Detail Information for IndEnz0002006392
IED ID IndEnz0002006392
Enzyme Type ID protease006392
Protein Name Protein hedgehog
Cleaved into: Protein hedgehog N-product
Hh-Np
N-Hh
; Protein hedgehog C-product
Hh-Cp
C-Hh
Gene Name hh CG4637
Organism Drosophila melanogaster (Fruit fly)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Protostomia Ecdysozoa Panarthropoda Arthropoda Mandibulata Pancrustacea Hexapoda Insecta Dicondylia Pterygota (winged insects) Neoptera Endopterygota Diptera Brachycera Muscomorpha Eremoneura Cyclorrhapha Schizophora Acalyptratae Ephydroidea Drosophilidae (pomace flies) Drosophilinae Drosophilini Drosophila (fruit flies) Sophophora melanogaster group melanogaster subgroup Drosophila melanogaster (Fruit fly)
Enzyme Sequence MDNHSSVPWASAASVTCLSLDAKCHSSSSSSSSKSAASSISAIPQEETQTMRHIAHTQRCLSRLTSLVALLLIVLPMVFSPAHSCGPGRGLGRHRARNLYPLVLKQTIPNLSEYTNSASGPLEGVIRRDSPKFKDLVPNYNRDILFRDEEGTGADRLMSKRCKEKLNVLAYSVMNEWPGIRLLVTESWDEDYHHGQESLHYEGRAVTIATSDRDQSKYGMLARLAVEAGFDWVSYVSRRHIYCSVKSDSSISSHVHGCFTPESTALLESGVRKPLGELSIGDRVLSMTANGQAVYSEVILFMDRNLEQMQNFVQLHTDGGAVLTVTPAHLVSVWQPESQKLTFVFADRIEEKNQVLVRDVETGELRPQRVVKVGSVRSKGVVAPLTREGTIVVNSVAASCYAVINSQSLAHWGLAPMRLLSTLEAWLPAKEQLHSSPKVVSSAQQQNGIHWYANALYKVKDYVLPQSWRHD
Enzyme Length 471
Uniprot Accession Number Q02936
Absorption
Active Site
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity
DNA Binding
EC Number
Enzyme Function FUNCTION: Intercellular signal essential for a variety of patterning events during development. Establishes the anterior-posterior axis of the embryonic segments and patterns the larval imaginal disks. Binds to the patched (ptc) receptor, which functions in association with smoothened (smo), to activate the transcription of target genes wingless (wg), decapentaplegic (dpp) and ptc. In the absence of hh, ptc represses the constitutive signaling activity of smo through fused (fu). Essential component of a signaling pathway which regulates the Duox-dependent gut immune response to bacterial uracil; required to activate Cad99C-dependent endosome formation, norpA-dependent Ca2+ mobilization and p38 MAPK, which are essential steps in the Duox-dependent production of reactive oxygen species (ROS) in response to intestinal bacterial infection (PubMed:25639794). During photoreceptor differentiation, it up-regulates transcription of Ubr3, which in turn promotes the hh-signaling pathway by mediating the ubiquitination and degradation of cos (PubMed:27195754). {ECO:0000269|PubMed:25639794, ECO:0000269|PubMed:27195754}.; FUNCTION: The hedgehog protein N-product constitutes the active species in both local and long-range signaling, whereas the C-terminal product has no signaling activity. It acts as a morphogen, and diffuses long distances despite its lipidation. Heparan sulfate proteoglycans of the extracellular matrix play an essential role in diffusion. Lipophorin is required for diffusion, probably by acting as vehicle for its movement, explaining how it can spread over long distances despite its lipidation.; FUNCTION: The hedgehog protein C-product, which mediates the autocatalytic activity, has no signaling activity.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Alternative sequence (2); Beta strand (16); Chain (3); Frameshift (1); Helix (6); Lipidation (2); Metal binding (9); Mutagenesis (4); Propeptide (1); Sequence conflict (4); Signal peptide (1); Site (4); Turn (4)
Keywords 3D-structure;Alternative splicing;Autocatalytic cleavage;Calcium;Cell membrane;Cytoplasm;Developmental protein;Hydrolase;Lipoprotein;Membrane;Metal-binding;Morphogen;Nucleus;Palmitate;Protease;Reference proteome;Secreted;Segmentation polarity protein;Signal
Interact With Q9VM64
Induction INDUCTION: Strongly up-regulated in the anterior midgut and the posterior midgut in response to bacterial uracil. {ECO:0000269|PubMed:25639794}.
Subcellular Location SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:1280560}. Cytoplasm {ECO:0000269|PubMed:1280560}. Note=Nuclear up to embryonic stage 10 and then at stage 11 shifts to the cytoplasm (PubMed:1280560). Also secreted in either cleaved or uncleaved form to mediate signaling to other cells (PubMed:1280560).; SUBCELLULAR LOCATION: [Protein hedgehog N-product]: Cell membrane {ECO:0000269|PubMed:12586063}; Lipid-anchor {ECO:0000269|PubMed:12586063}. Note=The N-terminal peptide remains associated with the cell surface (PubMed:12586063).; SUBCELLULAR LOCATION: [Protein hedgehog C-product]: Secreted, extracellular space {ECO:0000269|PubMed:12586063}. Note=The C-terminal peptide diffuses from the cell (PubMed:12586063).
Modified Residue
Post Translational Modification PTM: The C-terminal domain displays autoproteolytic activity. Cleavage of the full-length hedgehog protein is followed by the covalent attachment of a cholesterol moiety to the C-terminus of the newly generated N-terminal fragment (N-product).; PTM: Cholesterol attachment plays an essential role in restricting the spatial distribution of hedgehog activity to the cell surface.; PTM: N-terminal palmitoylation of the hedgehog N-product is required for the embryonic and larval patterning activities of the hedgehog signal. Rasp acts within the secretory pathway to catalyze the N-terminal palmitoylation of Hh. {ECO:0000269|PubMed:11486055}.
Signal Peptide SIGNAL 1..?; /evidence=ECO:0000255
Structure 3D Electron microscopy (1); X-ray crystallography (3)
Cross Reference PDB 1AT0; 2IBG; 6TD6; 6TYY;
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9053304; 9053330; 9056782; 9073437; 9092934; 9093849; 9093856; 9102309; 9121545; 9122207; 9139817; 9142491; 9161005; 9162485; 9165116; 9187141; 9215627; 9216058; 9223224; 9230308; 9230686; 9244291; 9244297; 9244298; 9256342; 9262397; 9264250; 9264255; 9272947; 9278137; 9292971; 9297966; 9303540; 9310318; 9310327; 9323126; 9326622; 9335503; 9338771; 9342040; 9342049; 9354777; 9354780; 9362458; 9367426; 9367427; 9374407; 9382827; 9385834; 9389656; 9392510; 9407023; 9409685; 9425353; 9428415; 9428507; 9431812; 9435287; 9435291; 9441692; 9442904; 9449459; 9463351; 9475999; 9489693; 9502727; 9504904; 9520436; 9529599; 9529611; 9533124; 9540409; 9545199; 9551858; 9565034; 9598333; 9598351; 9598352; 9598353; 9598354; 9601642; 9604939; 9619099; 9630745; 9635422; 9636080; 9649421; 9654009; 9654013; 9654015; 9654017; 9654019; 9654021; 9654036; 9654037; 9654040; 9655800; 9665119; 9665133; 9671305; 9671692; 9676197; 9693144; 9694625; 9695953; 9716535; 9716539; 9729484; 9729719; 9729722; 9729726; 9732270; 9733572; 9753669; 9753679; 9799432; 9799743; 9811578; 9813190; 9819565; 9825673; 9832527; 9835652; 9845360; 9845371; 9851920; 9852758; 9858670; 9862465; 9874371; 9876186; 9883719; 9887103; 9892553; 9914180; 9914181; 9927465; 9988216;
Motif
Gene Encoded By
Mass 52,150
Kinetics
Metal Binding METAL 149; /note=Calcium 1; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 150; /note=Calcium 1; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 150; /note=Calcium 2; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 155; /note=Calcium 1; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 185; /note=Calcium 1; via carbonyl oxygen; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 186; /note=Calcium 1; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 186; /note=Calcium 2; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 189; /note=Calcium 2; /evidence=ECO:0000250|UniProtKB:Q15465; METAL 191; /note=Calcium 2; /evidence=ECO:0000250|UniProtKB:Q15465
Rhea ID
Cross Reference Brenda