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). 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). 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). 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. Co-localizes with HHAT in the ER and Golgi membrane. 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. Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain. 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 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). 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). 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). Belongs to the hedgehog family. The several steps and mechanisms that permit controlled tiggy-winkle hedgehog dispersion and gradient formation remain controversial. The C-terminal part of the tiggy-winkle hedgehog protein precursor 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 (N-product). The protein is further modified by covalent addition of palmitate at the N-terminal of N-product, resulting to the dual-lipidated N-product. The latter 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 TWHHN can signal within embryonic tissues both at short and long-range.