Q62226 (SHH_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 145.
History...
Clusters with 
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Sonic hedgehog protein Short name=SHH Alternative name(s): HHG-1 Cleaved into the following 2 chains: | ||||
| Gene names |
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| Organism | Mus musculus (Mouse) [Reference proteome] | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus |
Protein attributes
| Sequence length | 437 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. In the absence of SHH, PTC represses the constitutive signaling activity of SMO. Also regulates another target, the gli oncogene. 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 By similarity. Ref.6 |
| Subunit structure | Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus. N-product is active as a multimer. Ref.9 Ref.11 |
| Subcellular location | Sonic hedgehog protein C-product: Secreted › extracellular space. Note: The C-terminal peptide diffuses from the cell. Ref.9 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. Ref.9 |
| Tissue specificity | 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 stage | First detectable during gastrulation. |
| Induction | By retinoic acid. |
| Post-translational modification | 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. N-palmitoylation of Cys-25 by HHAT is required for N-product multimerization and full activity. Ref.8 Ref.9 |
| Miscellaneous | Mice overexpressing Shh display digit duplications in both forelimbs and hindlimbs. |
| Sequence similarities | Belongs to the hedgehog family. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 24 | 24 | Potential | |||||||||||||||||||||||||||||||||||||
| Chain | 25 – 437 | 413 | Sonic hedgehog protein | PRO_0000013211 | ||||||||||||||||||||||||||||||||||||
| Chain | 25 – 198 | 174 | Sonic hedgehog protein N-product | PRO_0000013212 | ||||||||||||||||||||||||||||||||||||
| Chain | 199 – 437 | 239 | Sonic hedgehog protein C-product | PRO_0000013213 | ||||||||||||||||||||||||||||||||||||
Regions | ||||||||||||||||||||||||||||||||||||||||
| Compositional bias | 383 – 387 | 5 | Poly-Gly | |||||||||||||||||||||||||||||||||||||
Sites | ||||||||||||||||||||||||||||||||||||||||
| Site | 198 – 199 | 2 | Cleavage; by autolysis By similarity | |||||||||||||||||||||||||||||||||||||
| Site | 244 | 1 | Involved in cholesterol transfer By similarity | |||||||||||||||||||||||||||||||||||||
| Site | 268 | 1 | Involved in auto-cleavage By similarity | |||||||||||||||||||||||||||||||||||||
| Site | 271 | 1 | Essential for auto-cleavage By similarity | |||||||||||||||||||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||||||||||||||||||
| Lipidation | 25 | 1 | N-palmitoyl cysteine Ref.8 Ref.9 | |||||||||||||||||||||||||||||||||||||
| Lipidation | 198 | 1 | Cholesterol glycine ester Ref.7 | |||||||||||||||||||||||||||||||||||||
| Glycosylation | 279 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 25 | 1 | C → 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. Ref.8 Ref.9 | |||||||||||||||||||||||||||||||||||||
| Mutagenesis | 32 | 1 | G → 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. Ref.10 | |||||||||||||||||||||||||||||||||||||
| Mutagenesis | 89 | 1 | D → V: Moderately reduces Ptch1 binding in vitro and signaling potency in chicken embryo neural plate explant assays compared with wild-type sequence. Ref.10 | |||||||||||||||||||||||||||||||||||||
| Mutagenesis | 101 | 1 | Q → H: Does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions. Ref.10 | |||||||||||||||||||||||||||||||||||||
| Mutagenesis | 116 | 1 | N → K: Shows no change in activities at different temperatures. Ref.10 | |||||||||||||||||||||||||||||||||||||
| Mutagenesis | 118 | 1 | W → 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. Ref.10 | |||||||||||||||||||||||||||||||||||||
| Mutagenesis | 118 | 1 | W → 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. Ref.10 | |||||||||||||||||||||||||||||||||||||
| Mutagenesis | 189 | 1 | E → Q: Does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions. Ref.10 | |||||||||||||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||||||||
| Beta strand | 48 – 52 | 5 | ||||||||||||||||||||||||||||||||||||||
| Turn | 57 – 60 | 4 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 69 – 71 | 3 | ||||||||||||||||||||||||||||||||||||||
| Helix | 72 – 76 | 5 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 85 – 87 | 3 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 92 – 94 | 3 | ||||||||||||||||||||||||||||||||||||||
| Helix | 95 – 97 | 3 | ||||||||||||||||||||||||||||||||||||||
| Helix | 101 – 117 | 17 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 123 – 127 | 5 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 131 – 135 | 5 | ||||||||||||||||||||||||||||||||||||||
| Helix | 140 – 143 | 4 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 146 – 151 | 6 | ||||||||||||||||||||||||||||||||||||||
| Helix | 156 – 158 | 3 | ||||||||||||||||||||||||||||||||||||||
| Helix | 159 – 168 | 10 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 172 – 178 | 7 | ||||||||||||||||||||||||||||||||||||||
| Beta strand | 181 – 185 | 5 | ||||||||||||||||||||||||||||||||||||||
| Helix | 189 – 192 | 4 | ||||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [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], 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.  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] | "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, AUTOCATALYTIC CLEAVAGE. |
| [7] | "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. |
| [8] | "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. |
| [9] | "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. |
| [10] | "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. |
| [11] | "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. |
| [12] | "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. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | X76290 mRNA. Translation: CAA53922.1. AK077688 mRNA. Translation: BAC36956.1. BC063087 mRNA. Translation: AAH63087.1. | ||||||||||||||||||||||||||||||||||||
| IPI | IPI00123314. | ||||||||||||||||||||||||||||||||||||
| PIR | A49425. | ||||||||||||||||||||||||||||||||||||
| RefSeq | NP_033196.1. NM_009170.3. | ||||||||||||||||||||||||||||||||||||
| UniGene | Mm.57202. | ||||||||||||||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||||||||||||||
| PDBe RCSB PDB PDBj |
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| ProteinModelPortal | Q62226. | ||||||||||||||||||||||||||||||||||||
| SMR | Q62226. Positions 39-195, 199-351. | ||||||||||||||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||||||||||||||
| DIP | DIP-48537N. | ||||||||||||||||||||||||||||||||||||
| STRING | 10090.ENSMUSP00000002708. | ||||||||||||||||||||||||||||||||||||
Protein family/group databases | |||||||||||||||||||||||||||||||||||||
| MEROPS | C46.002. | ||||||||||||||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||||||||||||||
| PhosphoSite | Q62226. | ||||||||||||||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||||||||||||||
| PRIDE | Q62226. | ||||||||||||||||||||||||||||||||||||
Protocols and materials databases | |||||||||||||||||||||||||||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||||||||||||||
| Ensembl | ENSMUST00000002708; ENSMUSP00000002708; ENSMUSG00000002633. | ||||||||||||||||||||||||||||||||||||
| GeneID | 20423. | ||||||||||||||||||||||||||||||||||||
| KEGG | mmu:20423. | ||||||||||||||||||||||||||||||||||||
| UCSC | uc008wua.2. mouse. | ||||||||||||||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||||||||||||||
| CTD | 6469. | ||||||||||||||||||||||||||||||||||||
| MGI | MGI:98297. Shh. | ||||||||||||||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||||||||||||||
| eggNOG | NOG250647. | ||||||||||||||||||||||||||||||||||||
| GeneTree | ENSGT00390000001117. | ||||||||||||||||||||||||||||||||||||
| HOGENOM | HOG000233428. | ||||||||||||||||||||||||||||||||||||
| HOVERGEN | HBG005480. | ||||||||||||||||||||||||||||||||||||
| InParanoid | Q62226. | ||||||||||||||||||||||||||||||||||||
| KO | K11988. | ||||||||||||||||||||||||||||||||||||
| OMA | SWAHRAF. | ||||||||||||||||||||||||||||||||||||
| OrthoDB | EOG46WZ8G. | ||||||||||||||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||||||||||||||
| Bgee | Q62226. | ||||||||||||||||||||||||||||||||||||
| CleanEx | MM_SHH. | ||||||||||||||||||||||||||||||||||||
| Genevestigator | Q62226. | ||||||||||||||||||||||||||||||||||||
| GermOnline | ENSMUSG00000002633. Mus musculus. | ||||||||||||||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||||||||||||||
| Gene3D | 3.30.1380.10. 1 hit. | ||||||||||||||||||||||||||||||||||||
| InterPro | IPR001657. Hedgehog. IPR009045. Hedgehog_sig/DD-Pept_Zn-bd_dom. IPR000320. Hedgehog_signaling_dom. IPR001767. Hint_dom. IPR003586. Hint_dom_C. IPR003587. Hint_dom_N. IPR006141. Intein_splice_site. [Graphical view] | ||||||||||||||||||||||||||||||||||||
| Pfam | PF01085. HH_signal. 1 hit. PF01079. Hint. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||||||||
| PIRSF | PIRSF009400. Peptidase_C46. 1 hit. | ||||||||||||||||||||||||||||||||||||
| PRINTS | PR00632. SONICHHOG. | ||||||||||||||||||||||||||||||||||||
| SMART | SM00305. HintC. 1 hit. SM00306. HintN. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||||||||
| SUPFAM | SSF55166. Hedgehog_sig_N. 1 hit. | ||||||||||||||||||||||||||||||||||||
| PROSITE | PS50817. INTEIN_N_TER. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||||||||||||||
Other | |||||||||||||||||||||||||||||||||||||
| BindingDB | Q62226. | ||||||||||||||||||||||||||||||||||||
| ChEMBL | CHEMBL5387. | ||||||||||||||||||||||||||||||||||||
| EvolutionaryTrace | Q62226. | ||||||||||||||||||||||||||||||||||||
| NextBio | 298432. | ||||||||||||||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||||||||||||||
Entry information
| Entry name | SHH_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q62226 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |