| 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
Property Summary
| Ligand Count | 3 |
| NCBI Gene PubMed Count | 323 |
| PubMed Score | 598.09 |
| PubTator Score | 478.28 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| AMYOTROPHIC LATERAL SCLEROSIS 1 | 49 | 0.0 | 0.0 |
| Cardiomegaly | 116 | 0.0 | 0.0 |
| Disease | Target Count | P-value |
|---|---|---|
| juvenile dermatomyositis | 1187 | 5.5e-12 |
| ovarian cancer | 8520 | 1.7e-08 |
| group 4 medulloblastoma | 1855 | 5.8e-06 |
| pituitary cancer | 1972 | 4.2e-05 |
| atypical teratoid / rhabdoid tumor | 5112 | 5.0e-04 |
| glioblastoma | 5792 | 2.2e-03 |
| subependymal giant cell astrocytoma | 2287 | 2.4e-03 |
| pediatric high grade glioma | 1064 | 7.7e-03 |
| Multiple myeloma | 1332 | 9.6e-03 |
| primary pancreatic ductal adenocarcinoma | 1109 | 1.8e-02 |
| astrocytoma | 1146 | 2.6e-02 |
| Disease | log2 FC | p |
|---|---|---|
| astrocytoma | 2.000 | 2.6e-02 |
| atypical teratoid / rhabdoid tumor | 1.700 | 5.0e-04 |
| glioblastoma | 2.500 | 2.2e-03 |
| group 4 medulloblastoma | -1.700 | 5.8e-06 |
| juvenile dermatomyositis | 1.132 | 5.5e-12 |
| Multiple myeloma | 1.234 | 9.6e-03 |
| ovarian cancer | 3.000 | 1.7e-08 |
| pediatric high grade glioma | 1.100 | 7.7e-03 |
| pituitary cancer | -1.200 | 4.2e-05 |
| primary pancreatic ductal adenocarcinoma | 1.006 | 1.8e-02 |
| subependymal giant cell astrocytoma | 2.302 | 2.4e-03 |
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 //
