SHH_DANKE
ID SHH_DANKE Reviewed; 121 AA.
AC P79709; P79710;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Sonic hedgehog protein;
DE Short=SHH;
DE Flags: Fragments;
GN Name=shh;
OS Danio kerri (Blue danio) (Brachydanio kerri).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=38750;
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; U51340; AAB38571.1; -; Genomic_DNA.
DR EMBL; U51359; AAB38589.1; -; Genomic_DNA.
DR AlphaFoldDB; P79709; -.
DR SMR; P79709; -.
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..>121
FT /note="Sonic hedgehog protein"
FT /id="PRO_0000058727"
FT BINDING 60
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 61
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 61
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 76
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 77
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 77
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 80
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 82
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 91
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT BINDING 98
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q15465"
FT NON_CONS 63..64
FT /evidence="ECO:0000305"
FT NON_TER 1
FT NON_TER 121
SQ SEQUENCE 121 AA; 14012 MW; A58A2DE40573825C CRC64;
YGRRRHPKKL TPLAYKQFIP NVAEKTLGAS GRYEGKITRN SERFKELTPN YNPDIIFKDE
ENTVMNHWPG VKLRVTEGWD EDGHHFEESL HYEGRAVDIT TSDRDKSKYG TLSRLAVEAG
F
