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Sonic hedgehog protein; SHH; HHG-1; contains: sonic hedgehog protein N-product, sonic hedgehog protein C-product (SHH)

Function: - binds to patched (PTC) which interacts with smoothened (SMO) to activate transcription of target genes - in the absence of SHH, PTC represses constitutive signaling activity of SMO - also regualtes gli - intercellular signal essential for a variety of patterning events during development a) signal produced by the notochord induces ventral cell fate in the neural tube & somites b) polarizing signal for patterning of the anterior-posterior axis of the developing limb bud c) displays both floor plate- & motor neuron-inducing activity d) the threshold concentration of N-product required for motor neuron induction is 5-fold lower than that required for floor plate induction - the C-terminal domain displays an autoproteolysis activity & a cholesterol transferase activity a) both activities result in the cleavage of the full-length protein & covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (N-product) b) the N-product is the active species in both local & long-range signaling c) N-product is active as a multimer (putative) d) the C-product has no signaling activity - cholesterylation is required for N-product targeting to lipid rafts & multimerization (putative) - N-palmitoylation of Cys-24 by HHAT is required for N-product multimerization & full activity (putative) - interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus Structure: - belongs to the hedgehog family - C-terminal domain has autoproteolytic activity & cholesterol transferase activity Compartment: - sonic hedgehog protein C-product: - secreted, extracellular space (putative) - C-terminal peptide diffuses from the cell (putative) - sonic hedgehog protein N-product: - cell membrane; lipid-anchor (putative) - 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- & C-termini buried inside (putative) Expression: - expressed in fetal intestine, liver, lung, & kidney - SHH is expressed at Henson's node, throughout the notochord, floorplate of the neural tube, early gut endoderm & posterior of the limb buds; has been implicated in patterning of the ventral neural tube, the anterior-posterior limb axis & the ventral somites - SHH transcripts not detected in adult tissues Pathology: - defects in SHH are the cause of a) microphthalmia isolated with coloboma type 5 b) holoprosencephaly type 3 c) triphalangeal thumb-polysyndactyly syndrome - defects in SHH are a cause of solitary median maxillary central incisor

Interactions

molecular events

Related

holoprosencephaly type 3 (HPE3) Sonic hedgehog gene (Shh)

General

glycoprotein hedgehog family protein

Properties

SIZE: entity length = 462 aa MW = 50 kD COMPARTMENT: extracellular compartment MOTIF: signal sequence {1-23} peptide motif {197-198} aspartate residue {243} threonine residue {267} histidine residue {270} N-glycosylation site {N278} glycine-rich region {407-411}

References

  1. UniProt :accession Q15465
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/SHHID378.html
  3. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/SHH
  4. NIEHS-SNPs http://egp.gs.washington.edu/data/shh/
  5. Marigo V et al Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog. Genomics 28:44-51 1995 PMID: 7590746
  6. Entrez Gene :accession 6469

Component-of

molecular complex

Databases & Figures

OMIM correlations MORBIDMAP 600725 UniProt Q15465 PFAM correlations Entrez Gene 6469 Kegg hsa:6469 hedgehog/gli pathway