| + |
GPC6 | up-regulates activity 
binding
|
SHH |
0.465 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-264029 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31756413 |
Based on results from in vitro experiments, we had previously proposed that GPC6 stimulates Hh signaling by interacting with Hh and Patched1 (Ptc1), and facilitating/stabilizing their interaction. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SHH | down-regulates 
binding
|
CP |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-132672 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15618519 |
Binding of sonic hedgehog (shh) to patched (ptc) relieves the latter's tonic smoothened (smo), a receptor that spans the cell membrane seven times. Ptch exists in vertebrates as two isoforms, ptch1 and ptch2, which seem to be equivalent in terms of binding the three hh isoforms. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-118612 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14556242 |
Two genes were newly identified to be shh responsive in neuroepithelial cell line mns-70: the metal-binding protein ceruloplasmin (cp) and the serine protease inhibitor inter-alpha-trypsine inhibitor heavy chain h3 (itih3). cp appeared to be regulated by gli-independent pathways. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-61549 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9811851 |
Binding of sonic hedgehog (shh) to patched (ptc) relieves the latter's tonic smoothened (smo), a receptor that spans the cell membrane seven times. Ptch exists in vertebrates as two isoforms, ptch1 and ptch2, which seem to be equivalent in terms of binding the three hh isoforms. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154285 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17419683 |
Binding of sonic hedgehog (shh) to patched (ptc) relieves the latter's tonic smoothened (smo), a receptor that spans the cell membrane seven times. Ptch exists in vertebrates as two isoforms, ptch1 and ptch2, which seem to be equivalent in terms of binding the three hh isoforms. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| + |
SLITRK5 | down-regulates activity
binding
|
SHH |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268437 |
|
|
Mus musculus |
Osteoblast |
| pmid |
sentence |
| 34326333 |
SLITRK5 interacts with SHH and PTCH1. Mechanistically, SLITRK5 binds to hedgehog ligands via its extracellular domain and interacts with PTCH1 via its intracellular domain. SLITRK5 is present in the primary cilium, and loss of SLITRK5 enhances SMO ciliary enrichment upon SHH stimulation. Thus, SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts that may be attractive as a therapeutic target to enhance bone formation. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
SHH | down-regulates activity
binding
|
PTCH1 |
0.941 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-132675 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15618519 |
Binding of sonic hedgehog (shh) to patched (ptc) relieves the latter's tonic smoothened (smo), a receptor that spans the cell membrane seven times. .Ptch Exists in vertebrates as two isoforms, ptch1 and ptch2, which seem to be equivalent in terms of binding the three hh isoforms. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-118615 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14556242 |
In the responding cell, active Hedgehog binds to its receptor Patched, a 12-pass transmembrane protein, which frees Smoothened, an adjacent 7-pass transmembrane protein, for downstream signaling.Thus, a balance is created by the antagonism of Hedgehog and Patched, whose relative concentrations alternate with respect to each other. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-61552 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9811851 |
Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| Pathways: | Sonic Hedgehog |
| + |
SHH | up-regulates 
|
AKT1 |
0.484 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-157291 |
|
|
Homo sapiens |
Myoblast, Satellite Cell |
| pmid |
sentence |
| 17688959 |
Most importantly, we report that shh induces mapk/erk and phosphoinositide 3-kinase (pi3k)-dependent akt phosphorylation and that activation of both signaling pathways is essential for shh's signaling in muscle cells. However, the effect of shh on akt phosphorylation is more robust than that on mapk/erk, and data suggest that shh influences these pathways in a manner similar to igf-i. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle |
| + |
DISP1 | up-regulates activity
binding
|
SHH |
0.718 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-191888 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22902404 |
We show that the vertebrate homologue, dispatched-a (dispa) interacts with human sonic hedgehog (hshh) via its cholesterol anchor, and that this interaction is necessary for hshh secretion. binding to dispa is necessary but not sufficient for hshh secretion |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Sonic Hedgehog |
| + |
HHAT | up-regulates
palmitoylation
|
SHH |
0.67 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-124118 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15075292 |
Our molecular analysis of knockout mice deficient in skn, the murine homolog of the drosophila ski gene, which catalyzes hh palmitoylation, and gene-targeted mice producting a non palmitoylated form of shh indicates that hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161548 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18534984 |
Both the shh precursor and mature protein are n-palmitoylated by hhatn-palmitoylation of cys-24 by hhat is required for n-product multimerization and full activity |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
RORA | up-regulates quantity by expression
transcriptional regulation
|
SHH |
0.254 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266846 |
|
|
Mus musculus |
Cerebellar Purkinje Cell |
| pmid |
sentence |
| 19381306 |
RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
SHH | up-regulates
|
MYOD1 |
0.44 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-179632 |
|
|
Homo sapiens |
Satellite Cell |
| pmid |
sentence |
| 18662193 |
In addition, shh reactivation plays a regulatory role on myogenesis, as its inhibition impairs the activation of the myogenic regulatory factors myf-5 and myod, decreases the up-regulation of insulin-like growth factor (igf)-1 and reduces the number of myogenic satellite cells at injured site. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SHH | up-regulates activity
|
SMO |
0.74 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-148481 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 16885213 |
Binding of Hh to Ptch relieves the repression of Smo, allowing Smo to signal. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Sonic Hedgehog |
| + |
SHH | down-regulates activity
binding
|
PTCH2 |
0.796 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217776 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9811851 |
Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| + |
SHH | up-regulates activity
|
GLI2 |
0.72 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-148349 |
|
|
Homo sapiens |
Osteoblast |
| pmid |
sentence |
| 16880529 |
Finally, Sonic hedgehog (Shh) stimulates BMP-2 promoter activity and osteoblast differentiation, and the effects of Shh are mediated by Gli2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Sonic Hedgehog |
| + |
HHIP | down-regulates activity
binding
|
SHH |
0.893 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-65078 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 10050855 |
Hip encodes a membrane glycoprotein that binds to all three mammalian hedgehog proteins with an affinity comparable to that of ptc-1. our findings support a model in which hip attenuates hedgehog signalling as a result of binding to hedgehog proteins: a negative regulatory feedback loop established in this way could thus modulate the responses to any hedgehog signal. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Sonic Hedgehog |
| + |
BMP2 | down-regulates quantity by repression 
transcriptional regulation
|
SHH |
0.532 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188853 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19855020 |
On the other hand, bmp activity negatively regulates shh transcription and a bmp-shh nega-tive-feedback loop serves to confine shh expression during limb development. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EXTL1 | down-regulates
binding
|
SHH |
0.299 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-132606 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15614771 |
A study in mice suggests that ext1 proteins might negatively regulate shh signaling by synthesizing hspgs, which sequester the ligand |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
N-[(4-chlorophenyl)methyl]-2-[(2R,6S)-5,12-dioxo-2-phenyl-1-oxa-4-azacyclododec-8-en-6-yl]acetamide | down-regulates
chemical inhibition
|
SHH |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-174429 |
|
|
Homo sapiens |
Glioblastoma Cell |
| pmid |
sentence |
| 21679342 |
More recently, robotnikinin was identified as a compound that binds to shh and blocks its ability to induce pathway activity at the level of ptch. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-183465 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19151731 |
More recently, robotnikinin was identified as a compound that binds to shh and blocks its ability to induce pathway activity at the level of ptch. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| + |
SHH | up-regulates
|
AKT |
0.484 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244446 |
|
|
Homo sapiens |
Myoblast, Satellite Cell |
| pmid |
sentence |
| 17688959 |
Most importantly, we report that shh induces mapk/erk and phosphoinositide 3-kinase (pi3k)-dependent akt phosphorylation and that activation of both signaling pathways is essential for shh's signaling in muscle cells. However, the effect of shh on akt phosphorylation is more robust than that on mapk/erk, and data suggest that shh influences these pathways in a manner similar to igf-i. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle |
| + |
CDO1 | up-regulates
binding
|
SHH |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146461 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16647304 |
Cdo and boc bind shh through a high-affinity interaction with a specific fibronectin repeat that is essential for activity. We propose a model where cdo and boc enhance shh signaling within its target field. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle |
| + |
SHH | up-regulates
|
MYF5 |
0.42 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-179629 |
|
|
Homo sapiens |
Satellite Cell |
| pmid |
sentence |
| 18662193 |
Shh reactivation plays a regulatory role on myogenesis, as its inhibition impairs the activation of the myogenic regulatory factors myf-5 and myod, decreases the up-regulation of insulin-like growth factor (igf)-1 and reduces the number of myogenic satellite cells at injured site. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
SHH
- 
- 