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Q62226

- SHH_MOUSE

UniProt

Q62226 - SHH_MOUSE

Protein

Sonic hedgehog protein

Gene

Shh

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 160 (01 Oct 2014)
      Sequence version 2 (01 Jun 1998)
      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.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi90 – 901Calcium 13 Publications
    Metal bindingi91 – 911Calcium 13 Publications
    Metal bindingi91 – 911Calcium 23 Publications
    Metal bindingi96 – 961Calcium 13 Publications
    Metal bindingi126 – 1261Calcium 1; via carbonyl oxygen3 Publications
    Metal bindingi127 – 1271Calcium 13 Publications
    Metal bindingi127 – 1271Calcium 23 Publications
    Metal bindingi130 – 1301Calcium 23 Publications
    Metal bindingi132 – 1321Calcium 23 Publications
    Metal bindingi141 – 1411Zinc
    Metal bindingi148 – 1481Zinc
    Metal bindingi183 – 1831Zinc
    Sitei198 – 1992Cleavage; by autolysisBy similarity
    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. glycoprotein binding Source: MGI
    3. glycosaminoglycan binding Source: MGI
    4. laminin-1 binding Source: MGI
    5. patched binding Source: BHF-UCL
    6. protein binding Source: UniProtKB
    7. signal transducer activity Source: Ensembl
    8. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. anatomical structure development Source: MGI
    2. anatomical structure formation involved in morphogenesis Source: MGI
    3. androgen metabolic process Source: MGI
    4. angiogenesis Source: MGI
    5. anterior/posterior pattern specification Source: MGI
    6. apoptotic process Source: MGI
    7. apoptotic signaling pathway Source: Roslin
    8. artery development Source: MGI
    9. axon guidance Source: MGI
    10. Bergmann glial cell differentiation Source: MGI
    11. blood coagulation Source: MGI
    12. branching involved in prostate gland morphogenesis Source: MGI
    13. branching involved in salivary gland morphogenesis Source: MGI
    14. branching involved in ureteric bud morphogenesis Source: MGI
    15. branching morphogenesis of an epithelial tube Source: MGI
    16. bud outgrowth involved in lung branching Source: MGI
    17. camera-type eye development Source: MGI
    18. canonical Wnt signaling pathway Source: MGI
    19. CD4-positive or CD8-positive, alpha-beta T cell lineage commitment Source: BHF-UCL
    20. cell-cell signaling Source: MGI
    21. cell development Source: MGI
    22. cell fate commitment Source: MGI
    23. cell fate specification Source: MGI
    24. cell proliferation Source: MGI
    25. cellular response to lithium ion Source: MGI
    26. central nervous system development Source: MGI
    27. cerebellar granule cell precursor proliferation Source: UniProtKB
    28. determination of left/right asymmetry in lateral mesoderm Source: BHF-UCL
    29. determination of left/right symmetry Source: MGI
    30. developmental growth Source: MGI
    31. digestive tract morphogenesis Source: MGI
    32. dorsal/ventral neural tube patterning Source: BHF-UCL
    33. dorsal/ventral pattern formation Source: MGI
    34. ectoderm development Source: MGI
    35. embryonic digestive tract morphogenesis Source: BHF-UCL
    36. embryonic digit morphogenesis Source: Roslin
    37. embryonic foregut morphogenesis Source: MGI
    38. embryonic forelimb morphogenesis Source: MGI
    39. embryonic hindlimb morphogenesis Source: MGI
    40. embryonic limb morphogenesis Source: MGI
    41. embryonic morphogenesis Source: MGI
    42. embryonic organ development Source: MGI
    43. embryonic skeletal system development Source: MGI
    44. endocytosis Source: MGI
    45. epithelial cell proliferation involved in salivary gland morphogenesis Source: MGI
    46. epithelial-mesenchymal cell signaling Source: MGI
    47. epithelial-mesenchymal signaling involved in prostate gland development Source: MGI
    48. epithelial tube branching involved in lung morphogenesis Source: MGI
    49. establishment of cell polarity Source: MGI
    50. forebrain development Source: MGI
    51. formation of anatomical boundary Source: MGI
    52. hair follicle development Source: MGI
    53. hair follicle morphogenesis Source: MGI
    54. heart development Source: MGI
    55. heart looping Source: BHF-UCL
    56. hindbrain development Source: MGI
    57. hindgut morphogenesis Source: MGI
    58. inner ear development Source: MGI
    59. intein-mediated protein splicing Source: InterPro
    60. intermediate filament organization Source: MGI
    61. kidney development Source: MGI
    62. left lung development Source: MGI
    63. limb bud formation Source: MGI
    64. limb development Source: MGI
    65. lung-associated mesenchyme development Source: MGI
    66. lung development Source: MGI
    67. lung epithelium development Source: MGI
    68. lung lobe morphogenesis Source: MGI
    69. lung morphogenesis Source: MGI
    70. lymphoid progenitor cell differentiation Source: BHF-UCL
    71. male genitalia development Source: MGI
    72. mesenchymal cell proliferation Source: MGI
    73. mesenchymal cell proliferation involved in lung development Source: MGI
    74. mesenchymal smoothened signaling pathway involved in prostate gland development Source: MGI
    75. metanephric mesenchymal cell proliferation involved in metanephros development Source: UniProtKB
    76. metanephros development Source: UniProtKB
    77. midbrain development Source: MGI
    78. multicellular structure septum development Source: MGI
    79. myoblast differentiation Source: MGI
    80. myotube differentiation Source: MGI
    81. negative regulation of alpha-beta T cell differentiation Source: MGI
    82. negative regulation of apoptotic process Source: Roslin
    83. negative regulation of canonical Wnt signaling pathway Source: MGI
    84. negative regulation of cell differentiation Source: MGI
    85. negative regulation of cell migration Source: MGI
    86. negative regulation of cholesterol efflux Source: BHF-UCL
    87. negative regulation of gene expression Source: UniProtKB
    88. negative regulation of kidney smooth muscle cell differentiation Source: UniProtKB
    89. negative regulation of mesenchymal cell apoptotic process Source: MGI
    90. negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
    91. negative regulation of protein catabolic process Source: MGI
    92. negative regulation of T cell proliferation Source: MGI
    93. negative regulation of transcription elongation from RNA polymerase II promoter Source: MGI
    94. negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    95. negative regulation of ureter smooth muscle cell differentiation Source: UniProtKB
    96. negative regulation of Wnt signaling pathway Source: MGI
    97. negative thymic T cell selection Source: BHF-UCL
    98. neural crest cell migration Source: MGI
    99. neuroblast proliferation Source: MGI
    100. neuron fate commitment Source: MGI
    101. odontogenesis Source: MGI
    102. odontogenesis of dentin-containing tooth Source: MGI
    103. oligodendrocyte development Source: MGI
    104. oligodendrocyte differentiation Source: MGI
    105. organ formation Source: MGI
    106. osteoblast development Source: MGI
    107. palate development Source: MGI
    108. pancreas development Source: MGI
    109. patterning of blood vessels Source: MGI
    110. pattern specification process Source: MGI
    111. polarity specification of anterior/posterior axis Source: Roslin
    112. positive regulation of alpha-beta T cell differentiation Source: BHF-UCL
    113. positive regulation of cell differentiation Source: MGI
    114. positive regulation of cell division Source: Ensembl
    115. positive regulation of cell proliferation Source: MGI
    116. positive regulation of cerebellar granule cell precursor proliferation Source: MGI
    117. positive regulation of epithelial cell proliferation involved in prostate gland development Source: MGI
    118. positive regulation of gene expression Source: UniProtKB
    119. positive regulation of hh target transcription factor activity Source: BHF-UCL
    120. positive regulation of immature T cell proliferation in thymus Source: BHF-UCL
    121. positive regulation of kidney smooth muscle cell differentiation Source: UniProtKB
    122. positive regulation of mesenchymal cell proliferation Source: MGI
    123. positive regulation of mesenchymal cell proliferation involved in ureter development Source: UniProtKB
    124. positive regulation of neuroblast proliferation Source: MGI
    125. positive regulation of oligodendrocyte differentiation Source: MGI
    126. positive regulation of protein import into nucleus Source: MGI
    127. positive regulation of sclerotome development Source: Ensembl
    128. positive regulation of skeletal muscle cell proliferation Source: MGI
    129. positive regulation of skeletal muscle tissue development Source: MGI
    130. positive regulation of smoothened signaling pathway Source: UniProtKB
    131. positive regulation of striated muscle cell differentiation Source: MGI
    132. positive regulation of T cell differentiation in thymus Source: BHF-UCL
    133. positive regulation of transcription, DNA-templated Source: UniProtKB
    134. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    135. positive regulation of ureter smooth muscle cell differentiation Source: UniProtKB
    136. positive regulation of Wnt signaling pathway Source: MGI
    137. positive thymic T cell selection Source: BHF-UCL
    138. primary prostatic bud elongation Source: MGI
    139. prostate epithelial cord elongation Source: MGI
    140. prostate gland development Source: MGI
    141. protein localization to nucleus Source: MGI
    142. proteolysis Source: UniProtKB-KW
    143. regulation of cell proliferation Source: MGI
    144. regulation of epithelial cell proliferation involved in prostate gland development Source: MGI
    145. regulation of gene expression Source: MGI
    146. regulation of mesenchymal cell proliferation involved in prostate gland development Source: MGI
    147. regulation of odontogenesis Source: BHF-UCL
    148. regulation of prostatic bud formation Source: MGI
    149. regulation of proteolysis Source: MGI
    150. regulation of transcription, DNA-templated Source: MGI
    151. respiratory tube development Source: MGI
    152. right lung development Source: MGI
    153. salivary gland cavitation Source: MGI
    154. signal transduction Source: MGI
    155. skin development Source: MGI
    156. smoothened signaling pathway Source: MGI
    157. smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation Source: MGI
    158. somite development Source: BHF-UCL
    159. spinal cord dorsal/ventral patterning Source: MGI
    160. spinal cord motor neuron differentiation Source: MGI
    161. stem cell development Source: BHF-UCL
    162. striated muscle cell differentiation Source: MGI
    163. striated muscle tissue development Source: MGI
    164. T cell differentiation in thymus Source: BHF-UCL
    165. telencephalon regionalization Source: MGI
    166. thalamus development Source: MGI
    167. thymus development Source: BHF-UCL
    168. thyroid gland development Source: MGI
    169. trachea development Source: MGI
    170. trachea morphogenesis Source: MGI
    171. vasculature development Source: MGI
    172. vasculogenesis Source: MGI
    173. vasculogenesis involved in coronary vascular morphogenesis Source: DFLAT

    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
    Alternative name(s):
    HHG-1
    Cleaved into the following 2 chains:
    Alternative name(s):
    Sonic hedgehog protein 19 kDa product
    Alternative name(s):
    Sonic hedgehog protein 27 kDa product
    Gene namesi
    Name:Shh
    Synonyms:Hhg1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:98297. 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. cell surface Source: MGI
    2. extracellular matrix Source: MGI
    3. extracellular space Source: MGI
    4. membrane Source: MGI
    5. membrane raft Source: MGI
    6. nucleus Source: MGI
    7. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi25 – 251C → S: Strongly reduces effects of in vivo overexpression; impairs multimer formation; does not affect subcellular location to lipid rafts. Homozygous mice are characterized by a smaller size and holoprosencephaly at E10.5, and shortening of limbs at E13.5. They die soon after birth. 2 Publications
    Mutagenesisi32 – 321G → R: Introduces a cleavage site for a furin-like protease resulting in abnormal protein processing; cleavage at this site removes 11 amino acids from the N-terminal domain and reduces affinity of Shh for Ptch1 and signaling potency in assays using chicken embryo neural plate explants and mouse C3H10T1/2 stem cells. 1 Publication
    Mutagenesisi89 – 891D → V: Moderately reduces Ptch1 binding in vitro and signaling potency in chicken embryo neural plate explant assays compared with wild-type sequence. 1 Publication
    Mutagenesisi101 – 1011Q → H: Does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions. 1 Publication
    Mutagenesisi116 – 1161N → K: Shows no change in activities at different temperatures. 1 Publication
    Mutagenesisi118 – 1181W → G: Causes a failure of Shh processing leading to retention of the immature glycosylated protein within the endoplasmic reticulum of transfected cells; causes a temperature-dependent conformational change that allows Shh to bind Ptch1 at 4 or 32 degrees Celsius but not at 37 degrees Celsius; drastically reduces signaling potency in chicken embryo neural plate explant assays. 1 Publication
    Mutagenesisi118 – 1181W → R: Causes a failure of Shh processing leading to retention of the immature glycosylated protein within the endoplasmic reticulum of transfected cells; causes a temperature-dependent conformational change that allows Shh to bind Ptch1 at 4 or 32 degrees Celsius but not at 37 degrees Celsius; drastically reduces signaling potency in chicken embryo neural plate explant assays. 1 Publication
    Mutagenesisi189 – 1891E → Q: Does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Sequence AnalysisAdd
    BLAST
    Chaini25 – 437413Sonic hedgehog proteinPRO_0000013211Add
    BLAST
    Chaini25 – 198174Sonic hedgehog protein N-productPRO_0000013212Add
    BLAST
    Chaini199 – 437239Sonic hedgehog protein C-productPRO_0000013213Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi25 – 251N-palmitoyl cysteine2 Publications
    Lipidationi198 – 1981Cholesterol glycine ester1 Publication
    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.3 Publications
    Cholesterylation is required for N-product targeting to lipid rafts and multimerization.1 Publication
    N-palmitoylation of Cys-25 by HHAT is required for N-product multimerization and full activity.2 Publications

    Keywords - PTMi

    Autocatalytic cleavage, Glycoprotein, Lipoprotein, Palmitate

    Proteomic databases

    PRIDEiQ62226.

    PTM databases

    PhosphoSiteiQ62226.

    Expressioni

    Tissue specificityi

    Expressed in a number of embryonic tissues including the notochord, ventral neural tube, floor plate, lung bud, zone of polarizing activity and posterior distal mesenchyme of limbs. In the adult, expressed in lung and neural retina.

    Developmental stagei

    First detectable during gastrulation.

    Inductioni

    By retinoic acid.

    Gene expression databases

    BgeeiQ62226.
    CleanExiMM_SHH.
    GenevestigatoriQ62226.

    Interactioni

    Subunit structurei

    Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus. N-product is active as a multimer. Interacts with BOC and CDON. Interacts with HHIP.6 Publications

    Protein-protein interaction databases

    BioGridi203220. 10 interactions.
    DIPiDIP-48537N.
    STRINGi10090.ENSMUSP00000002708.

    Structurei

    Secondary structure

    1
    437
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi48 – 525
    Turni57 – 604
    Beta strandi69 – 713
    Helixi72 – 765
    Beta strandi85 – 873
    Beta strandi92 – 943
    Helixi95 – 973
    Helixi101 – 11717
    Beta strandi123 – 1275
    Beta strandi131 – 1355
    Helixi140 – 1434
    Beta strandi146 – 1516
    Helixi156 – 1583
    Helixi159 – 16810
    Beta strandi172 – 1787
    Beta strandi181 – 1855
    Helixi189 – 1924

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1VHHX-ray1.70A34-195[»]
    2WFXX-ray3.20A40-191[»]
    2WG4X-ray3.15A40-191[»]
    3D1MX-ray1.70A/B26-189[»]
    3N1RX-ray2.13A40-195[»]
    4C4MX-ray1.74A40-195[»]
    4C4NX-ray2.36A/B40-195[»]
    ProteinModelPortaliQ62226.
    SMRiQ62226. Positions 39-195, 199-351.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ62226.

    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.3 Publications

    Sequence similaritiesi

    Belongs to the hedgehog family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG250647.
    GeneTreeiENSGT00390000001117.
    HOGENOMiHOG000233428.
    HOVERGENiHBG005480.
    InParanoidiQ62226.
    KOiK11988.
    OMAiHSWAHRA.
    OrthoDBiEOG779NZ5.
    PhylomeDBiQ62226.
    TreeFamiTF106458.

    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.

    Q62226-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLLLLARCFL VILASSLLVC PGLACGPGRG FGKRRHPKKL TPLAYKQFIP    50
    NVAEKTLGAS GRYEGKITRN SERFKELTPN YNPDIIFKDE ENTGADRLMT 100
    QRCKDKLNAL AISVMNQWPG VKLRVTEGWD EDGHHSEESL HYEGRAVDIT 150
    TSDRDRSKYG MLARLAVEAG FDWVYYESKA HIHCSVKAEN SVAAKSGGCF 200
    PGSATVHLEQ GGTKLVKDLR PGDRVLAADD QGRLLYSDFL TFLDRDEGAK 250
    KVFYVIETLE PRERLLLTAA HLLFVAPHND SGPTPGPSAL FASRVRPGQR 300
    VYVVAERGGD RRLLPAAVHS VTLREEEAGA YAPLTAHGTI LINRVLASCY 350
    AVIEEHSWAH RAFAPFRLAH ALLAALAPAR TDGGGGGSIP AAQSATEARG 400
    AEPTAGIHWY SQLLYHIGTW LLDSETMHPL GMAVKSS 437
    Length:437
    Mass (Da):47,773
    Last modified:June 1, 1998 - v2
    Checksum:iD0EB72F08E7860EF
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X76290 mRNA. Translation: CAA53922.1.
    AK077688 mRNA. Translation: BAC36956.1.
    BC063087 mRNA. Translation: AAH63087.1.
    CCDSiCCDS19146.1.
    PIRiA49425.
    RefSeqiNP_033196.1. NM_009170.3.
    UniGeneiMm.57202.

    Genome annotation databases

    EnsembliENSMUST00000002708; ENSMUSP00000002708; ENSMUSG00000002633.
    GeneIDi20423.
    KEGGimmu:20423.
    UCSCiuc008wua.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X76290 mRNA. Translation: CAA53922.1 .
    AK077688 mRNA. Translation: BAC36956.1 .
    BC063087 mRNA. Translation: AAH63087.1 .
    CCDSi CCDS19146.1.
    PIRi A49425.
    RefSeqi NP_033196.1. NM_009170.3.
    UniGenei Mm.57202.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1VHH X-ray 1.70 A 34-195 [» ]
    2WFX X-ray 3.20 A 40-191 [» ]
    2WG4 X-ray 3.15 A 40-191 [» ]
    3D1M X-ray 1.70 A/B 26-189 [» ]
    3N1R X-ray 2.13 A 40-195 [» ]
    4C4M X-ray 1.74 A 40-195 [» ]
    4C4N X-ray 2.36 A/B 40-195 [» ]
    ProteinModelPortali Q62226.
    SMRi Q62226. Positions 39-195, 199-351.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 203220. 10 interactions.
    DIPi DIP-48537N.
    STRINGi 10090.ENSMUSP00000002708.

    Chemistry

    BindingDBi Q62226.
    ChEMBLi CHEMBL5387.

    Protein family/group databases

    MEROPSi C46.002.

    PTM databases

    PhosphoSitei Q62226.

    Proteomic databases

    PRIDEi Q62226.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000002708 ; ENSMUSP00000002708 ; ENSMUSG00000002633 .
    GeneIDi 20423.
    KEGGi mmu:20423.
    UCSCi uc008wua.2. mouse.

    Organism-specific databases

    CTDi 6469.
    MGIi MGI:98297. Shh.

    Phylogenomic databases

    eggNOGi NOG250647.
    GeneTreei ENSGT00390000001117.
    HOGENOMi HOG000233428.
    HOVERGENi HBG005480.
    InParanoidi Q62226.
    KOi K11988.
    OMAi HSWAHRA.
    OrthoDBi EOG779NZ5.
    PhylomeDBi Q62226.
    TreeFami TF106458.

    Miscellaneous databases

    EvolutionaryTracei Q62226.
    NextBioi 298432.
    PROi Q62226.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q62226.
    CleanExi MM_SHH.
    Genevestigatori Q62226.

    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. "Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity."
      Echelard Y., Epstein D.J., St Jacques B., Shen L., Mohler J., McMahon J.A., McMahon A.P.
      Cell 75:1417-1430(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C57BL/6J.
      Tissue: Embryo.
    2. McMahon A.P.
      Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION TO 122.
    3. "Products, genetic linkage and limb patterning activity of a murine hedgehog gene."
      Chang D.T., Lopez A., von Kessler D.P., Chiang C., Simandl B.K., Zhao R., Seldin M.F., Fallon J.F., Beachy P.A.
      Development 120:3339-3353(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEOLYTIC PROCESSING, AUTOCATALYTIC CLEAVAGE.
    4. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Limb.
    6. "Proteolytic processing yields two secreted forms of sonic hedgehog."
      Bumcrot D.A., Takada R., McMahon A.P.
      Mol. Cell. Biol. 15:2294-2303(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING, GLYCOSYLATION, SUBCELLULAR LOCATION.
    7. "Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis."
      Roelink H., Porter J.A., Chiang C., Tanabe Y., Chang D.T., Beachy P.A., Jessell T.M.
      Cell 81:445-455(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PROTEOLYTIC PROCESSING, AUTOCATALYTIC CLEAVAGE.
    8. "Cholesterol modification of hedgehog signaling proteins in animal development."
      Porter J.A., Young K.E., Beachy P.A.
      Science 274:255-259(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHOLESTERYLATION AT GLY-198.
    9. "Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal."
      Chamoun Z., Mann R.K., Nellen D., von Kessler D.P., Bellotto M., Beachy P.A., Basler K.
      Science 293:2080-2084(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PALMITOYLATION AT CYS-25, MUTAGENESIS OF CYS-25.
    10. "RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways."
      Gold D.A., Baek S.H., Schork N.J., Rose D.W., Larsen D.D., Sachs B.D., Rosenfeld M.G., Hamilton B.A.
      Neuron 40:1119-1131(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CEREBELLAR DEVELOPMENT.
    11. "Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates."
      Chen M.-H., Li Y.-J., Kawakami T., Xu S.-M., Chuang P.-T.
      Genes Dev. 18:641-659(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PALMITOYLATION AT CYS-25, MUTAGENESIS OF CYS-25, SUBUNIT, SUBCELLULAR LOCATION.
    12. "Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly."
      Maity T., Fuse N., Beachy P.A.
      Proc. Natl. Acad. Sci. U.S.A. 102:17026-17031(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF GLY-32; ASP-89; GLN-101; ASN-116; TRP-118 AND GLU-189.
    13. "Mammalian Gup1, a homolog of Saccharomyces cerevisiae glycerol uptake/transporter 1, acts as a negative regulator for N-terminal palmitoylation of Sonic hedgehog."
      Abe Y., Kita Y., Niikura T.
      FEBS J. 275:318-331(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HHATL.
    14. "A potential catalytic site revealed by the 1.7-A crystal structure of the amino-terminal signalling domain of Sonic hedgehog."
      Hall T.M.T., Porter J.A., Beachy P.A., Leahy D.J.
      Nature 378:212-216(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 34-195 IN COMPLEX WITH ZINC IONS.
    15. "The mode of Hedgehog binding to Ihog homologues is not conserved across different phyla."
      McLellan J.S., Zheng X., Hauk G., Ghirlando R., Beachy P.A., Leahy D.J.
      Nature 455:979-983(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 26-189 IN COMPLEX WITH CDON; CALCIUM AND ZINC IONS, DOMAIN, INTERACTION WITH CDON.
    16. "Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP."
      Bishop B., Aricescu A.R., Harlos K., O'Callaghan C.A., Jones E.Y., Siebold C.
      Nat. Struct. Mol. Biol. 16:698-703(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 40-191 IN COMPLEX WITH HHIP; CALCIUM AND ZINC IONS, DOMAIN, INTERACTION WITH HHIP.
    17. "All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner."
      Kavran J.M., Ward M.D., Oladosu O.O., Mulepati S., Leahy D.J.
      J. Biol. Chem. 285:24584-24590(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 26-189 IN COMPLEX WITH CALCIUM AND ZINC IONS, DOMAIN, INTERACTION WITH BOC AND CDON.

    Entry informationi

    Entry nameiSHH_MOUSE
    AccessioniPrimary (citable) accession number: Q62226
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: June 1, 1998
    Last modified: October 1, 2014
    This is version 160 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Mice overexpressing Shh display digit duplications in both forelimbs and hindlimbs.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3