| Tbio | Kinase suppressor of Ras 2 |
Location-regulated scaffold connecting MEK to RAF. Has very low protein kinase activity and can phosphorylate MAP2K1 at several Ser and Thr residues with very low efficiency (in vitro). Interaction with BRAF enhances KSR2-mediated phosphorylation of MAP2K1 (in vitro). Blocks MAP3K8 kinase activity and MAP3K8-mediated signaling. Acts as a negative regulator of MAP3K3-mediated activation of ERK, JNK and NF-kappa-B pathways, inhibiting MAP3K3-mediated interleukin-8 production.
Comments
| Disease | Target Count | P-value |
|---|---|---|
| lung carcinoma | 2844 | 1.55158680524817E-37 |
| posterior fossa group A ependymoma | 1511 | 2.82332206081106E-12 |
| pediatric high grade glioma | 2712 | 1.18658290158265E-9 |
| glioblastoma | 5572 | 2.31780197649086E-8 |
| pilocytic astrocytoma | 3086 | 1.92397878991546E-7 |
| medulloblastoma, large-cell | 6234 | 4.15480328723634E-7 |
| group 3 medulloblastoma | 2254 | 4.51617532299339E-7 |
| oligodendroglioma | 2849 | 1.55415091525116E-6 |
| atypical teratoid / rhabdoid tumor | 4369 | 1.29218186203755E-5 |
| primitive neuroectodermal tumor | 3031 | 8.65866071725902E-5 |
| interstitial cystitis | 2299 | 6.21364242865138E-4 |
| astrocytic glioma | 2241 | 0.0088356688283309 |
| subependymal giant cell astrocytoma | 2287 | 0.00941114921042439 |
| Disease | log2 FC | p |
|---|---|---|
| astrocytic glioma | -1.700 | 0.009 |
| posterior fossa group A ependymoma | -2.700 | 0.000 |
| glioblastoma | -3.900 | 0.000 |
| oligodendroglioma | -1.200 | 0.000 |
| group 3 medulloblastoma | -4.300 | 0.000 |
| atypical teratoid / rhabdoid tumor | -2.900 | 0.000 |
| medulloblastoma, large-cell | -3.700 | 0.000 |
| primitive neuroectodermal tumor | -2.600 | 0.000 |
| interstitial cystitis | -2.100 | 0.001 |
| pediatric high grade glioma | -3.400 | 0.000 |
| pilocytic astrocytoma | -2.600 | 0.000 |
| subependymal giant cell astrocytoma | -2.954 | 0.009 |
| lung carcinoma | 2.000 | 0.000 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Macaque | OMA EggNOG Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA Inparanoid |
| Dog | OMA EggNOG Inparanoid |
| Cow | OMA EggNOG Inparanoid |
| Pig | OMA EggNOG Inparanoid |
| Opossum | OMA EggNOG Inparanoid |
| Anole lizard | OMA Inparanoid |
| PMID | Text |
|---|---|
| 24672054 | KSR2 deficiency affects stromal interaction molecule 1 (STIM1)/ORAI1 puncta formation, which is correlated with cytoskeleton disorganization. |
| 24209692 | Study explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEKERK pathway and impair cellular fatty acid oxidation and glucose oxidation in transfected cells. |
| 23303246 | study demonstrated that miR-31 upregulated IL-2 expression via reduction of its up-stream kinase suppressor, KSR2, and is a component of T cell activation |
| 21441910 | KSR interacts with a regulatory Raf molecule in cis to induce a conformational switch of MEK, facilitating MEK's phosphorylation by a separate catalytic Raf molecule in trans |
| 21403620 | The involvement of KSR2 in regulation of cell proliferation was predicted by a KSR2-centered network analysis. |
| 20945381 | Oncoprotein Cot1 represses kinase suppressors of Ras1/2 and 1,25-dihydroxyvitamin D3-induced differentiation of human acute myeloid leukemia cells. |
| 20628086 | Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) |
| 20379614 | Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) |
| 19913121 | Observational study of gene-disease association. (HuGE Navigator) |
| 19563921 | KSR-2 may act as a scaffold protein similar as KSR-1 to mediate the MAPK core (RAF-MEK-ERK) signaling but with a distinct RAF isoform specificity; KSR-2 may only mediate the A-RAF signaling while KSR-1 transduces signals only from c-RAF. |
| More... |
MDEENMTKSEEQQPLSLQKALQQCELVQNMIDLSISNLEGLRTKCATSNDLTQKEIRTLESKLVKYFSRQ 1 - 70 LSCKKKVALQERNAELDGFPQLRHWFRIVDVRKEVLEEISPGQLSLEDLLEMTDEQVCETVEKYGANREE 71 - 140 CARLNASLSCLRNVHMSGGNLSKQDWTIQWPTTETGKENNPVCPPEPTPWIRTHLSQSPRVPSKCVQHYC 141 - 210 HTSPTPGAPVYTHVDRLTVDAYPGLCPPPPLESGHRSLPPSPRQRHAVRTPPRTPNIVTTVTPPGTPPMR 211 - 280 KKNKLKPPGTPPPSSRKLIHLIPGFTALHRSKSHEFQLGHRVDEAHTPKAKKKSKPLNLKIHSSVGSCEN 281 - 350 IPSQQRSPLLSERSLRSFFVGHAPFLPSTPPVHTEANFSANTLSVPRWSPQIPRRDLGNSIKHRFSTKYW 351 - 420 MSQTCTVCGKGMLFGLKCKNCKLKCHNKCTKEAPPCHLLIIHRGDPARLVRTESVPCDINNPLRKPPRYS 421 - 490 DLHISQTLPKTNKINKDHIPVPYQPDSSSNPSSTTSSTPSSPAPPLPPSATPPSPLHPSPQCTRQQKNFN 491 - 560 LPASHYYKYKQQFIFPDVVPVPETPTRAPQVILHPVTSNPILEGNPLLQIEVEPTSENEEVHDEAEESED 561 - 630 DFEEMNLSLLSARSFPRKASQTSIFLQEWDIPFEQLEIGELIGKGRFGQVYHGRWHGEVAIRLIDIERDN 631 - 700 EDQLKAFKREVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYSVVRDAKIVLDVNKTRQIAQEI 701 - 770 VKGMGYLHAKGILHKDLKSKNVFYDNGKVVITDFGLFSISGVLQAGRREDKLRIQNGWLCHLAPEIIRQL 771 - 840 SPDTEEDKLPFSKHSDVFALGTIWYELHAREWPFKTQPAEAIIWQMGTGMKPNLSQIGMGKEISDILLFC 841 - 910 WAFEQEERPTFTKLMDMLEKLPKRNRRLSHPGHFWKSAEL 911 - 950 //
| PMID | Year | Title |
|---|---|---|
| 24672054 | 2014 | The KSR2-calcineurin complex regulates STIM1-ORAI1 dynamics and store-operated calcium entry (SOCE). |
| 24209692 | 2013 | KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation. |
| 23793025 | 2013 | Genome-wide meta-analysis identifies new susceptibility loci for migraine. |
| 23472165 | 2013 | Genome-wide association study link novel loci to endometriosis. |
| 23303246 | 2013 | miR-31 regulates interleukin 2 and kinase suppressor of ras 2 during T cell activation. |
| 22589738 | 2012 | Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. |
| 21441910 | 2011 | A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK. |
| 21403620 | 2010 | Kinase suppressor of Ras 2 is involved in regulation of cell proliferation and is up-regulated in human invasive ductal carcinomas of breast. |
| 20945381 | 2011 | Oncoprotein Cot1 represses kinase suppressors of Ras1/2 and 1,25-dihydroxyvitamin D3-induced differentiation of human acute myeloid leukemia cells. |
| 20628086 | 2010 | Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. |
| More... |
