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Protein

Sonic hedgehog protein

Gene

Shh

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Intercellular signal essential for a variety of patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required for motor neuron induction is 5-fold lower than that required for floor plate induction. Activates the transcription of target genes by interacting with its receptor PTCH1 to prevent normal inhibition by PTCH1 on the constitutive signaling activity of SMO.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi90 – 901Calcium 13 Publications
Metal bindingi91 – 911Calcium 13 Publications
Metal bindingi91 – 911Calcium 23 Publications
Metal bindingi96 – 961Calcium 13 Publications
Metal bindingi126 – 1261Calcium 1; via carbonyl oxygen3 Publications
Metal bindingi127 – 1271Calcium 13 Publications
Metal bindingi127 – 1271Calcium 23 Publications
Metal bindingi130 – 1301Calcium 23 Publications
Metal bindingi132 – 1321Calcium 23 Publications
Metal bindingi141 – 1411Zinc
Metal bindingi148 – 1481Zinc
Metal bindingi183 – 1831Zinc
Sitei198 – 1992Cleavage; by autolysisBy similarity
Sitei244 – 2441Involved in cholesterol transferBy similarity
Sitei268 – 2681Involved in auto-cleavageBy similarity
Sitei271 – 2711Essential for auto-cleavageBy similarity

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • glycoprotein binding Source: MGI
  • glycosaminoglycan binding Source: MGI
  • laminin-1 binding Source: MGI
  • patched binding Source: Roslin
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • anatomical structure development Source: MGI
  • anatomical structure formation involved in morphogenesis Source: MGI
  • androgen metabolic process Source: MGI
  • angiogenesis Source: MGI
  • anterior/posterior pattern specification Source: MGI
  • apoptotic process Source: MGI
  • apoptotic signaling pathway Source: Roslin
  • artery development Source: MGI
  • axon guidance Source: MGI
  • Bergmann glial cell differentiation Source: MGI
  • blood coagulation Source: MGI
  • branching involved in prostate gland morphogenesis Source: MGI
  • branching involved in salivary gland morphogenesis Source: MGI
  • branching involved in ureteric bud morphogenesis Source: MGI
  • branching morphogenesis of an epithelial tube Source: MGI
  • bud outgrowth involved in lung branching Source: MGI
  • camera-type eye development Source: MGI
  • canonical Wnt signaling pathway Source: MGI
  • CD4-positive or CD8-positive, alpha-beta T cell lineage commitment Source: BHF-UCL
  • cell-cell signaling Source: MGI
  • cell development Source: MGI
  • cell fate commitment Source: MGI
  • cell fate specification Source: MGI
  • cell proliferation Source: MGI
  • cellular response to lithium ion Source: MGI
  • central nervous system development Source: MGI
  • cerebellar granule cell precursor proliferation Source: UniProtKB
  • determination of left/right asymmetry in lateral mesoderm Source: BHF-UCL
  • determination of left/right symmetry Source: MGI
  • developmental growth Source: MGI
  • digestive tract morphogenesis Source: MGI
  • dorsal/ventral neural tube patterning Source: BHF-UCL
  • dorsal/ventral pattern formation Source: MGI
  • ectoderm development Source: MGI
  • embryonic digestive tract morphogenesis Source: BHF-UCL
  • embryonic digit morphogenesis Source: Roslin
  • embryonic foregut morphogenesis Source: MGI
  • embryonic forelimb morphogenesis Source: MGI
  • embryonic hindlimb morphogenesis Source: MGI
  • embryonic limb morphogenesis Source: MGI
  • embryonic morphogenesis Source: MGI
  • embryonic organ development Source: MGI
  • embryonic skeletal system development Source: MGI
  • endocytosis Source: MGI
  • epithelial cell proliferation involved in salivary gland morphogenesis Source: MGI
  • epithelial-mesenchymal cell signaling Source: MGI
  • epithelial-mesenchymal signaling involved in prostate gland development Source: MGI
  • epithelial tube branching involved in lung morphogenesis Source: MGI
  • establishment of cell polarity Source: MGI
  • forebrain development Source: MGI
  • formation of anatomical boundary Source: MGI
  • hair follicle development Source: MGI
  • hair follicle morphogenesis Source: MGI
  • heart development Source: MGI
  • heart looping Source: BHF-UCL
  • hindbrain development Source: MGI
  • hindgut morphogenesis Source: MGI
  • inner ear development Source: MGI
  • intein-mediated protein splicing Source: InterPro
  • intermediate filament organization Source: MGI
  • kidney development Source: MGI
  • left lung development Source: MGI
  • limb bud formation Source: MGI
  • limb development Source: MGI
  • lung-associated mesenchyme development Source: MGI
  • lung development Source: MGI
  • lung epithelium development Source: MGI
  • lung lobe morphogenesis Source: MGI
  • lung morphogenesis Source: MGI
  • lymphoid progenitor cell differentiation Source: BHF-UCL
  • male genitalia development Source: MGI
  • mesenchymal cell proliferation Source: MGI
  • mesenchymal cell proliferation involved in lung development Source: MGI
  • mesenchymal smoothened signaling pathway involved in prostate gland development Source: MGI
  • metanephric mesenchymal cell proliferation involved in metanephros development Source: UniProtKB
  • metanephros development Source: UniProtKB
  • midbrain development Source: MGI
  • multicellular structure septum development Source: MGI
  • myoblast differentiation Source: MGI
  • myotube differentiation Source: MGI
  • negative regulation of alpha-beta T cell differentiation Source: MGI
  • negative regulation of apoptotic process Source: Roslin
  • negative regulation of canonical Wnt signaling pathway Source: MGI
  • negative regulation of cell differentiation Source: MGI
  • negative regulation of cell migration Source: MGI
  • negative regulation of cholesterol efflux Source: BHF-UCL
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of kidney smooth muscle cell differentiation Source: UniProtKB
  • negative regulation of mesenchymal cell apoptotic process Source: MGI
  • negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • negative regulation of protein catabolic process Source: MGI
  • negative regulation of T cell proliferation Source: MGI
  • negative regulation of transcription elongation from RNA polymerase II promoter Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • negative regulation of ureter smooth muscle cell differentiation Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: MGI
  • negative thymic T cell selection Source: BHF-UCL
  • neural crest cell migration Source: MGI
  • neuroblast proliferation Source: MGI
  • neuron fate commitment Source: MGI
  • odontogenesis Source: MGI
  • odontogenesis of dentin-containing tooth Source: MGI
  • oligodendrocyte development Source: MGI
  • oligodendrocyte differentiation Source: MGI
  • organ formation Source: MGI
  • osteoblast development Source: MGI
  • palate development Source: MGI
  • pancreas development Source: MGI
  • patterning of blood vessels Source: MGI
  • pattern specification process Source: MGI
  • polarity specification of anterior/posterior axis Source: Roslin
  • positive regulation of alpha-beta T cell differentiation Source: BHF-UCL
  • positive regulation of cell differentiation Source: MGI
  • positive regulation of cell division Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of cerebellar granule cell precursor proliferation Source: MGI
  • positive regulation of epithelial cell proliferation involved in prostate gland development Source: MGI
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of hh target transcription factor activity Source: BHF-UCL
  • positive regulation of immature T cell proliferation in thymus Source: BHF-UCL
  • positive regulation of kidney smooth muscle cell differentiation Source: UniProtKB
  • positive regulation of mesenchymal cell proliferation Source: MGI
  • positive regulation of mesenchymal cell proliferation involved in ureter development Source: UniProtKB
  • positive regulation of neuroblast proliferation Source: MGI
  • positive regulation of oligodendrocyte differentiation Source: MGI
  • positive regulation of protein import into nucleus Source: MGI
  • positive regulation of sclerotome development Source: MGI
  • positive regulation of skeletal muscle cell proliferation Source: MGI
  • positive regulation of skeletal muscle tissue development Source: MGI
  • positive regulation of smoothened signaling pathway Source: UniProtKB
  • positive regulation of striated muscle cell differentiation Source: MGI
  • positive regulation of T cell differentiation in thymus Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of ureter smooth muscle cell differentiation Source: UniProtKB
  • positive regulation of Wnt signaling pathway Source: MGI
  • positive thymic T cell selection Source: BHF-UCL
  • primary prostatic bud elongation Source: MGI
  • prostate epithelial cord elongation Source: MGI
  • prostate gland development Source: MGI
  • protein localization to nucleus Source: MGI
  • regulation of cell proliferation Source: MGI
  • regulation of epithelial cell proliferation involved in prostate gland development Source: MGI
  • regulation of gene expression Source: MGI
  • regulation of mesenchymal cell proliferation involved in prostate gland development Source: MGI
  • regulation of odontogenesis Source: BHF-UCL
  • regulation of prostatic bud formation Source: MGI
  • regulation of protein localization to nucleus Source: MGI
  • regulation of proteolysis Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • respiratory tube development Source: MGI
  • right lung development Source: MGI
  • salivary gland cavitation Source: MGI
  • signal transduction Source: MGI
  • skin development Source: MGI
  • smoothened signaling pathway Source: MGI
  • smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation Source: MGI
  • somite development Source: BHF-UCL
  • spinal cord dorsal/ventral patterning Source: MGI
  • spinal cord motor neuron differentiation Source: MGI
  • stem cell development Source: BHF-UCL
  • striated muscle cell differentiation Source: MGI
  • striated muscle tissue development Source: MGI
  • T cell differentiation in thymus Source: BHF-UCL
  • telencephalon regionalization Source: MGI
  • thalamus development Source: MGI
  • thymus development Source: BHF-UCL
  • thyroid gland development Source: MGI
  • trachea development Source: MGI
  • trachea morphogenesis Source: MGI
  • vasculature development Source: MGI
  • vasculogenesis Source: MGI
  • vasculogenesis involved in coronary vascular morphogenesis Source: DFLAT
  • ventral spinal cord interneuron specification Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_282161. Release of Hh-Np from the secreting cell.
REACT_295321. Ligand-receptor interactions.
REACT_335449. Class B/2 (Secretin family receptors).
REACT_347264. Hedgehog ligand biogenesis.

Protein family/group databases

MEROPSiC46.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Sonic hedgehog protein
Short name:
SHH
Alternative name(s):
HHG-1
Cleaved into the following 2 chains:
Alternative name(s):
Sonic hedgehog protein 19 kDa product
Alternative name(s):
Sonic hedgehog protein 27 kDa product
Gene namesi
Name:Shh
Synonyms:Hhg1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:98297. Shh.

Subcellular locationi

Sonic hedgehog protein C-product :
Sonic hedgehog protein N-product :
  • Cell membrane; Lipid-anchor

  • Note: The N-product either remains associated with lipid rafts at the cell surface, or forms freely diffusible active multimers with its hydrophobic lipid-modified N- and C-termini buried inside.

GO - Cellular componenti

  • cell surface Source: MGI
  • extracellular region Source: Reactome
  • extracellular space Source: MGI
  • membrane Source: MGI
  • membrane raft Source: MGI
  • nucleus Source: MGI
  • plasma membrane Source: Reactome
  • proteinaceous extracellular matrix Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi25 – 251C → S: Strongly reduces effects of in vivo overexpression; impairs multimer formation; does not affect subcellular location to lipid rafts. Homozygous mice are characterized by a smaller size and holoprosencephaly at E10.5, and shortening of limbs at E13.5. They die soon after birth. 2 Publications
Mutagenesisi32 – 321G → R: Introduces a cleavage site for a furin-like protease resulting in abnormal protein processing; cleavage at this site removes 11 amino acids from the N-terminal domain and reduces affinity of Shh for Ptch1 and signaling potency in assays using chicken embryo neural plate explants and mouse C3H10T1/2 stem cells. 1 Publication
Mutagenesisi89 – 891D → V: Moderately reduces Ptch1 binding in vitro and signaling potency in chicken embryo neural plate explant assays compared with wild-type sequence. 1 Publication
Mutagenesisi101 – 1011Q → H: Does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions. 1 Publication
Mutagenesisi116 – 1161N → K: Shows no change in activities at different temperatures. 1 Publication
Mutagenesisi118 – 1181W → G: Causes a failure of Shh processing leading to retention of the immature glycosylated protein within the endoplasmic reticulum of transfected cells; causes a temperature-dependent conformational change that allows Shh to bind Ptch1 at 4 or 32 degrees Celsius but not at 37 degrees Celsius; drastically reduces signaling potency in chicken embryo neural plate explant assays. 1 Publication
Mutagenesisi118 – 1181W → R: Causes a failure of Shh processing leading to retention of the immature glycosylated protein within the endoplasmic reticulum of transfected cells; causes a temperature-dependent conformational change that allows Shh to bind Ptch1 at 4 or 32 degrees Celsius but not at 37 degrees Celsius; drastically reduces signaling potency in chicken embryo neural plate explant assays. 1 Publication
Mutagenesisi189 – 1891E → Q: Does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Chaini25 – 437413Sonic hedgehog proteinPRO_0000013211Add
BLAST
Chaini25 – 198174Sonic hedgehog protein N-productPRO_0000013212Add
BLAST
Chaini199 – 437239Sonic hedgehog protein C-productPRO_0000013213Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi25 – 251N-palmitoyl cysteine2 Publications
Lipidationi198 – 1981Cholesterol glycine ester1 Publication
Glycosylationi279 – 2791N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity. 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 (N-product). The N-product is the active species in both local and long-range signaling, whereas the C-product has no signaling activity.3 Publications
Cholesterylation is required for N-product targeting to lipid rafts and multimerization.1 Publication
N-palmitoylation of Cys-25 by HHAT is required for N-product multimerization and full activity.2 Publications

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PRIDEiQ62226.

PTM databases

PhosphoSiteiQ62226.

Expressioni

Tissue specificityi

Expressed in a number of embryonic tissues including the notochord, ventral neural tube, floor plate, lung bud, zone of polarizing activity and posterior distal mesenchyme of limbs. In the adult, expressed in lung and neural retina.

Developmental stagei

First detectable during gastrulation.

Inductioni

By retinoic acid.

Gene expression databases

BgeeiQ62226.
CleanExiMM_SHH.
GenevisibleiQ62226. MM.

Interactioni

Subunit structurei

Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus. N-product is active as a multimer. Interacts with BOC and CDON. Interacts with HHIP.6 Publications

Protein-protein interaction databases

BioGridi203220. 10 interactions.
DIPiDIP-48537N.
STRINGi10090.ENSMUSP00000002708.

Structurei

Secondary structure

1
437
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi48 – 525Combined sources
Turni57 – 604Combined sources
Beta strandi69 – 713Combined sources
Helixi72 – 765Combined sources
Beta strandi85 – 873Combined sources
Beta strandi92 – 943Combined sources
Helixi95 – 973Combined sources
Helixi101 – 11717Combined sources
Beta strandi123 – 1275Combined sources
Beta strandi131 – 1355Combined sources
Helixi140 – 1434Combined sources
Beta strandi146 – 1516Combined sources
Helixi156 – 1583Combined sources
Helixi159 – 16810Combined sources
Beta strandi172 – 1787Combined sources
Beta strandi181 – 1855Combined sources
Helixi189 – 1924Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1VHHX-ray1.70A34-195[»]
2WFXX-ray3.20A40-191[»]
2WG4X-ray3.15A40-191[»]
3D1MX-ray1.70A/B26-189[»]
3N1RX-ray2.13A40-195[»]
4C4MX-ray1.74A40-195[»]
4C4NX-ray2.36A/B40-195[»]
ProteinModelPortaliQ62226.
SMRiQ62226. Positions 39-195, 199-351.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ62226.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi383 – 3875Poly-Gly

Domaini

The 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.3 Publications

Sequence similaritiesi

Belongs to the hedgehog family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG250647.
GeneTreeiENSGT00390000001117.
HOGENOMiHOG000233428.
HOVERGENiHBG005480.
InParanoidiQ62226.
KOiK11988.
OMAiHSWAHRA.
OrthoDBiEOG779NZ5.
PhylomeDBiQ62226.
TreeFamiTF106458.

Family and domain databases

Gene3Di2.170.16.10. 1 hit.
3.30.1380.10. 1 hit.
InterProiIPR001657. Hedgehog.
IPR028992. Hedgehog/Intein_dom.
IPR009045. Hedgehog_sig/DD-Pept_Zn-bd_dom.
IPR000320. Hedgehog_signalling_dom.
IPR001767. Hint_dom.
IPR003586. Hint_dom_C.
IPR003587. Hint_dom_N.
IPR006141. Intein_N.
[Graphical view]
PfamiPF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
[Graphical view]
PIRSFiPIRSF009400. Peptidase_C46. 1 hit.
PRINTSiPR00632. SONICHHOG.
SMARTiSM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
[Graphical view]
SUPFAMiSSF51294. SSF51294. 1 hit.
SSF55166. SSF55166. 1 hit.
PROSITEiPS50817. INTEIN_N_TER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q62226-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLLLLARCFL VILASSLLVC PGLACGPGRG FGKRRHPKKL TPLAYKQFIP
60 70 80 90 100
NVAEKTLGAS GRYEGKITRN SERFKELTPN YNPDIIFKDE ENTGADRLMT
110 120 130 140 150
QRCKDKLNAL AISVMNQWPG VKLRVTEGWD EDGHHSEESL HYEGRAVDIT
160 170 180 190 200
TSDRDRSKYG MLARLAVEAG FDWVYYESKA HIHCSVKAEN SVAAKSGGCF
210 220 230 240 250
PGSATVHLEQ GGTKLVKDLR PGDRVLAADD QGRLLYSDFL TFLDRDEGAK
260 270 280 290 300
KVFYVIETLE PRERLLLTAA HLLFVAPHND SGPTPGPSAL FASRVRPGQR
310 320 330 340 350
VYVVAERGGD RRLLPAAVHS VTLREEEAGA YAPLTAHGTI LINRVLASCY
360 370 380 390 400
AVIEEHSWAH RAFAPFRLAH ALLAALAPAR TDGGGGGSIP AAQSATEARG
410 420 430
AEPTAGIHWY SQLLYHIGTW LLDSETMHPL GMAVKSS
Length:437
Mass (Da):47,773
Last modified:June 1, 1998 - v2
Checksum:iD0EB72F08E7860EF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X76290 mRNA. Translation: CAA53922.1.
AK077688 mRNA. Translation: BAC36956.1.
BC063087 mRNA. Translation: AAH63087.1.
CCDSiCCDS19146.1.
PIRiA49425.
RefSeqiNP_033196.1. NM_009170.3.
UniGeneiMm.57202.

Genome annotation databases

EnsembliENSMUST00000002708; ENSMUSP00000002708; ENSMUSG00000002633.
GeneIDi20423.
KEGGimmu:20423.
UCSCiuc008wua.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X76290 mRNA. Translation: CAA53922.1.
AK077688 mRNA. Translation: BAC36956.1.
BC063087 mRNA. Translation: AAH63087.1.
CCDSiCCDS19146.1.
PIRiA49425.
RefSeqiNP_033196.1. NM_009170.3.
UniGeneiMm.57202.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1VHHX-ray1.70A34-195[»]
2WFXX-ray3.20A40-191[»]
2WG4X-ray3.15A40-191[»]
3D1MX-ray1.70A/B26-189[»]
3N1RX-ray2.13A40-195[»]
4C4MX-ray1.74A40-195[»]
4C4NX-ray2.36A/B40-195[»]
ProteinModelPortaliQ62226.
SMRiQ62226. Positions 39-195, 199-351.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203220. 10 interactions.
DIPiDIP-48537N.
STRINGi10090.ENSMUSP00000002708.

Chemistry

BindingDBiQ62226.
ChEMBLiCHEMBL5387.

Protein family/group databases

MEROPSiC46.002.

PTM databases

PhosphoSiteiQ62226.

Proteomic databases

PRIDEiQ62226.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000002708; ENSMUSP00000002708; ENSMUSG00000002633.
GeneIDi20423.
KEGGimmu:20423.
UCSCiuc008wua.2. mouse.

Organism-specific databases

CTDi6469.
MGIiMGI:98297. Shh.

Phylogenomic databases

eggNOGiNOG250647.
GeneTreeiENSGT00390000001117.
HOGENOMiHOG000233428.
HOVERGENiHBG005480.
InParanoidiQ62226.
KOiK11988.
OMAiHSWAHRA.
OrthoDBiEOG779NZ5.
PhylomeDBiQ62226.
TreeFamiTF106458.

Enzyme and pathway databases

ReactomeiREACT_282161. Release of Hh-Np from the secreting cell.
REACT_295321. Ligand-receptor interactions.
REACT_335449. Class B/2 (Secretin family receptors).
REACT_347264. Hedgehog ligand biogenesis.

Miscellaneous databases

EvolutionaryTraceiQ62226.
NextBioi298432.
PROiQ62226.
SOURCEiSearch...

Gene expression databases

BgeeiQ62226.
CleanExiMM_SHH.
GenevisibleiQ62226. MM.

Family and domain databases

Gene3Di2.170.16.10. 1 hit.
3.30.1380.10. 1 hit.
InterProiIPR001657. Hedgehog.
IPR028992. Hedgehog/Intein_dom.
IPR009045. Hedgehog_sig/DD-Pept_Zn-bd_dom.
IPR000320. Hedgehog_signalling_dom.
IPR001767. Hint_dom.
IPR003586. Hint_dom_C.
IPR003587. Hint_dom_N.
IPR006141. Intein_N.
[Graphical view]
PfamiPF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
[Graphical view]
PIRSFiPIRSF009400. Peptidase_C46. 1 hit.
PRINTSiPR00632. SONICHHOG.
SMARTiSM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
[Graphical view]
SUPFAMiSSF51294. SSF51294. 1 hit.
SSF55166. SSF55166. 1 hit.
PROSITEiPS50817. INTEIN_N_TER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity."
    Echelard Y., Epstein D.J., St Jacques B., Shen L., Mohler J., McMahon J.A., McMahon A.P.
    Cell 75:1417-1430(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
    Tissue: Embryo.
  2. McMahon A.P.
    Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION TO 122.
  3. "Products, genetic linkage and limb patterning activity of a murine hedgehog gene."
    Chang D.T., Lopez A., von Kessler D.P., Chiang C., Simandl B.K., Zhao R., Seldin M.F., Fallon J.F., Beachy P.A.
    Development 120:3339-3353(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEOLYTIC PROCESSING, AUTOCATALYTIC CLEAVAGE.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Limb.
  6. "Proteolytic processing yields two secreted forms of sonic hedgehog."
    Bumcrot D.A., Takada R., McMahon A.P.
    Mol. Cell. Biol. 15:2294-2303(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING, GLYCOSYLATION, SUBCELLULAR LOCATION.
  7. "Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis."
    Roelink H., Porter J.A., Chiang C., Tanabe Y., Chang D.T., Beachy P.A., Jessell T.M.
    Cell 81:445-455(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PROTEOLYTIC PROCESSING, AUTOCATALYTIC CLEAVAGE.
  8. "Cholesterol modification of hedgehog signaling proteins in animal development."
    Porter J.A., Young K.E., Beachy P.A.
    Science 274:255-259(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHOLESTERYLATION AT GLY-198.
  9. "Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal."
    Chamoun Z., Mann R.K., Nellen D., von Kessler D.P., Bellotto M., Beachy P.A., Basler K.
    Science 293:2080-2084(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION AT CYS-25, MUTAGENESIS OF CYS-25.
  10. "RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways."
    Gold D.A., Baek S.H., Schork N.J., Rose D.W., Larsen D.D., Sachs B.D., Rosenfeld M.G., Hamilton B.A.
    Neuron 40:1119-1131(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CEREBELLAR DEVELOPMENT.
  11. "Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates."
    Chen M.-H., Li Y.-J., Kawakami T., Xu S.-M., Chuang P.-T.
    Genes Dev. 18:641-659(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION AT CYS-25, MUTAGENESIS OF CYS-25, SUBUNIT, SUBCELLULAR LOCATION.
  12. "Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly."
    Maity T., Fuse N., Beachy P.A.
    Proc. Natl. Acad. Sci. U.S.A. 102:17026-17031(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF GLY-32; ASP-89; GLN-101; ASN-116; TRP-118 AND GLU-189.
  13. "Mammalian Gup1, a homolog of Saccharomyces cerevisiae glycerol uptake/transporter 1, acts as a negative regulator for N-terminal palmitoylation of Sonic hedgehog."
    Abe Y., Kita Y., Niikura T.
    FEBS J. 275:318-331(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HHATL.
  14. "A potential catalytic site revealed by the 1.7-A crystal structure of the amino-terminal signalling domain of Sonic hedgehog."
    Hall T.M.T., Porter J.A., Beachy P.A., Leahy D.J.
    Nature 378:212-216(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 34-195 IN COMPLEX WITH ZINC IONS.
  15. "The mode of Hedgehog binding to Ihog homologues is not conserved across different phyla."
    McLellan J.S., Zheng X., Hauk G., Ghirlando R., Beachy P.A., Leahy D.J.
    Nature 455:979-983(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 26-189 IN COMPLEX WITH CDON; CALCIUM AND ZINC IONS, DOMAIN, INTERACTION WITH CDON.
  16. "Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP."
    Bishop B., Aricescu A.R., Harlos K., O'Callaghan C.A., Jones E.Y., Siebold C.
    Nat. Struct. Mol. Biol. 16:698-703(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 40-191 IN COMPLEX WITH HHIP; CALCIUM AND ZINC IONS, DOMAIN, INTERACTION WITH HHIP.
  17. "All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner."
    Kavran J.M., Ward M.D., Oladosu O.O., Mulepati S., Leahy D.J.
    J. Biol. Chem. 285:24584-24590(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 26-189 IN COMPLEX WITH CALCIUM AND ZINC IONS, DOMAIN, INTERACTION WITH BOC AND CDON.

Entry informationi

Entry nameiSHH_MOUSE
AccessioniPrimary (citable) accession number: Q62226
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: June 24, 2015
This is version 169 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Mice overexpressing Shh display digit duplications in both forelimbs and hindlimbs.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.