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
  • signal produced by the notochord induces ventral cell fate in the neural tube & somites
  • polarizing signal for patterning of the anterior-posterior axis of the developing limb bud
  • displays both floor plate- & 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
• the C-terminal domain displays an autoproteolysis activity & a cholesterol transferase activity
  • 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)
  • the N-product is the active species in both local & long-range signaling
  • N-product is active as a multimer (putative)
  • 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
  • microphthalmia isolated with coloboma type 5
  • holoprosencephaly type 3
  • triphalangeal thumb-polysyndactyly syndrome
• defects in SHH are a cause of solitary median maxillary central incisor

More general terms

• hedgehog family protein
• glycoprotein

Additional terms

• holoprosencephaly type 3 (HPE3)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=6469
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:6469
• OMIM: https://mirror.omim.org/entry/142945
• OMIM: https://mirror.omim.org/entry/147250
• OMIM: https://mirror.omim.org/entry/174500
• OMIM: https://mirror.omim.org/entry/600725
• OMIM: https://mirror.omim.org/entry/611638
• UniProt: http://www.uniprot.org/uniprot/Q15465.html