Q63673 · SHH_RAT
- ProteinSonic hedgehog protein
- GeneShh
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids437 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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).
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).
Catalytic activity
Sonic hedgehog protein
cholesterol + glycyl-L-cysteinyl-[protein] + H+ = [protein]-C-terminal glycyl cholesterol ester + N-terminal L-cysteinyl-[protein]This reaction proceeds in the forward direction.
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 90 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 91 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 91 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 96 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 126 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 127 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 127 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 130 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 132 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 141 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 148 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 183 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Site | 198-199 | Cleavage; by autolysis | ||||
Sequence: GC | ||||||
Site | 244 | Involved in cholesterol transfer | ||||
Sequence: D | ||||||
Site | 268 | Involved in auto-cleavage | ||||
Sequence: T | ||||||
Site | 271 | Essential for auto-cleavage | ||||
Sequence: H |
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSonic hedgehog protein
- EC number
- Short namesSHH
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ63673
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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
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
- Cellular component
PTM/Processing
Features
Showing features for signal, lipidation, chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-24 | |||||
Sequence: MLLLLARCFLVALASSLLVCPGLA | ||||||
Lipidation | 25 | N-palmitoyl cysteine | ||||
Sequence: C | ||||||
Chain | PRO_0000013215 | 25-198 | Sonic hedgehog protein N-product | |||
Sequence: CGPGRGFGKRQHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKITRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKARIHCSVKAENSVAAKSDG | ||||||
Chain | PRO_0000013214 | 25-437 | Sonic hedgehog protein | |||
Sequence: CGPGRGFGKRQHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKITRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKARIHCSVKAENSVAAKSDGCFPGSATVHLEQGGTKLVKDLSPGDRVLAADDQGRLLYSDFLTFLDRDEGAKKVFYVIETREPRERLLLTAAHLLFVAPHNDSGPTPGPSPLFASRVRPGQRVYVVAERGGDRRLLPAAVHSVTLREEAAGAYAPLTADGTILINRVLASCYAVIEEHSWAHRAFAPFRLAHALLAALAPARTDGGGGGSIPAPQSVAEARGAGPPAGIHWYSQLLYHIGTWLLDSETLHPLGMAVKSS | ||||||
Lipidation | 198 | Cholesterol glycine ester | ||||
Sequence: G | ||||||
Glycosylation | 279 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
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).
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).
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).
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
- PTM
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 33-39 | Cardin-Weintraub | ||||
Sequence: KRQHPKK |
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).
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
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length437
- Mass (Da)47,630
- Last updated1996-11-01 v1
- Checksum0DBFC19F0D1662A0
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
G3V6T0 | G3V6T0_RAT | Shh | 437 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L27340 EMBL· GenBank· DDBJ | AAA20999.1 EMBL· GenBank· DDBJ | mRNA |