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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)DescriptionActionsGraphical viewLength
Metal bindingi90Calcium 1By similarity1
Metal bindingi91Calcium 1By similarity1
Metal bindingi91Calcium 2By similarity1
Metal bindingi96Calcium 1By similarity1
Metal bindingi126Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi127Calcium 1By similarity1
Metal bindingi127Calcium 2By similarity1
Metal bindingi130Calcium 2By similarity1
Metal bindingi132Calcium 2By similarity1
Metal bindingi141ZincBy similarity1
Metal bindingi148ZincBy similarity1
Metal bindingi183ZincBy similarity1
Sitei244Involved in cholesterol transferBy similarity1
Sitei268Involved in auto-cleavageBy similarity1
Sitei271Essential for auto-cleavageBy similarity1

GO - Molecular functioni

GO - Biological processi

  • androgen metabolic process Source: UniProtKB
  • apoptotic signaling pathway Source: UniProtKB
  • axon guidance Source: UniProtKB
  • branching involved in blood vessel morphogenesis Source: UniProtKB
  • branching involved in ureteric bud morphogenesis Source: UniProtKB
  • branching morphogenesis of an epithelial tube Source: UniProtKB
  • CD4-positive or CD8-positive, alpha-beta T cell lineage commitment Source: UniProtKB
  • cell-cell signaling Source: UniProtKB
  • cell development Source: UniProtKB
  • cell fate specification Source: UniProtKB
  • central nervous system development Source: UniProtKB
  • cerebellar granule cell precursor proliferation Source: UniProtKB
  • commissural neuron axon guidance Source: RGD
  • digestive tract mesoderm development Source: RGD
  • dorsal/ventral pattern formation Source: UniProtKB
  • embryo development Source: UniProtKB
  • embryonic digit morphogenesis Source: UniProtKB
  • embryonic limb morphogenesis Source: UniProtKB
  • epithelial tube branching involved in lung morphogenesis Source: RGD
  • forebrain development Source: UniProtKB
  • fungiform papilla development Source: RGD
  • fungiform papilla formation Source: RGD
  • fungiform papilla morphogenesis Source: RGD
  • heart development Source: UniProtKB
  • hindbrain development Source: UniProtKB
  • intein-mediated protein splicing Source: InterPro
  • liver regeneration Source: RGD
  • lung development Source: UniProtKB
  • lymphoid progenitor cell differentiation Source: UniProtKB
  • male genitalia development Source: UniProtKB
  • male genitalia morphogenesis Source: RGD
  • metanephric mesenchymal cell proliferation involved in metanephros development Source: UniProtKB
  • metanephros development Source: UniProtKB
  • midbrain development Source: UniProtKB
  • negative regulation of apoptotic process Source: RGD
  • negative regulation of cell differentiation Source: UniProtKB
  • negative regulation of cell migration Source: UniProtKB
  • negative regulation of kidney smooth muscle cell differentiation Source: UniProtKB
  • negative regulation of neuron death Source: RGD
  • negative regulation of ureter smooth muscle cell differentiation Source: UniProtKB
  • negative thymic T cell selection Source: UniProtKB
  • neural crest cell migration Source: UniProtKB
  • neural tube formation Source: RGD
  • neuroblast proliferation Source: UniProtKB
  • neuron fate commitment Source: UniProtKB
  • pattern specification process Source: UniProtKB
  • polarity specification of anterior/posterior axis Source: UniProtKB
  • positive regulation of alpha-beta T cell differentiation Source: UniProtKB
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of endothelial cell chemotaxis Source: RGD
  • positive regulation of immature T cell proliferation in thymus Source: UniProtKB
  • positive regulation of kidney smooth muscle cell differentiation Source: UniProtKB
  • positive regulation of mesenchymal cell proliferation involved in ureter development Source: UniProtKB
  • positive regulation of neuroblast proliferation Source: RGD
  • positive regulation of neuron differentiation Source: RGD
  • positive regulation of neurotrophin production Source: RGD
  • positive regulation of oligodendrocyte progenitor proliferation Source: RGD
  • positive regulation of penile erection Source: RGD
  • positive regulation of photoreceptor cell differentiation Source: RGD
  • positive regulation of smoothened signaling pathway Source: UniProtKB
  • positive regulation of sprouting angiogenesis Source: RGD
  • positive regulation of T cell differentiation in thymus Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of ureter smooth muscle cell differentiation Source: UniProtKB
  • positive thymic T cell selection Source: UniProtKB
  • prostate gland development Source: RGD
  • regulation of cell proliferation Source: RGD
  • regulation of epithelial cell differentiation Source: RGD
  • regulation of proteolysis Source: UniProtKB
  • response to axon injury Source: RGD
  • response to estradiol Source: RGD
  • response to ethanol Source: RGD
  • response to hypoxia Source: RGD
  • response to organonitrogen compound Source: RGD
  • response to retinoic acid Source: RGD
  • smoothened signaling pathway Source: UniProtKB
  • spinal cord dorsal/ventral patterning Source: MGI
  • stem cell development Source: UniProtKB
  • T cell differentiation in thymus Source: UniProtKB
  • telencephalon regionalization Source: RGD
  • thymus development Source: UniProtKB
  • tongue development Source: RGD
  • tongue morphogenesis Source: RGD
  • vasculogenesis Source: UniProtKB
  • ventral spinal cord interneuron specification Source: MGI
  • zona limitans intrathalamica formation Source: RGD

Keywordsi

Molecular functionDevelopmental protein, Hydrolase, Protease
LigandCalcium, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3673. Shh.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000001321425 – 437Sonic hedgehog proteinAdd BLAST413
ChainiPRO_000001321525 – 198Sonic hedgehog protein N-productAdd BLAST174
ChainiPRO_0000013216199 – 437Sonic hedgehog protein C-productAdd BLAST239

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi25N-palmitoyl cysteineBy similarity1
Lipidationi198Cholesterol glycine esterBy similarity1
Glycosylationi279N-linked (GlcNAc...) asparagineSequence analysis1

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei198 – 199Cleavage; by autolysis2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiQ63673.
PRIDEiQ63673.

Expressioni

Tissue specificityi

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

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000008497.

Structurei

3D structure databases

ProteinModelPortaliQ63673.
SMRiQ63673.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi383 – 387Poly-Gly5

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

eggNOGiKOG3638. Eukaryota.
ENOG410XQA3. LUCA.
HOGENOMiHOG000233428.
HOVERGENiHBG005480.
InParanoidiQ63673.
KOiK11988.
PhylomeDBiQ63673.

Family and domain databases

Gene3Di3.30.1380.10. 1 hit.
InterProiView protein in InterPro
IPR001657. 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.
PfamiView protein in Pfam
PF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
PIRSFiPIRSF009400. Peptidase_C46. 1 hit.
PRINTSiPR00632. SONICHHOG.
SMARTiView protein in SMART
SM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
SUPFAMiSSF51294. SSF51294. 1 hit.
SSF55166. SSF55166. 1 hit.
PROSITEiView protein in PROSITE
PS50817. INTEIN_N_TER. 1 hit.

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.

Similar proteinsi

Entry informationi

Entry nameiSHH_RAT
AccessioniPrimary (citable) accession number: Q63673
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: September 27, 2017
This is version 150 of the entry and version 1 of the sequence. See 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