Shh
entrez
29499
canonical
uniprot
Q63673
canonical
ensembl
ENSRNOG00000006120
resolver
ensp
ENSRNOP00000008497
resolver
genesymbol
Shh
resolver
genesymbol_syn
Vhh-1
resolver
uniprot_entry
SHH_RAT
resolver
amino_acid_sequence
MLLLLARCFLVALASSLLVCPGLACGPGRGFGKRQHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKITRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKARIHCSVKAENSVAAKSDGCFPGSATVHLEQGGTKLVKDLSPGDRVLAADDQGRLLYSDFLTFLDRDEGAKKVFYVIETREPRERLLLTAAHLLFVAPHNDSGPTPGPSPLFASRVRPGQRVYVVAERGGDRRLLPAAVHSVTLREEAAGAYAPLTADGTILINRVLASCYAVIEEHSWAHRAFAPFRLAHALLAALAPARTDGGGGGSIPAPQSVAEARGAGPPAGIHWYSQLLYHIGTWLLDSETLHPLGMAVKSS
uniprot
proteins
ec_number
3.1.-.-
uniprot
proteins
function
FUNCTION: [Sonic hedgehog protein]: Precursor of sonic hedgehog, a morphogen that activates the smoothened signaling pathway, and which is essential for a variety of patterning events during development (By similarity). The C-terminal part of the precursor displays an autoproteolysis and a cholesterol transferase activity, resulting (1) in the cleavage of the full-length protein into two parts, Sonic hedgehog protein N-product and C-product (ShhN and ShhC, respectively) and (2) covalent attachment of a cholesterol moiety to the C-terminus of the newly generated ShhN (By similarity). Both autoproteolysis and a cholesterol transferase activities occur in the endoplasmic reticulum (By similarity). Following additional lipidation, ShhN acts as a morphogen, while ShhC is degraded in the endoplasmic reticulum (By similarity). {ECO:0000250|UniProtKB:Q62226}.; FUNCTION: [Sonic hedgehog protein N-product]: The dually lipidated sonic hedgehog protein N-product (ShhN) is a morphogen that activates the smoothened signaling pathway, and which is essential for a variety of patterning events during development (By similarity). Acts by binding to the patched receptor (PTCH1 or PTCH2), relieving smoothened (SMO) inhibition by patched, activating the smoothened signaling pathway and transcription of target genes (By similarity). In the absence of SHH, patched represses the constitutive signaling activity of SMO (By similarity). ShhN is widely expressed and plays a key role in the patterning of the central nervous system and limb development (By similarity). 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). {ECO:0000250|UniProtKB:Q15465, ECO:0000250|UniProtKB:Q62226}.
uniprot
proteins
mass_dalton
47630
uniprot
proteins
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 endoplasmic reticulum (By similarity). {ECO:0000250|UniProtKB:Q15465, ECO:0000250|UniProtKB:Q62226}.; PTM: [Sonic hedgehog protein N-product]: Dually lipidated: a cholesterol moiety is attached to its C-terminus following cleavage (PubMed:11395778). N-palmitoylated by HHAT following cholesterylation; palmitoylation is required for sonic hedgehog protein N-product multimerization and full activity (By similarity). It is a prerequisite for the membrane-proximal positioning (By similarity). The lipidated N- and C-terminal peptides of ShhN can be cleaved (shedding) (By similarity). The N-terminal palmitoylated peptide is cleaved at the Cardin-Weintraub (CW) motif site (By similarity). The cleavage reduces the interactions with heparan sulfate and is enhanced by SCUBE2 (By similarity). {ECO:0000250|UniProtKB:Q15465, ECO:0000269|PubMed:11395778}.
uniprot
proteins
protein_family
Hedgehog family
uniprot
proteins
pubmed
11395778
uniprot
proteins
pubmed
8124714
uniprot
proteins
sequence_length
437
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Sonic hedgehog protein]: 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]: Secreted {ECO:0000269|PubMed:11395778}. Cell membrane {ECO:0000250|UniProtKB:Q15465}; Lipid-anchor {ECO:0000250|UniProtKB:Q15465}. Note=The dual-lipidated sonic hedgehog protein N-product (ShhN) is firmly tethered to the cell membrane where it forms multimers (PubMed:11395778). Further solubilization from the cell surface is achieved by SCUBE2 carrier, which promotes its release from producing cells, allowing it to act as a morphogen for distant signaling (By similarity). ShhN is then transferred to the CDON-BOC heterodimer and GAS1 coreceptors to reach the patched receptor (PTCH1 or PTCH2) (By similarity). {ECO:0000250|UniProtKB:Q15465, ECO:0000269|PubMed:11395778}.
uniprot
proteins