ID   SHH_PSEPR               Reviewed;          58 AA.
AC   P79839;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   03-AUG-2022, entry version 85.
DE   RecName: Full=Sonic hedgehog protein;
DE            Short=SHH;
DE   Flags: Fragment;
GN   Name=shh;
OS   Pseudorasbora parva.
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Gobionidae; Sarcocheilichthyinae; Pseudorasbora.
OX   NCBI_TaxID=51549;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Muscle;
RX   PubMed=8917540; DOI=10.1073/pnas.93.23.13036;
RA   Zardoya R., Abouheif E., Meyer A.;
RT   "Evolutionary analyses of hedgehog and Hoxd-10 genes in fish species
RT   closely related to the zebrafish.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:13036-13041(1996).
CC   -!- FUNCTION: Intercellular signal essential for a variety of patterning
CC       events during development. Signal produced by the notochord that
CC       induces somite patterning, dorso-ventral patterning of the brain and
CC       early patterning of the developing eyes. Displays floor plate-inducing
CC       activity. Binds to the patched (PTC) receptor, which functions in
CC       association with smoothened (SMO), to activate the transcription of
CC       target genes. In the absence of SHH, PTC represses the constitutive
CC       signaling activity of SMO (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: N-product is active as a multimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Cell membrane
CC       {ECO:0000250}. Note=Sonic hedgehog protein C-product: Secreted,
CC       extracellular space. Sonic hedgehog protein N-product: Cell membrane;
CC       Lipid-anchor. The C-terminal peptide diffuses from the cell, while the
CC       N-product either remains associated with lipid rafts at the cell
CC       surface, or forms freely diffusible active multimers with its
CC       hydrophobic lipid-modified N- and C-termini buried inside.
CC       {ECO:0000250}.
CC   -!- DOMAIN: The sonic hedgehog protein N-product binds calcium and zinc
CC       ions; this stabilizes the protein fold and is essential for protein-
CC       protein interactions mediated by this domain. {ECO:0000250}.
CC   -!- PTM: The C-terminal domain displays an autoproteolysis activity and a
CC       cholesterol transferase activity. Both activities result in the
CC       cleavage of the full-length protein and covalent attachment of a
CC       cholesterol moiety to the C-terminal of the newly generated N-terminal
CC       fragment (N-product). The N-product is the active species in both local
CC       and long-range signaling, whereas the C-product has no signaling
CC       activity.
CC   -!- PTM: Cholesterylation is required for N-product targeting to lipid
CC       rafts and multimerization. {ECO:0000250}.
CC   -!- PTM: N-palmitoylation is required for N-product multimerization and
CC       full activity. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the hedgehog family. {ECO:0000305}.
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DR   EMBL; U51358; AAB38594.1; -; Genomic_DNA.
DR   AlphaFoldDB; P79839; -.
DR   SMR; P79839; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0007267; P:cell-cell signaling; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.1380.10; -; 1.
DR   InterPro; IPR001657; Hedgehog.
DR   InterPro; IPR009045; Hedgehog_sig/DD-Pept_Zn-bd_sf.
DR   InterPro; IPR000320; Hedgehog_signalling_dom.
DR   Pfam; PF01085; HH_signal; 1.
DR   PRINTS; PR00632; SONICHHOG.
DR   SUPFAM; SSF55166; SSF55166; 1.
PE   3: Inferred from homology;
KW   Autocatalytic cleavage; Calcium; Cell membrane; Developmental protein;
KW   Hydrolase; Lipoprotein; Membrane; Metal-binding; Palmitate; Protease;
KW   Secreted; Zinc.
FT   CHAIN           <1..>58
FT                   /note="Sonic hedgehog protein"
FT                   /id="PRO_0000058732"
FT   BINDING         13
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q15465"
FT   BINDING         14
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q15465"
FT   BINDING         14
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q15465"
FT   BINDING         17
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q15465"
FT   BINDING         19
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q15465"
FT   BINDING         28
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q15465"
FT   BINDING         35
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q15465"
FT   NON_TER         1
FT   NON_TER         58
SQ   SEQUENCE   58 AA;  6608 MW;  BDEAB71BD19FA6B9 CRC64;
     VMNQWPGVNL RVTEGWDEDG HHFEESLHYE GRAVDITTSD RDKSKYGTLS RLAVEAGF