritic growth cone	ISO
GO:0044295	axonal growth cone	ISO
GO:0060170	ciliary membrane	IDA
GO:0060170	ciliary membrane	TAS
GO:0005794	Golgi apparatus	ISO
GO:0005901	caveola	ISO

Reactome Pathway

Reactome ID	Reactome Term	Evidence
R-MMU-162582	Signal Transduction	IEA
R-MMU-1852241	Organelle biogenesis and maintenance	IEA
R-MMU-5358351	Signaling by Hedgehog	IEA
R-MMU-5610787	Hedgehog 'off' state	IEA
R-MMU-5617833	Cilium Assembly	IEA
R-MMU-5620920	Cargo trafficking to the periciliary membrane	IEA
R-MMU-5620922	BBSome-mediated cargo-targeting to cilium	IEA
R-MMU-5632684	Hedgehog 'on' state	IEA
R-MMU-5635838	Activation of SMO	IEA

Functional annotations

Keywords

Keyword ID	Keyword Term
KW-0002	3D-structure
KW-0966	Cell projection
KW-0217	Developmental protein
KW-1015	Disulfide bond
KW-0297	G-protein coupled receptor
KW-0325	Glycoprotein
KW-0472	Membrane
KW-0675	Receptor
KW-1185	Reference proteome
KW-0732	Signal
KW-0807	Transducer
KW-0812	Transmembrane
KW-1133	Transmembrane helix

Interpro

InterPro ID	InterPro Term
IPR015526	Frizzled/SFRP
IPR000539	Frizzled/Smoothened_TM
IPR020067	Frizzled_dom
IPR036790	Frizzled_dom_sf
IPR017981	GPCR_2-like
IPR026544	SMO
IPR041771	SMO_CRD

PROSITE

PROSITE ID	PROSITE Term
PS50038	FZ
PS50261	G_PROTEIN_RECEP_F2_4

Pfam

Pfam ID	Pfam Term
PF01534	Frizzled
PF01392	Fz

Gene: Smo

Basic information

Gene expression information

Gene expression during embryonic days (E11.5~E18.5) ~ adult days (Ps) in the lip and palate tissues. (X-axis: days, Y-axis: tissues)

Protein structural annotations

3D structure in PDB database

Protein disorder information

Orthologous information

Other genetic variants/mutations

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO:Biological Process

GO:Cellular Component

Reactome Pathway

Functional annotations

Keywords

Interpro

PROSITE

Pfam

Protein-protein interaction

Protein-miRNA interaction