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Q63673

- SHH_RAT

UniProt

Q63673 - SHH_RAT

Protein

Sonic hedgehog protein

Gene

Shh

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    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. protein binding Source: RGD
    5. receptor binding Source: RGD
    6. 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

    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-SubCell
    10. transport vesicle Source: RGD

    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

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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: October 1, 2014
    This is version 134 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