CleftGeneDB-Search

Gene: Shh

Basic information

Tag	Content
Uniprot ID	Q62226
Entrez ID	20423
Genbank protein ID	CAA53922.1; BAC36956.1; AAH63087.1;
Genbank nucleotide ID	NM_009170.3
Ensembl protein ID	ENSMUSP00000002708
Ensembl nucleotide ID	ENSMUSG00000002633
Gene name	Sonic hedgehog protein
Gene symbol	Shh
Organism	Mus musculus
NCBI taxa ID	10090
Cleft type	CPO
Developmental stage	E11.5, E12.0, E12.5, E13.0, E14.0, E13.5, E14.5, E14.5-15.0, E15.0, E16.0, E15.5, E16.5
Data sources	Manually collected
Reference	15576405; 15269168; 15199404; 19304890; 23975680; 18694563; 19394325; 30235284; 17525797; 17468181;
Functional description	Sonic hedgehog protein.The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (PubMed:8824192, PubMed:7891723). Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN (PubMed:8824192). Both activities occur in the reticulum endoplasmic (PubMed:21357747). Once cleaved, ShhC is degraded in the endoplasmic reticulum (PubMed:21357747).
Sequence	MLLLLARCFL VILASSLLVC PGLACGPGRG FGKRRHPKKL TPLAYKQFIP NVAEKTLGAS 60 GRYEGKITRN SERFKELTPN YNPDIIFKDE ENTGADRLMT QRCKDKLNAL AISVMNQWPG 120 VKLRVTEGWD EDGHHSEESL HYEGRAVDIT TSDRDRSKYG MLARLAVEAG FDWVYYESKA 180 HIHCSVKAEN SVAAKSGGCF PGSATVHLEQ GGTKLVKDLR PGDRVLAADD QGRLLYSDFL 240 TFLDRDEGAK KVFYVIETLE PRERLLLTAA HLLFVAPHND SGPTPGPSAL FASRVRPGQR 300 VYVVAERGGD RRLLPAAVHS VTLREEEAGA YAPLTAHGTI LINRVLASCY AVIEEHSWAH 360 RAFAPFRLAH ALLAALAPAR TDGGGGGSIP AAQSATEARG AEPTAGIHWY SQLLYHIGTW 420 LLDSETMHPL GMAVKSS 437

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
1VHH
2WFX
2WG4
3D1M
3N1R
4C4M
4C4N
1VHH
2WG4

Protein disorder information

Orthologous information

Relation	Gene symbol	Entrez ID	UniProt ID	Cleft type	Developmental stage	Species	Evidence	Details
1:1 ortholog	SHH		A0A452FUF0			Capra hircus	Prediction	More>>
1:1 ortholog	SHH	6469	Q15465			Homo sapiens	Prediction	More>>
1:1 ortholog	Shh	20423	Q62226	CPO	E11.5, E12.0, E12.5, E13.0, E14.0, E13.5, E14.5, E14.5-15.0, E15.0, E16.0, E15.5, E16.5	Mus musculus	Publication	More>>
1:1 ortholog	SHH	743371	A0A2I3SFH2			Pan troglodytes	Prediction	More>>
1:1 ortholog	SHH	100352774	G1TCI1			Oryctolagus cuniculus	Prediction	More>>
1:1 ortholog	Shh		G3V6T0			Rattus norvegicus	Prediction	More>>

Other genetic variants/mutations

ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
rs221886881	p.Gly282Glu	missense variant	-	NC_000071.6:g.28458324C>T	UniProt
rs239951257	p.Ala401Ser	missense variant	-	NC_000071.6:g.28457968C>A	UniProt
rs216598691	p.Ala401Val	missense variant	-	NC_000071.6:g.28457967G>A	UniProt

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID	GO Term	Evidence
GO:0005113	patched binding	ISO
GO:0005113	patched binding	IPI
GO:0005113	patched binding	IBA
GO:0005509	calcium ion binding	ISS
GO:0005509	calcium ion binding	ISO
GO:0005509	calcium ion binding	IBA
GO:0005515	protein binding	IPI
GO:0005515	protein binding	IDA
GO:0005539	glycosaminoglycan binding	IDA
GO:0008270	zinc ion binding	ISS
GO:0008270	zinc ion binding	ISO
GO:0043237	laminin-1 binding	IDA
GO:0016787	hydrolase activity	IDA

GO:Biological Process

GO ID	GO Term	Evidence
GO:0000122	negative regulation of transcription by RNA polymerase II	IMP
GO:0000122	negative regulation of transcription by RNA polymerase II	IDA
GO:0001525	angiogenesis	IDA
GO:0001525	angiogenesis	IGI
GO:0001525	angiogenesis	IMP
GO:0001569	branching involved in blood vessel morphogenesis	IMP
GO:0001570	vasculogenesis	IDA
GO:0001656	metanephros development	IMP
GO:0001658	branching involved in ureteric bud morphogenesis	IMP
GO:0001708	cell fate specification	IMP
GO:0001708	cell fate specification	IGI
GO:0001708	cell fate specification	IDA
GO:0001708	cell fate specification	IBA
GO:0001755	neural crest cell migration	IMP
GO:0001822	kidney development	IMP
GO:0001841	neural tube formation	ISO
GO:0001942	hair follicle development	IMP
GO:0001944	vasculature development	IMP
GO:0001947	heart looping	IMP
GO:0002052	positive regulation of neuroblast proliferation	ISO
GO:0002052	positive regulation of neuroblast proliferation	IDA
GO:0002053	positive regulation of mesenchymal cell proliferation	IMP
GO:0002076	osteoblast development	IDA
GO:0002320	lymphoid progenitor cell differentiation	ISO
GO:0002320	lymphoid progenitor cell differentiation	IMP
GO:0003140	determination of left/right asymmetry in lateral mesoderm	IMP
GO:0006355	regulation of transcription, DNA-templated	IMP
GO:0006897	endocytosis	IDA
GO:0007165	signal transduction	TAS
GO:0007224	smoothened signaling pathway	IMP
GO:0007224	smoothened signaling pathway	IGI
GO:0007224	smoothened signaling pathway	IBA
GO:0007224	smoothened signaling pathway	IDA
GO:0007228	positive regulation of hh target transcription factor activity	IMP
GO:0007228	positive regulation of hh target transcription factor activity	IDA
GO:0007228	positive regulation of hh target transcription factor activity	IGI
GO:0007267	cell-cell signaling	IMP
GO:0007368	determination of left/right symmetry	IMP
GO:0007389	pattern specification process	IMP
GO:0007389	pattern specification process	IGI
GO:0007398	ectoderm development	IMP
GO:0007405	neuroblast proliferation	IDA
GO:0007411	axon guidance	IDA
GO:0007411	axon guidance	IMP
GO:0007417	central nervous system development	IMP
GO:0007442	hindgut morphogenesis	IMP
GO:0007502	digestive tract mesoderm development	ISO
GO:0007507	heart development	IMP
GO:0007596	blood coagulation	IMP
GO:0008209	androgen metabolic process	IMP
GO:0008283	cell population proliferation	IGI
GO:0008284	positive regulation of cell population proliferation	ISO
GO:0008284	positive regulation of cell population proliferation	IDA
GO:0008284	positive regulation of cell population proliferation	IMP
GO:0008284	positive regulation of cell population proliferation	IGI
GO:0009949	polarity specification of anterior/posterior axis	IMP
GO:0009952	anterior/posterior pattern specification	IMP
GO:0009953	dorsal/ventral pattern formation	IGI
GO:0010463	mesenchymal cell proliferation	IMP
GO:0010468	regulation of gene expression	ISO
GO:0010468	regulation of gene expression	IMP
GO:0010468	regulation of gene expression	IGI
GO:0010468	regulation of gene expression	IBA
GO:0010468	regulation of gene expression	IDA
GO:0010628	positive regulation of gene expression	IMP
GO:0010629	negative regulation of gene expression	IMP
GO:0014003	oligodendrocyte development	IDA
GO:0014706	striated muscle tissue development	IMP
GO:0014858	positive regulation of skeletal muscle cell proliferation	IMP
GO:0014902	myotube differentiation	IMP
GO:0016539	intein-mediated protein splicing	IEA
GO:0021513	spinal cord dorsal/ventral patterning	ISO
GO:0021513	spinal cord dorsal/ventral patterning	IMP
GO:0021521	ventral spinal cord interneuron specification	ISO
GO:0021522	spinal cord motor neuron differentiation	IGI
GO:0021794	thalamus development	IGI
GO:0021794	thalamus development	IMP
GO:0021871	forebrain regionalization	IMP
GO:0021904	dorsal/ventral neural tube patterning	IDA
GO:0021904	dorsal/ventral neural tube patterning	IGI
GO:0021904	dorsal/ventral neural tube patterning	IMP
GO:0021924	cell proliferation in external granule layer	IDA
GO:0021930	cerebellar granule cell precursor proliferation	IGI
GO:0021930	cerebellar granule cell precursor proliferation	IDA
GO:0021938	smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation	IDA
GO:0021938	smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation	IMP
GO:0021940	positive regulation of cerebellar granule cell precursor proliferation	IDA
GO:0021978	telencephalon regionalization	ISO
GO:0021978	telencephalon regionalization	IMP
GO:0022006	zona limitans intrathalamica formation	ISO
GO:0030010	establishment of cell polarity	IDA
GO:0030162	regulation of proteolysis	IDA
GO:0030177	positive regulation of Wnt signaling pathway	IMP
GO:0030178	negative regulation of Wnt signaling pathway	IDA
GO:0030323	respiratory tube development	IMP
GO:0030324	lung development	IGI
GO:0030324	lung development	IMP
GO:0030326	embryonic limb morphogenesis	IGI
GO:0030326	embryonic limb morphogenesis	IMP
GO:0030336	negative regulation of cell migration	IDA
GO:0030539	male genitalia development	IMP
GO:0030850	prostate gland development	IMP
GO:0030878	thyroid gland development	IMP
GO:0030900	forebrain development	IGI
GO:0030901	midbrain development	IGI
GO:0030902	hindbrain development	IMP
GO:0030902	hindbrain development	IGI
GO:0031016	pancreas development	IMP
GO:0031016	pancreas development	IGI
GO:0031069	hair follicle morphogenesis	IMP
GO:0032435	negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP
GO:0032901	positive regulation of neurotrophin production	ISO
GO:0033077	T cell differentiation in thymus	IMP
GO:0033089	positive regulation of T cell differentiation in thymus	IMP
GO:0033092	positive regulation of immature T cell proliferation in thymus	IMP
GO:0034244	negative regulation of transcription elongation from RNA polymerase II promoter	IDA
GO:0034504	protein localization to nucleus	IDA
GO:0035115	embryonic forelimb morphogenesis	IMP
GO:0035116	embryonic hindlimb morphogenesis	IMP
GO:0042127	regulation of cell population proliferation	ISO
GO:0042127	regulation of cell population proliferation	IDA
GO:0042130	negative regulation of T cell proliferation	IMP
GO:0042177	negative regulation of protein catabolic process	IMP
GO:0042307	positive regulation of protein import into nucleus	IGI
GO:0042475	odontogenesis of dentin-containing tooth	IMP
GO:0042476	odontogenesis	IDA
GO:0042481	regulation of odontogenesis	IMP
GO:0042733	embryonic digit morphogenesis	IMP
GO:0042733	embryonic digit morphogenesis	IGI
GO:0043010	camera-type eye development	IDA
GO:0043010	camera-type eye development	IMP
GO:0043010	camera-type eye development	IGI
GO:0043066	negative regulation of apoptotic process	ISO
GO:0043066	negative regulation of apoptotic process	IDA
GO:0043066	negative regulation of apoptotic process	IGI
GO:0043066	negative regulation of apoptotic process	IMP
GO:0043369	CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	ISO
GO:0043369	CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	IMP
GO:0043586	tongue development	ISO
GO:0043587	tongue morphogenesis	ISO
GO:0043588	skin development	IMP
GO:0045059	positive thymic T cell selection	IMP
GO:0045060	negative thymic T cell selection	IMP
GO:0045109	intermediate filament organization	IMP
GO:0045165	cell fate commitment	IGI
GO:0045445	myoblast differentiation	IDA
GO:0045471	response to ethanol	ISO
GO:0045596	negative regulation of cell differentiation	IDA
GO:0045596	negative regulation of cell differentiation	IMP
GO:0045597	positive regulation of cell differentiation	IMP
GO:0045666	positive regulation of neuron differentiation	ISO
GO:0045880	positive regulation of smoothened signaling pathway	ISS
GO:0045880	positive regulation of smoothened signaling pathway	ISO
GO:0045880	positive regulation of smoothened signaling pathway	IMP
GO:0045893	positive regulation of transcription, DNA-templated	ISO
GO:0045893	positive regulation of transcription, DNA-templated	IDA
GO:0045944	positive regulation of transcription by RNA polymerase II	IGI
GO:0045944	positive regulation of transcription by RNA polymerase II	IMP
GO:0045944	positive regulation of transcription by RNA polymerase II	IDA
GO:0046534	positive regulation of photoreceptor cell differentiation	ISO
GO:0046638	positive regulation of alpha-beta T cell differentiation	IMP
GO:0046639	negative regulation of alpha-beta T cell differentiation	IMP
GO:0048468	cell development	IMP
GO:0048538	thymus development	IMP
GO:0048546	digestive tract morphogenesis	IMP
GO:0048557	embryonic digestive tract morphogenesis	IMP
GO:0048557	embryonic digestive tract morphogenesis	TAS
GO:0048568	embryonic organ development	IMP
GO:0048589	developmental growth	IMP
GO:0048598	embryonic morphogenesis	IMP
GO:0048617	embryonic foregut morphogenesis	IMP
GO:0048643	positive regulation of skeletal muscle tissue development	IMP
GO:0048645	animal organ formation	IMP
GO:0048646	anatomical structure formation involved in morphogenesis	IMP
GO:0048663	neuron fate commitment	IMP
GO:0048678	response to axon injury	ISO
GO:0048706	embryonic skeletal system development	IGI
GO:0048709	oligodendrocyte differentiation	IGI
GO:0048709	oligodendrocyte differentiation	IBA
GO:0048714	positive regulation of oligodendrocyte differentiation	IDA
GO:0048745	smooth muscle tissue development	IEA
GO:0048754	branching morphogenesis of an epithelial tube	IMP
GO:0048808	male genitalia morphogenesis	ISO
GO:0048839	inner ear development	IGI
GO:0048839	inner ear development	IMP
GO:0048856	anatomical structure development	IMP
GO:0048859	formation of anatomical boundary	IMP
GO:0048864	stem cell development	IMP
GO:0051146	striated muscle cell differentiation	IDA
GO:0051146	striated muscle cell differentiation	IMP
GO:0051155	positive regulation of striated muscle cell differentiation	IMP
GO:0051781	positive regulation of cell division	ISO
GO:0060020	Bergmann glial cell differentiation	IDA
GO:0060021	roof of mouth development	IMP
GO:0060070	canonical Wnt signaling pathway	IDA
GO:0060173	limb development	IGI
GO:0060173	limb development	IMP
GO:0060174	limb bud formation	IMP
GO:0060406	positive regulation of penile erection	ISO
GO:0060425	lung morphogenesis	IMP
GO:0060428	lung epithelium development	IMP
GO:0060438	trachea development	IMP
GO:0060439	trachea morphogenesis	IMP
GO:0060441	epithelial tube branching involved in lung morphogenesis	IMP
GO:0060442	branching involved in prostate gland morphogenesis	IDA
GO:0060445	branching involved in salivary gland morphogenesis	IGI
GO:0060445	branching involved in salivary gland morphogenesis	IMP
GO:0060447	bud outgrowth involved in lung branching	IMP
GO:0060458	right lung development	IMP
GO:0060459	left lung development	IMP
GO:0060463	lung lobe morphogenesis	IMP
GO:0060484	lung-associated mesenchyme development	IMP
GO:0060516	primary prostatic bud elongation	IDA
GO:0060523	prostate epithelial cord elongation	IDA
GO:0060662	salivary gland cavitation	IDA
GO:0060664	epithelial cell proliferation involved in salivary gland morphogenesis	IMP
GO:0060684	epithelial-mesenchymal cell signaling	IMP
GO:0060685	regulation of prostatic bud formation	IMP
GO:0060685	regulation of prostatic bud formation	IDA
GO:0060738	epithelial-mesenchymal signaling involved in prostate gland development	ISO
GO:0060738	epithelial-mesenchymal signaling involved in prostate gland development	IGI
GO:0060768	regulation of epithelial cell proliferation involved in prostate gland development	IMP
GO:0060769	positive regulation of epithelial cell proliferation involved in prostate gland development	IMP
GO:0060782	regulation of mesenchymal cell proliferation involved in prostate gland development	IMP
GO:0060783	mesenchymal smoothened signaling pathway involved in prostate gland development	IMP
GO:0060840	artery development	IGI
GO:0060840	artery development	IMP
GO:0060916	mesenchymal cell proliferation involved in lung development	IDA
GO:0060979	vasculogenesis involved in coronary vascular morphogenesis	TAS
GO:0061053	somite development	IMP
GO:0061189	positive regulation of sclerotome development	ISO
GO:0061196	fungiform papilla development	ISO
GO:0061197	fungiform papilla morphogenesis	ISO
GO:0061198	fungiform papilla formation	ISO
GO:0070447	positive regulation of oligodendrocyte progenitor proliferation	ISO
GO:0071285	cellular response to lithium ion	IDA
GO:0071542	dopaminergic neuron differentiation	TAS
GO:0071679	commissural neuron axon guidance	ISO
GO:0072136	metanephric mesenchymal cell proliferation involved in metanephros development	IMP
GO:0072205	metanephric collecting duct development	IEA
GO:0090090	negative regulation of canonical Wnt signaling pathway	IMP
GO:0090370	negative regulation of cholesterol efflux	IMP
GO:0097190	apoptotic signaling pathway	IDA
GO:1900180	regulation of protein localization to nucleus	ISO
GO:1901215	negative regulation of neuron death	ISO
GO:1903672	positive regulation of sprouting angiogenesis	ISO
GO:1904339	negative regulation of dopaminergic neuron differentiation	IMP
GO:1905327	tracheoesophageal septum formation	IMP
GO:2000062	negative regulation of ureter smooth muscle cell differentiation	IDA
GO:2000063	positive regulation of ureter smooth muscle cell differentiation	IMP
GO:2000357	negative regulation of kidney smooth muscle cell differentiation	IDA
GO:2000358	positive regulation of kidney smooth muscle cell differentiation	IDA
GO:2000729	positive regulation of mesenchymal cell proliferation involved in ureter development	IMP
GO:2001028	positive regulation of endothelial cell chemotaxis	ISO
GO:2001054	negative regulation of mesenchymal cell apoptotic process	IMP

GO:Cellular Component

GO ID	GO Term	Evidence
GO:0005576	extracellular region	TAS
GO:0005615	extracellular space	ISO
GO:0005615	extracellular space	IDA
GO:0005615	extracellular space	IBA
GO:0005634	nucleus	ISO
GO:0005783	endoplasmic reticulum	ISO
GO:0005794	Golgi apparatus	ISO
GO:0005886	plasma membrane	TAS
GO:0008021	synaptic vesicle	ISO
GO:0009986	cell surface	IDA
GO:0016020	membrane	IDA
GO:0030133	transport vesicle	ISO
GO:0030424	axon	ISO
GO:0030425	dendrite	ISO
GO:0031012	extracellular matrix	IDA
GO:0043025	neuronal cell body	ISO
GO:0045121	membrane raft	ISO
GO:0045121	membrane raft	IDA

Reactome Pathway

Reactome ID	Reactome Term	Evidence
R-MMU-162582	Signal Transduction	IEA
R-MMU-5358346	Hedgehog ligand biogenesis	IEA
R-MMU-5358351	Signaling by Hedgehog	IEA
R-MMU-5362798	Release of Hh-Np from the secreting cell	IEA
R-MMU-5632681	Ligand-receptor interactions	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-0068	Autocatalytic cleavage
KW-0106	Calcium
KW-1003	Cell membrane
KW-0217	Developmental protein
KW-0325	Glycoprotein
KW-0378	Hydrolase
KW-0449	Lipoprotein
KW-0472	Membrane
KW-0479	Metal-binding
KW-0564	Palmitate
KW-0645	Protease
KW-1185	Reference proteome
KW-0732	Signal
KW-0862	Zinc

Interpro

InterPro ID	InterPro Term
IPR001657	Hedgehog
IPR001767	Hedgehog_Hint
IPR009045	Hedgehog_sig/DD-Pept_Zn-bd_sf
IPR000320	Hedgehog_signalling_dom
IPR003586	Hint_dom_C
IPR003587	Hint_dom_N
IPR036844	Hint_dom_sf
IPR006141	Intein_N

PROSITE

PROSITE ID	PROSITE Term
PS50817	INTEIN_N_TER

Pfam

Pfam ID	Pfam Term
PF01085	HH_signal
PF01079	Hint

Gene: Shh

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