Q90419 · TWHH_DANRE
- ProteinTiggy-winkle hedgehog protein
- Geneshhb
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids416 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Tiggy-winkle hedgehog protein
The C-terminal part of the tiggy-winkle 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 (N-product and C-product) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (By similarity).
Both activities occur in the reticulum endoplasmic (By similarity).
Once cleaved, the C-product is degraded in the endoplasmic reticulum (By similarity).
Both activities result in the cleavage of the full-length protein into two parts (N-product and C-product) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (By similarity).
Both activities occur in the reticulum endoplasmic (By similarity).
Once cleaved, the C-product is degraded in the endoplasmic reticulum (By similarity).
Tiggy-winkle hedgehog protein N-product
The dually lipidated tiggy-winkle hedgehog protein N-product is a morphogen which is essential for a variety of patterning events during development (By similarity).
Involved in dorso-ventral patterning of the brain and in early patterning of the developing eyes (PubMed:7583153).
Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (By similarity).
Involved in dorso-ventral patterning of the brain and in early patterning of the developing eyes (PubMed:7583153).
Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (By similarity).
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 92 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 93 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 93 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 98 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 128 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 129 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 129 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 132 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 134 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 143 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 150 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 185 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Site | 200-201 | Cleavage; by autolysis | ||||
Sequence: GC | ||||||
Site | 270 | Involved in auto-cleavage | ||||
Sequence: T | ||||||
Site | 273 | 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 nameTiggy-winkle hedgehog protein
- EC number
- Short namesTWHH
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Actinopterygii > Neopterygii > Teleostei > Ostariophysi > Cypriniformes > Danionidae > Danioninae > Danio
Accessions
- Primary accessionQ90419
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Tiggy-winkle hedgehog protein N-product
Cell membrane ; Lipid-anchor
Note: The dual-lipidated tiggy-winkle hedgehog protein N-product (TWHHN) 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
Tiggy-winkle hedgehog protein
Note: Co-localizes with HHAT in the ER and Golgi membrane.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 273 | Loss of autoproteolytic cleavage. | ||||
Sequence: H → A |
PTM/Processing
Features
Showing features for signal, lipidation, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-26 | |||||
Sequence: MDVRLHLKQFALLCFISLLLTPCGLA | ||||||
Lipidation | 27 | N-palmitoyl cysteine | ||||
Sequence: C | ||||||
Chain | PRO_0000013257 | 27-200 | Tiggy-winkle hedgehog protein N-product | |||
Sequence: CGPGRGYGKRRHPKKLTPLAYKQFIPNVAEKTLGASGKYEGKITRNSERFKELIPNYNPDIIFKDEENTNADRLMTKRCKDKLNSLAISVMNHWPGVKLRVTEGWDEDGHHLEESLHYEGRAVDITTSDRDKSKYGMLSRLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGG | ||||||
Chain | PRO_0000013256 | 27-416 | Tiggy-winkle hedgehog protein | |||
Sequence: CGPGRGYGKRRHPKKLTPLAYKQFIPNVAEKTLGASGKYEGKITRNSERFKELIPNYNPDIIFKDEENTNADRLMTKRCKDKLNSLAISVMNHWPGVKLRVTEGWDEDGHHLEESLHYEGRAVDITTSDRDKSKYGMLSRLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGGCFPGSGTVTLGDGTRKPIKDLKVGDRVLAADEKGNVLISDFIMFIDHDPTTRRQFIVIETSEPFTKLTLTAAHLVFVGNSSAASGITATFASNVKPGDTVLVWEDTCESLKSVTVKRIYTEEHEGSFAPVTAHGTIIVDQVLASCYAVIENHKWAHWAFAPVRLCHKLMTWLFPARESNVNFQEDGIHWYSNMLFHIGSWLLDRDSFHPLGILHLS | ||||||
Lipidation | 200 | Cholesterol glycine ester | ||||
Sequence: G |
Post-translational modification
Tiggy-winkle 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 into two parts (N-product and C-product) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (By similarity).
Cholesterylation is required for the tiggy-winkle hedgehog protein N-product targeting to lipid rafts and multimerization (By similarity).
N-product is the active species in both local and long-range signaling, whereas the C-product is degraded in the reticulum endoplasmic (By similarity).
Both activities result in the cleavage of the full-length protein into two parts (N-product and C-product) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (By similarity).
Cholesterylation is required for the tiggy-winkle hedgehog protein N-product targeting to lipid rafts and multimerization (By similarity).
N-product is the active species in both local and long-range signaling, whereas the C-product is degraded in the reticulum endoplasmic (By similarity).
Tiggy-winkle hedgehog protein N-product
N-palmitoylation by HHAT of N-product is required for tiggy-winkle 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).
Tiggy-winkle hedgehog protein N-product
The lipidated N- and C-terminal peptides of N-product 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
Expression
Tissue specificity
Expressed in the ventral midline of the neural tube and brain. In the developing brain, expression occurs in domains that include a discrete region in the floor of the diencephalon. Not detected in the notochord or developing fin bud.
Gene expression databases
Interaction
Subunit
Tiggy-winkle hedgehog protein N-product
Multimer.
Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the TWHH 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 BOC and CDON (By similarity).
Interacts with HHIP (By similarity).
Interacts with DISP1 via its cholesterol anchor (By similarity).
Interacts with SCUBE2 (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Domain
Tiggy-winkle 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.
Tiggy-winkle hedgehog protein N-product
The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized TWHHN (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.
- Length416
- Mass (Da)46,576
- Last updated1996-11-01 v1
- Checksum61EC2218309CFE59
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q6DBX7 | Q6DBX7_DANRE | shhb | 416 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U30710 EMBL· GenBank· DDBJ | AAC59741.1 EMBL· GenBank· DDBJ | mRNA | ||
U68237 EMBL· GenBank· DDBJ | AAB38678.1 EMBL· GenBank· DDBJ | Genomic DNA |