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Q62226 (SHH_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 158. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sonic hedgehog protein

Short name=SHH
Alternative name(s):
HHG-1
Gene names
Name:Shh
Synonyms:Hhg1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length437 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.9

Subunit structure

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. Ref.10 Ref.12 Ref.14 Ref.15 Ref.16

Subcellular location

Sonic hedgehog protein C-product: Secretedextracellular space. Note: The C-terminal peptide diffuses from the cell. Ref.10

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. Ref.10

Tissue specificity

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 stage

First detectable during gastrulation.

Induction

By retinoic acid.

Domain

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. Ref.14 Ref.15 Ref.16

Post-translational modification

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.

Cholesterylation is required for N-product targeting to lipid rafts and multimerization.

N-palmitoylation of Cys-25 by HHAT is required for N-product multimerization and full activity. Ref.8 Ref.10

Miscellaneous

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

Sequence similarities

Belongs to the hedgehog family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   DomainSignal
   LigandCalcium
Metal-binding
Zinc
   Molecular functionDevelopmental protein
Hydrolase
Protease
   PTMAutocatalytic cleavage
Glycoprotein
Lipoprotein
Palmitate
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBergmann glial cell differentiation

Inferred from direct assay PubMed 10375501. Source: MGI

CD4-positive or CD8-positive, alpha-beta T cell lineage commitment

Inferred from mutant phenotype PubMed 17227833. Source: BHF-UCL

T cell differentiation in thymus

Inferred from mutant phenotype PubMed 19273836. Source: BHF-UCL

anatomical structure development

Inferred from mutant phenotype PubMed 11485934. Source: MGI

anatomical structure formation involved in morphogenesis

Inferred from mutant phenotype PubMed 9768363. Source: MGI

androgen metabolic process

Inferred from mutant phenotype PubMed 15013801. Source: MGI

angiogenesis

Inferred from direct assay PubMed 16778080. Source: MGI

anterior/posterior pattern specification

Inferred from mutant phenotype PubMed 11118883PubMed 11389830. Source: MGI

apoptotic process

Inferred from genetic interaction PubMed 19029980. Source: MGI

apoptotic signaling pathway

Inferred from direct assay PubMed 11044396. Source: Roslin

artery development

Inferred from mutant phenotype PubMed 16968815. Source: MGI

axon guidance

Inferred from direct assay PubMed 12679031. Source: MGI

blood coagulation

Inferred from mutant phenotype PubMed 8835524. Source: MGI

branching involved in prostate gland morphogenesis

Inferred from direct assay PubMed 10208740. Source: MGI

branching involved in salivary gland morphogenesis

Inferred from mutant phenotype PubMed 15042696. Source: MGI

branching involved in ureteric bud morphogenesis

Inferred from mutant phenotype PubMed 16396903. Source: MGI

branching morphogenesis of an epithelial tube

Inferred from mutant phenotype PubMed 15042696PubMed 15305287PubMed 9768363. Source: MGI

bud outgrowth involved in lung branching

Inferred from mutant phenotype PubMed 9731532. Source: MGI

camera-type eye development

Inferred from direct assay PubMed 12195432. Source: MGI

canonical Wnt signaling pathway

Inferred from direct assay PubMed 17284610. Source: MGI

cell death

Inferred from mutant phenotype. Source: MGI

cell development

Inferred from mutant phenotype PubMed 15183722PubMed 16236765. Source: MGI

cell fate commitment

Inferred from genetic interaction PubMed 17504941. Source: MGI

cell fate specification

Inferred from direct assay PubMed 18076286. Source: MGI

cell proliferation

Inferred from genetic interaction PubMed 19056373. Source: MGI

cell-cell signaling

Inferred from mutant phenotype PubMed 15199404PubMed 16492970. Source: MGI

cellular response to lithium ion

Inferred from direct assay PubMed 17284610. Source: MGI

central nervous system development

Inferred from mutant phenotype PubMed 12435628. Source: MGI

cerebellar granule cell precursor proliferation

Inferred from genetic interaction Ref.9. Source: UniProtKB

determination of left/right asymmetry in lateral mesoderm

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

determination of left/right symmetry

Inferred from mutant phenotype PubMed 10385121PubMed 10411502PubMed 10500184. Source: MGI

developmental growth

Inferred from mutant phenotype PubMed 11044393. Source: MGI

digestive tract morphogenesis

Inferred from mutant phenotype PubMed 9731532. Source: MGI

dorsal/ventral neural tube patterning

Inferred from mutant phenotype PubMed 21209331. Source: BHF-UCL

dorsal/ventral pattern formation

Inferred from genetic interaction PubMed 15269168PubMed 21552265. Source: MGI

ectoderm development

Inferred from mutant phenotype PubMed 11118883. Source: MGI

embryonic digestive tract morphogenesis

Traceable author statement PubMed 11001584. Source: BHF-UCL

embryonic digit morphogenesis

Inferred from mutant phenotype PubMed 11044396. Source: Roslin

embryonic foregut morphogenesis

Inferred from mutant phenotype PubMed 9731532. Source: MGI

embryonic forelimb morphogenesis

Inferred from mutant phenotype PubMed 11118883PubMed 11476582. Source: MGI

embryonic hindlimb morphogenesis

Inferred from mutant phenotype PubMed 11118883. Source: MGI

embryonic limb morphogenesis

Inferred from mutant phenotype PubMed 11389830PubMed 15315763. Source: MGI

embryonic morphogenesis

Inferred from mutant phenotype PubMed 16492970PubMed 17881493. Source: MGI

embryonic organ development

Inferred from mutant phenotype PubMed 15680353. Source: MGI

embryonic skeletal system development

Inferred from genetic interaction PubMed 17504941. Source: MGI

endocytosis

Inferred from direct assay PubMed 18477453. Source: MGI

epithelial cell proliferation involved in salivary gland morphogenesis

Inferred from mutant phenotype PubMed 15042696. Source: MGI

epithelial tube branching involved in lung morphogenesis

Inferred from mutant phenotype PubMed 10500184PubMed 9731532. Source: MGI

epithelial-mesenchymal cell signaling

Inferred from mutant phenotype PubMed 19304890. Source: MGI

epithelial-mesenchymal signaling involved in prostate gland development

Inferred from genetic interaction PubMed 15987773. Source: MGI

establishment of cell polarity

Inferred from direct assay PubMed 16332353. Source: MGI

forebrain development

Inferred from genetic interaction PubMed 16020517. Source: MGI

formation of anatomical boundary

Inferred from mutant phenotype PubMed 9731532. Source: MGI

hair follicle development

Inferred from mutant phenotype PubMed 16054035. Source: MGI

hair follicle morphogenesis

Inferred from mutant phenotype PubMed 11520664PubMed 14623238PubMed 9768360. Source: MGI

heart development

Inferred from mutant phenotype PubMed 10500184PubMed 11172440PubMed 15936751. Source: MGI

heart looping

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

hindbrain development

Inferred from mutant phenotype PubMed 15183722. Source: MGI

hindgut morphogenesis

Inferred from mutant phenotype PubMed 11485934. Source: MGI

inner ear development

Inferred from mutant phenotype PubMed 17395647. Source: MGI

intein-mediated protein splicing

Inferred from electronic annotation. Source: InterPro

intermediate filament organization

Inferred from mutant phenotype PubMed 11171399. Source: MGI

kidney development

Inferred from mutant phenotype PubMed 11172440. Source: MGI

left lung development

Inferred from mutant phenotype PubMed 10500184. Source: MGI

limb bud formation

Inferred from mutant phenotype PubMed 11118883. Source: MGI

limb development

Inferred from mutant phenotype PubMed 19223390. Source: MGI

lung development

Inferred from mutant phenotype PubMed 15136151PubMed 15305287PubMed 17187775PubMed 9731532PubMed 9768363. Source: MGI

lung epithelium development

Inferred from mutant phenotype PubMed 9731532. Source: MGI

lung lobe morphogenesis

Inferred from mutant phenotype PubMed 9731532. Source: MGI

lung morphogenesis

Inferred from mutant phenotype PubMed 10500184. Source: MGI

lung-associated mesenchyme development

Inferred from mutant phenotype PubMed 9731532. Source: MGI

lymphoid progenitor cell differentiation

Inferred from mutant phenotype PubMed 14764698. Source: BHF-UCL

male genitalia development

Inferred from mutant phenotype PubMed 11684660. Source: MGI

mesenchymal cell proliferation

Inferred from mutant phenotype PubMed 9731532. Source: MGI

mesenchymal cell proliferation involved in lung development

Inferred from direct assay PubMed 9006067. Source: MGI

mesenchymal smoothened signaling pathway involved in prostate gland development

Inferred from mutant phenotype PubMed 12221011. Source: MGI

metanephric mesenchymal cell proliferation involved in metanephros development

Inferred from mutant phenotype PubMed 12399320. Source: UniProtKB

metanephros development

Inferred from mutant phenotype PubMed 12399320. Source: UniProtKB

midbrain development

Inferred from genetic interaction PubMed 16020517. Source: MGI

multicellular structure septum development

Inferred from mutant phenotype PubMed 9731532. Source: MGI

myoblast differentiation

Inferred from direct assay PubMed 15238161. Source: MGI

myotube differentiation

Inferred from mutant phenotype PubMed 11171399. Source: MGI

negative regulation of T cell proliferation

Inferred from mutant phenotype PubMed 10981962. Source: MGI

negative regulation of Wnt signaling pathway

Inferred from direct assay PubMed 9356179. Source: MGI

negative regulation of alpha-beta T cell differentiation

Inferred from mutant phenotype PubMed 10981962. Source: MGI

negative regulation of apoptotic process

Inferred from direct assay PubMed 11044396. Source: Roslin

negative regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype PubMed 17284610. Source: MGI

negative regulation of cell differentiation

Inferred from direct assay PubMed 15337776. Source: MGI

negative regulation of cell migration

Inferred from direct assay PubMed 15337776. Source: MGI

negative regulation of cholesterol efflux

Inferred from mutant phenotype PubMed 21931618. Source: BHF-UCL

negative regulation of gene expression

Inferred from mutant phenotype PubMed 16396903. Source: UniProtKB

negative regulation of kidney smooth muscle cell differentiation

Inferred from direct assay PubMed 12399320. Source: UniProtKB

negative regulation of mesenchymal cell apoptotic process

Inferred from mutant phenotype PubMed 19422820. Source: MGI

negative regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype PubMed 16611981. Source: MGI

negative regulation of protein catabolic process

Inferred from mutant phenotype PubMed 16611981. Source: MGI

negative regulation of transcription elongation from RNA polymerase II promoter

Inferred from direct assay PubMed 17284610. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 21447550. Source: BHF-UCL

negative regulation of ureter smooth muscle cell differentiation

Inferred from direct assay PubMed 12399320. Source: UniProtKB

negative thymic T cell selection

Inferred from mutant phenotype PubMed 17227833. Source: BHF-UCL

neural crest cell migration

Inferred from mutant phenotype PubMed 15936751. Source: MGI

neuroblast proliferation

Inferred from direct assay PubMed 15337776. Source: MGI

neuron fate commitment

Inferred from mutant phenotype PubMed 16221724. Source: MGI

odontogenesis

Inferred from direct assay PubMed 10781055. Source: MGI

odontogenesis of dentin-containing tooth

Inferred from mutant phenotype PubMed 11044393. Source: MGI

oligodendrocyte development

Inferred from direct assay PubMed 8660874. Source: MGI

oligodendrocyte differentiation

Inferred from genetic interaction PubMed 11171336PubMed 11493571PubMed 15880651. Source: MGI

organ formation

Inferred from mutant phenotype PubMed 15013801. Source: MGI

osteoblast development

Inferred from direct assay PubMed 16880529. Source: MGI

palate development

Inferred from mutant phenotype PubMed 19304890. Source: MGI

pancreas development

Inferred from mutant phenotype PubMed 10821773PubMed 11044404. Source: MGI

pattern specification process

Inferred from mutant phenotype PubMed 12231626. Source: MGI

patterning of blood vessels

Inferred from mutant phenotype PubMed 15936751. Source: MGI

polarity specification of anterior/posterior axis

Inferred from mutant phenotype PubMed 11044396. Source: Roslin

positive regulation of T cell differentiation in thymus

Inferred from mutant phenotype PubMed 19109233. Source: BHF-UCL

positive regulation of Wnt signaling pathway

Inferred from mutant phenotype PubMed 11520664. Source: MGI

positive regulation of alpha-beta T cell differentiation

Inferred from mutant phenotype PubMed 14764698. Source: BHF-UCL

positive regulation of cell differentiation

Inferred from mutant phenotype PubMed 10357934. Source: MGI

positive regulation of cell division

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from direct assay PubMed 11748155. Source: MGI

positive regulation of cerebellar granule cell precursor proliferation

Inferred from direct assay PubMed 10027293. Source: MGI

positive regulation of epithelial cell proliferation involved in prostate gland development

Inferred from mutant phenotype PubMed 12221011. Source: MGI

positive regulation of gene expression

Inferred from mutant phenotype PubMed 16396903. Source: UniProtKB

positive regulation of hh target transcription factor activity

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

positive regulation of immature T cell proliferation in thymus

Inferred from mutant phenotype PubMed 14764698PubMed 19273836. Source: BHF-UCL

positive regulation of kidney smooth muscle cell differentiation

Inferred from direct assay PubMed 12399320. Source: UniProtKB

positive regulation of mesenchymal cell proliferation

Inferred from mutant phenotype PubMed 9731532. Source: MGI

positive regulation of mesenchymal cell proliferation involved in ureter development

Inferred from mutant phenotype PubMed 12399320. Source: UniProtKB

positive regulation of neuroblast proliferation

Inferred from direct assay PubMed 11748155. Source: MGI

positive regulation of oligodendrocyte differentiation

Inferred from direct assay PubMed 11171336. Source: MGI

positive regulation of protein import into nucleus

Inferred from genetic interaction PubMed 17043310. Source: MGI

positive regulation of sclerotome development

Inferred from electronic annotation. Source: Ensembl

positive regulation of skeletal muscle cell proliferation

Inferred from mutant phenotype PubMed 11171399. Source: MGI

positive regulation of skeletal muscle tissue development

Inferred from mutant phenotype PubMed 11171399. Source: MGI

positive regulation of smoothened signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of striated muscle cell differentiation

Inferred from mutant phenotype PubMed 11171399. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 21447550. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12399320. Source: UniProtKB

positive regulation of ureter smooth muscle cell differentiation

Inferred from mutant phenotype PubMed 12399320. Source: UniProtKB

positive thymic T cell selection

Inferred from mutant phenotype PubMed 17227833. Source: BHF-UCL

primary prostatic bud elongation

Inferred from direct assay PubMed 10208740. Source: MGI

prostate epithelial cord elongation

Inferred from direct assay PubMed 15013801. Source: MGI

prostate gland development

Inferred from mutant phenotype PubMed 10208740PubMed 15013801. Source: MGI

protein localization to nucleus

Inferred from direct assay PubMed 19952108. Source: MGI

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of cell proliferation

Inferred from direct assay PubMed 12756179. Source: MGI

regulation of epithelial cell proliferation involved in prostate gland development

Inferred from mutant phenotype PubMed 12221011. Source: MGI

regulation of gene expression

Inferred from direct assay PubMed 22179047. Source: MGI

regulation of mesenchymal cell proliferation involved in prostate gland development

Inferred from mutant phenotype PubMed 12221011. Source: MGI

regulation of odontogenesis

Inferred from mutant phenotype PubMed 21447550. Source: BHF-UCL

regulation of prostatic bud formation

Inferred from direct assay PubMed 18393306. Source: MGI

regulation of proteolysis

Inferred from direct assay PubMed 15136151. Source: MGI

regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 11171399PubMed 11412027. Source: MGI

respiratory tube development

Inferred from mutant phenotype PubMed 9731532. Source: MGI

right lung development

Inferred from mutant phenotype PubMed 10500184. Source: MGI

salivary gland cavitation

Inferred from direct assay PubMed 16332353. Source: MGI

signal transduction

Traceable author statement PubMed 11684660. Source: MGI

skin development

Inferred from mutant phenotype PubMed 10331973. Source: MGI

smoothened signaling pathway

Inferred from direct assay PubMed 8906787. Source: MGI

smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation

Inferred from direct assay PubMed 10375501. Source: MGI

somite development

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

spinal cord dorsal/ventral patterning

Inferred from mutant phenotype PubMed 11748151. Source: MGI

spinal cord motor neuron differentiation

Inferred from genetic interaction PubMed 21552265. Source: MGI

stem cell development

Inferred from mutant phenotype PubMed 12843296. Source: BHF-UCL

striated muscle cell differentiation

Inferred from direct assay PubMed 15238161. Source: MGI

striated muscle tissue development

Inferred from mutant phenotype PubMed 11171399. Source: MGI

telencephalon regionalization

Inferred from mutant phenotype PubMed 11060228. Source: MGI

thalamus development

Inferred from mutant phenotype PubMed 19357274. Source: MGI

thymus development

Inferred from mutant phenotype PubMed 19109233. Source: BHF-UCL

thyroid gland development

Inferred from mutant phenotype PubMed 16968815. Source: MGI

trachea development

Inferred from mutant phenotype PubMed 9731532. Source: MGI

trachea morphogenesis

Inferred from mutant phenotype PubMed 9731532. Source: MGI

vasculature development

Inferred from mutant phenotype PubMed 17881493. Source: MGI

vasculogenesis

Inferred from direct assay PubMed 15294868. Source: MGI

vasculogenesis involved in coronary vascular morphogenesis

Traceable author statement PubMed 20299672. Source: DFLAT

   Cellular_componentcell surface

Inferred from direct assay PubMed 15576403. Source: MGI

extracellular matrix

Inferred from direct assay PubMed 11476578. Source: MGI

extracellular space

Inferred from direct assay PubMed 10027293PubMed 7891723. Source: MGI

membrane

Inferred from direct assay PubMed 18477453. Source: MGI

membrane raft

Inferred from direct assay Ref.10. Source: MGI

nucleus

Inferred from direct assay PubMed 11724907. Source: MGI

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncalcium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

glycoprotein binding

Inferred from direct assay PubMed 11476578. Source: MGI

glycosaminoglycan binding

Inferred from direct assay PubMed 11476578. Source: MGI

laminin-1 binding

Inferred from direct assay PubMed 15056720. Source: MGI

patched binding

Inferred from physical interaction PubMed 9811851. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.12PubMed 19478089. Source: UniProtKB

signal transducer activity

Inferred from electronic annotation. Source: Ensembl

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 437413Sonic hedgehog protein
PRO_0000013211
Chain25 – 198174Sonic hedgehog protein N-product
PRO_0000013212
Chain199 – 437239Sonic hedgehog protein C-product
PRO_0000013213

Regions

Compositional bias383 – 3875Poly-Gly

Sites

Metal binding901Calcium 1
Metal binding911Calcium 1
Metal binding911Calcium 2
Metal binding961Calcium 1
Metal binding1261Calcium 1; via carbonyl oxygen
Metal binding1271Calcium 1
Metal binding1271Calcium 2
Metal binding1301Calcium 2
Metal binding1321Calcium 2
Metal binding1411Zinc
Metal binding1481Zinc
Metal binding1831Zinc
Site198 – 1992Cleavage; by autolysis By similarity
Site2441Involved in cholesterol transfer By similarity
Site2681Involved in auto-cleavage By similarity
Site2711Essential for auto-cleavage By similarity

Amino acid modifications

Lipidation251N-palmitoyl cysteine Ref.8 Ref.10
Lipidation1981Cholesterol glycine ester Ref.7
Glycosylation2791N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis251C → 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. Ref.8 Ref.10
Mutagenesis321G → 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. Ref.11
Mutagenesis891D → V: Moderately reduces Ptch1 binding in vitro and signaling potency in chicken embryo neural plate explant assays compared with wild-type sequence. Ref.11
Mutagenesis1011Q → H: Does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions. Ref.11
Mutagenesis1161N → K: Shows no change in activities at different temperatures. Ref.11
Mutagenesis1181W → 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. Ref.11
Mutagenesis1181W → 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. Ref.11
Mutagenesis1891E → Q: Does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions. Ref.11

Secondary structure

................................ 437
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q62226 [UniParc].

Last modified June 1, 1998. Version 2.
Checksum: D0EB72F08E7860EF

FASTA43747,773
        10         20         30         40         50         60 
MLLLLARCFL VILASSLLVC PGLACGPGRG FGKRRHPKKL TPLAYKQFIP NVAEKTLGAS 

        70         80         90        100        110        120 
GRYEGKITRN SERFKELTPN YNPDIIFKDE ENTGADRLMT QRCKDKLNAL AISVMNQWPG 

       130        140        150        160        170        180 
VKLRVTEGWD EDGHHSEESL HYEGRAVDIT TSDRDRSKYG MLARLAVEAG FDWVYYESKA 

       190        200        210        220        230        240 
HIHCSVKAEN SVAAKSGGCF PGSATVHLEQ GGTKLVKDLR PGDRVLAADD QGRLLYSDFL 

       250        260        270        280        290        300 
TFLDRDEGAK KVFYVIETLE PRERLLLTAA HLLFVAPHND SGPTPGPSAL FASRVRPGQR 

       310        320        330        340        350        360 
VYVVAERGGD RRLLPAAVHS VTLREEEAGA YAPLTAHGTI LINRVLASCY AVIEEHSWAH 

       370        380        390        400        410        420 
RAFAPFRLAH ALLAALAPAR TDGGGGGSIP AAQSATEARG AEPTAGIHWY SQLLYHIGTW 

       430 
LLDSETMHPL GMAVKSS 

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References

« Hide 'large scale' references
[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], 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. expand/collapse author list , 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]"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, AUTOCATALYTIC CLEAVAGE.
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.
[16]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X76290 mRNA. Translation: CAA53922.1.
AK077688 mRNA. Translation: BAC36956.1.
BC063087 mRNA. Translation: AAH63087.1.
CCDSCCDS19146.1.
PIRA49425.
RefSeqNP_033196.1. NM_009170.3.
UniGeneMm.57202.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ62226.
SMRQ62226. Positions 39-195, 199-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203220. 10 interactions.
DIPDIP-48537N.
STRING10090.ENSMUSP00000002708.

Chemistry

BindingDBQ62226.
ChEMBLCHEMBL5387.

Protein family/group databases

MEROPSC46.002.

PTM databases

PhosphoSiteQ62226.

Proteomic databases

PRIDEQ62226.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000002708; ENSMUSP00000002708; ENSMUSG00000002633.
GeneID20423.
KEGGmmu:20423.
UCSCuc008wua.2. mouse.

Organism-specific databases

CTD6469.
MGIMGI:98297. Shh.

Phylogenomic databases

eggNOGNOG250647.
GeneTreeENSGT00390000001117.
HOGENOMHOG000233428.
HOVERGENHBG005480.
InParanoidQ62226.
KOK11988.
OMAHSWAHRA.
OrthoDBEOG779NZ5.
PhylomeDBQ62226.
TreeFamTF106458.

Gene expression databases

BgeeQ62226.
CleanExMM_SHH.
GenevestigatorQ62226.

Family and domain databases

Gene3D2.170.16.10. 1 hit.
3.30.1380.10. 1 hit.
InterProIPR001657. 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_splice_site.
[Graphical view]
PfamPF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
[Graphical view]
PIRSFPIRSF009400. Peptidase_C46. 1 hit.
PRINTSPR00632. SONICHHOG.
SMARTSM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
[Graphical view]
SUPFAMSSF51294. SSF51294. 1 hit.
SSF55166. SSF55166. 1 hit.
PROSITEPS50817. INTEIN_N_TER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ62226.
NextBio298432.
PROQ62226.
SOURCESearch...

Entry information

Entry nameSHH_MOUSE
AccessionPrimary (citable) accession number: Q62226
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 158 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot