InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Shh

Summary

InnateDB Protein

IDBP-144311.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Shh

Protein Name

sonic hedgehog

Synonyms

9530036O11Rik; Dsh; Hhg1; Hx; Hxl3; M100081;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000002708

InnateDB Gene

IDBG-144309 (Shh)

Protein Structure

UniProt Annotation

Function

Intercellular signal essential for a variety of patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior- posterior axis of the developing limb bud. Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required for motor neuron induction is 5-fold lower than that required for floor plate induction. Activates the transcription of target genes by interacting with its receptor PTCH1 to prevent normal inhibition by PTCH1 on the constitutive signaling activity of SMO. {ECO:0000269PubMed:14687547, ECO:0000269PubMed:7736596}.

Subcellular Localization

Sonic hedgehog protein C-product: Secreted, extracellular space. Note=The C-terminal peptide diffuses from the cell.Sonic hedgehog protein N-product: Cell membrane; Lipid-anchor. Note=The N-product either remains associated with lipid rafts at the cell surface, or forms freely diffusible active multimers with its hydrophobic lipid-modified N- and C-termini buried inside.

Disease Associations

Tissue Specificity

Expressed in a number of embryonic tissues including the notochord, ventral neural tube, floor plate, lung bud, zone of polarizing activity and posterior distal mesenchyme of limbs. In the adult, expressed in lung and neural retina.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 16 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	17 [view]
Protein-Protein	10 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	5 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001948	glycoprotein binding
GO:0004871	signal transducer activity
GO:0005113	patched binding
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0005539	glycosaminoglycan binding
GO:0008233	peptidase activity
GO:0008270	zinc ion binding
GO:0043237	laminin-1 binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001525	angiogenesis
GO:0001569	patterning of blood vessels
GO:0001570	vasculogenesis
GO:0001656	metanephros development
GO:0001658	branching involved in ureteric bud morphogenesis
GO:0001708	cell fate specification
GO:0001755	neural crest cell migration
GO:0001822	kidney development
GO:0001942	hair follicle development
GO:0001944	vasculature development
GO:0001947	heart looping
GO:0002052	positive regulation of neuroblast proliferation
GO:0002053	positive regulation of mesenchymal cell proliferation
GO:0002076	osteoblast development
GO:0002320	lymphoid progenitor cell differentiation
GO:0003140	determination of left/right asymmetry in lateral mesoderm
GO:0006355	regulation of transcription, DNA-templated
GO:0006508	proteolysis
GO:0006897	endocytosis
GO:0006915	apoptotic process
GO:0007154	cell communication
GO:0007165	signal transduction
GO:0007224	smoothened signaling pathway
GO:0007228	positive regulation of hh target transcription factor activity
GO:0007267	cell-cell signaling
GO:0007275	multicellular organismal development
GO:0007368	determination of left/right symmetry
GO:0007389	pattern specification process
GO:0007398	ectoderm development
GO:0007405	neuroblast proliferation
GO:0007411	axon guidance
GO:0007417	central nervous system development
GO:0007442	hindgut morphogenesis
GO:0007507	heart development
GO:0007596	blood coagulation
GO:0008209	androgen metabolic process
GO:0008283	cell proliferation
GO:0008284	positive regulation of cell proliferation
GO:0009949	polarity specification of anterior/posterior axis
GO:0009952	anterior/posterior pattern specification
GO:0009953	dorsal/ventral pattern formation
GO:0010463	mesenchymal cell proliferation
GO:0010468	regulation of gene expression
GO:0010628	positive regulation of gene expression
GO:0010629	negative regulation of gene expression
GO:0014003	oligodendrocyte development
GO:0014706	striated muscle tissue development
GO:0014858	positive regulation of skeletal muscle cell proliferation
GO:0014902	myotube differentiation
GO:0016539	intein-mediated protein splicing
GO:0021513	spinal cord dorsal/ventral patterning
GO:0021522	spinal cord motor neuron differentiation
GO:0021794	thalamus development
GO:0021904	dorsal/ventral neural tube patterning
GO:0021930	cerebellar granule cell precursor proliferation
GO:0021938	smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation
GO:0021940	positive regulation of cerebellar granule cell precursor proliferation
GO:0021978	telencephalon regionalization
GO:0030010	establishment of cell polarity
GO:0030162	regulation of proteolysis
GO:0030177	positive regulation of Wnt signaling pathway
GO:0030178	negative regulation of Wnt signaling pathway
GO:0030323	respiratory tube development
GO:0030324	lung development
GO:0030326	embryonic limb morphogenesis
GO:0030336	negative regulation of cell migration
GO:0030539	male genitalia development
GO:0030850	prostate gland development
GO:0030878	thyroid gland development
GO:0030900	forebrain development
GO:0030901	midbrain development
GO:0030902	hindbrain development
GO:0031016	pancreas development
GO:0031069	hair follicle morphogenesis
GO:0032435	negative regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0033077	T cell differentiation in thymus
GO:0033089	positive regulation of T cell differentiation in thymus
GO:0033092	positive regulation of immature T cell proliferation in thymus
GO:0034244	negative regulation of transcription elongation from RNA polymerase II promoter
GO:0034504	protein localization to nucleus
GO:0035115	embryonic forelimb morphogenesis
GO:0035116	embryonic hindlimb morphogenesis
GO:0042127	regulation of cell proliferation
GO:0042130	negative regulation of T cell proliferation
GO:0042177	negative regulation of protein catabolic process
GO:0042307	positive regulation of protein import into nucleus
GO:0042475	odontogenesis of dentin-containing tooth
GO:0042476	odontogenesis
GO:0042481	regulation of odontogenesis
GO:0042733	embryonic digit morphogenesis
GO:0043010	camera-type eye development
GO:0043066	negative regulation of apoptotic process
GO:0043369	CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
GO:0043588	skin development
GO:0045059	positive thymic T cell selection
GO:0045060	negative thymic T cell selection
GO:0045109	intermediate filament organization
GO:0045165	cell fate commitment
GO:0045445	myoblast differentiation
GO:0045596	negative regulation of cell differentiation
GO:0045597	positive regulation of cell differentiation
GO:0045880	positive regulation of smoothened signaling pathway
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046638	positive regulation of alpha-beta T cell differentiation
GO:0046639	negative regulation of alpha-beta T cell differentiation
GO:0048468	cell development
GO:0048538	thymus development
GO:0048546	digestive tract morphogenesis
GO:0048557	embryonic digestive tract morphogenesis
GO:0048568	embryonic organ development
GO:0048589	developmental growth
GO:0048598	embryonic morphogenesis
GO:0048617	embryonic foregut morphogenesis
GO:0048643	positive regulation of skeletal muscle tissue development
GO:0048645	organ formation
GO:0048646	anatomical structure formation involved in morphogenesis
GO:0048663	neuron fate commitment
GO:0048706	embryonic skeletal system development
GO:0048709	oligodendrocyte differentiation
GO:0048714	positive regulation of oligodendrocyte differentiation
GO:0048754	branching morphogenesis of an epithelial tube
GO:0048839	inner ear development
GO:0048856	anatomical structure development
GO:0048859	formation of anatomical boundary
GO:0048864	stem cell development
GO:0051146	striated muscle cell differentiation
GO:0051155	positive regulation of striated muscle cell differentiation
GO:0051781	positive regulation of cell division
GO:0060020	Bergmann glial cell differentiation
GO:0060021	palate development
GO:0060070	canonical Wnt signaling pathway
GO:0060173	limb development
GO:0060174	limb bud formation
GO:0060425	lung morphogenesis
GO:0060428	lung epithelium development
GO:0060438	trachea development
GO:0060439	trachea morphogenesis
GO:0060441	epithelial tube branching involved in lung morphogenesis
GO:0060442	branching involved in prostate gland morphogenesis
GO:0060445	branching involved in salivary gland morphogenesis
GO:0060447	bud outgrowth involved in lung branching
GO:0060458	right lung development
GO:0060459	left lung development
GO:0060463	lung lobe morphogenesis
GO:0060484	lung-associated mesenchyme development
GO:0060516	primary prostatic bud elongation
GO:0060523	prostate epithelial cord elongation
GO:0060662	salivary gland cavitation
GO:0060664	epithelial cell proliferation involved in salivary gland morphogenesis
GO:0060684	epithelial-mesenchymal cell signaling
GO:0060685	regulation of prostatic bud formation
GO:0060738	epithelial-mesenchymal signaling involved in prostate gland development
GO:0060768	regulation of epithelial cell proliferation involved in prostate gland development
GO:0060769	positive regulation of epithelial cell proliferation involved in prostate gland development
GO:0060782	regulation of mesenchymal cell proliferation involved in prostate gland development
GO:0060783	mesenchymal smoothened signaling pathway involved in prostate gland development
GO:0060840	artery development
GO:0060916	mesenchymal cell proliferation involved in lung development
GO:0060979	vasculogenesis involved in coronary vascular morphogenesis
GO:0061053	somite development
GO:0061189	positive regulation of sclerotome development
GO:0071285	cellular response to lithium ion
GO:0072001	renal system development
GO:0072136	metanephric mesenchymal cell proliferation involved in metanephros development
GO:0080125	multicellular structure septum development
GO:0090090	negative regulation of canonical Wnt signaling pathway
GO:0090370	negative regulation of cholesterol efflux
GO:0097190	apoptotic signaling pathway
GO:1900180	regulation of protein localization to nucleus
GO:2000062	negative regulation of ureter smooth muscle cell differentiation
GO:2000063	positive regulation of ureter smooth muscle cell differentiation
GO:2000357	negative regulation of kidney smooth muscle cell differentiation
GO:2000358	positive regulation of kidney smooth muscle cell differentiation
GO:2000729	positive regulation of mesenchymal cell proliferation involved in ureter development
GO:2001054	negative regulation of mesenchymal cell apoptotic process

Cellular Component

GO:0005615	extracellular space
GO:0005634	nucleus
GO:0005886	plasma membrane
GO:0009986	cell surface
GO:0016020	membrane
GO:0031012	extracellular matrix
GO:0045121	membrane raft

Protein Structure and Domains

PDB ID

MGI:98297

InterPro

IPR000320 Hedgehog, N-terminal signalling domain
IPR001657 Hedgehog protein
IPR001767 Hedgehog protein, Hint domain
IPR003586 Hint domain C-terminal
IPR003587 Hint domain N-terminal
IPR006141 Intein splice site
IPR009045 Hedgehog signalling/DD-peptidase zinc-binding domain
IPR028992 Hedgehog/Intein (Hint) domain

PFAM

PF01085
PF01079

PRINTS

PR00632

PIRSF

PIRSF009400

SMART

SM00305
SM00306

TIGRFAMs

Post-translational Modifications

Modification

Cross-References