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 14-OCT-2015, entry version 96. 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 common newt). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Amphibia; Batrachia; Caudata; Salamandroidea; Salamandridae; OC 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 RT animal cap explants."; RL Biochem. Biophys. Res. Commun. 218:395-401(1996). CC -!- FUNCTION: Intercellular signal essential for a variety of CC patterning events during development and metamorphosis. Involved CC in limb formation, patterning of the central nervous system and CC ventral somite differentiation. Induces ectopic cement gland CC formation in embryos. Binds to the patched (PTC) receptor, which CC functions in association with smoothened (SMO), to activate the CC transcription of target genes. In the absence of SHH, PTC CC represses the constitutive signaling activity of SMO (By CC 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}. Note=The C-terminal peptide CC diffuses from the cell. CC -!- SUBCELLULAR LOCATION: Sonic hedgehog protein N-product: Cell CC membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}. Note=The N- CC product either remains associated with lipid rafts at the cell CC surface, or forms freely diffusible active multimers with its CC hydrophobic lipid-modified N- and C-termini buried inside. CC {ECO:0000250}. CC -!- INDUCTION: Activated by activin, basic fibroblast growth factor CC (BFGF) and fork head. CC -!- DOMAIN: The sonic hedgehog protein N-product binds calcium and CC zinc ions; this stabilizes the protein fold and is essential for CC protein-protein interactions mediated by this domain. CC {ECO:0000250}. CC -!- PTM: The C-terminal domain displays an autoproteolysis activity CC and a cholesterol transferase activity. Both activities result in CC the cleavage of the full-length protein and covalent attachment of CC a cholesterol moiety to the C-terminal of the newly generated N- CC terminal fragment (N-product). The N-product is the active species CC in both local and long-range signaling, whereas the C-product has CC no signaling 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 ProteinModelPortal; Q90385; -. DR SMR; Q90385; 41-197. DR MEROPS; C46.002; -. DR HOVERGEN; HBG005480; -. 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:0007275; P:multicellular organismal development; IEA:UniProtKB-KW. DR Gene3D; 2.170.16.10; -; 1. DR Gene3D; 3.30.1380.10; -; 1. DR InterPro; IPR001657; Hedgehog. DR InterPro; IPR028992; Hedgehog/Intein_dom. DR InterPro; IPR009045; Hedgehog_sig/DD-Pept_Zn-bd_dom. DR InterPro; IPR000320; Hedgehog_signalling_dom. DR InterPro; IPR001767; Hint_dom. DR InterPro; IPR003586; Hint_dom_C. DR InterPro; IPR003587; Hint_dom_N. 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 {ECO:0000255}. FT CHAIN 27 432 Sonic hedgehog protein. FT /FTId=PRO_0000013223. FT CHAIN 27 200 Sonic hedgehog protein N-product. FT /FTId=PRO_0000013224. FT CHAIN 201 432 Sonic hedgehog protein C-product. FT /FTId=PRO_0000013225. FT METAL 92 92 Calcium 1. {ECO:0000250}. FT METAL 93 93 Calcium 1. {ECO:0000250}. FT METAL 93 93 Calcium 2. {ECO:0000250}. FT METAL 98 98 Calcium 1. {ECO:0000250}. FT METAL 128 128 Calcium 1; via carbonyl oxygen. FT {ECO:0000250}. FT METAL 129 129 Calcium 1. {ECO:0000250}. FT METAL 129 129 Calcium 2. {ECO:0000250}. FT METAL 132 132 Calcium 2. {ECO:0000250}. FT METAL 134 134 Calcium 2. {ECO:0000250}. FT METAL 143 143 Zinc. {ECO:0000250}. FT METAL 150 150 Zinc. {ECO:0000250}. FT METAL 185 185 Zinc. {ECO:0000250}. FT SITE 200 201 Cleavage; by autolysis. {ECO:0000250}. FT SITE 268 268 Involved in auto-cleavage. {ECO:0000250}. FT SITE 271 271 Essential for auto-cleavage. FT {ECO:0000250}. FT LIPID 27 27 N-palmitoyl cysteine. {ECO:0000250}. FT LIPID 200 200 Cholesterol glycine ester. {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 //