HH_DROYA
ID HH_DROYA Reviewed; 465 AA.
AC B4PN49;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Protein hedgehog {ECO:0000250|UniProtKB:Q02936};
DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q62226};
DE Contains:
DE RecName: Full=Protein hedgehog N-product {ECO:0000250|UniProtKB:Q02936};
DE Flags: Precursor;
GN Name=hh {ECO:0000250|UniProtKB:Q02936}; ORFNames=GE23980;
OS Drosophila yakuba (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7245;
RN [1] {ECO:0000312|EMBL:EDW98104.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tai18E2 / Tucson 14021-0261.01 {ECO:0000312|EMBL:EDW98104.1};
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: [Protein hedgehog]: The C-terminal part of the hedgehog
CC protein precursor displays an autoproteolysis activity that results in
CC the cleavage of the full-length protein into two parts (N-product and
CC C-product) (By similarity). In addition, the C-terminal part displays a
CC cholesterol transferase activity that results by the covalent
CC attachment of a cholesterol moiety to the C-terminal of the newly
CC generated N-product (By similarity). Once cleaved, the C-product has no
CC signaling activity and diffuses from the cell (By similarity).
CC {ECO:0000250|UniProtKB:Q02936, ECO:0000250|UniProtKB:Q62226}.
CC -!- FUNCTION: [Protein hedgehog N-product]: The dually lipidated hedgehog
CC protein N-product is a morphogen which is 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 functions in
CC association with smoothened (smo), to activate the transcription of
CC target genes wingless (wg), decapentaplegic (dpp) and ptc. In the
CC absence of hh, ptc represses the constitutive signaling activity of smo
CC through fused (fu). Essential component of a signaling pathway which
CC regulates the Duox-dependent gut immune response to bacterial uracil;
CC required to activate Cad99C-dependent endosome formation, norpA-
CC dependent Ca2+ mobilization and p38 MAPK, which are essential steps in
CC the Duox-dependent production of reactive oxygen species (ROS) in
CC response to intestinal bacterial infection. During photoreceptor
CC differentiation, it up-regulates transcription of Ubr3, which in turn
CC promotes the hh-signaling pathway by mediating the ubiquitination and
CC degradation of cos. {ECO:0000250|UniProtKB:Q02936}.
CC -!- CATALYTIC ACTIVITY: [Protein hedgehog]:
CC Reaction=cholesterol + glycyl-L-cysteinyl-[protein] + H(+) = [protein]-
CC C-terminal glycyl cholesterol ester + N-terminal L-cysteinyl-
CC [protein]; Xref=Rhea:RHEA:59504, Rhea:RHEA-COMP:12707, Rhea:RHEA-
CC COMP:15369, Rhea:RHEA-COMP:15374, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:65250, ChEBI:CHEBI:143135,
CC ChEBI:CHEBI:143140; Evidence={ECO:0000250|UniProtKB:Q62226};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59505;
CC Evidence={ECO:0000250|UniProtKB:Q62226};
CC -!- SUBUNIT: Interacts with shf. {ECO:0000250|UniProtKB:Q02936}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q02936}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q02936}. Note=Nuclear up to embryonic stage 10
CC and then at stage 11 shifts to the cytoplasm. Also secreted in either
CC cleaved or uncleaved form to mediate signaling to other cells.
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}. Note=The N-terminal peptide remains
CC associated with the cell surface. 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
CC lipidation. {ECO:0000250|UniProtKB:Q02936}.
CC -!- PTM: [Protein hedgehog]: The C-terminal part of the hedgehog protein
CC precursor displays an autoproteolysis activity that results in the
CC cleavage of the full-length protein into two parts (N-product and C-
CC product) (By similarity). In addition, the C-terminal part displays a
CC cholesterol transferase activity that results by the covalent
CC attachment of a cholesterol moiety to the C-terminal of the newly
CC generated N-product (By similarity). The N-product is the active
CC species in both local and long-range signaling, whereas the C-product
CC has no signaling activity (By similarity).
CC {ECO:0000250|UniProtKB:Q02936, ECO:0000250|UniProtKB:Q15465,
CC ECO:0000250|UniProtKB:Q62226}.
CC -!- PTM: [Protein hedgehog N-product]: Cholesterylation is required for N-
CC product targeting to lipid rafts and multimerization.
CC {ECO:0000250|UniProtKB:Q62226}.
CC -!- PTM: [Protein hedgehog N-product]: N-palmitoylation by Rasp of the
CC hedgehog N-product, within the secretory pathway, is required for the
CC embryonic and larval patterning activities of the hedgehog signal.
CC {ECO:0000250|UniProtKB:Q02936}.
CC -!- SIMILARITY: Belongs to the hedgehog family. {ECO:0000255}.
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DR EMBL; CM000160; EDW98104.1; -; Genomic_DNA.
DR RefSeq; XP_002098392.1; XM_002098356.2.
DR AlphaFoldDB; B4PN49; -.
DR BMRB; B4PN49; -.
DR SMR; B4PN49; -.
DR STRING; 7245.FBpp0268990; -.
DR MEROPS; C46.001; -.
DR EnsemblMetazoa; FBtr0270498; FBpp0268990; FBgn0241122.
DR GeneID; 6537851; -.
DR KEGG; dya:Dyak_GE23980; -.
DR eggNOG; KOG3638; Eukaryota.
DR HOGENOM; CLU_034686_0_0_1; -.
DR OMA; APAVRGC; -.
DR OrthoDB; 1169356at2759; -.
DR PhylomeDB; B4PN49; -.
DR Proteomes; UP000002282; Chromosome 3R.
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; Segmentation polarity protein;
KW Signal.
FT SIGNAL 1..?
FT /evidence="ECO:0000255"
FT PROPEP ?..78
FT /evidence="ECO:0000255"
FT /id="PRO_0000383090"
FT CHAIN 79..465
FT /note="Protein hedgehog"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT /id="PRO_0000383091"
FT CHAIN 79..251
FT /note="Protein hedgehog N-product"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT /id="PRO_0000383092"
FT BINDING 143
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 144
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 144
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 149
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 180
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 180
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 183
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 185
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="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; 51571 MW; 0EBE8B86FB16F8A7 CRC64;
MDNTSSVPWA SAASVTCLSL DAKCHSSSAK STASSISATP ESQTMRHIAH TQRCLSRLTS
LVALLLIVLP MNFSPAHSCG PGRGLGRHRA RNLYPLVLKQ TIPNLSEYTN SASGPLEGVI
RRDSPKFKDL VPNYNRDILF RDEEGTGADR LMSKRCREKL NLLAYSVMNE WPGIRLLVTE
SWDEDYHHGQ ESLHYEGRAV TIATSDRDQS KYGMLARLAV EAGFDWVSYV SRRHIYCSVK
SDSSISSHVH GCFTPESTAL LESGVRKPLG ELSIGDRVLS MTANGQAVYS EVILFMDRNL
EQMQNFVQLH TDGGAVLTVT PAHLISVWQP ESQKLTFVFA DRIEEKNQVL VRDSETGELR
PQRVIKVGSV RSKGVVAPLT REGTIVVNSV AASCYAVINS QSLAHWGLAP MRLLSTLEAW
LPAKEQLHSS PKVVSSAEQQ NGIHWYANAL YKVKDYVLPQ SWRHD
