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Q63673 (SHH_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | 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
Gene names
Name:Shh
Synonyms:Vhh-1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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 By similarity.

Subunit structure

Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus. Interacts with BOC and CDON. Interacts with HHIP By similarity. N-product is active as a multimer. Ref.2

Subcellular location

Sonic hedgehog protein C-product: Secretedextracellular space. Note: The C-terminal peptide diffuses from the cell. Ref.2

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.2

Tissue specificity

Expressed in the node, notochord, floor plate, and posterior limb bud mesenchyme.

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 By similarity.

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 By similarity.

N-palmitoylation of Cys-25 by HHAT is required for N-product multimerization and full activity By similarity.

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 termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processCD4-positive or CD8-positive, alpha-beta T cell lineage commitment

Inferred from sequence or structural similarity. Source: UniProtKB

T cell differentiation in thymus

Inferred from sequence or structural similarity. Source: UniProtKB

androgen metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProt

axon guidance

Inferred from sequence or structural similarity. Source: UniProtKB

branching involved in ureteric bud morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

branching morphogenesis of an epithelial tube

Inferred from sequence or structural similarity. Source: UniProtKB

cell development

Inferred from sequence or structural similarity. Source: UniProtKB

cell fate specification

Inferred from sequence or structural similarity. Source: UniProtKB

cell-cell signaling

Inferred from sequence or structural similarity. Source: UniProtKB

central nervous system development

Inferred from sequence or structural similarity. Source: UniProtKB

cerebellar granule cell precursor proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

digestive tract mesoderm development

Inferred from direct assay PubMed 9368764. Source: RGD

dorsal/ventral pattern formation

Inferred from sequence or structural similarity. Source: UniProtKB

embryo development

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic digit morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic limb morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

epithelial tube branching involved in lung morphogenesis

Inferred from expression pattern PubMed 8769111. Source: RGD

forebrain development

Inferred from sequence or structural similarity. Source: UniProtKB

fungiform papilla development

Inferred from mutant phenotype PubMed 15581865. Source: RGD

fungiform papilla formation

Inferred from mutant phenotype PubMed 15581865. Source: RGD

fungiform papilla morphogenesis

Inferred from mutant phenotype PubMed 15581865. Source: RGD

heart development

Inferred from sequence or structural similarity. Source: UniProtKB

hindbrain development

Inferred from sequence or structural similarity. Source: UniProtKB

intein-mediated protein splicing

Inferred from electronic annotation. Source: InterPro

lung development

Inferred from sequence or structural similarity. Source: UniProtKB

lymphoid progenitor cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

male genitalia development

Inferred from sequence or structural similarity. Source: UniProtKB

male genitalia morphogenesis

Inferred from mutant phenotype PubMed 12533405. Source: RGD

metanephric mesenchymal cell proliferation involved in metanephros development

Inferred from sequence or structural similarity. Source: UniProtKB

metanephros development

Inferred from sequence or structural similarity. Source: UniProtKB

midbrain development

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 16988214. Source: RGD

negative regulation of cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of kidney smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of ureter smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative thymic T cell selection

Inferred from sequence or structural similarity. Source: UniProtKB

neural crest cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

neural tube formation

Inferred from mutant phenotype Ref.1. Source: RGD

neuroblast proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

neuron fate commitment

Inferred from sequence or structural similarity. Source: UniProtKB

pattern specification process

Inferred from sequence or structural similarity. Source: UniProtKB

patterning of blood vessels

Inferred from sequence or structural similarity. Source: UniProtKB

polarity specification of anterior/posterior axis

Inferred from sequence or structural similarity. Source: UniProt

positive regulation of T cell differentiation in thymus

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of alpha-beta T cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of immature T cell proliferation in thymus

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of kidney smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mesenchymal cell proliferation involved in ureter development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuroblast proliferation

Inferred from direct assay PubMed 12469128. Source: RGD

positive regulation of neuron differentiation

Inferred from mutant phenotype Ref.1. Source: RGD

positive regulation of oligodendrocyte progenitor proliferation

Inferred from direct assay PubMed 12237843. Source: RGD

positive regulation of penile erection

Inferred from mutant phenotype PubMed 12533405. Source: RGD

positive regulation of photoreceptor cell differentiation

Inferred from direct assay PubMed 9236238. Source: RGD

positive regulation of smoothened signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ureter smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive thymic T cell selection

Inferred from sequence or structural similarity. Source: UniProtKB

prostate gland development

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of epithelial cell differentiation

Inferred from expression pattern PubMed 14651923. Source: RGD

regulation of proteolysis

Inferred from sequence or structural similarity. Source: UniProtKB

response to axon injury

Inferred from mutant phenotype PubMed 15356205. Source: RGD

response to estradiol

Inferred from expression pattern PubMed 15328011. Source: RGD

response to ethanol

Inferred from direct assay PubMed 19139721. Source: RGD

response to hypoxia

Inferred from expression pattern PubMed 18228117. Source: RGD

response to organonitrogen compound

Inferred from expression pattern PubMed 16369776. Source: RGD

response to retinoic acid

Inferred from expression pattern PubMed 10633866. Source: RGD

smoothened signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

spinal cord dorsal/ventral patterning

Inferred from direct assay PubMed 9230312. Source: MGI

stem cell development

Inferred from sequence or structural similarity. Source: UniProtKB

telencephalon regionalization

Inferred from mutant phenotype PubMed 9811591. Source: RGD

thymus development

Inferred from sequence or structural similarity. Source: UniProtKB

tongue development

Inferred from mutant phenotype PubMed 15581865. Source: RGD

tongue morphogenesis

Inferred from mutant phenotype PubMed 15581865. Source: RGD

vasculogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

ventral spinal cord interneuron specification

Inferred from direct assay PubMed 9230312. Source: MGI

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 19139721. Source: RGD

axon

Inferred from direct assay PubMed 21182949. Source: RGD

cell surface

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite

Inferred from direct assay PubMed 21182949. Source: RGD

endoplasmic reticulum

Inferred from direct assay PubMed 19139721. Source: RGD

extracellular space

Inferred from sequence or structural similarity. Source: UniProtKB

membrane raft

Inferred from sequence or structural similarity. Source: UniProtKB

neuronal cell body

Inferred from direct assay PubMed 21182949. Source: RGD

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

transport vesicle

Inferred from direct assay PubMed 19139721. Source: RGD

   Molecular_functioncalcium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

laminin-1 binding

Inferred from sequence or structural similarity. Source: UniProtKB

peptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 19139721. Source: RGD

receptor binding

Traceable author statement PubMed 12417650. Source: RGD

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_0000013214
Chain25 – 198174Sonic hedgehog protein N-product
PRO_0000013215
Chain199 – 437239Sonic hedgehog protein C-product
PRO_0000013216

Regions

Compositional bias383 – 3875Poly-Gly

Sites

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

Amino acid modifications

Lipidation251N-palmitoyl cysteine By similarity
Lipidation1981Cholesterol glycine ester By similarity
Glycosylation2791N-linked (GlcNAc...) Potential

Sequences

Sequence LengthMass (Da)Tools
Q63673 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 0DBFC19F0D1662A0

FASTA43747,630
        10         20         30         40         50         60 
MLLLLARCFL VALASSLLVC PGLACGPGRG FGKRQHPKKL 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 
RIHCSVKAEN SVAAKSDGCF PGSATVHLEQ GGTKLVKDLS PGDRVLAADD QGRLLYSDFL 

       250        260        270        280        290        300 
TFLDRDEGAK KVFYVIETRE PRERLLLTAA HLLFVAPHND SGPTPGPSPL FASRVRPGQR 

       310        320        330        340        350        360 
VYVVAERGGD RRLLPAAVHS VTLREEAAGA YAPLTADGTI LINRVLASCY AVIEEHSWAH 

       370        380        390        400        410        420 
RAFAPFRLAH ALLAALAPAR TDGGGGGSIP APQSVAEARG AGPPAGIHWY SQLLYHIGTW 

       430 
LLDSETLHPL GMAVKSS 

« Hide

References

[1]"Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord."
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.
Cell 76:761-775(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Embryonic floor plate.
[2]"A freely diffusible form of Sonic hedgehog mediates long-range signalling."
Zeng X., Goetz J.A., Suber L.M., Scott W.J. Jr., Schreiner C.M., Robbins D.J.
Nature 411:716-720(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L27340 mRNA. Translation: AAA20999.1.
PIRB53193.
RefSeqNP_058917.1. NM_017221.1.
UniGeneRn.10432.

3D structure databases

ProteinModelPortalQ63673.
SMRQ63673. Positions 39-195.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000008497.

Protein family/group databases

MEROPSC46.002.

Proteomic databases

PRIDEQ63673.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID29499.
KEGGrno:29499.

Organism-specific databases

CTD6469.
RGD3673. Shh.

Phylogenomic databases

eggNOGNOG250647.
HOGENOMHOG000233428.
HOVERGENHBG005480.
InParanoidQ63673.
KOK11988.
PhylomeDBQ63673.

Gene expression databases

GenevestigatorQ63673.

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

NextBio609396.
PROQ63673.

Entry information

Entry nameSHH_RAT
AccessionPrimary (citable) accession number: Q63673
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 133 of the entry and version 1 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