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Q63673

- SHH_RAT

UniProt

Q63673 - SHH_RAT

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Protein
Sonic hedgehog protein
Gene
Shh, Vhh-1
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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi90 – 901Calcium 1 By similarity
Metal bindingi91 – 911Calcium 1 By similarity
Metal bindingi91 – 911Calcium 2 By similarity
Metal bindingi96 – 961Calcium 1 By similarity
Metal bindingi126 – 1261Calcium 1; via carbonyl oxygen By similarity
Metal bindingi127 – 1271Calcium 1 By similarity
Metal bindingi127 – 1271Calcium 2 By similarity
Metal bindingi130 – 1301Calcium 2 By similarity
Metal bindingi132 – 1321Calcium 2 By similarity
Metal bindingi141 – 1411Zinc By similarity
Metal bindingi148 – 1481Zinc By similarity
Metal bindingi183 – 1831Zinc By similarity
Sitei198 – 1992Cleavage; by autolysis
Sitei244 – 2441Involved in cholesterol transfer By similarity
Sitei268 – 2681Involved in auto-cleavage By similarity
Sitei271 – 2711Essential for auto-cleavage By similarity

GO - Molecular functioni

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

GO - Biological processi

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

GO - Cellular componenti

  1. Golgi apparatus Source: RGD
  2. axon Source: RGD
  3. cell surface Source: UniProtKB
  4. dendrite Source: RGD
  5. endoplasmic reticulum Source: RGD
  6. extracellular space Source: UniProtKB
  7. membrane raft Source: UniProtKB
  8. neuronal cell body Source: RGD
  9. plasma membrane Source: UniProtKB-SubCell
  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 – 2424 Reviewed prediction
Add
BLAST
Chaini25 – 437413Sonic hedgehog protein
PRO_0000013214Add
BLAST
Chaini25 – 198174Sonic hedgehog protein N-product
PRO_0000013215Add
BLAST
Chaini199 – 437239Sonic hedgehog protein C-product
PRO_0000013216Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi25 – 251N-palmitoyl cysteine By similarity
Lipidationi198 – 1981Cholesterol glycine ester By similarity
Glycosylationi279 – 2791N-linked (GlcNAc...) Reviewed prediction

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.1 Publication

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000008497.

Structurei

3D structure databases

ProteinModelPortaliQ63673.
SMRiQ63673. Positions 39-195.

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.

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

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MLLLLARCFL VALASSLLVC PGLACGPGRG FGKRQHPKKL TPLAYKQFIP    50
NVAEKTLGAS GRYEGKITRN SERFKELTPN YNPDIIFKDE ENTGADRLMT 100
QRCKDKLNAL AISVMNQWPG VKLRVTEGWD EDGHHSEESL HYEGRAVDIT 150
TSDRDRSKYG MLARLAVEAG FDWVYYESKA RIHCSVKAEN SVAAKSDGCF 200
PGSATVHLEQ GGTKLVKDLS PGDRVLAADD QGRLLYSDFL TFLDRDEGAK 250
KVFYVIETRE PRERLLLTAA HLLFVAPHND SGPTPGPSPL FASRVRPGQR 300
VYVVAERGGD RRLLPAAVHS VTLREEAAGA YAPLTADGTI LINRVLASCY 350
AVIEEHSWAH RAFAPFRLAH ALLAALAPAR TDGGGGGSIP APQSVAEARG 400
AGPPAGIHWY SQLLYHIGTW LLDSETLHPL GMAVKSS 437
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: July 9, 2014
This is version 133 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

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