ID SHH_CYNPY STANDARD; PRT; 432 AA. AC Q90385; DT 15-JUL-1999 (Rel. 38, Created) DT 15-JUL-1999 (Rel. 38, Last sequence update) DT 15-JUL-1999 (Rel. 38, Last annotation update) DE SONIC HEDGEHOG PROTEIN PRECURSOR (SHH). GN SHH. OS Cynops pyrrhogaster (Japanese common newt). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Amphibia; OC Batrachia; Caudata; Salamandroidea; Salamandridae; Cynops. RN [1] RP SEQUENCE FROM N.A. RC TISSUE=EMBRYO; RX MEDLINE; 96136334. 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). CC -!- SUBCELLULAR LOCATION: THE C-TERMINAL PEPTIDE DIFFUSES FROM THE CC CELL, WHILE THE N-TERMINAL PEPTIDE REMAINS ASSOCIATED WITH THE CC CELL SURFACE. IS ALSO SECRETED IN EITHER CLEAVED OR UNCLEAVED FORM CC TO MEDIATE SIGNALING TO OTHER CELLS (BY SIMILARITY). CC -!- INDUCTION: ACTIVATED BY ACTIVIN, BASIC FIBROBLAST GROWTH FACTOR CC (BFGF) AND FORK HEAD. 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). THIS COVALENT MODIFICATION APPEARS CC TO PLAY AN ESSENTIAL ROLE IN RESTRICTING THE SPATIAL DISTRIBUTION CC OF THE PROTEIN ACTIVITY TO THE CELL SURFACE. THE N-PRODUCT IS THE CC ACTIVE SPECIES IN BOTH LOCAL AND LONG-RANGE SIGNALING, WHEREAS THE CC C-PRODUCT HAS NO SIGNALING ACTIVITY (BY SIMILARITY). CC -!- SIMILARITY: BELONGS TO THE HEDGEHOG FAMILY. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- 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; -. DR PFAM; PF01079; Hint; 1. DR PFAM; PF01085; HH_signal; 1. KW Developmental protein; Autocatalytic cleavage; Hydrolase; Protease; KW Signal. FT SIGNAL 1 26 POTENTIAL. FT CHAIN 27 432 SONIC HEDGEHOG PROTEIN. FT CHAIN 27 200 SONIC HEDGEHOG PROTEIN N-PRODUCT. FT CHAIN 201 432 SONIC HEDGEHOG PROTEIN C-PRODUCT. FT SITE 200 201 CLEAVAGE (AUTO-) (BY SIMILARITY). FT SITE 268 268 INVOLVED IN AUTO-CLEAVAGE (BY FT SIMILARITY). FT ACT_SITE 271 271 ESSENTIAL FOR AUTO-CLEAVAGE (BY FT SIMILARITY). FT BINDING 200 200 CHOLESTEROL (BY SIMILARITY). SQ SEQUENCE 432 AA; 47847 MW; 6FA354C3 CRC32; 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 //