Q63673 · SHH_RAT

  • Protein
    Sonic hedgehog protein
  • Gene
    Shh
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Sonic hedgehog protein

The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity).
Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN (By similarity).
Both activities occur in the reticulum endoplasmic (By similarity).
Once cleaved, ShhC is degraded in the endoplasmic reticulum (By similarity).

Sonic hedgehog protein N-product

The dually lipidated sonic hedgehog protein N-product (ShhNp) is a morphogen which is essential for a variety of patterning events during development. Induces ventral cell fate in the neural tube and somites (By similarity).
Involved in the patterning of the anterior-posterior axis of the developing limb bud (By similarity).
Essential for axon guidance (By similarity).
Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (By similarity).
In the absence of SHH, PTCH1 represses the constitutive signaling activity of SMO (By similarity).

Caution

The several steps and mechanisms that permit controlled Shh dispersion and gradient formation remain controversial. The ShhNC C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity resulting in the cleavage and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (ShhN). The protein is further modified by covalent addition of palmitate at the N-terminal of ShhN, resulting to the dual-lipidated Shh (ShhNp). ShhNp is firmly tethered to the cell membrane where it forms multimers. Further solubilization and release from the cell surface seem to be achieved through different mechanisms, including the interaction with DISP1 and SCUBE2, movement by lipoprotein particles, transport by cellular extensions called cytonemes or by proteolytic removal of both terminal lipidated peptides. Once released, the fully processed Shh can signal within embryonic tissues both at short and long-range.

Catalytic activity

Features

Showing features for binding site, site.

TypeIDPosition(s)Description
Binding site90Ca2+ 1 (UniProtKB | ChEBI)
Binding site91Ca2+ 1 (UniProtKB | ChEBI)
Binding site91Ca2+ 2 (UniProtKB | ChEBI)
Binding site96Ca2+ 1 (UniProtKB | ChEBI)
Binding site126Ca2+ 1 (UniProtKB | ChEBI)
Binding site127Ca2+ 1 (UniProtKB | ChEBI)
Binding site127Ca2+ 2 (UniProtKB | ChEBI)
Binding site130Ca2+ 2 (UniProtKB | ChEBI)
Binding site132Ca2+ 2 (UniProtKB | ChEBI)
Binding site141Zn2+ (UniProtKB | ChEBI)
Binding site148Zn2+ (UniProtKB | ChEBI)
Binding site183Zn2+ (UniProtKB | ChEBI)
Site198-199Cleavage; by autolysis
Site244Involved in cholesterol transfer
Site268Involved in auto-cleavage
Site271Essential for auto-cleavage

GO annotations

AspectTerm
Cellular Componentaxon
Cellular Componentcell surface
Cellular Componentdendrite
Cellular Componentendoplasmic reticulum
Cellular Componentendoplasmic reticulum membrane
Cellular Componentextracellular matrix
Cellular Componentextracellular space
Cellular Componentglutamatergic synapse
Cellular ComponentGolgi apparatus
Cellular ComponentGolgi membrane
Cellular Componenthippocampal mossy fiber to CA3 synapse
Cellular Componentmembrane
Cellular Componentmembrane raft
Cellular Componentneuronal cell body
Cellular Componentplasma membrane
Cellular Componentpostsynapse
Cellular Componentpresynapse
Cellular Componentsynaptic vesicle
Molecular Functioncalcium ion binding
Molecular Functioncholesterol-protein transferase activity
Molecular Functionglycosaminoglycan binding
Molecular Functionlaminin-1 binding
Molecular Functionpatched binding
Molecular Functionpeptidase activity
Molecular Functionzinc ion binding
Biological Processalpha-beta T cell differentiation
Biological Processanatomical structure formation involved in morphogenesis
Biological Processandrogen metabolic process
Biological Processangiogenesis
Biological Processanimal organ formation
Biological Processanterior/posterior pattern specification
Biological Processapoptotic signaling pathway
Biological Processartery development
Biological Processastrocyte differentiation
Biological Processaxon guidance
Biological ProcessBergmann glial cell differentiation
Biological Processblood coagulation
Biological Processbranching involved in blood vessel morphogenesis
Biological Processbranching involved in prostate gland morphogenesis
Biological Processbranching involved in salivary gland morphogenesis
Biological Processbranching involved in ureteric bud morphogenesis
Biological Processbranching morphogenesis of an epithelial tube
Biological Processbud outgrowth involved in lung branching
Biological Processcamera-type eye development
Biological Processcanonical Wnt signaling pathway
Biological ProcessCD4-positive or CD8-positive, alpha-beta T cell lineage commitment
Biological Processcell development
Biological Processcell fate commitment
Biological Processcell fate specification
Biological Processcell migration
Biological Processcell population proliferation
Biological Processcell proliferation in external granule layer
Biological Processcell-cell signaling
Biological Processcellular response to lithium ion
Biological Processcentral nervous system development
Biological Processcerebellar granule cell precursor proliferation
Biological Processcommissural neuron axon guidance
Biological Processdetermination of left/right asymmetry in lateral mesoderm
Biological Processdetermination of left/right symmetry
Biological Processdevelopmental growth
Biological Processdigestive tract mesoderm development
Biological Processdigestive tract morphogenesis
Biological Processdorsal/ventral neural tube patterning
Biological Processdorsal/ventral pattern formation
Biological Processectoderm development
Biological Processembryonic digestive tract morphogenesis
Biological Processembryonic digit morphogenesis
Biological Processembryonic foregut morphogenesis
Biological Processembryonic forelimb morphogenesis
Biological Processembryonic hindlimb morphogenesis
Biological Processembryonic limb morphogenesis
Biological Processembryonic morphogenesis
Biological Processembryonic organ development
Biological Processembryonic skeletal system development
Biological Processendocytosis
Biological Processepithelial cell proliferation
Biological Processepithelial cell proliferation involved in prostate gland development
Biological Processepithelial cell proliferation involved in salivary gland morphogenesis
Biological Processepithelial tube branching involved in lung morphogenesis
Biological Processepithelial-mesenchymal cell signaling
Biological Processepithelial-mesenchymal signaling involved in prostate gland development
Biological Processestablishment of epithelial cell polarity
Biological Processforebrain development
Biological Processforebrain regionalization
Biological Processformation of anatomical boundary
Biological Processfungiform papilla development
Biological Processfungiform papilla formation
Biological Processfungiform papilla morphogenesis
Biological Processgene expression
Biological Processhair follicle development
Biological Processhair follicle morphogenesis
Biological Processheart development
Biological Processheart looping
Biological Processhindbrain development
Biological Processhindgut morphogenesis
Biological Processinner ear development
Biological Processintein-mediated protein splicing
Biological Processintermediate filament organization
Biological Processkidney development
Biological Processleft lung development
Biological Processlimb bud formation
Biological Processlimb development
Biological Processliver regeneration
Biological Processlung development
Biological Processlung epithelium development
Biological Processlung lobe morphogenesis
Biological Processlung morphogenesis
Biological Processlung-associated mesenchyme development
Biological Processlymphoid progenitor cell differentiation
Biological Processmale genitalia development
Biological Processmale genitalia morphogenesis
Biological Processmesenchymal cell apoptotic process
Biological Processmesenchymal cell proliferation
Biological Processmesenchymal cell proliferation involved in lung development
Biological Processmesenchymal smoothened signaling pathway involved in prostate gland development
Biological Processmetanephric collecting duct development
Biological Processmetanephric mesenchymal cell proliferation involved in metanephros development
Biological Processmetanephros development
Biological Processmidbrain development
Biological Processmyoblast differentiation
Biological Processmyotube differentiation
Biological Processnegative regulation of alpha-beta T cell differentiation
Biological Processnegative regulation of apoptotic process
Biological Processnegative regulation of canonical Wnt signaling pathway
Biological Processnegative regulation of cell differentiation
Biological Processnegative regulation of cell migration
Biological Processnegative regulation of cholesterol efflux
Biological Processnegative regulation of dopaminergic neuron differentiation
Biological Processnegative regulation of gene expression
Biological Processnegative regulation of kidney smooth muscle cell differentiation
Biological Processnegative regulation of mesenchymal cell apoptotic process
Biological Processnegative regulation of neuron differentiation
Biological Processnegative regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Processnegative regulation of protein catabolic process
Biological Processnegative regulation of T cell differentiation in thymus
Biological Processnegative regulation of T cell proliferation
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processnegative regulation of transcription elongation by RNA polymerase II
Biological Processnegative regulation of ureter smooth muscle cell differentiation
Biological Processnegative regulation of Wnt signaling pathway
Biological Processnegative thymic T cell selection
Biological Processneural crest cell migration
Biological Processneural tube formation
Biological Processneuroblast proliferation
Biological Processneuron differentiation
Biological Processneuron fate commitment
Biological Processodontogenesis
Biological Processodontogenesis of dentin-containing tooth
Biological Processoligodendrocyte development
Biological Processoligodendrocyte differentiation
Biological Processosteoblast development
Biological Processpancreas development
Biological Processpattern specification process
Biological Processpolarity specification of anterior/posterior axis
Biological Processpositive regulation of alpha-beta T cell differentiation
Biological Processpositive regulation of astrocyte differentiation
Biological Processpositive regulation of cell division
Biological Processpositive regulation of cell population proliferation
Biological Processpositive regulation of cerebellar granule cell precursor proliferation
Biological Processpositive regulation of DNA-templated transcription
Biological Processpositive regulation of endothelial cell chemotaxis
Biological Processpositive regulation of epithelial cell proliferation
Biological Processpositive regulation of epithelial cell proliferation involved in prostate gland development
Biological Processpositive regulation of gene expression
Biological Processpositive regulation of immature T cell proliferation in thymus
Biological Processpositive regulation of kidney smooth muscle cell differentiation
Biological Processpositive regulation of mesenchymal cell proliferation
Biological Processpositive regulation of mesenchymal cell proliferation involved in ureter development
Biological Processpositive regulation of neuroblast proliferation
Biological Processpositive regulation of neuron differentiation
Biological Processpositive regulation of neurotrophin production
Biological Processpositive regulation of oligodendrocyte differentiation
Biological Processpositive regulation of oligodendrocyte progenitor proliferation
Biological Processpositive regulation of penile erection
Biological Processpositive regulation of photoreceptor cell differentiation
Biological Processpositive regulation of protein import into nucleus
Biological Processpositive regulation of sclerotome development
Biological Processpositive regulation of skeletal muscle cell proliferation
Biological Processpositive regulation of skeletal muscle tissue development
Biological Processpositive regulation of smoothened signaling pathway
Biological Processpositive regulation of sprouting angiogenesis
Biological Processpositive regulation of striated muscle cell differentiation
Biological Processpositive regulation of T cell differentiation in thymus
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processpositive regulation of ureter smooth muscle cell differentiation
Biological Processpositive regulation of Wnt signaling pathway
Biological Processpositive thymic T cell selection
Biological Processprimary prostatic bud elongation
Biological Processprostate epithelial cord elongation
Biological Processprostate gland development
Biological Processprotein autoprocessing
Biological Processprotein import into nucleus
Biological Processprotein localization to nucleus
Biological Processregulation of cell population proliferation
Biological Processregulation of DNA-templated transcription
Biological Processregulation of epithelial cell differentiation
Biological Processregulation of epithelial cell proliferation involved in prostate gland development
Biological Processregulation of gene expression
Biological Processregulation of glial cell proliferation
Biological Processregulation of mesenchymal cell proliferation involved in prostate gland development
Biological Processregulation of odontogenesis
Biological Processregulation of prostatic bud formation
Biological Processregulation of protein localization to nucleus
Biological Processregulation of proteolysis
Biological Processregulation of stem cell proliferation
Biological Processrespiratory tube development
Biological Processresponse to axon injury
Biological Processresponse to estradiol
Biological Processresponse to ethanol
Biological Processresponse to hypoxia
Biological Processresponse to retinoic acid
Biological Processright lung development
Biological Processroof of mouth development
Biological Processsalivary gland cavitation
Biological Processself proteolysis
Biological Processskeletal muscle cell proliferation
Biological Processskeletal muscle fiber differentiation
Biological Processskeletal muscle tissue development
Biological Processskin development
Biological Processsmooth muscle tissue development
Biological Processsmoothened signaling pathway
Biological Processsomite development
Biological Processspinal cord dorsal/ventral patterning
Biological Processspinal cord motor neuron differentiation
Biological Processstem cell development
Biological Processstem cell proliferation
Biological Processstriated muscle cell differentiation
Biological Processstriated muscle tissue development
Biological ProcessT cell differentiation in thymus
Biological ProcessT cell proliferation
Biological Processtelencephalon regionalization
Biological Processthalamus development
Biological Processthymus development
Biological Processthyroid gland development
Biological Processtongue development
Biological Processtongue morphogenesis
Biological Processtrachea development
Biological Processtrachea morphogenesis
Biological Processtracheoesophageal septum formation
Biological Processtrunk neural crest cell migration
Biological Processvasculature development
Biological Processvasculogenesis
Biological Processventral spinal cord interneuron specification
Biological Processzona limitans intrathalamica formation

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Sonic hedgehog protein
  • EC number
  • Short names
    SHH
  • Alternative names
    • Shh unprocessed N-terminal signaling and C-terminal autoprocessing domains
      (ShhNC
      )
  • Cleaved into 1 chains

Gene names

    • Name
      Shh
    • Synonyms
      Vhh-1

Organism names

  • Taxonomic identifier
  • Strain
    • Sprague-Dawley
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    Q63673

Proteomes

Organism-specific databases

Subcellular Location

Sonic hedgehog protein

Note: Co-localizes with HHAT in the ER and Golgi membrane.

Sonic hedgehog protein N-product

Cell membrane
; Lipid-anchor
Note: The dual-lipidated sonic hedgehog protein N-product (ShhNp) is firmly tethered to the cell membrane where it forms multimers (By similarity).
Further solubilization and release from the cell surface seem to be achieved through different mechanisms, including the interaction with DISP1 and SCUBE2, movement by lipoprotein particles, transport by cellular extensions called cytonemes or by the proteolytic removal of both terminal lipidated peptides

Keywords

PTM/Processing

Features

Showing features for signal, lipidation, chain, glycosylation.

TypeIDPosition(s)Description
Signal1-24
Lipidation25N-palmitoyl cysteine
ChainPRO_000001321525-198Sonic hedgehog protein N-product
ChainPRO_000001321425-437Sonic hedgehog protein
Lipidation198Cholesterol glycine ester
Glycosylation279N-linked (GlcNAc...) asparagine

Post-translational modification

Sonic hedgehog protein

The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (By similarity).
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 (ShhN) (By similarity).
Cholesterylation is required for the sonic hedgehog protein N-product targeting to lipid rafts and multimerization (By similarity).
ShhN is the active species in both local and long-range signaling, whereas the C-product (ShhC) is degraded in the reticulum endoplasmic (By similarity).

Sonic hedgehog protein N-product

N-palmitoylation by HHAT of ShhN is required for sonic hedgehog protein N-product multimerization and full activity (By similarity).
It is a prerequisite for the membrane-proximal positioning and the subsequent shedding of this N-terminal peptide (By similarity).

Sonic hedgehog protein N-product

The lipidated N- and C-terminal peptides of ShhNp can be cleaved (shedding) (By similarity).
The N-terminal palmitoylated peptide is cleaved at the Cardin-Weintraub (CW) motif site (By similarity).
The cleavage reduced the interactions with heparan sulfate (By similarity).
The cleavage is enhanced by SCUBE2 (By similarity).

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed in the node, notochord, floor plate, and posterior limb bud mesenchyme.

Interaction

Subunit

Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus (By similarity).
Interacts with BOC and CDON (By similarity).
Interacts with HHIP (By similarity).
Interacts with DISP1 via its cholesterol anchor (By similarity).
Interacts with SCUBE2 (By similarity).
Interacts with glypican GPC3 (By similarity).

Sonic hedgehog protein N-product

Multimer.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for motif.

TypeIDPosition(s)Description
Motif33-39Cardin-Weintraub

Domain

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.

Sonic hedgehog protein N-product

The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized ShhNp (By similarity).
The N-terminal palmitoylated peptide is cleaved at the Heparan sulfate-binding Cardin-Weintraub (CW) motif site (By similarity).
The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (By similarity).

Sequence similarities

Belongs to the hedgehog family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    437
  • Mass (Da)
    47,630
  • Last updated
    1996-11-01 v1
  • Checksum
    0DBFC19F0D1662A0
MLLLLARCFLVALASSLLVCPGLACGPGRGFGKRQHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKITRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKARIHCSVKAENSVAAKSDGCFPGSATVHLEQGGTKLVKDLSPGDRVLAADDQGRLLYSDFLTFLDRDEGAKKVFYVIETREPRERLLLTAAHLLFVAPHNDSGPTPGPSPLFASRVRPGQRVYVVAERGGDRRLLPAAVHSVTLREEAAGAYAPLTADGTILINRVLASCYAVIEEHSWAHRAFAPFRLAHALLAALAPARTDGGGGGSIPAPQSVAEARGAGPPAGIHWYSQLLYHIGTWLLDSETLHPLGMAVKSS

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
G3V6T0G3V6T0_RATShh437

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
L27340
EMBL· GenBank· DDBJ
AAA20999.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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