HH_DROME
ID HH_DROME Reviewed; 471 AA.
AC Q02936; A4V396; Q9VCQ4;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 4.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Protein hedgehog {ECO:0000305};
DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q62226};
DE Contains:
DE RecName: Full=Protein hedgehog N-product;
DE Short=Hh-Np;
DE Short=N-Hh;
DE Flags: Precursor;
GN Name=hh {ECO:0000312|FlyBase:FBgn0004644};
GN ORFNames=CG4637 {ECO:0000312|FlyBase:FBgn0004644};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM LONG), FUNCTION,
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RC STRAIN=Canton-S; TISSUE=Embryo;
RX PubMed=8166882; DOI=10.1016/0378-1119(93)90392-g;
RA Tashiro S., Michiue T., Higashijima S., Zenno S., Ishimaru S.,
RA Takahashi F., Orihara M., Kojima T., Saigo K.;
RT "Structure and expression of hedgehog, a Drosophila segment-polarity gene
RT required for cell-cell communication.";
RL Gene 124:183-189(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DEVELOPMENTAL STAGE, AND
RP TISSUE SPECIFICITY.
RX PubMed=1394430; DOI=10.1016/0092-8674(92)90264-d;
RA Lee J.J., von Kessler D.P., Parks S., Beachy P.A.;
RT "Secretion and localized transcription suggest a role in positional
RT signaling for products of the segmentation gene hedgehog.";
RL Cell 71:33-50(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, SUBCELLULAR
RP LOCATION, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RC STRAIN=Oregon-R; TISSUE=Embryo;
RX PubMed=1280560; DOI=10.1242/dev.115.4.957;
RA Mohler J., Vani K.;
RT "Molecular organization and embryonic expression of the hedgehog gene
RT involved in cell-cell communication in segmental patterning of
RT Drosophila.";
RL Development 115:957-971(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), FUNCTION, DEVELOPMENTAL STAGE,
RP AND TISSUE SPECIFICITY.
RC STRAIN=Oregon-R; TISSUE=Embryo;
RX PubMed=1340474; DOI=10.1101/gad.6.12b.2635;
RA Tabata T., Eaton S., Kornberg T.B.;
RT "The Drosophila hedgehog gene is expressed specifically in posterior
RT compartment cells and is a target of engrailed regulation.";
RL Genes Dev. 6:2635-2645(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [6]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [7]
RP AUTOCATALYTIC CLEAVAGE, AND PROTEOLYTIC PROCESSING.
RX PubMed=7885476; DOI=10.1038/374363a0;
RA Porter J.A., von Kessler D.P., Ekker S.C., Young K.E., Lee J.J., Moses K.,
RA Beachy P.A.;
RT "The product of hedgehog autoproteolytic cleavage active in local and long-
RT range signalling.";
RL Nature 374:363-366(1995).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF CYS-85.
RX PubMed=11319862; DOI=10.1006/dbio.2001.0218;
RA Lee J.D., Kraus P., Gaiano N., Nery S., Kohtz J., Fishell G., Loomis C.A.,
RA Treisman J.E.;
RT "An acylatable residue of Hedgehog is differentially required in Drosophila
RT and mouse limb development.";
RL Dev. Biol. 233:122-136(2001).
RN [9]
RP PALMITOYLATION AT CYS-85, CHOLESTERYLATION AT GLY-257, MUTAGENESIS OF
RP CYS-85, AND MASS SPECTROMETRY.
RX PubMed=11486055; DOI=10.1126/science.1064437;
RA Chamoun Z., Mann R.K., Nellen D., von Kessler D.P., Bellotto M.,
RA Beachy P.A., Basler K.;
RT "Skinny hedgehog, an acyltransferase required for palmitoylation and
RT activity of the hedgehog signal.";
RL Science 293:2080-2084(2001).
RN [10]
RP ROLE OF CHOLESTEROL, AND SUBCELLULAR LOCATION.
RX PubMed=12586063; DOI=10.1016/s1534-5807(03)00031-5;
RA Gallet A., Rodriguez R., Ruel L., Therond P.P.;
RT "Cholesterol modification of hedgehog is required for trafficking and
RT movement, revealing an asymmetric cellular response to hedgehog.";
RL Dev. Cell 4:191-204(2003).
RN [11]
RP INTERACTION WITH SHF.
RX PubMed=15691765; DOI=10.1016/j.devcel.2004.12.018;
RA Gorfinkiel N., Sierra J., Callejo A., Ibanez C., Guerrero I.;
RT "The Drosophila ortholog of the human wnt inhibitor factor shifted controls
RT the diffusion of lipid-modified hedgehog.";
RL Dev. Cell 8:241-253(2005).
RN [12]
RP ROLE OF LIPOPHORIN IN MOVEMENT.
RX PubMed=15875013; DOI=10.1038/nature03504;
RA Panakova D., Sprong H., Marois E., Thiele C., Eaton S.;
RT "Lipoprotein particles are required for Hedgehog and Wingless signalling.";
RL Nature 435:58-65(2005).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION BY BACTERIAL URACIL, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=25639794; DOI=10.1016/j.chom.2014.12.012;
RA Lee K.A., Kim B., Bhin J., Kim D.H., You H., Kim E.K., Kim S.H., Ryu J.H.,
RA Hwang D., Lee W.J.;
RT "Bacterial uracil modulates Drosophila DUOX-dependent gut immunity via
RT Hedgehog-induced signaling endosomes.";
RL Cell Host Microbe 17:191-204(2015).
RN [14]
RP FUNCTION.
RX PubMed=27195754; DOI=10.1371/journal.pgen.1006054;
RA Li T., Fan J., Blanco-Sanchez B., Giagtzoglou N., Lin G., Yamamoto S.,
RA Jaiswal M., Chen K., Zhang J., Wei W., Lewis M.T., Groves A.K.,
RA Westerfield M., Jia J., Bellen H.J.;
RT "Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-
RT 2 and Kif7 through Poly-ubiquitination.";
RL PLoS Genet. 12:E1006054-E1006054(2016).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 258-402, AND MUTAGENESIS OF
RP ASP-303; THR-326 AND HIS-329.
RX PubMed=9335337; DOI=10.1016/s0092-8674(01)80011-8;
RA Hall T.M.T., Porter J.A., Young K.E., Koonin E.V., Beachy P.A., Leahy D.J.;
RT "Crystal structure of a Hedgehog autoprocessing domain: homology between
RT Hedgehog and self-splicing proteins.";
RL Cell 91:85-97(1997).
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) (PubMed:7885476). In addition, the C-terminal part displays
CC a 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 (PubMed:12586063).
CC {ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:12586063,
CC ECO:0000269|PubMed:7885476}.
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 (PubMed:25639794, PubMed:27195754,
CC PubMed:8166882, PubMed:1394430, PubMed:1340474, PubMed:11319862).
CC Establishes the anterior-posterior axis of the embryonic segments and
CC patterns the larval imaginal disks. Binds to the patched (ptc)
CC receptor, which functions in association with smoothened (smo), to
CC activate the transcription of target genes wingless (wg),
CC decapentaplegic (dpp) and ptc. In the absence of hh, ptc represses the
CC constitutive signaling activity of smo through fused (fu). Essential
CC component of a signaling pathway which regulates the Duox-dependent gut
CC immune response to bacterial uracil; required to activate Cad99C-
CC dependent endosome formation, norpA-dependent Ca2+ mobilization and p38
CC MAPK, which are essential steps in the Duox-dependent production of
CC reactive oxygen species (ROS) in response to intestinal bacterial
CC infection (PubMed:25639794). During photoreceptor differentiation, it
CC up-regulates transcription of Ubr3, which in turn promotes the hh-
CC signaling pathway by mediating the ubiquitination and degradation of
CC cos (PubMed:27195754, PubMed:25639794, PubMed:8166882, PubMed:1394430,
CC PubMed:1340474, PubMed:11319862). {ECO:0000269|PubMed:11319862,
CC ECO:0000269|PubMed:1340474, ECO:0000269|PubMed:1394430,
CC ECO:0000269|PubMed:25639794, ECO:0000269|PubMed:27195754,
CC ECO:0000269|PubMed:8166882}.
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:0000269|PubMed:15691765}.
CC -!- INTERACTION:
CC Q02936-1; Q9VM64: ihog; NbExp=6; IntAct=EBI-15609026, EBI-94134;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:1280560}. Cytoplasm
CC {ECO:0000269|PubMed:1280560}. Note=Nuclear up to embryonic stage 10 and
CC then at stage 11 shifts to the cytoplasm (PubMed:1280560). Also
CC secreted in either cleaved or uncleaved form to mediate signaling to
CC other cells (PubMed:1280560).
CC -!- SUBCELLULAR LOCATION: [Protein hedgehog N-product]: Cell membrane
CC {ECO:0000269|PubMed:12586063}; Lipid-anchor
CC {ECO:0000269|PubMed:12586063}. Note=The N-terminal peptide remains
CC associated with the cell surface (PubMed:12586063). Heparan sulfate
CC proteoglycans of the extracellular matrix play an essential role in
CC diffusion. Lipophorin is required for diffusion, probably by acting as
CC vehicle for its movement, explaining how it can spread over long
CC distances despite its lipidation (PubMed:15875013).
CC {ECO:0000269|PubMed:15875013}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long; Synonyms=A, B;
CC IsoId=Q02936-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q02936-2; Sequence=VSP_002065, VSP_002066;
CC -!- TISSUE SPECIFICITY: In embryos, expression starts at stage 5 as a few
CC stripes at the anterior and posterior ends, this expands to 17 stripes
CC during stages 8-11 (PubMed:8166882, PubMed:1280560, PubMed:1340474).
CC Expression is also seen in CNS and some PNS cells until stage 13-14,
CC and in foregut, hindgut and salivary glands (PubMed:1340474). In
CC larvae, expression is seen in the posterior compartment of the wing,
CC leg and antennal imaginal disks (PubMed:1394430, PubMed:1340474). In
CC adults, high level of expression in specific regions of the
CC proventriculus and hindgut, with slightly lower levels of expression in
CC the posterior midgut (PubMed:25639794). Relatively low levels of
CC expression in the anterior midgut region (PubMed:25639794).
CC {ECO:0000269|PubMed:1280560, ECO:0000269|PubMed:1340474,
CC ECO:0000269|PubMed:1394430, ECO:0000269|PubMed:25639794,
CC ECO:0000269|PubMed:8166882}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos, larvae and pupae at high
CC levels with maximum expression in 6-12 hours embryos and 0-24 hours
CC pupae (PubMed:8166882, PubMed:1394430, PubMed:1280560, PubMed:1340474).
CC Low levels of expression are seen in adults (PubMed:8166882,
CC PubMed:1394430). {ECO:0000269|PubMed:1280560,
CC ECO:0000269|PubMed:1340474, ECO:0000269|PubMed:1394430,
CC ECO:0000269|PubMed:8166882}.
CC -!- INDUCTION: Strongly up-regulated in the anterior midgut and the
CC posterior midgut in response to bacterial uracil.
CC {ECO:0000269|PubMed:25639794}.
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) (PubMed:7885476). 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:Q15465, ECO:0000250|UniProtKB:Q62226,
CC ECO:0000269|PubMed:7885476}.
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:0000269|PubMed:11486055}.
CC -!- MASS SPECTROMETRY: [Protein hedgehog N-product]: Mass=20238.44;
CC Method=MALDI; Evidence={ECO:0000269|PubMed:11486055};
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown severely reduces adult
CC survival following the ingestion of E.carotovora. Abolishes Cad99C-
CC dependent formation of endosomes and DUOX-dependent up-regulation of
CC reactive oxygen species (ROS) in the intestines of adults fed bacteria-
CC derived uracil. {ECO:0000269|PubMed:25639794}.
CC -!- SIMILARITY: Belongs to the hedgehog family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA28604.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L05404; AAA28604.1; ALT_FRAME; mRNA.
DR EMBL; L05405; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L02793; AAA16458.1; -; Unassigned_DNA.
DR EMBL; Z11840; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; S66384; AAB28646.1; -; mRNA.
DR EMBL; AE014297; AAF56102.1; -; Genomic_DNA.
DR EMBL; AE014297; ABC66186.1; -; Genomic_DNA.
DR PIR; A46400; A46400.
DR RefSeq; NP_001034065.1; NM_001038976.1. [Q02936-1]
DR PDB; 1AT0; X-ray; 1.90 A; A=258-402.
DR PDB; 2IBG; X-ray; 2.20 A; E/F/G/H=99-248.
DR PDB; 6TD6; EM; 4.76 A; B=1-471.
DR PDB; 6TYY; X-ray; 1.36 A; A=258-403.
DR PDBsum; 1AT0; -.
DR PDBsum; 2IBG; -.
DR PDBsum; 6TD6; -.
DR PDBsum; 6TYY; -.
DR AlphaFoldDB; Q02936; -.
DR BMRB; Q02936; -.
DR SMR; Q02936; -.
DR BioGRID; 67682; 79.
DR DIP; DIP-51313N; -.
DR IntAct; Q02936; 2.
DR STRING; 7227.FBpp0099945; -.
DR MEROPS; C46.001; -.
DR PaxDb; Q02936; -.
DR PRIDE; Q02936; -.
DR EnsemblMetazoa; FBtr0100506; FBpp0099945; FBgn0004644. [Q02936-1]
DR GeneID; 42737; -.
DR KEGG; dme:Dmel_CG4637; -.
DR UCSC; CG4637-RA; d. melanogaster. [Q02936-1]
DR UCSC; CG4637-RB; d. melanogaster.
DR CTD; 42737; -.
DR FlyBase; FBgn0004644; hh.
DR VEuPathDB; VectorBase:FBgn0004644; -.
DR eggNOG; KOG3638; Eukaryota.
DR GeneTree; ENSGT00940000161132; -.
DR HOGENOM; CLU_034686_0_0_1; -.
DR InParanoid; Q02936; -.
DR OMA; CGPGPRY; -.
DR PhylomeDB; Q02936; -.
DR Reactome; R-DME-209338; Assembly of the 'signalling complexes'.
DR Reactome; R-DME-209471; Formation and transport of the N-HH ligand.
DR Reactome; R-DME-5358346; Hedgehog ligand biogenesis.
DR Reactome; R-DME-5362798; Release of Hh-Np from the secreting cell.
DR SignaLink; Q02936; -.
DR BioGRID-ORCS; 42737; 0 hits in 3 CRISPR screens.
DR EvolutionaryTrace; Q02936; -.
DR GenomeRNAi; 42737; -.
DR PRO; PR:Q02936; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0004644; Expressed in endoderm anlage (Drosophila) and 48 other tissues.
DR Genevisible; Q02936; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030139; C:endocytic vesicle; IDA:FlyBase.
DR GO; GO:0005768; C:endosome; IDA:FlyBase.
DR GO; GO:0005576; C:extracellular region; IDA:FlyBase.
DR GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0016015; F:morphogen activity; IDA:FlyBase.
DR GO; GO:0005113; F:patched binding; IPI:FlyBase.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0007487; P:analia development; TAS:FlyBase.
DR GO; GO:0035288; P:anterior head segmentation; TAS:FlyBase.
DR GO; GO:0048099; P:anterior/posterior lineage restriction, imaginal disc; TAS:FlyBase.
DR GO; GO:0001746; P:Bolwig's organ morphogenesis; IMP:FlyBase.
DR GO; GO:0001708; P:cell fate specification; IBA:GO_Central.
DR GO; GO:0045168; P:cell-cell signaling involved in cell fate commitment; IMP:UniProtKB.
DR GO; GO:0007386; P:compartment pattern specification; TAS:FlyBase.
DR GO; GO:0001745; P:compound eye morphogenesis; IMP:FlyBase.
DR GO; GO:0001751; P:compound eye photoreceptor cell differentiation; TAS:FlyBase.
DR GO; GO:0035231; P:cytoneme assembly; IMP:FlyBase.
DR GO; GO:0048066; P:developmental pigmentation; TAS:FlyBase.
DR GO; GO:0009880; P:embryonic pattern specification; IEP:UniProtKB.
DR GO; GO:0008544; P:epidermis development; TAS:FlyBase.
DR GO; GO:0007427; P:epithelial cell migration, open tracheal system; IMP:FlyBase.
DR GO; GO:0007440; P:foregut morphogenesis; TAS:FlyBase.
DR GO; GO:0035224; P:genital disc anterior/posterior pattern formation; IEP:FlyBase.
DR GO; GO:0035215; P:genital disc development; IMP:FlyBase.
DR GO; GO:0035232; P:germ cell attraction; TAS:FlyBase.
DR GO; GO:0008354; P:germ cell migration; IMP:FlyBase.
DR GO; GO:0008347; P:glial cell migration; IMP:FlyBase.
DR GO; GO:0007506; P:gonadal mesoderm development; IMP:FlyBase.
DR GO; GO:0007507; P:heart development; TAS:FlyBase.
DR GO; GO:0060914; P:heart formation; IMP:FlyBase.
DR GO; GO:0007442; P:hindgut morphogenesis; IMP:FlyBase.
DR GO; GO:0007446; P:imaginal disc growth; TAS:FlyBase.
DR GO; GO:0007476; P:imaginal disc-derived wing morphogenesis; IMP:FlyBase.
DR GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro.
DR GO; GO:0035217; P:labial disc development; IMP:FlyBase.
DR GO; GO:0007478; P:leg disc morphogenesis; TAS:FlyBase.
DR GO; GO:0016335; P:morphogenesis of larval imaginal disc epithelium; IMP:FlyBase.
DR GO; GO:0002385; P:mucosal immune response; IMP:FlyBase.
DR GO; GO:0034111; P:negative regulation of homotypic cell-cell adhesion; IDA:FlyBase.
DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:FlyBase.
DR GO; GO:0007280; P:pole cell migration; IGI:FlyBase.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IMP:FlyBase.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IDA:FlyBase.
DR GO; GO:0035289; P:posterior head segmentation; TAS:FlyBase.
DR GO; GO:0007458; P:progression of morphogenetic furrow involved in compound eye morphogenesis; IMP:FlyBase.
DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB.
DR GO; GO:2000495; P:regulation of cell proliferation involved in compound eye morphogenesis; IMP:FlyBase.
DR GO; GO:2000274; P:regulation of epithelial cell migration, open tracheal system; IMP:FlyBase.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IMP:FlyBase.
DR GO; GO:0007367; P:segment polarity determination; IMP:FlyBase.
DR GO; GO:0007224; P:smoothened signaling pathway; IDA:FlyBase.
DR GO; GO:0035277; P:spiracle morphogenesis, open tracheal system; IMP:FlyBase.
DR GO; GO:0035154; P:terminal cell fate specification, open tracheal system; IMP:FlyBase.
DR GO; GO:0035290; P:trunk segmentation; TAS:FlyBase.
DR GO; GO:0007418; P:ventral midline development; IMP:FlyBase.
DR GO; GO:0048100; P:wing disc anterior/posterior pattern formation; TAS:FlyBase.
DR GO; GO:0035222; P:wing disc pattern formation; IDA:FlyBase.
DR GO; GO:0007473; P:wing disc proximal/distal pattern formation; TAS:FlyBase.
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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autocatalytic cleavage; Calcium;
KW Cell membrane; Cytoplasm; Developmental protein; Hydrolase; Lipoprotein;
KW Membrane; Metal-binding; Morphogen; Nucleus; Palmitate; Protease;
KW Reference proteome; Segmentation polarity protein; Signal.
FT SIGNAL 1..?
FT /evidence="ECO:0000255"
FT PROPEP ?..84
FT /evidence="ECO:0000255"
FT /id="PRO_0000383048"
FT CHAIN 85..471
FT /note="Protein hedgehog"
FT /id="PRO_0000013202"
FT CHAIN 85..257
FT /note="Protein hedgehog N-product"
FT /id="PRO_0000013203"
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 150
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 150
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 155
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 185
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 186
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 186
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 189
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 191
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT SITE 257..258
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:7885476"
FT SITE 303
FT /note="Involved in cholesterol transfer"
FT /evidence="ECO:0000269|PubMed:9335337"
FT SITE 326
FT /note="Involved in auto-cleavage"
FT /evidence="ECO:0000269|PubMed:9335337"
FT SITE 329
FT /note="Essential for auto-cleavage"
FT /evidence="ECO:0000269|PubMed:7885476,
FT ECO:0000269|PubMed:9335337"
FT LIPID 85
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:11486055"
FT LIPID 257
FT /note="Cholesterol glycine ester"
FT /evidence="ECO:0000269|PubMed:11486055"
FT VAR_SEQ 161..192
FT /note="RCKEKLNVLAYSVMNEWPGIRLLVTESWDEDY -> VRKTLKHRKLVTKFVI
FT HHWESFAYRNHCDKVT (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_002065"
FT VAR_SEQ 193..471
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_002066"
FT MUTAGEN 85
FT /note="C->S: N-product is made but fails to undergo
FT palmitoylation."
FT /evidence="ECO:0000269|PubMed:11319862,
FT ECO:0000269|PubMed:11486055"
FT MUTAGEN 303
FT /note="D->A: No cholesterol transfer."
FT /evidence="ECO:0000269|PubMed:9335337"
FT MUTAGEN 326
FT /note="T->A: Greatly reduced autoprocessing activity."
FT /evidence="ECO:0000269|PubMed:9335337"
FT MUTAGEN 329
FT /note="H->A: No autoprocessing activity."
FT /evidence="ECO:0000269|PubMed:9335337"
FT CONFLICT 156
FT /note="R -> G (in Ref. 1; AAA28604)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="D -> H (in Ref. 1; AAA28604)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="V -> L (in Ref. 1; AAA28604)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="Q -> P (in Ref. 3; Z11840)"
FT /evidence="ECO:0000305"
FT STRAND 107..111
FT /evidence="ECO:0007829|PDB:2IBG"
FT TURN 116..119
FT /evidence="ECO:0007829|PDB:2IBG"
FT HELIX 131..135
FT /evidence="ECO:0007829|PDB:2IBG"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:2IBG"
FT HELIX 160..176
FT /evidence="ECO:0007829|PDB:2IBG"
FT STRAND 182..188
FT /evidence="ECO:0007829|PDB:2IBG"
FT HELIX 199..202
FT /evidence="ECO:0007829|PDB:2IBG"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:2IBG"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:2IBG"
FT HELIX 218..228
FT /evidence="ECO:0007829|PDB:2IBG"
FT STRAND 231..234
FT /evidence="ECO:0007829|PDB:2IBG"
FT STRAND 241..244
FT /evidence="ECO:0007829|PDB:2IBG"
FT STRAND 264..267
FT /evidence="ECO:0007829|PDB:6TYY"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:6TYY"
FT TURN 275..277
FT /evidence="ECO:0007829|PDB:6TYY"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:6TYY"
FT STRAND 293..317
FT /evidence="ECO:0007829|PDB:6TYY"
FT STRAND 322..325
FT /evidence="ECO:0007829|PDB:6TYY"
FT STRAND 329..335
FT /evidence="ECO:0007829|PDB:6TYY"
FT TURN 336..339
FT /evidence="ECO:0007829|PDB:6TYY"
FT STRAND 340..345
FT /evidence="ECO:0007829|PDB:6TYY"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:6TYY"
FT STRAND 354..358
FT /evidence="ECO:0007829|PDB:6TYY"
FT TURN 360..362
FT /evidence="ECO:0007829|PDB:6TYY"
FT STRAND 365..393
FT /evidence="ECO:0007829|PDB:6TYY"
FT STRAND 396..402
FT /evidence="ECO:0007829|PDB:6TYY"
SQ SEQUENCE 471 AA; 52150 MW; 8ECD796A92FE7043 CRC64;
MDNHSSVPWA SAASVTCLSL DAKCHSSSSS SSSKSAASSI SAIPQEETQT MRHIAHTQRC
LSRLTSLVAL LLIVLPMVFS PAHSCGPGRG LGRHRARNLY PLVLKQTIPN LSEYTNSASG
PLEGVIRRDS PKFKDLVPNY NRDILFRDEE GTGADRLMSK RCKEKLNVLA YSVMNEWPGI
RLLVTESWDE DYHHGQESLH YEGRAVTIAT SDRDQSKYGM LARLAVEAGF DWVSYVSRRH
IYCSVKSDSS ISSHVHGCFT PESTALLESG VRKPLGELSI GDRVLSMTAN GQAVYSEVIL
FMDRNLEQMQ NFVQLHTDGG AVLTVTPAHL VSVWQPESQK LTFVFADRIE EKNQVLVRDV
ETGELRPQRV VKVGSVRSKG VVAPLTREGT IVVNSVAASC YAVINSQSLA HWGLAPMRLL
STLEAWLPAK EQLHSSPKVV SSAQQQNGIH WYANALYKVK DYVLPQSWRH D
