ID HH_DROER Reviewed; 465 AA. AC B3P7F8; DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot. DT 02-SEP-2008, sequence version 1. DT 19-JAN-2010, entry version 11. DE RecName: Full=Protein hedgehog; DE Contains: DE RecName: Full=Protein hedgehog N-product; DE Contains: DE RecName: Full=Protein hedgehog C-product; DE Flags: Precursor; GN Name=hh; ORFNames=GG12458; OS Drosophila erecta (Fruit fly). OC Eukaryota; Metazoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7220; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Tucson 14021-0224.01; RX PubMed=17994087; DOI=10.1038/nature06341; RG Drosophila 12 genomes consortium; RT "Evolution of genes and genomes on the Drosophila phylogeny."; RL Nature 450:203-218(2007). CC -!- FUNCTION: Intercellular signal essential for a variety of CC patterning events during development. Establishes the anterior- CC posterior axis of the embryonic segments and patterns the larval CC imaginal disks. Binds to the patched (ptc) receptor, which CC functions in association with smoothened (smo), to activate the CC transcription of target genes wingless (wg), decapentaplegic (dpp) CC and ptc. In the absence of hh, ptc represses the constitutive CC signaling activity of smo through fused (fu) (By similarity). CC -!- FUNCTION: The hedgehog protein N-product constitutes the active CC species in both local and long-range signaling, whereas the C- CC terminal product has no signaling activity. It acts as a CC morphogen, and diffuses long distances despite its lipidation. CC Heparan sulfate proteoglycans of the extracellular matrix play an CC essential role in diffusion. Lipophorin is required for diffusion, CC probably by acting as vehicle for its movement, explaining how it CC can spread over long distances despite its lipidation (By CC similarity). CC -!- FUNCTION: The hedgehog protein C-product, which mediates the CC autocatalytic activity, has no signaling activity (By similarity). CC -!- SUBUNIT: Interacts with shf (By similarity). CC -!- SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasm (By CC similarity). CC -!- SUBCELLULAR LOCATION: Protein hedgehog N-product: Cell membrane; CC Lipid-anchor; Extracellular side (By similarity). CC -!- SUBCELLULAR LOCATION: Protein hedgehog C-product: Secreted, CC extracellular space (By similarity). CC -!- PTM: The C-terminal domain displays autoproteolytic activity. CC Cleavage of the full-length hedgehog protein is followed by the CC covalent attachment of a cholesterol moiety to the C-terminus of CC the newly generated N-terminal fragment (N-product) (By CC similarity). CC -!- PTM: Cholesterol attachment plays an essential role in restricting CC the spatial distribution of hedgehog activity to the cell surface CC (By similarity). CC -!- PTM: N-terminal palmitoylation of the hedgehog N-product is CC required for the embryonic and larval patterning activities of the CC hedgehog signal. Rasp acts within the secretory pathway to CC catalyze the N-terminal palmitoylation of Hh (By similarity). CC -!- SIMILARITY: Belongs to the hedgehog family. 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; CH954182; EDV54047.1; -; Genomic_DNA. DR RefSeq; XP_001982177.1; -. DR GeneID; 6554619; -. DR KEGG; der:Dere_GG12458; -. DR FlyBase; FBgn0104746; Dere\GG12458. DR OrthoDB; EOG9HT902; -. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-KW. DR GO; GO:0016015; F:morphogen activity; IEA:UniProtKB-KW. DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW. DR GO; GO:0009653; P:anatomical structure morphogenesis; IEA:UniProtKB-KW. DR GO; GO:0045168; P:cell-cell signaling involved in cell fate s...; ISS:UniProtKB. DR GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro. DR GO; GO:0006508; P:proteolysis; IEA:InterPro. DR GO; GO:0007367; P:segment polarity determination; ISS:UniProtKB. DR InterPro; IPR009045; Hedgehog/DD-pept_Zn-bd. DR InterPro; IPR003586; Hedgehog_hint_C. DR InterPro; IPR003587; Hedgehog_hint_N. DR InterPro; IPR000320; Hedgehog_signaling_dom. DR InterPro; IPR006141; Intein_splicing_site. DR InterPro; IPR001657; Peptidase_C46. DR InterPro; IPR001767; Peptidase_C46_hint. 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 PROSITE; PS50817; INTEIN_N_TER; 1. PE 3: Inferred from homology; KW Autocatalytic cleavage; Cell membrane; Cytoplasm; KW Developmental protein; Hydrolase; Lipoprotein; Membrane; Morphogen; KW Nucleus; Palmitate; Protease; Secreted; Segmentation polarity protein; KW Signal. FT SIGNAL 1 ? Potential. FT PROPEP ? 78 Potential. FT /FTId=PRO_0000383054. FT CHAIN 79 465 Protein hedgehog. FT /FTId=PRO_0000383055. FT CHAIN 79 251 Protein hedgehog N-product. FT /FTId=PRO_0000383056. FT CHAIN 252 465 Protein hedgehog C-product. FT /FTId=PRO_0000383057. FT SITE 251 252 Cleavage; by autolysis (By similarity). FT SITE 297 297 Involved in cholesterol transfer (By FT similarity). FT SITE 320 320 Involved in auto-cleavage (By FT similarity). FT SITE 323 323 Essential for auto-cleavage (By FT similarity). FT LIPID 79 79 N-palmitoyl cysteine (By similarity). FT LIPID 251 251 Cholesterol glycine ester (By FT similarity). SQ SEQUENCE 465 AA; 51569 MW; DE0AEEFA4E52362D CRC64; MDNTSSVPWA SAASVTCLSL DAKCHSSSAK SAASSISASP ETQAMRHIAH TQRCLSRLTS LVALLLIVLP MTFSPAHSCG PGRGLGRHRA RNLYPLVLKQ TIPNLSEYTN SASGPLEGVI RRDSPKFKDL VPNYNRDILF RDEEGTGADR LMSKRCREKL NLLAYSVMNE WPGIRLLVTE SWDEDYHHGQ ESLHYEGRAV TIATSDRDQS KYGMLARLAV EAGFDWVSYV SRRHIYCSVK SDSSISSHVH GCFTPESTAL LENGVRKPLG ELSIGDRVLS MTANGQAVYS EVILFMDRNL EQMQNFVQLH TDGEAVLTVT PAHLVSVWQA ESQKLTFVFA DRVEEKNQVL VRDVETGELR PQRVVKVGSV RSKGVVAPLT REGTIVVNSV AASCYAVINS QSLAHWGLAP MRLLSTLEAW LPAKEQLHSS PKVVTTAEQQ NGIHWYANAL YKVKDYVLPQ SWRHD //