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 29-SEP-2021, entry version 71. DE RecName: Full=Protein hedgehog {ECO:0000250|UniProtKB:Q02936}; DE Contains: DE RecName: Full=Protein hedgehog N-product {ECO:0000250|UniProtKB:Q02936}; DE Contains: DE RecName: Full=Protein hedgehog C-product {ECO:0000250|UniProtKB:Q02936}; DE Flags: Precursor; GN Name=hh {ECO:0000250|UniProtKB:Q02936}; ORFNames=GG12458; OS Drosophila erecta (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; OC Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7220; RN [1] {ECO:0000312|EMBL:EDV54047.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Tucson 14021-0224.01 {ECO:0000312|EMBL:EDV54047.1}; 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 patterning CC events during development. Establishes the anterior-posterior axis of CC the embryonic segments and patterns the larval imaginal disks. Binds to CC the patched (ptc) receptor, which functions in association with CC smoothened (smo), to activate the transcription of target genes CC wingless (wg), decapentaplegic (dpp) and ptc. In the absence of hh, ptc CC represses the constitutive signaling activity of smo through fused (fu) CC (By similarity). {ECO:0000250|UniProtKB:Q02936}. CC -!- FUNCTION: The hedgehog protein N-product constitutes the active species CC in both local and long-range signaling, whereas the C-terminal product CC has no signaling activity. It acts as a morphogen, and diffuses long CC distances despite its lipidation. Heparan sulfate proteoglycans of the CC extracellular matrix play an essential role in diffusion. Lipophorin is CC required for diffusion, probably by acting as vehicle for its movement, CC explaining how it can spread over long distances despite its lipidation CC (By similarity). {ECO:0000250|UniProtKB:Q02936}. CC -!- FUNCTION: The hedgehog protein C-product, which mediates the CC autocatalytic activity, has no signaling activity. CC {ECO:0000250|UniProtKB:Q02936}. CC -!- SUBUNIT: Interacts with shf. {ECO:0000250|UniProtKB:Q02936}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q02936}. Cytoplasm CC {ECO:0000250|UniProtKB:Q02936}. CC -!- SUBCELLULAR LOCATION: [Protein hedgehog N-product]: Cell membrane CC {ECO:0000250|UniProtKB:Q02936}; Lipid-anchor CC {ECO:0000250|UniProtKB:Q02936}; Extracellular side CC {ECO:0000250|UniProtKB:Q02936}. CC -!- SUBCELLULAR LOCATION: [Protein hedgehog C-product]: Secreted, CC extracellular space {ECO:0000250|UniProtKB:Q02936}. CC -!- PTM: The C-terminal domain displays autoproteolytic activity. Cleavage CC of the full-length hedgehog protein is followed by the covalent CC attachment of a cholesterol moiety to the C-terminus of the newly CC generated N-terminal fragment (N-product) (By similarity). CC {ECO:0000250}. CC -!- PTM: Cholesterol attachment plays an essential role in restricting the CC spatial distribution of hedgehog activity to the cell surface. CC {ECO:0000250}. CC -!- PTM: N-terminal palmitoylation of the hedgehog N-product is required CC for the embryonic and larval patterning activities of the hedgehog CC signal. Rasp acts within the secretory pathway to catalyze the N- CC terminal palmitoylation of Hh (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the hedgehog family. {ECO:0000255}. 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; XM_001982141.2. DR BMRB; B3P7F8; -. DR SMR; B3P7F8; -. DR STRING; 7220.FBpp0131004; -. DR MEROPS; C46.001; -. DR PRIDE; B3P7F8; -. DR EnsemblMetazoa; FBtr0132512; FBpp0131004; FBgn0104746. DR GeneID; 6554619; -. DR KEGG; der:6554619; -. DR eggNOG; KOG3638; Eukaryota. DR HOGENOM; CLU_034686_0_0_1; -. DR OMA; QTDGLHW; -. DR OrthoDB; 1169356at2759; -. DR PhylomeDB; B3P7F8; -. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0030139; C:endocytic vesicle; IEA:EnsemblMetazoa. DR GO; GO:0005768; C:endosome; IEA:EnsemblMetazoa. 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-SubCell. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0016015; F:morphogen activity; IEA:UniProtKB-KW. DR GO; GO:0005113; F:patched binding; IEA:EnsemblMetazoa. DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW. DR GO; GO:0001746; P:Bolwig's organ morphogenesis; IEA:EnsemblMetazoa. DR GO; GO:0045168; P:cell-cell signaling involved in cell fate commitment; ISS:UniProtKB. DR GO; GO:0035231; P:cytoneme assembly; IEA:EnsemblMetazoa. DR GO; GO:0007427; P:epithelial cell migration, open tracheal system; IEA:EnsemblMetazoa. DR GO; GO:0035224; P:genital disc anterior/posterior pattern formation; IEA:EnsemblMetazoa. DR GO; GO:0008347; P:glial cell migration; IEA:EnsemblMetazoa. DR GO; GO:0007506; P:gonadal mesoderm development; IEA:EnsemblMetazoa. DR GO; GO:0060914; P:heart formation; IEA:EnsemblMetazoa. DR GO; GO:0007442; P:hindgut morphogenesis; IEA:EnsemblMetazoa. DR GO; GO:0007476; P:imaginal disc-derived wing morphogenesis; IEA:EnsemblMetazoa. DR GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro. DR GO; GO:0035217; P:labial disc development; IEA:EnsemblMetazoa. DR GO; GO:0016335; P:morphogenesis of larval imaginal disc epithelium; IEA:EnsemblMetazoa. DR GO; GO:0002385; P:mucosal immune response; IEA:EnsemblMetazoa. DR GO; GO:0034111; P:negative regulation of homotypic cell-cell adhesion; IEA:EnsemblMetazoa. DR GO; GO:0045861; P:negative regulation of proteolysis; IEA:EnsemblMetazoa. DR GO; GO:0007280; P:pole cell migration; IEA:EnsemblMetazoa. DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:EnsemblMetazoa. DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IEA:EnsemblMetazoa. DR GO; GO:0007458; P:progression of morphogenetic furrow involved in compound eye morphogenesis; IEA:EnsemblMetazoa. DR GO; GO:0016540; P:protein autoprocessing; IEA:EnsemblMetazoa. DR GO; GO:2000495; P:regulation of cell proliferation involved in compound eye morphogenesis; IEA:EnsemblMetazoa. DR GO; GO:2000274; P:regulation of epithelial cell migration, open tracheal system; IEA:EnsemblMetazoa. DR GO; GO:0007346; P:regulation of mitotic cell cycle; IEA:EnsemblMetazoa. DR GO; GO:0007367; P:segment polarity determination; ISS:UniProtKB. DR GO; GO:0007224; P:smoothened signaling pathway; IEA:EnsemblMetazoa. DR GO; GO:0035277; P:spiracle morphogenesis, open tracheal system; IEA:EnsemblMetazoa. DR GO; GO:0035154; P:terminal cell fate specification, open tracheal system; IEA:EnsemblMetazoa. DR GO; GO:0007418; P:ventral midline development; IEA:EnsemblMetazoa. DR GO; GO:0035222; P:wing disc pattern formation; IEA:EnsemblMetazoa. 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 3: Inferred from homology; KW Autocatalytic cleavage; Calcium; Cell membrane; Cytoplasm; KW Developmental protein; Hydrolase; Lipoprotein; Membrane; Metal-binding; KW Morphogen; Nucleus; Palmitate; Protease; Secreted; KW Segmentation polarity protein; Signal. FT SIGNAL 1..? FT /evidence="ECO:0000255" FT PROPEP ?..78 FT /evidence="ECO:0000255" FT /id="PRO_0000383054" FT CHAIN 79..465 FT /note="Protein hedgehog" FT /evidence="ECO:0000250|UniProtKB:Q02936" FT /id="PRO_0000383055" FT CHAIN 79..251 FT /note="Protein hedgehog N-product" FT /evidence="ECO:0000250|UniProtKB:Q02936" FT /id="PRO_0000383056" FT CHAIN 252..465 FT /note="Protein hedgehog C-product" FT /evidence="ECO:0000250|UniProtKB:Q02936" FT /id="PRO_0000383057" FT METAL 143 FT /note="Calcium 1" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 144 FT /note="Calcium 1" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 144 FT /note="Calcium 2" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 149 FT /note="Calcium 1" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 179 FT /note="Calcium 1; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 180 FT /note="Calcium 1" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 180 FT /note="Calcium 2" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 183 FT /note="Calcium 2" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT METAL 185 FT /note="Calcium 2" FT /evidence="ECO:0000250|UniProtKB:Q15465" FT SITE 251..252 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000250|UniProtKB:Q02936" FT SITE 297 FT /note="Involved in cholesterol transfer" FT /evidence="ECO:0000250|UniProtKB:Q02936" FT SITE 320 FT /note="Involved in auto-cleavage" FT /evidence="ECO:0000250|UniProtKB:Q02936" FT SITE 323 FT /note="Essential for auto-cleavage" FT /evidence="ECO:0000250|UniProtKB:Q02936" FT LIPID 79 FT /note="N-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:Q02936" FT LIPID 251 FT /note="Cholesterol glycine ester" FT /evidence="ECO:0000250|UniProtKB:Q02936" 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 //