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Protein

Sonic hedgehog protein

Gene

Shh

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi90 – 901Calcium 1By similarity
Metal bindingi91 – 911Calcium 1By similarity
Metal bindingi91 – 911Calcium 2By similarity
Metal bindingi96 – 961Calcium 1By similarity
Metal bindingi126 – 1261Calcium 1; via carbonyl oxygenBy similarity
Metal bindingi127 – 1271Calcium 1By similarity
Metal bindingi127 – 1271Calcium 2By similarity
Metal bindingi130 – 1301Calcium 2By similarity
Metal bindingi132 – 1321Calcium 2By similarity
Metal bindingi141 – 1411ZincBy similarity
Metal bindingi148 – 1481ZincBy similarity
Metal bindingi183 – 1831ZincBy similarity
Sitei198 – 1992Cleavage; by autolysis
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
  • laminin-1 binding Source: UniProtKB
  • peptidase activity Source: UniProtKB-KW
  • receptor binding Source: RGD
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Protein family/group databases

MEROPSiC46.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Sonic hedgehog protein
Short name:
SHH
Cleaved into the following 2 chains:
Gene namesi
Name:Shh
Synonyms:Vhh-1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3673. 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

  • axon Source: RGD
  • cell surface Source: UniProtKB
  • dendrite Source: RGD
  • endoplasmic reticulum Source: RGD
  • extracellular space Source: UniProtKB
  • Golgi apparatus Source: RGD
  • membrane raft Source: UniProtKB
  • neuronal cell body Source: RGD
  • plasma membrane Source: UniProtKB-SubCell
  • transport vesicle Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Chaini25 – 437413Sonic hedgehog proteinPRO_0000013214Add
BLAST
Chaini25 – 198174Sonic hedgehog protein N-productPRO_0000013215Add
BLAST
Chaini199 – 437239Sonic hedgehog protein C-productPRO_0000013216Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi25 – 251N-palmitoyl cysteineBy similarity
Lipidationi198 – 1981Cholesterol glycine esterBy similarity
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.
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

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PRIDEiQ63673.

Expressioni

Tissue specificityi

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

Gene expression databases

GenevisibleiQ63673. RN.

Interactioni

Subunit structurei

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.By similarity1 Publication

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000008497.

Structurei

3D structure databases

ProteinModelPortaliQ63673.
SMRiQ63673. Positions 39-195.
ModBaseiSearch...
MobiDBiSearch...

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.By similarity

Sequence similaritiesi

Belongs to the hedgehog family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG250647.
HOGENOMiHOG000233428.
HOVERGENiHBG005480.
InParanoidiQ63673.
KOiK11988.
PhylomeDBiQ63673.

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.

Q63673-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLLLLARCFL VALASSLLVC PGLACGPGRG FGKRQHPKKL 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 RIHCSVKAEN SVAAKSDGCF
210 220 230 240 250
PGSATVHLEQ GGTKLVKDLS PGDRVLAADD QGRLLYSDFL TFLDRDEGAK
260 270 280 290 300
KVFYVIETRE PRERLLLTAA HLLFVAPHND SGPTPGPSPL FASRVRPGQR
310 320 330 340 350
VYVVAERGGD RRLLPAAVHS VTLREEAAGA YAPLTADGTI LINRVLASCY
360 370 380 390 400
AVIEEHSWAH RAFAPFRLAH ALLAALAPAR TDGGGGGSIP APQSVAEARG
410 420 430
AGPPAGIHWY SQLLYHIGTW LLDSETLHPL GMAVKSS
Length:437
Mass (Da):47,630
Last modified:November 1, 1996 - v1
Checksum:i0DBFC19F0D1662A0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27340 mRNA. Translation: AAA20999.1.
PIRiB53193.
RefSeqiNP_058917.1. NM_017221.1.
UniGeneiRn.10432.

Genome annotation databases

GeneIDi29499.
KEGGirno:29499.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27340 mRNA. Translation: AAA20999.1.
PIRiB53193.
RefSeqiNP_058917.1. NM_017221.1.
UniGeneiRn.10432.

3D structure databases

ProteinModelPortaliQ63673.
SMRiQ63673. Positions 39-195.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000008497.

Protein family/group databases

MEROPSiC46.002.

Proteomic databases

PRIDEiQ63673.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi29499.
KEGGirno:29499.

Organism-specific databases

CTDi6469.
RGDi3673. Shh.

Phylogenomic databases

eggNOGiNOG250647.
HOGENOMiHOG000233428.
HOVERGENiHBG005480.
InParanoidiQ63673.
KOiK11988.
PhylomeDBiQ63673.

Miscellaneous databases

NextBioi609396.
PROiQ63673.

Gene expression databases

GenevisibleiQ63673. RN.

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

  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.

Entry informationi

Entry nameiSHH_RAT
AccessioniPrimary (citable) accession number: Q63673
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: June 24, 2015
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.