LMPD Database

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LMP002984

UniProt Annotations

Entry Information
Gene Namesonic hedgehog
Protein EntrySHH_HUMAN
UniProt IDQ15465
SpeciesHuman
Comments
Comment typeDescription
DiseaseHoloprosencephaly 3 (HPE3) [MIM
DiseaseMicrophthalmia, isolated, with coloboma, 5 (MCOPCB5) [MIM
DiseasePreaxial polydactyly 2 (PPD2) [MIM
DiseaseSolitary median maxillary central incisor (SMMCI) [MIM
DiseaseTriphalangeal thumb-polysyndactyly syndrome (TPTPS) [MIM
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
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 (By similarity).
Mass SpectrometryMass=19.560; Method=Electrospray; Range=24-197; Note=Soluble N-product, purified from insect cells.; Evidence= ;
Mass SpectrometryMass=20.167; Method=Electrospray; Range=24-197; Note=Membrane-bound N-product, purified from insect cells.; Evidence= ;
PtmCholesterylation is required for N-product targeting to lipid rafts and multimerization.
PtmN-palmitoylation of Cys-24 by HHAT is required for N-product multimerization and full activity.
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.
SimilarityBelongs to the hedgehog family.
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 {ECO
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 (By similarity). Interacts with HHIP. {ECO
Tissue SpecificityExpressed in fetal intestine, liver, lung, and kidney. Not expressed in adult tissues.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/SHHID378.html";
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/shh/";