| Tchem | SHC-transforming protein 1 |
Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis.
This gene encodes three main isoforms that differ in activities and subcellular location. While all three are adapter proteins in signal transduction pathways, the longest (p66Shc) may be involved in regulating life span and the effects of reactive oxygen species. The other two isoforms, p52Shc and p46Shc, link activated receptor tyrosine kinases to the Ras pathway by recruitment of the GRB2/SOS complex. p66Shc is not involved in Ras activation. Unlike the other two isoforms, p46Shc is targeted to the mitochondrial matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]
This gene encodes three main isoforms that differ in activities and subcellular location. While all three are adapter proteins in signal transduction pathways, the longest (p66Shc) may be involved in regulating life span and the effects of reactive oxygen species. The other two isoforms, p52Shc and p46Shc, link activated receptor tyrosine kinases to the Ras pathway by recruitment of the GRB2/SOS complex. p66Shc is not involved in Ras activation. Unlike the other two isoforms, p46Shc is targeted to the mitochondrial matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]
Comments
| Disease | Target Count |
|---|---|
| AMYOTROPHIC LATERAL SCLEROSIS 1 | 49 |
| Cardiomegaly | 66 |
| Disease | Target Count | P-value |
|---|---|---|
| juvenile dermatomyositis | 1189 | 5.52802446305844E-12 |
| ovarian cancer | 8492 | 1.69152167975251E-8 |
| group 4 medulloblastoma | 1875 | 5.751822093744E-6 |
| pituitary cancer | 1972 | 4.17137588197895E-5 |
| atypical teratoid / rhabdoid tumor | 4369 | 4.96921599190351E-4 |
| glioblastoma | 5572 | 0.0022229244259674 |
| subependymal giant cell astrocytoma | 2287 | 0.00238822762481229 |
| pediatric high grade glioma | 2712 | 0.00767716541987887 |
| Multiple myeloma | 1328 | 0.00955185887493794 |
| primary pancreatic ductal adenocarcinoma | 1271 | 0.0177265247616104 |
| astrocytoma | 1493 | 0.0261870415162742 |
| Disease | log2 FC | p |
|---|---|---|
| Multiple myeloma | 1.234 | 0.010 |
| glioblastoma | 2.500 | 0.002 |
| astrocytoma | 2.000 | 0.026 |
| atypical teratoid / rhabdoid tumor | 1.700 | 0.000 |
| juvenile dermatomyositis | 1.132 | 0.000 |
| primary pancreatic ductal adenocarcinoma | 1.006 | 0.018 |
| pediatric high grade glioma | 1.100 | 0.008 |
| group 4 medulloblastoma | -1.700 | 0.000 |
| subependymal giant cell astrocytoma | 2.302 | 0.002 |
| ovarian cancer | 3.000 | 0.000 |
| pituitary cancer | -1.200 | 0.000 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Macaque | OMA EggNOG Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA EggNOG Inparanoid |
| Dog | OMA EggNOG Inparanoid |
| Cow | OMA EggNOG Inparanoid |
| Opossum | OMA EggNOG Inparanoid |
| Xenopus | OMA Inparanoid |
| PMID | Text |
|---|---|
| 26680585 | Data suggest SHC1 (SH2 domain protein C1) expression down-regulates epithelial-mesenchymal transition by repressing TGFB-induced SMAD2/3 activation through differential partitioning of receptors at cell surface of mammocytes/keratinocytes. |
| 26551075 | Finally, a crystal structure of EGFR in complex with a primed Shc1 peptide reveals the structural basis for EGFR substrate specificity. |
| 26464652 | The silence of p66(Shc) in HCT8 cells reduced the proliferation and accelerated the apoptosis, in addition, the expression of pro-apoptotic proteins caspase-3, caspase-9, Bax was enhanced and the expression of anti-apoptotic protein Bcl-2 was declined. |
| 26122877 | In mice and humans, reduced p66Shc levels protect from obesity, but not from ectopic fat accumulation, glucose intolerance and insulin resistance. |
| 25961473 | These data demonstrate that the p52Shc phosphorylation level is altered by the solution environment without affecting the fraction of active c-Src. |
| 25815500 | Hyperoxia can increase the expression of PKCbeta in alveolar epithelial cells and production of mitochondrial reactive oxygen species and decrease mitochondrial membrane potential. |
| 25810038 | p53-dependent augmentation of p66(Shc) expression and function represents a key signalling response contributing to beta cell apoptosis under conditions of lipotoxicity |
| 25680868 | p66ShcA was upregulated in hearts of patients with ischemic heart disease without heart failure |
| 25217205 | Data show that ouabain-induced glioblastoma cells apoptosis and increased reactive oxygen species (ROS) generation in extracellular signal-related kinases ERK1/2-Shc signaling adaptor protein p66SHC-dependent pathway. |
| 25147340 | p66(Shc) plays a vital part in canonical Wnt signaling in the endothelium and mediates Wnt3a-stimulated endothelial oxidative stress and dysfunction. |
| More... |
MDLLPPKPKYNPLRNESLSSLEEGASGSTPPEELPSPSASSLGPILPPLPGDDSPTTLCSFFPRMSNLRL 1 - 70 ANPAGGRPGSKGEPGRAADDGEGIVGAAMPDSGPLPLLQDMNKLSGGGGRRTRVEGGQLGGEEWTRHGSF 71 - 140 VNKPTRGWLHPNDKVMGPGVSYLVRYMGCVEVLQSMRALDFNTRTQVTREAISLVCEAVPGAKGATRRRK 141 - 210 PCSRPLSSILGRSNLKFAGMPITLTVSTSSLNLMAADCKQIIANHHMQSISFASGGDPDTAEYVAYVAKD 211 - 280 PVNQRACHILECPEGLAQDVISTIGQAFELRFKQYLRNPPKLVTPHDRMAGFDGSAWDEEEEEPPDHQYY 281 - 350 NDFPGKEPPLGGVVDMRLREGAAPGAARPTAPNAQTPSHLGATLPVGQPVGGDPEVRKQMPPPPPCPGRE 351 - 420 LFDDPSYVNVQNLDKARQAVGGAGPPNPAINGSAPRDLFDMKPFEDALRVPPPPQSVSMAEQLRGEPWFH 421 - 490 GKLSRREAEALLQLNGDFLVRESTTTPGQYVLTGLQSGQPKHLLLVDPEGVVRTKDHRFESVSHLISYHM 491 - 560 DNHLPIISAGSELCLQQPVERKL 561 - 583 //
| PMID | Year | Title |
|---|---|---|
| 26680585 | 2015 | ShcA Protects against Epithelial-Mesenchymal Transition through Compartmentalized Inhibition of TGF-?-Induced Smad Activation. |
| 26551075 | 2015 | EGF-receptor specificity for phosphotyrosine-primed substrates provides signal integration with Src. |
| 26464652 | 2015 | The silence of p66(Shc) in HCT8 cells inhibits the viability via PI3K/AKT/Mdm-2/p53 signaling pathway. |
| 26122877 | 2015 | p66Shc deletion or deficiency protects from obesity but not metabolic dysfunction in mice and humans. |
| 25961473 | 2015 | Conformation-Dependent Human p52Shc Phosphorylation by Human c-Src. |
| 25815500 | 2015 | [Roles of PKC?/P66Shc oxidative stress signal pathway in mediating hyperoxia-induced ROS production in alveolar epithelial cells]. |
| 25810038 | 2015 | The p66(Shc) redox adaptor protein is induced by saturated fatty acids and mediates lipotoxicity-induced apoptosis in pancreatic beta cells. |
| 25680868 | 2015 | The p66ShcA adaptor protein regulates healing after myocardial infarction. |
| 25416956 | 2014 | A proteome-scale map of the human interactome network. |
| 25217205 | 2015 | Ouabain elicits human glioblastoma cells apoptosis by generating reactive oxygen species in ERK-p66SHC-dependent pathway. |
| More... |
