| IED ID | IndEnz0002008724 |
| Enzyme Type ID | protease008724 |
| Protein Name |
Sonic hedgehog protein Shh unprocessed N-terminal signaling and C-terminal autoprocessing domains ShhNC VHH-1 X-SHH Cleaved into: Sonic hedgehog protein N-product ShhN Shh N-terminal processed signaling domains ShhNp |
| Gene Name | shh |
| Organism | Xenopus laevis (African clawed frog) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amphibia Batrachia Anura Pipoidea Pipidae Xenopodinae Xenopus Xenopus Xenopus laevis (African clawed frog) |
| Enzyme Sequence | MLVATQSLLLLSFICTLVTPPGLACGPGRGIGKRRHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKITRNSDCFKELTPNYNPDIMFKDEESTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHLEESLHYEGRAVDITTSDRDRSKYGMLGRLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGGCFPAGARVMVEFGGTKAVKDLRPGDRVLSSDPQGNLLYSDFLMFIDQERDVKKLFYVIETSQRKIRLTAAHLLFVAQTKVNGTRSFKSVFASNIQPGDLIYTADPKTMTLKAVKVEKVDLEEDTGAYAPLTAHGTVVIDQVLASCYAVIEEHTWAHLAFAPLRFGMSLSSYIYPRDSSPPSGLQPHHQVDLQSHHQVDLQSHHQVDLQSHHQLEGIHWYSQLLYQIGTWLLDSNSLHPLGMATKSS |
| Enzyme Length | 444 |
| Uniprot Accession Number | Q92000 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme 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). {ECO:0000250|UniProtKB:Q15465, ECO:0000250|UniProtKB:Q62226}.; FUNCTION: [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). {ECO:0000250|UniProtKB:Q15465, ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:7551564, ECO:0000269|PubMed:7630736, ECO:0000269|PubMed:7671800}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (2); Lipidation (2); Metal binding (12); Motif (1); Region (1); Repeat (3); Sequence conflict (3); Signal peptide (1); Site (3) |
| Keywords | Autocatalytic cleavage;Calcium;Cell membrane;Developmental protein;Endoplasmic reticulum;Golgi apparatus;Hydrolase;Lipoprotein;Membrane;Metal-binding;Palmitate;Protease;Repeat;Signal;Zinc |
| Interact With | |
| Induction | INDUCTION: By thyroid hormone. {ECO:0000269|PubMed:7630736}. |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q15465}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q15465}. Note=Co-localizes with HHAT in the ER and Golgi membrane. {ECO:0000250|UniProtKB:Q15465}.; SUBCELLULAR LOCATION: [Sonic hedgehog protein N-product]: Cell membrane {ECO:0000250|UniProtKB:Q62226}; Lipid-anchor {ECO:0000250|UniProtKB:Q62226}. 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. {ECO:0000250|UniProtKB:Q62226}. |
| Modified Residue | |
| Post Translational Modification | PTM: [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). {ECO:0000250|UniProtKB:Q62226}.; PTM: [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). {ECO:0000250|UniProtKB:Q62226}.; PTM: [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). {ECO:0000250|UniProtKB:Q62226}. |
| Signal Peptide | SIGNAL 1..24; /evidence=ECO:0000250|UniProtKB:Q15465 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 33..39; /note=Cardin-Weintraub; /evidence=ECO:0000250|UniProtKB:Q62226 |
| Gene Encoded By | |
| Mass | 49,453 |
| Kinetics | |
| Metal Binding | METAL 90; /note=Calcium 1; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 91; /note=Calcium 1; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 91; /note=Calcium 2; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 96; /note=Calcium 1; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 126; /note=Calcium 1; via carbonyl oxygen; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 127; /note=Calcium 1; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 127; /note=Calcium 2; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 130; /note=Calcium 2; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 132; /note=Calcium 2; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 141; /note=Zinc; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 148; /note=Zinc; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 183; /note=Zinc; /evidence=ECO:0000250|UniProtKB:Q15465 |
| Rhea ID | |
| Cross Reference Brenda |