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Q63673

- SHH_RAT

UniProt

Q63673 - SHH_RAT

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Protein

Sonic hedgehog protein

Gene

Shh

Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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

  1. calcium ion binding Source: UniProtKB
  2. laminin-1 binding Source: UniProtKB
  3. peptidase activity Source: UniProtKB-KW
  4. receptor binding Source: RGD
  5. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. androgen metabolic process Source: UniProtKB
  2. apoptotic signaling pathway Source: UniProt
  3. axon guidance Source: UniProtKB
  4. branching involved in ureteric bud morphogenesis Source: UniProtKB
  5. branching morphogenesis of an epithelial tube Source: UniProtKB
  6. CD4-positive or CD8-positive, alpha-beta T cell lineage commitment Source: UniProtKB
  7. cell-cell signaling Source: UniProtKB
  8. cell development Source: UniProtKB
  9. cell fate specification Source: UniProtKB
  10. central nervous system development Source: UniProtKB
  11. cerebellar granule cell precursor proliferation Source: UniProtKB
  12. digestive tract mesoderm development Source: RGD
  13. dorsal/ventral pattern formation Source: UniProtKB
  14. embryo development Source: UniProtKB
  15. embryonic digit morphogenesis Source: UniProtKB
  16. embryonic limb morphogenesis Source: UniProtKB
  17. epithelial tube branching involved in lung morphogenesis Source: RGD
  18. forebrain development Source: UniProtKB
  19. fungiform papilla development Source: RGD
  20. fungiform papilla formation Source: RGD
  21. fungiform papilla morphogenesis Source: RGD
  22. heart development Source: UniProtKB
  23. hindbrain development Source: UniProtKB
  24. intein-mediated protein splicing Source: InterPro
  25. lung development Source: UniProtKB
  26. lymphoid progenitor cell differentiation Source: UniProtKB
  27. male genitalia development Source: UniProtKB
  28. male genitalia morphogenesis Source: RGD
  29. metanephric mesenchymal cell proliferation involved in metanephros development Source: UniProtKB
  30. metanephros development Source: UniProtKB
  31. midbrain development Source: UniProtKB
  32. negative regulation of apoptotic process Source: RGD
  33. negative regulation of cell differentiation Source: UniProtKB
  34. negative regulation of cell migration Source: UniProtKB
  35. negative regulation of kidney smooth muscle cell differentiation Source: UniProtKB
  36. negative regulation of ureter smooth muscle cell differentiation Source: UniProtKB
  37. negative thymic T cell selection Source: UniProtKB
  38. neural crest cell migration Source: UniProtKB
  39. neural tube formation Source: RGD
  40. neuroblast proliferation Source: UniProtKB
  41. neuron fate commitment Source: UniProtKB
  42. patterning of blood vessels Source: UniProtKB
  43. pattern specification process Source: UniProtKB
  44. polarity specification of anterior/posterior axis Source: UniProt
  45. positive regulation of alpha-beta T cell differentiation Source: UniProtKB
  46. positive regulation of cell proliferation Source: UniProtKB
  47. positive regulation of immature T cell proliferation in thymus Source: UniProtKB
  48. positive regulation of kidney smooth muscle cell differentiation Source: UniProtKB
  49. positive regulation of mesenchymal cell proliferation involved in ureter development Source: UniProtKB
  50. positive regulation of neuroblast proliferation Source: RGD
  51. positive regulation of neuron differentiation Source: RGD
  52. positive regulation of oligodendrocyte progenitor proliferation Source: RGD
  53. positive regulation of penile erection Source: RGD
  54. positive regulation of photoreceptor cell differentiation Source: RGD
  55. positive regulation of smoothened signaling pathway Source: UniProtKB
  56. positive regulation of T cell differentiation in thymus Source: UniProtKB
  57. positive regulation of transcription, DNA-templated Source: UniProtKB
  58. positive regulation of ureter smooth muscle cell differentiation Source: UniProtKB
  59. positive thymic T cell selection Source: UniProtKB
  60. prostate gland development Source: UniProtKB
  61. regulation of cell proliferation Source: UniProtKB
  62. regulation of epithelial cell differentiation Source: RGD
  63. regulation of proteolysis Source: UniProtKB
  64. response to axon injury Source: RGD
  65. response to estradiol Source: RGD
  66. response to ethanol Source: RGD
  67. response to hypoxia Source: RGD
  68. response to organonitrogen compound Source: RGD
  69. response to retinoic acid Source: RGD
  70. smoothened signaling pathway Source: UniProtKB
  71. spinal cord dorsal/ventral patterning Source: MGI
  72. stem cell development Source: UniProtKB
  73. T cell differentiation in thymus Source: UniProtKB
  74. telencephalon regionalization Source: RGD
  75. thymus development Source: UniProtKB
  76. tongue development Source: RGD
  77. tongue morphogenesis Source: RGD
  78. vasculogenesis Source: UniProtKB
  79. ventral spinal cord interneuron specification Source: MGI
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: Unplaced

Organism-specific databases

RGDi3673. Shh.

Subcellular locationi

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

  1. axon Source: RGD
  2. cell surface Source: UniProtKB
  3. dendrite Source: RGD
  4. endoplasmic reticulum Source: RGD
  5. extracellular space Source: UniProtKB
  6. Golgi apparatus Source: RGD
  7. membrane raft Source: UniProtKB
  8. neuronal cell body Source: RGD
  9. plasma membrane Source: UniProtKB-KW
  10. 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

GenevestigatoriQ63673.

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_splice_site.
[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:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
L27340 mRNA. Translation: AAA20999.1 .
PIRi B53193.
RefSeqi NP_058917.1. NM_017221.1.
UniGenei Rn.10432.

3D structure databases

ProteinModelPortali Q63673.
SMRi Q63673. Positions 39-195.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000008497.

Protein family/group databases

MEROPSi C46.002.

Proteomic databases

PRIDEi Q63673.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 29499.
KEGGi rno:29499.

Organism-specific databases

CTDi 6469.
RGDi 3673. Shh.

Phylogenomic databases

eggNOGi NOG250647.
HOGENOMi HOG000233428.
HOVERGENi HBG005480.
InParanoidi Q63673.
KOi K11988.
PhylomeDBi Q63673.

Miscellaneous databases

NextBioi 609396.
PROi Q63673.

Gene expression databases

Genevestigatori Q63673.

Family and domain databases

Gene3Di 2.170.16.10. 1 hit.
3.30.1380.10. 1 hit.
InterProi 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_splice_site.
[Graphical view ]
Pfami PF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
[Graphical view ]
PIRSFi PIRSF009400. Peptidase_C46. 1 hit.
PRINTSi PR00632. SONICHHOG.
SMARTi SM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
[Graphical view ]
SUPFAMi SSF51294. SSF51294. 1 hit.
SSF55166. SSF55166. 1 hit.
PROSITEi PS50817. INTEIN_N_TER. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 135 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