ID SHH_CYNPY Reviewed; 432 AA. AC Q90385; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 29-SEP-2021, entry version 111. DE RecName: Full=Sonic hedgehog protein; DE Short=SHH; DE Contains: DE RecName: Full=Sonic hedgehog protein N-product; DE Contains: DE RecName: Full=Sonic hedgehog protein C-product; DE Flags: Precursor; GN Name=SHH; OS Cynops pyrrhogaster (Japanese fire-bellied newt) (Molge pyrrhogaster). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia; OC Batrachia; Caudata; Salamandroidea; Salamandridae; Pleurodelinae; Cynops. OX NCBI_TaxID=8330; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Embryo; RX PubMed=8573168; DOI=10.1006/bbrc.1996.0069; RA Takabatake T., Takahashi T.C., Inoue K., Ogawa M., Takeshima K.; RT "Activation of two Cynops genes, fork head and sonic hedgehog, in animal RT cap explants."; RL Biochem. Biophys. Res. Commun. 218:395-401(1996). CC -!- FUNCTION: Intercellular signal essential for a variety of patterning CC events during development and metamorphosis. Involved in limb CC formation, patterning of the central nervous system and ventral somite CC differentiation. Induces ectopic cement gland formation in embryos. CC Binds to the patched (PTC) receptor, which functions in association CC with smoothened (SMO), to activate the transcription of target genes. CC In the absence of SHH, PTC represses the constitutive signaling CC activity of SMO (By similarity). {ECO:0000250}. CC -!- SUBUNIT: N-product is active as a multimer. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Sonic hedgehog protein C-product]: Secreted, CC extracellular space {ECO:0000250|UniProtKB:Q62226}. Note=The C-terminal CC peptide diffuses from the cell. {ECO:0000250|UniProtKB:Q62226}. CC -!- SUBCELLULAR LOCATION: [Sonic hedgehog protein N-product]: Cell membrane CC {ECO:0000250|UniProtKB:Q62226}; Lipid-anchor CC {ECO:0000250|UniProtKB:Q62226}. Note=The N-product either remains CC associated with lipid rafts at the cell surface, or forms freely CC diffusible active multimers with its hydrophobic lipid-modified N- and CC C-termini buried inside. {ECO:0000250|UniProtKB:Q62226}. CC -!- INDUCTION: Activated by activin, basic fibroblast growth factor (BFGF) CC and fork head. CC -!- DOMAIN: The sonic hedgehog protein N-product binds calcium and zinc CC ions; this stabilizes the protein fold and is essential for protein- CC protein interactions mediated by this domain. {ECO:0000250}. CC -!- PTM: The C-terminal domain displays an autoproteolysis activity and a CC cholesterol transferase activity. Both activities result in the CC cleavage of the full-length protein and covalent attachment of a CC cholesterol moiety to the C-terminal of the newly generated N-terminal CC fragment (N-product). The N-product is the active species in both local CC and long-range signaling, whereas the C-product has no signaling CC activity. CC -!- PTM: Cholesterylation is required for N-product targeting to lipid CC rafts and multimerization. {ECO:0000250}. CC -!- PTM: N-palmitoylation of Cys-27 by HHAT is required for N-product CC multimerization and full activity. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the hedgehog family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D63339; BAA09657.1; -; mRNA. DR SMR; Q90385; -. DR MEROPS; C46.002; -. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW. DR GO; GO:0007267; P:cell-cell signaling; IEA:InterPro. DR GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro. DR GO; GO:0016540; P:protein autoprocessing; IEA:InterPro. DR Gene3D; 3.30.1380.10; -; 1. DR InterPro; IPR001657; Hedgehog. DR InterPro; IPR001767; Hedgehog_Hint. DR InterPro; IPR009045; Hedgehog_sig/DD-Pept_Zn-bd_sf. DR InterPro; IPR000320; Hedgehog_signalling_dom. DR InterPro; IPR003586; Hint_dom_C. DR InterPro; IPR003587; Hint_dom_N. DR InterPro; IPR036844; Hint_dom_sf. DR InterPro; IPR006141; Intein_N. DR Pfam; PF01085; HH_signal; 1. DR Pfam; PF01079; Hint; 1. DR PIRSF; PIRSF009400; Peptidase_C46; 1. DR PRINTS; PR00632; SONICHHOG. DR SMART; SM00305; HintC; 1. DR SMART; SM00306; HintN; 1. DR SUPFAM; SSF51294; SSF51294; 1. DR SUPFAM; SSF55166; SSF55166; 1. DR PROSITE; PS50817; INTEIN_N_TER; 1. PE 2: Evidence at transcript level; KW Autocatalytic cleavage; Calcium; Cell membrane; Developmental protein; KW Hydrolase; Lipoprotein; Membrane; Metal-binding; Palmitate; Protease; KW Secreted; Signal; Zinc. FT SIGNAL 1..26 FT /evidence="ECO:0000255" FT CHAIN 27..432 FT /note="Sonic hedgehog protein" FT /id="PRO_0000013223" FT CHAIN 27..200 FT /note="Sonic hedgehog protein N-product" FT /id="PRO_0000013224" FT CHAIN 201..432 FT /note="Sonic hedgehog protein C-product" FT /id="PRO_0000013225" FT METAL 92 FT /note="Calcium 1" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 93 FT /note="Calcium 1" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 93 FT /note="Calcium 2" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 98 FT /note="Calcium 1" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 128 FT /note="Calcium 1; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 129 FT /note="Calcium 1" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 129 FT /note="Calcium 2" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 132 FT /note="Calcium 2" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 134 FT /note="Calcium 2" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 143 FT /note="Zinc" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 150 FT /note="Zinc" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 185 FT /note="Zinc" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT SITE 200..201 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000250" FT SITE 268 FT /note="Involved in auto-cleavage" FT /evidence="ECO:0000250" FT SITE 271 FT /note="Essential for auto-cleavage" FT /evidence="ECO:0000250" FT LIPID 27 FT /note="N-palmitoyl cysteine" FT /evidence="ECO:0000250" FT LIPID 200 FT /note="Cholesterol glycine ester" FT /evidence="ECO:0000250" SQ SEQUENCE 432 AA; 47847 MW; B455C7E746C8E5A8 CRC64; MDEMILLRRV LLAGFICALL VPSGLSCGPG RGIGTRKRFK KLTPLAYKQF TPNVPEKTLG ASGRYEGKIT RNSERFKELT PNYNPDIIFK DEENTGADRL MTQRCKDKLN ALAISVMNQW PGVKLRVTEG WDEDGHHFEE SLHYEGRAVD ITTSDRDRSK YGMLARLAAE AGFDWVYFES KAHIHCSVKA ENSVAAKSGG CFPGSATVAL EQGVRIPVKD LRPGDRVLAA DGLGKLVYSD FLLFMDKEET VRKVFYVIET SRERVRLTAA HLLFVGQAHP GNDSGGDFRS VFGSAGFRSM FASSVRAGHR VLTVDREGRG LREATVERVY LEEATGAYAP VTAHGTVVID RVLASCYAVI EEHSWAHWAF APLRVGLGIL SFFSPQDYSS HSPPAPSQSE GVHWYSEILY RIGTWVLQED TIHPLGMAAK SS //