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Sonic hedgehog protein (SHH) (Shh unprocessed N-terminal signaling and C-terminal autoprocessing domains) (ShhNC) [Cleaved into: Sonic hedgehog protein N-product (ShhN) (Shh N-terminal processed signaling domains) (ShhNp)]

 SHH_RAT                 Reviewed;         437 AA.
Q63673;
15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
22-NOV-2017, entry version 152.
RecName: Full=Sonic hedgehog protein;
Short=SHH;
AltName: Full=Shh unprocessed N-terminal signaling and C-terminal autoprocessing domains {ECO:0000250|UniProtKB:Q62226};
Short=ShhNC {ECO:0000250|UniProtKB:Q62226};
Contains:
RecName: Full=Sonic hedgehog protein N-product;
Short=ShhN;
AltName: Full=Shh N-terminal processed signaling domains {ECO:0000250|UniProtKB:Q62226};
Short=ShhNp {ECO:0000250|UniProtKB:Q62226};
Flags: Precursor;
Name=Shh {ECO:0000312|RGD:3673}; Synonyms=Vhh-1;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
STRAIN=Sprague-Dawley; TISSUE=Embryonic floor plate;
PubMed=8124714; DOI=10.1016/0092-8674(94)90514-2;
Roelink H., Augsburger A., Heemskerk J., Korzh V., Norlin S.,
Ruiz i Altaba A., Tanabe Y., Placzek M., Edlund T., Jessell T.M.,
Dodd J.;
"Floor plate and motor neuron induction by vhh-1, a vertebrate homolog
of hedgehog expressed by the notochord.";
Cell 76:761-775(1994).
[2]
SUBUNIT, AND SUBCELLULAR LOCATION.
PubMed=11395778; DOI=10.1038/35079648;
Zeng X., Goetz J.A., Suber L.M., Scott W.J. Jr., Schreiner C.M.,
Robbins D.J.;
"A freely diffusible form of Sonic hedgehog mediates long-range
signalling.";
Nature 411:716-720(2001).
-!- FUNCTION: Sonic hedgehog protein: The C-terminal part of the sonic
hedgehog protein precursor displays an autoproteolysis and a
cholesterol transferase activity (By similarity). Both activities
result in the cleavage of the full-length protein into two parts
(ShhN and ShhC) followed by the covalent attachment of a
cholesterol moiety to the C-terminal of the newly generated ShhN
(By similarity). Both activities occur in the reticulum
endoplasmic (By similarity). Once cleaved, ShhC is degraded in the
endoplasmic reticulum (By similarity).
{ECO:0000250|UniProtKB:Q15465, ECO:0000250|UniProtKB:Q62226}.
-!- FUNCTION: Sonic hedgehog protein N-product: The dually lipidated
sonic hedgehog protein N-product (ShhNp) is a morphogen which is
essential for a variety of patterning events during development.
Induces ventral cell fate in the neural tube and somites (By
similarity). Involved in the patterning of the anterior-posterior
axis of the developing limb bud (By similarity). Essential for
axon guidance (By similarity). Binds to the patched (PTCH1)
receptor, which functions in association with smoothened (SMO), to
activate the transcription of target genes (By similarity). In the
absence of SHH, PTCH1 represses the constitutive signaling
activity of SMO (By similarity). {ECO:0000250|UniProtKB:Q15465,
ECO:0000250|UniProtKB:Q62226}.
-!- SUBUNIT: Interacts with HHATL/GUP1 which negatively regulates
HHAT-mediated palmitoylation of the SHH N-terminus (By
similarity). ShhNp is active as a multimer (By similarity).
Interacts with BOC and CDON (By similarity). Interacts with HHIP
(By similarity). Interacts with DISP1 via its cholesterol anchor
(By similarity). Interacts with SCUBE2 (By similarity).
{ECO:0000250|UniProtKB:Q15465, ECO:0000250|UniProtKB:Q62226,
ECO:0000269|PubMed:11395778}.
-!- SUBCELLULAR LOCATION: Sonic hedgehog protein N-product: Cell
membrane {ECO:0000250|UniProtKB:Q62226}; Lipid-anchor
{ECO:0000250|UniProtKB:Q62226}. Note=The dual-lipidated sonic
hedgehog protein N-product (ShhNp) is firmly tethered to the cell
membrane where it forms multimers (By similarity). Further
solubilization and release from the cell surface seem to be
achieved through different mechanisms, including the interaction
with DISP1 and SCUBE2, movement by lipoprotein particles,
transport by cellular extensions called cytonemes or by the
proteolytic removal of both terminal lipidated peptides.
{ECO:0000250|UniProtKB:Q62226}.
-!- TISSUE SPECIFICITY: Expressed in the node, notochord, floor plate,
and posterior limb bud mesenchyme. {ECO:0000269|PubMed:8124714}.
-!- DOMAIN: Sonic hedgehog protein N-product: Binds calcium and zinc
ions; this stabilizes the protein fold and is essential for
protein-protein interactions mediated by this domain.
{ECO:0000250|UniProtKB:Q62226}.
-!- DOMAIN: Sonic hedgehog protein N-product: The Cardin-Weintraub
(CW) motif is required for heparan sulfate binding of the
solubilized ShhNp (By similarity). The N-terminal palmitoylated
peptide is cleaved at the Heparan sulfate-binding Cardin-Weintraub
(CW) motif site (By similarity). The cleavage reduced the
interactions with heparan sulfate. The cleavage is enhanced by
SCUBE2 (By similarity). {ECO:0000250|UniProtKB:Q62226}.
-!- PTM: Sonic hedgehog protein: The C-terminal domain displays an
autoproteolysis activity and a cholesterol transferase activity
(By similarity). Both activities result in the cleavage of the
full-length protein and covalent attachment of a cholesterol
moiety to the C-terminal of the newly generated N-terminal
fragment (ShhN) (By similarity). Cholesterylation is required for
the sonic hedgehog protein N-product targeting to lipid rafts and
multimerization (By similarity). ShhN is the active species in
both local and long-range signaling, whereas the C-product (ShhC)
is degraded in the reticulum endoplasmic (By similarity).
{ECO:0000250|UniProtKB:Q62226}.
-!- PTM: Sonic hedgehog protein N-product: N-palmitoylation by HHAT of
ShhN is required for sonic hedgehog protein N-product
multimerization and full activity (By similarity). It is a
prerequisite for the membrane-proximal positioning and the
subsequent shedding of this N-terminal peptide (By similarity).
{ECO:0000250|UniProtKB:Q62226}.
-!- PTM: Sonic hedgehog protein N-product: The lipidated N- and C-
terminal peptides of ShhNp can be cleaved (shedding) (By
similarity). The N-terminal palmitoylated peptide is cleaved at
the Cardin-Weintraub (CW) motif site (By similarity). The cleavage
reduced the interactions with heparan sulfate (By similarity). The
cleavage is enhanced by SCUBE2 (By similarity).
{ECO:0000250|UniProtKB:Q62226}.
-!- SIMILARITY: Belongs to the hedgehog family. {ECO:0000305}.
-!- CAUTION: The several steps and mechanisms that permit controlled
Shh dispersion and gradient formation remain controversial. The
ShhNC C-terminal domain displays an autoproteolysis activity and a
cholesterol transferase activity resulting in the cleavage and
covalent attachment of a cholesterol moiety to the C-terminal of
the newly generated N-terminal fragment (ShhN). The protein is
further modified by covalent addition of palmitate at the N-
terminal of ShhN, resulting to the dual-lipidated Shh (ShhNp).
ShhNp is firmly tethered to the cell membrane where it forms
multimers. Further solubilization and release from the cell
surface seem to be achieved through different mechanisms,
including the interaction with DISP1 and SCUBE2, movement by
lipoprotein particles, transport by cellular extensions called
cytonemes or by proteolytic removal of both terminal lipidated
peptides. Once released, the fully processed Shh can signal within
embryonic tissues both at short and long-range.
{ECO:0000250|UniProtKB:Q62226}.
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EMBL; L27340; AAA20999.1; -; mRNA.
PIR; B53193; B53193.
RefSeq; NP_058917.1; NM_017221.1.
UniGene; Rn.10432; -.
ProteinModelPortal; Q63673; -.
SMR; Q63673; -.
STRING; 10116.ENSRNOP00000008497; -.
MEROPS; C46.002; -.
PaxDb; Q63673; -.
PRIDE; Q63673; -.
GeneID; 29499; -.
KEGG; rno:29499; -.
CTD; 6469; -.
RGD; 3673; Shh.
eggNOG; KOG3638; Eukaryota.
eggNOG; ENOG410XQA3; LUCA.
HOGENOM; HOG000233428; -.
HOVERGEN; HBG005480; -.
InParanoid; Q63673; -.
KO; K11988; -.
PhylomeDB; Q63673; -.
PRO; PR:Q63673; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0030424; C:axon; IDA:RGD.
GO; GO:0009986; C:cell surface; ISS:UniProtKB.
GO; GO:0030425; C:dendrite; IDA:RGD.
GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
GO; GO:0005615; C:extracellular space; IDA:RGD.
GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
GO; GO:0016020; C:membrane; ISO:RGD.
GO; GO:0045121; C:membrane raft; IDA:RGD.
GO; GO:0043025; C:neuronal cell body; IDA:RGD.
GO; GO:0005634; C:nucleus; IDA:RGD.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0005578; C:proteinaceous extracellular matrix; ISO:RGD.
GO; GO:0008021; C:synaptic vesicle; IDA:RGD.
GO; GO:0030133; C:transport vesicle; IDA:RGD.
GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
GO; GO:0005539; F:glycosaminoglycan binding; ISO:RGD.
GO; GO:0043237; F:laminin-1 binding; ISS:UniProtKB.
GO; GO:0005113; F:patched binding; ISO:RGD.
GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
GO; GO:0048856; P:anatomical structure development; ISO:RGD.
GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; ISO:RGD.
GO; GO:0008209; P:androgen metabolic process; ISS:UniProtKB.
GO; GO:0001525; P:angiogenesis; ISO:RGD.
GO; GO:0048645; P:animal organ formation; ISO:RGD.
GO; GO:0009952; P:anterior/posterior pattern specification; ISO:RGD.
GO; GO:0097190; P:apoptotic signaling pathway; ISS:UniProtKB.
GO; GO:0060840; P:artery development; ISO:RGD.
GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
GO; GO:0060020; P:Bergmann glial cell differentiation; ISO:RGD.
GO; GO:0007596; P:blood coagulation; ISO:RGD.
GO; GO:0001569; P:branching involved in blood vessel morphogenesis; ISS:UniProtKB.
GO; GO:0060442; P:branching involved in prostate gland morphogenesis; ISO:RGD.
GO; GO:0060445; P:branching involved in salivary gland morphogenesis; ISO:RGD.
GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISS:UniProtKB.
GO; GO:0060447; P:bud outgrowth involved in lung branching; ISO:RGD.
GO; GO:0043010; P:camera-type eye development; ISO:RGD.
GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:RGD.
GO; GO:0043369; P:CD4-positive or CD8-positive, alpha-beta T cell lineage commitment; ISS:UniProtKB.
GO; GO:0048468; P:cell development; ISS:UniProtKB.
GO; GO:0045165; P:cell fate commitment; ISO:RGD.
GO; GO:0001708; P:cell fate specification; ISS:UniProtKB.
GO; GO:0008283; P:cell proliferation; ISO:RGD.
GO; GO:0021924; P:cell proliferation in external granule layer; ISO:RGD.
GO; GO:0007267; P:cell-cell signaling; ISS:UniProtKB.
GO; GO:0071285; P:cellular response to lithium ion; ISO:RGD.
GO; GO:0007417; P:central nervous system development; ISS:UniProtKB.
GO; GO:0021930; P:cerebellar granule cell precursor proliferation; ISS:UniProtKB.
GO; GO:0071679; P:commissural neuron axon guidance; IMP:RGD.
GO; GO:0003140; P:determination of left/right asymmetry in lateral mesoderm; ISO:RGD.
GO; GO:0007368; P:determination of left/right symmetry; ISO:RGD.
GO; GO:0048589; P:developmental growth; ISO:RGD.
GO; GO:0007502; P:digestive tract mesoderm development; IDA:RGD.
GO; GO:0048546; P:digestive tract morphogenesis; ISO:RGD.
GO; GO:0021904; P:dorsal/ventral neural tube patterning; ISO:RGD.
GO; GO:0009953; P:dorsal/ventral pattern formation; ISS:UniProtKB.
GO; GO:0007398; P:ectoderm development; ISO:RGD.
GO; GO:0009790; P:embryo development; ISS:UniProtKB.
GO; GO:0048557; P:embryonic digestive tract morphogenesis; ISO:RGD.
GO; GO:0042733; P:embryonic digit morphogenesis; ISS:UniProtKB.
GO; GO:0048617; P:embryonic foregut morphogenesis; ISO:RGD.
GO; GO:0035115; P:embryonic forelimb morphogenesis; ISO:RGD.
GO; GO:0035116; P:embryonic hindlimb morphogenesis; ISO:RGD.
GO; GO:0030326; P:embryonic limb morphogenesis; ISS:UniProtKB.
GO; GO:0048598; P:embryonic morphogenesis; ISO:RGD.
GO; GO:0048568; P:embryonic organ development; ISO:RGD.
GO; GO:0048706; P:embryonic skeletal system development; ISO:RGD.
GO; GO:0006897; P:endocytosis; ISO:RGD.
GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; ISO:RGD.
GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IEP:RGD.
GO; GO:0060684; P:epithelial-mesenchymal cell signaling; ISO:RGD.
GO; GO:0060738; P:epithelial-mesenchymal signaling involved in prostate gland development; ISO:RGD.
GO; GO:0030010; P:establishment of cell polarity; ISO:RGD.
GO; GO:0030900; P:forebrain development; ISS:UniProtKB.
GO; GO:0021871; P:forebrain regionalization; ISO:RGD.
GO; GO:0048859; P:formation of anatomical boundary; ISO:RGD.
GO; GO:0061196; P:fungiform papilla development; IMP:RGD.
GO; GO:0061198; P:fungiform papilla formation; IMP:RGD.
GO; GO:0061197; P:fungiform papilla morphogenesis; IMP:RGD.
GO; GO:0001942; P:hair follicle development; ISO:RGD.
GO; GO:0031069; P:hair follicle morphogenesis; ISO:RGD.
GO; GO:0007507; P:heart development; ISS:UniProtKB.
GO; GO:0001947; P:heart looping; ISO:RGD.
GO; GO:0030902; P:hindbrain development; ISS:UniProtKB.
GO; GO:0007442; P:hindgut morphogenesis; ISO:RGD.
GO; GO:0048839; P:inner ear development; ISO:RGD.
GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro.
GO; GO:0045109; P:intermediate filament organization; ISO:RGD.
GO; GO:0001822; P:kidney development; ISO:RGD.
GO; GO:0060459; P:left lung development; ISO:RGD.
GO; GO:0060174; P:limb bud formation; ISO:RGD.
GO; GO:0060173; P:limb development; ISO:RGD.
GO; GO:0097421; P:liver regeneration; IEP:RGD.
GO; GO:0030324; P:lung development; ISS:UniProtKB.
GO; GO:0060428; P:lung epithelium development; ISO:RGD.
GO; GO:0060463; P:lung lobe morphogenesis; ISO:RGD.
GO; GO:0060425; P:lung morphogenesis; ISO:RGD.
GO; GO:0060484; P:lung-associated mesenchyme development; ISO:RGD.
GO; GO:0002320; P:lymphoid progenitor cell differentiation; ISS:UniProtKB.
GO; GO:0030539; P:male genitalia development; ISS:UniProtKB.
GO; GO:0048808; P:male genitalia morphogenesis; IMP:RGD.
GO; GO:0010463; P:mesenchymal cell proliferation; ISO:RGD.
GO; GO:0060916; P:mesenchymal cell proliferation involved in lung development; ISO:RGD.
GO; GO:0060783; P:mesenchymal smoothened signaling pathway involved in prostate gland development; ISO:RGD.
GO; GO:0072136; P:metanephric mesenchymal cell proliferation involved in metanephros development; ISS:UniProtKB.
GO; GO:0001656; P:metanephros development; ISS:UniProtKB.
GO; GO:0030901; P:midbrain development; ISS:UniProtKB.
GO; GO:0045445; P:myoblast differentiation; ISO:RGD.
GO; GO:0014902; P:myotube differentiation; ISO:RGD.
GO; GO:0046639; P:negative regulation of alpha-beta T cell differentiation; ISO:RGD.
GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
GO; GO:0045596; P:negative regulation of cell differentiation; ISS:UniProtKB.
GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
GO; GO:0090370; P:negative regulation of cholesterol efflux; ISO:RGD.
GO; GO:1904339; P:negative regulation of dopaminergic neuron differentiation; ISO:RGD.
GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
GO; GO:2000357; P:negative regulation of kidney smooth muscle cell differentiation; ISS:UniProtKB.
GO; GO:2001054; P:negative regulation of mesenchymal cell apoptotic process; ISO:RGD.
GO; GO:1901215; P:negative regulation of neuron death; IMP:RGD.
GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
GO; GO:0042177; P:negative regulation of protein catabolic process; ISO:RGD.
GO; GO:0042130; P:negative regulation of T cell proliferation; ISO:RGD.
GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; ISO:RGD.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISO:RGD.
GO; GO:2000062; P:negative regulation of ureter smooth muscle cell differentiation; ISS:UniProtKB.
GO; GO:0030178; P:negative regulation of Wnt signaling pathway; ISO:RGD.
GO; GO:0045060; P:negative thymic T cell selection; ISS:UniProtKB.
GO; GO:0001755; P:neural crest cell migration; ISS:UniProtKB.
GO; GO:0001841; P:neural tube formation; IMP:RGD.
GO; GO:0007405; P:neuroblast proliferation; ISS:UniProtKB.
GO; GO:0048663; P:neuron fate commitment; ISS:UniProtKB.
GO; GO:0042476; P:odontogenesis; ISO:RGD.
GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISO:RGD.
GO; GO:0014003; P:oligodendrocyte development; ISO:RGD.
GO; GO:0048709; P:oligodendrocyte differentiation; ISO:RGD.
GO; GO:0002076; P:osteoblast development; ISO:RGD.
GO; GO:0060021; P:palate development; ISO:RGD.
GO; GO:0031016; P:pancreas development; ISO:RGD.
GO; GO:0007389; P:pattern specification process; ISS:UniProtKB.
GO; GO:0009949; P:polarity specification of anterior/posterior axis; ISS:UniProtKB.
GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; ISS:UniProtKB.
GO; GO:0045597; P:positive regulation of cell differentiation; ISO:RGD.
GO; GO:0051781; P:positive regulation of cell division; ISO:RGD.
GO; GO:0008284; P:positive regulation of cell proliferation; IDA:RGD.
GO; GO:0021940; P:positive regulation of cerebellar granule cell precursor proliferation; ISO:RGD.
GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; IDA:RGD.
GO; GO:0060769; P:positive regulation of epithelial cell proliferation involved in prostate gland development; ISO:RGD.
GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
GO; GO:0007228; P:positive regulation of hh target transcription factor activity; ISO:RGD.
GO; GO:0033092; P:positive regulation of immature T cell proliferation in thymus; ISS:UniProtKB.
GO; GO:2000358; P:positive regulation of kidney smooth muscle cell differentiation; ISS:UniProtKB.
GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISO:RGD.
GO; GO:2000729; P:positive regulation of mesenchymal cell proliferation involved in ureter development; ISS:UniProtKB.
GO; GO:0002052; P:positive regulation of neuroblast proliferation; IMP:RGD.
GO; GO:0045666; P:positive regulation of neuron differentiation; IMP:RGD.
GO; GO:0032901; P:positive regulation of neurotrophin production; IMP:RGD.
GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; ISO:RGD.
GO; GO:0070447; P:positive regulation of oligodendrocyte progenitor proliferation; IDA:RGD.
GO; GO:0060406; P:positive regulation of penile erection; IMP:RGD.
GO; GO:0046534; P:positive regulation of photoreceptor cell differentiation; IDA:RGD.
GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:RGD.
GO; GO:0061189; P:positive regulation of sclerotome development; ISO:RGD.
GO; GO:0014858; P:positive regulation of skeletal muscle cell proliferation; ISO:RGD.
GO; GO:0048643; P:positive regulation of skeletal muscle tissue development; ISO:RGD.
GO; GO:0045880; P:positive regulation of smoothened signaling pathway; ISS:UniProtKB.
GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IDA:RGD.
GO; GO:0051155; P:positive regulation of striated muscle cell differentiation; ISO:RGD.
GO; GO:0033089; P:positive regulation of T cell differentiation in thymus; ISS:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISO:RGD.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
GO; GO:2000063; P:positive regulation of ureter smooth muscle cell differentiation; ISS:UniProtKB.
GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISO:RGD.
GO; GO:0045059; P:positive thymic T cell selection; ISS:UniProtKB.
GO; GO:0060516; P:primary prostatic bud elongation; ISO:RGD.
GO; GO:0060523; P:prostate epithelial cord elongation; ISO:RGD.
GO; GO:0030850; P:prostate gland development; IEP:RGD.
GO; GO:0034504; P:protein localization to nucleus; ISO:RGD.
GO; GO:0042127; P:regulation of cell proliferation; IDA:RGD.
GO; GO:0030856; P:regulation of epithelial cell differentiation; IEP:RGD.
GO; GO:0060768; P:regulation of epithelial cell proliferation involved in prostate gland development; ISO:RGD.
GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
GO; GO:0060782; P:regulation of mesenchymal cell proliferation involved in prostate gland development; ISO:RGD.
GO; GO:0042481; P:regulation of odontogenesis; ISO:RGD.
GO; GO:0060685; P:regulation of prostatic bud formation; ISO:RGD.
GO; GO:1900180; P:regulation of protein localization to nucleus; ISO:RGD.
GO; GO:0030162; P:regulation of proteolysis; ISS:UniProtKB.
GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
GO; GO:0072001; P:renal system development; ISO:RGD.
GO; GO:0030323; P:respiratory tube development; ISO:RGD.
GO; GO:0048678; P:response to axon injury; IMP:RGD.
GO; GO:0032355; P:response to estradiol; IEP:RGD.
GO; GO:0045471; P:response to ethanol; IDA:RGD.
GO; GO:0001666; P:response to hypoxia; IEP:RGD.
GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
GO; GO:0032526; P:response to retinoic acid; IEP:RGD.
GO; GO:0060458; P:right lung development; ISO:RGD.
GO; GO:0060662; P:salivary gland cavitation; ISO:RGD.
GO; GO:0043588; P:skin development; ISO:RGD.
GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB.
GO; GO:0021938; P:smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation; ISO:RGD.
GO; GO:0061053; P:somite development; ISO:RGD.
GO; GO:0021513; P:spinal cord dorsal/ventral patterning; IDA:MGI.
GO; GO:0021522; P:spinal cord motor neuron differentiation; ISO:RGD.
GO; GO:0048864; P:stem cell development; ISS:UniProtKB.
GO; GO:0051146; P:striated muscle cell differentiation; ISO:RGD.
GO; GO:0014706; P:striated muscle tissue development; ISO:RGD.
GO; GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB.
GO; GO:0021978; P:telencephalon regionalization; IMP:RGD.
GO; GO:0021794; P:thalamus development; ISO:RGD.
GO; GO:0048538; P:thymus development; ISS:UniProtKB.
GO; GO:0030878; P:thyroid gland development; ISO:RGD.
GO; GO:0043586; P:tongue development; IMP:RGD.
GO; GO:0043587; P:tongue morphogenesis; IMP:RGD.
GO; GO:0060438; P:trachea development; ISO:RGD.
GO; GO:0060439; P:trachea morphogenesis; ISO:RGD.
GO; GO:1905327; P:tracheoesophageal septum formation; ISO:RGD.
GO; GO:0001944; P:vasculature development; ISO:RGD.
GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB.
GO; GO:0021521; P:ventral spinal cord interneuron specification; IDA:MGI.
GO; GO:0022006; P:zona limitans intrathalamica formation; IDA:RGD.
Gene3D; 3.30.1380.10; -; 1.
InterPro; IPR001657; Hedgehog.
InterPro; IPR009045; Hedgehog_sig/DD-Pept_Zn-bd_sf.
InterPro; IPR000320; Hedgehog_signalling_dom.
InterPro; IPR001767; Hint_dom.
InterPro; IPR003586; Hint_dom_C.
InterPro; IPR003587; Hint_dom_N.
InterPro; IPR036844; Hint_dom_sf.
InterPro; IPR006141; Intein_N.
Pfam; PF01085; HH_signal; 1.
Pfam; PF01079; Hint; 1.
PIRSF; PIRSF009400; Peptidase_C46; 1.
PRINTS; PR00632; SONICHHOG.
SMART; SM00305; HintC; 1.
SMART; SM00306; HintN; 1.
SUPFAM; SSF51294; SSF51294; 1.
SUPFAM; SSF55166; SSF55166; 1.
PROSITE; PS50817; INTEIN_N_TER; 1.
1: Evidence at protein level;
Autocatalytic cleavage; Calcium; Cell membrane; Complete proteome;
Developmental protein; Glycoprotein; Hydrolase; Lipoprotein; Membrane;
Metal-binding; Palmitate; Protease; Reference proteome; Signal; Zinc.
SIGNAL 1 24 {ECO:0000250|UniProtKB:Q15465}.
CHAIN 25 437 Sonic hedgehog protein.
/FTId=PRO_0000013214.
CHAIN 25 198 Sonic hedgehog protein N-product.
/FTId=PRO_0000013215.
MOTIF 33 39 Cardin-Weintraub.
{ECO:0000250|UniProtKB:Q62226}.
COMPBIAS 383 387 Poly-Gly.
METAL 90 90 Calcium 1.
{ECO:0000250|UniProtKB:Q15465}.
METAL 91 91 Calcium 1.
{ECO:0000250|UniProtKB:Q15465}.
METAL 91 91 Calcium 2.
{ECO:0000250|UniProtKB:Q15465}.
METAL 96 96 Calcium 1.
{ECO:0000250|UniProtKB:Q15465}.
METAL 126 126 Calcium 1; via carbonyl oxygen.
{ECO:0000250|UniProtKB:Q15465}.
METAL 127 127 Calcium 1.
{ECO:0000250|UniProtKB:Q15465}.
METAL 127 127 Calcium 2.
{ECO:0000250|UniProtKB:Q15465}.
METAL 130 130 Calcium 2.
{ECO:0000250|UniProtKB:Q15465}.
METAL 132 132 Calcium 2.
{ECO:0000250|UniProtKB:Q15465}.
METAL 141 141 Zinc. {ECO:0000250|UniProtKB:Q15465}.
METAL 148 148 Zinc. {ECO:0000250|UniProtKB:Q15465}.
METAL 183 183 Zinc. {ECO:0000250|UniProtKB:Q15465}.
SITE 198 199 Cleavage; by autolysis.
SITE 244 244 Involved in cholesterol transfer.
{ECO:0000250}.
SITE 268 268 Involved in auto-cleavage. {ECO:0000250}.
SITE 271 271 Essential for auto-cleavage.
{ECO:0000250}.
LIPID 25 25 N-palmitoyl cysteine. {ECO:0000250}.
LIPID 198 198 Cholesterol glycine ester. {ECO:0000250}.
CARBOHYD 279 279 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
SEQUENCE 437 AA; 47630 MW; 0DBFC19F0D1662A0 CRC64;
MLLLLARCFL VALASSLLVC PGLACGPGRG FGKRQHPKKL TPLAYKQFIP NVAEKTLGAS
GRYEGKITRN SERFKELTPN YNPDIIFKDE ENTGADRLMT QRCKDKLNAL AISVMNQWPG
VKLRVTEGWD EDGHHSEESL HYEGRAVDIT TSDRDRSKYG MLARLAVEAG FDWVYYESKA
RIHCSVKAEN SVAAKSDGCF PGSATVHLEQ GGTKLVKDLS PGDRVLAADD QGRLLYSDFL
TFLDRDEGAK KVFYVIETRE PRERLLLTAA HLLFVAPHND SGPTPGPSPL FASRVRPGQR
VYVVAERGGD RRLLPAAVHS VTLREEAAGA YAPLTADGTI LINRVLASCY AVIEEHSWAH
RAFAPFRLAH ALLAALAPAR TDGGGGGSIP APQSVAEARG AGPPAGIHWY SQLLYHIGTW
LLDSETLHPL GMAVKSS


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