LMPD Database

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LMP002282

UniProt Annotations

Entry Information
Gene Namesonic hedgehog
Protein EntrySHH_MOUSE
UniProt IDQ62226
SpeciesMouse
Comments
Comment typeDescription
Developmental StageFirst detectable during gastrulation.
DomainThe sonic hedgehog protein N-product binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain. {ECO:0000269|PubMed:18794898, ECO:0000269|PubMed:19561611, ECO:0000269|PubMed:20519495}.
FunctionIntercellular 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:0000269|PubMed:14687547, ECO:0000269|PubMed:7736596}.
InductionBy retinoic acid.
MiscellaneousMice overexpressing Shh display digit duplications in both forelimbs and hindlimbs.
PtmCholesterylation is required for N-product targeting to lipid rafts and multimerization. {ECO:0000269|PubMed:8824192}.
PtmN-palmitoylation of Cys-25 by HHAT is required for N-product multimerization and full activity. {ECO:0000269|PubMed:11486055, ECO:0000269|PubMed:15075292}.
PtmThe C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity. Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N- terminal fragment (N-product). The N-product is the active species in both local and long-range signaling, whereas the C-product has no signaling activity. {ECO:0000269|PubMed:7720571, ECO:0000269|PubMed:7736596, ECO:0000269|PubMed:7891723}.
SimilarityBelongs to the hedgehog family. {ECO:0000305}.
Subcellular LocationSonic hedgehog protein C-product: Secreted, extracellular space. Note=The C-terminal peptide diffuses from the cell.
Subcellular LocationSonic 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.
SubunitInteracts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus. N-product is active as a multimer. Interacts with BOC and CDON. Interacts with HHIP. {ECO:0000269|PubMed:15075292, ECO:0000269|PubMed:18081866, ECO:0000269|PubMed:18794898, ECO:0000269|PubMed:19561611, ECO:0000269|PubMed:20519495, ECO:0000269|PubMed:7477329}.
Tissue SpecificityExpressed 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.