IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
P18146 | Q04206 | 2 | binding | up-regulates | 0.433 | The early growth response transcription factor egr-1 can also interact with rela in vitro and regulate nf-kappab transcriptional activity in vivo | SIGNOR-75001 |
P51812 | P84243 | 1 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun. | SIGNOR-138471 |
Q9NRF8 | P48729 | 0 | phosphorylation | down-regulates | 0.2 | Hctps2 ser(568) was phosphorylated by casein kinase 1 both in vitro and in vivo. Mutation of ser(568) (s568a) significantly increased hctps2 activity, demonstrating that ser(568) is a major inhibitory phosphorylation site. | SIGNOR-167623 |
O95405 | P37173 | 2 | binding | up-regulates activity | 0.57 | Sara functions to recruit smad2 to the tgfbeta receptor by controlling the subcellular localization of smad2 and by interacting with the tgfbeta receptor complex | SIGNOR-245093 |
P24723 | P29474 | 1 | phosphorylation | down-regulates activity | 0.2 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251634 |
Q15382 | Q92574 | 2 | binding | down-regulates activity | 0.911 | Tsc1 and tsc2 proteins, which together inhibit rheb through the gap activity of tsc2. | SIGNOR-162096 |
P43405 | Q9NRF2 | 0 | dephosphorylation | down-regulates activity | 0.2 | SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK. | SIGNOR-268445 |
P30086 | P04049 | 2 | binding | down-regulates | 0.762 | Suppression of raf-1 kinase activity and map kinase by rkip. Rkip binds to raf-1, mek and erk, but not to ras. | SIGNOR-70838 |
P63092 | Q14833 | 2 | binding | up-regulates activity | 0.344 | MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits. | SIGNOR-264082 |
O43193 | O95837 | 2 | binding | up-regulates activity | 0.435 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257132 |
Q16539 | O00206 | 0 | phosphorylation | up-regulates activity | 0.416 | Binding of S100A9 to TLR4 stimulates the phosphorylation of JNK, ERK1/2, and p38 MAPK, which leads to the activation of c-Jun, CREB, and NF-κB. Activation of neutrophils by S100A9 also proceeds via p38 MAPK, JNK, and ERK1/2 phosphorylation. | SIGNOR-263652 |
P04899 | Q99835 | 2 | binding | up-regulates activity | 0.429 | it was proposed that Smo might signal through activation of Gi proteins to reduce PKA activity. | SIGNOR-199162 |
P53778 | P15172 | 1 | phosphorylation | up-regulates activity | 0.446 | We determined that p38-gamma directly phosphorylated MyoD on Ser199 and Ser200, which results in enhanced occupancy of MyoD on the promoter of myogenin together with markedly decreased transcriptional activity. Phosphorylation of MyoD by p38-γ directs the assembly of a repressive transcriptional complex at the Myogenin promoter. | SIGNOR-276273 |
Q9H9S0 | P26358 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.432 | Oct4 and Nanog upregulate Dnmt1 through direct binding to its promoter, thereby leading to the repressed expression of p16 and p21 and genes associated with development and lineage differentiation | SIGNOR-253157 |
Q13772 | P37231 | 2 | binding | up-regulates | 0.449 | Identification of ara70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma. / ppargamma and ara70 interact in the absence of the ppargamma ligand 15-deoxy-delta12,14-prostaglandin j2, although the addition of exogenous ligand enhances this interaction. | SIGNOR-67687 |
Q6X9E4 | Q8N6P7 | 2 | binding | down-regulates quantity by destabilization | 0.342 | FBXW12 causes depletion of endogenous and plasmid-derived IL-22R in lung epithelia, binds the E3 ligase constituent Skp-1, and facilitates ubiquitination of IL-22R in vitro. | SIGNOR-272426 |
P19544 | Q96IZ0 | 2 | binding | down-regulates activity | 0.501 | We identified par-4 (for prostate apoptosis response) as a WT1-interacting protein that itself functions as a transcriptional repressor. Functionally, par-4 inhibited transcription activated by WT1 | SIGNOR-240596 |
Q9Y2H0 | Q9UPX8 | 1 | relocalization | up-regulates activity | 0.744 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264596 |
Q16649 | P08700 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.527 | NF-IL3A transactivates the IL-3 promoter through the A region sequences. | SIGNOR-266222 |
A6NLU0 | P14635 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.32 | We conclude that, like many RING-finger containing proteins, RFPL4 is an E3 ubiquitin ligase. The specificity of its expression and these interactions suggest that RFPL4 targets cyclin B1 for proteasomal degradation, a key aspect of oocyte cell cycle control during meiosis and the crucial oocyte-to-embryo transition to mitosis. | SIGNOR-271476 |
O15527 | P04637 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.429 | Using gel-shift assays, we showed that p53 binds to its putative cis-elements within the hOGG1 promoter. In addition we demonstrated that supplementing p53 in HCT116p53-/- cells enhanced the transcription of hOGG1. | SIGNOR-255440 |
P49137 | P26651 | 1 | phosphorylation | down-regulates activity | 0.699 | We confirm phosphorylation of TTP by MK2 and identify specific phosphorylation sites at Ser52, Ser105, Ser58, Ser176, Ser178, and Ser316. If MK2 regulates translation in part by TTP phosphorylation, TTP should be a repressor of translation when dephosphorylated and an activator of (or neutral to) translation when phosphorylated. | SIGNOR-250153 |
P06127 | P68400 | 0 | phosphorylation | up-regulates | 0.342 | In this study, we use jurkat t cell transfectants of cd5 cytoplasmic tail mutants to reveal phosphorylation sites relevant to signal transduction. Our results show that casein kinase ii (ckii) is responsible for the constitutive phosphorylation of cd5 molecules at a cluster of three serine residues located at the extreme c terminus (s458, s459, and s461) | SIGNOR-62311 |
Q07912 | O00308 | 1 | phosphorylation | up-regulates activity | 0.342 | ACK1 phosphorylates WWP2 at the 2, 3-linker and partially activates the ubiquitination ligase activity.|Activation of E3 ubiquitin ligase WWP2 by non-receptor tyrosine kinase ACK1. | SIGNOR-279302 |
A8MYZ6 | Q13627 | 0 | phosphorylation | down-regulates | 0.305 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity | SIGNOR-183680 |
Q9UPS6 | Q16695 | 1 | methylation | down-regulates activity | 0.2 | SETD1B encodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks. | SIGNOR-265577 |
Q8WXG1 | Q05516 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Promoter regions from the PLZF-regulated transcripts Rsad2 and Ifit2 were fused to luciferase and activity was measured after IFN treatment. Overexpression of PLZF in RCC1 or ACHN cells produced a dose-dependent induction of the reporter promoters. | SIGNOR-261023 |
P63096 | P41146 | 2 | binding | up-regulates activity | 0.463 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256722 |
O75807 | Q99933 | 0 | null | down-regulates activity | 0.444 | Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions.|BAG-1 negatively modulates GADD34-bound PP1 activity, and the expression of BAG-1 isoforms can also mask GADD34-mediated inhibition of colony formation and suppression of transcription. Our findings suggest that BAG-1 may function to suppress the GADD34-mediated cellular stress response and support a role for BAG-1 in the survival of cells undergoing stress. | SIGNOR-254117 |
Q13477 | Q8TAU0 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.428 | We provide evidence that NKX2.3 can activate MAdCAM-1 transcription directly | SIGNOR-266219 |
Q12947 | P20226 | 2 | binding | up-regulates activity | 0.408 | The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB. | SIGNOR-220373 |
P14635 | Q12834 | 2 | binding | down-regulates quantity by destabilization | 0.968 | These results suggested that cyclin A is a target of the Cdc20-associated APC/C in human cells. | SIGNOR-272578 |
Q99717 | P12757 | 2 | binding | down-regulates | 0.448 | Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad8. | SIGNOR-95474 |
P11309 | P08183 | 1 | dephosphorylation | up-regulates activity | 0.438 | Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function|P-gp is known to be phosphorylated at Ser667, Ser671, and Ser683 by PKA; at Ser661, Ser667, and Ser671 by PKC; and at Ser683 by Pim-1|simultaneous expression of PP5 and PPP2R3C reduced the phosphorylation detected by the antibodies that specifically recognize serine/threonine phosphorylated by PKA or serine phosphorylated by PKC. These results suggest that the PP5/PPP2R3C complex dephosphorylates PKA- and PKC-phosphorylated serine residues on P-gp | SIGNOR-272511 |
Q9NRP7 | P29372 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Here, we show that MID1 catalyzes the ubiquitination and proteasomal cleavage of the GLI3 regulator Fu. | SIGNOR-272466 |
P53350 | P08670 | 1 | phosphorylation | up-regulates | 0.2 | We observed that plk1 phosphorylates vimentin on ser82, which in turn regulates cell surface levels of 1 integrin. | SIGNOR-159386 |
P05412 | P01137 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.542 | MAPKs have cis-acting regulatory elements in the mouse-TGF promoter region, which respond to various transcription factors, including specificity protein-1 and activating protein 1. Thus, it is possible that apoptotic cell-induced TGF-beta mRNA expression is mediated through activation of these transcription factors via MAPK signaling. Xiao et al. reported that all of the MAPK members, including p38/ERK/JNK, are required for apoptotic Jurkat cells up-regulation of TGF-beta production | SIGNOR-251713 |
Q9UHC7 | P04637 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.431 | Makorin Ring Finger Protein 1 (MKRN1) is a transcriptional co-regulator and an E3 ligase. Here, we show that MKRN1 simultaneously functions as a differentially negative regulator of p53 and p21. In normal conditions, MKRN1 could destabilize both p53 and p21 through ubiquitination and proteasome-dependent degradation. As a result, depletion of MKRN1 induced growth arrest through activation of p53 and p21. K291 and K292 of p53 are required for MKRN1-mediated degradation and ubiquitination of p53 | SIGNOR-271846 |
P35680 | P61457 | 2 | binding | up-regulates activity | 0.581 | Overexpression in a human kidney cell line showed that wild-type PCBD1 binds HNF1B to costimulate the FXYD2 promoter, the activity of which is instrumental in Mg(2+) reabsorption in the DCT. | SIGNOR-254910 |
Q13698 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.449 | To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2. | SIGNOR-263113 |
P12259 | P00734 | 0 | null | up-regulates activity | 0.882 | Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind | SIGNOR-263530 |
P10912 | Q16829 | 0 | dephosphorylation | down-regulates | 0.313 | Identification of protein tyrosine phosphatases with specificity for the ligand-activated growth hormone receptor. | SIGNOR-104545 |
Q8NHY2 | P17676 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We show expression of c/EBPβ in microglia is regulated post-translationally by the ubiquitin ligase COP1 (also called RFWD2). In the absence of COP1, c/EBPβ accumulates rapidly and drives a potent pro-inflammatory and neurodegeneration-related gene program, evidenced by increased neurotoxicity in microglia-neuronal co-cultures. | SIGNOR-261924 |
Q9Y5Y9 | Q92913 | 2 | binding | down-regulates activity | 0.2 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253439 |
P55211 | P28482 | 0 | phosphorylation | down-regulates activity | 0.533 | ERK/MAPK phosphorylates caspase-9 at Thr(125), and this phosphorylation is crucial for caspase-9 inhibition | SIGNOR-148616 |
Q99767 | Q9ULB1 | 2 | binding | up-regulates activity | 0.636 | Mint1 and Mint2 Interact with the Cytoplasmic Domain of Neurexin I. The interaction of Mint1 with neurexins is mediated by its PDZ domains and allows the formation of mixed CASK-Mint complexes. Both CASK and Mint1 can bind directly to neurexins and to each other. Therefore, the assembly of various multimeric complexes could proceed as CASK could be indirectly recruited to neurexin-bound Mint1 and vice versa. | SIGNOR-264039 |
P06493 | Q5BJF6 | 1 | phosphorylation | up-regulates activity | 0.543 | Phosphorylation of hCenexin1 at S796 is critical for the hCenexin1-Plk1 interaction.Here we show that a splice variant of hODF2 called hCenexin1, but not hODF2 itself, efficiently localizes to somatic centrosomes via a variant-specific C-terminal extension and recruits Plk1 through a Cdc2-dependent phospho-S796 motif within the extension. This interaction and Plk1 activity were important for proper recruitment of pericentrin and gamma-tubulin, and, ultimately, for formation of normal bipolar spindles. | SIGNOR-273584 |
Q04759 | Q9UEW8 | 1 | phosphorylation | up-regulates activity | 0.487 | Recombinant SPAK was phosphorylated on Ser-311 in its kinase domain by PKCtheta, but not by PKCalpha. This synergistic activity, as well as the receptor-induced SPAK activation, required the PKCtheta-interacting region of SPAK, and Ser-311 mutation greatly reduced these activities of SPAK. | SIGNOR-276007 |
O43318 | O75901 | 1 | phosphorylation | up-regulates activity | 0.2 | As expected, increased expression of TAK1 induced by LV-TAK1 stimulated p-RASSF9, whereas p-MEK and p-ERK were reduced.|We further identified RASSF9 as a downstream target of TAK1 which phosphorylates RASSF9 at S284. | SIGNOR-279534 |
P49137 | O95816 | 1 | phosphorylation | up-regulates | 0.366 | We provided definite evidence that mapkapk2 phosphorylates bag2 at ser 20 in vitro and in vivo. These results demonstrate that bag2 is a novel component of the p38 mapk signaling pathways. | SIGNOR-126953 |
Q9C0C7 | O15111 | 0 | phosphorylation | up-regulates activity | 0.2 | Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. | SIGNOR-272974 |
P84243 | Q13185 | 2 | binding | up-regulates activity | 0.2 | A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing. | SIGNOR-264494 |
P50613 | P10276 | 1 | phosphorylation | up-regulates | 0.546 | However, only the coexpression of cdk7 stimulated ser-77 phosphorylation in vivo and enhanced transactivation by rar alpha, but not by a s77a rar mutant. | SIGNOR-49693 |
P33981 | P53350 | 0 | phosphorylation | up-regulates activity | 0.381 | Here, we demonstrate that Plk1 promotes checkpoint signaling at kinetochores through the phosphorylation of at least two Mps1 substrates, including KNL-1 and Mps1 itself. As a result, Plk1 activity enhances Mps1 catalytic activity as well as the recruitment of the SAC components Mad1:C-Mad2 and Bub3:BubR1 to kinetochores. Plk1 Targets Mps1 Autophosphorylation Sites In Vitro | SIGNOR-276199 |
P49841 | Q6IA17 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Activation of GSK3beta promotes Sigirr degradation in the proteasome .|Taken together, IL-37-induced Sigirr internalization is dependent on phosphorylation of Sigirr in T372 residue by GSK3\u03b2. | SIGNOR-279053 |
Q02156 | P48751 | 1 | phosphorylation | up-regulates activity | 0.309 | We conclude that following Ang II stimulation of cells, PKCepsilon phosphorylates serine 67 of the AE3 cytoplasmic domain, inducing the Ang II-induced increase in anion transport observed in the hypertrophic myocardium. | SIGNOR-249127 |
P63096 | P17948 | 0 | phosphorylation | up-regulates activity | 0.257 | RTKs directly phosphorylate Gαi on Y154, 155, and Y320. | SIGNOR-277230 |
Q13362 | P04637 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.611 | Ablation of the B56gamma protein by RNAi, which abolishes the Thr55 dephosphorylation in response to DNA damage, reduces p53 stabilization, Bax expression and cell apoptosis. To investigate the molecular mechanisms, we have shown that the endogenous B56gamma protein level and association with p53 increase after DNA damage. Finally, we demonstrate that Thr55 dephosphorylation is required for B56gamma3-mediated inhibition of cell proliferation and cell transformation. | SIGNOR-268154 |
Q9Y5G2 | Q9Y5I2 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265710 |
P08754 | P48145 | 2 | binding | up-regulates activity | 0.435 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256818 |
P23470 | P42229 | 1 | dephosphorylation | up-regulates activity | 0.265 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254730 |
P11802 | P15172 | 2 | binding | down-regulates | 0.511 | In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms. | SIGNOR-176527 |
P02649 | P02647 | 0 | relocalization | up-regulates activity | 0.738 | ApoA-I stimulates apoE secretion in mature human adipocytes. The regulation of apoE secretion by apoA-I, is neither dependent upon an increase in gene transcription, nor upon increased release from the Golgi. It may therefore be assumed that, in macrophage models, apoE is stored mainly in the cytoplasm and/or on the cell surface, with apoA-I enabling secretion of this cytoplasmic pool | SIGNOR-252105 |
Q9Y566 | P12814 | 1 | relocalization | up-regulates activity | 0.273 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264583 |
Q9UQM7 | O95180 | 1 | phosphorylation | down-regulates activity | 0.272 | we also discovered that a novel CaMKII-phosphorylated site, S2137, underwent dephosphorylation by calcineurin. | SIGNOR-277871 |
P52333 | Q15910 | 1 | phosphorylation | up-regulates activity | 0.428 | These results demonstrate that phosphorylation of EZH2 by JAK3 on the Y244 increases the interaction with Polymerase II and decreases the association with PRC2 components promoting the expression of non-canonical genes.|To explore the mechanism of JAK3 mediated EZH2 activation, the authors performed co-immunoprecipitation assays, which revealed interaction of EZH2 with JAK3 and polymerase II. | SIGNOR-278518 |
P16615 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.397 | SERCA2 and SERCA2 mutants S38A, S167A, and S531A were expressed in HEK-293 cells and tested for phosphorylation with CaM kinase. Mutant S38A was not phosphorylated, while mutants S167A and S531A were phosphorylated, suggesting that Ser38 is the site of CaM kinase phosphorylation in SERCA2. This conclusion was supported by the observation that phosphorylation of SERCA2 and mutants S167A and S531A by CaM kinase increased the Vmax for Ca2+ transport, while the Vmax for Ca2+ transport by mutant S38A was unaffected by exposure to a phosphorylation reaction mix. | SIGNOR-250616 |
O43182 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.581 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260462 |
P43405 | Q7Z6Z7 | 1 | phosphorylation | up-regulates activity | 0.2 | Collectively, these data suggest that TNF induced tyrosine phosphorylation of Mule by Syk contributes to its E3 ligase activity. | SIGNOR-280150 |
P04637 | O15391 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.572 | YY2 activated the p53 promoter. However, in contrast to YY1, which represses the activity of c-Fos, YY2 increased the activity of the c-Fos promoter. | SIGNOR-266213 |
P20309 | P63096 | 2 | binding | up-regulates activity | 0.277 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256739 |
Q04771 | P27037 | 2 | binding | up-regulates | 0.664 | The major bmp7 type i receptor observed was alk2, | SIGNOR-60234 |
P05114 | O75582 | 0 | phosphorylation | down-regulates activity | 0.62 | HMGN1 (formerly known as HMG-14) phosphorylation at Ser6 occurs concomitantly with IE gene expression. | MSK2 seems to be the most important kinase responsible for this modification |Accordingly, it was suggested that HMGN1 phosphorylation reduces binding of the protein to the nucleosomes | SIGNOR-262988 |
P58753 | O00206 | 2 | binding | up-regulates activity | 0.78 | Here we describe a protein, Mal (MyD88-adapter-like), which joins MyD88 as a cytoplasmic TlR-domain-containing protein in the human genome. Mal activates NF-_B, Jun amino-terminal kinase and extracellular signal-regulated kinase-1 and -2. | SIGNOR-252064 |
O95747 | P55017 | 1 | phosphorylation | up-regulates | 0.388 | We demonstrate that the spak and osr1 kinases that are activated by wnk1 phosphorylate human ncc at three conserved residues (thr46, thr55 and thr60) / our results also indicate that phosphorylation of thr60 plays the most crucial role in triggering the activation of ncc in hek293 cells and its mutation also inhibits phosphorylation of the adjacent thr46 and thr55 sites. | SIGNOR-160833 |
P06213 | P29350 | 2 | phosphorylation | up-regulates | 0.359 | Insulin stimulates the phosphorylation of tyr538 and the catalytic activity of ptp1c, a protein tyrosine phosphatase with src homology-2 domains. these results suggest that ptp1c is a target protein for the insulin receptor tyrosine kinase | SIGNOR-26870 |
Q13489 | Q12933 | 2 | ubiquitination | down-regulates quantity by destabilization | 0.892 | Traf3-binding receptors stabilize nik by activating ciap-dependent degradation of traf2 and traf3. | SIGNOR-182131 |
P12931 | O00206 | 1 | phosphorylation | up-regulates activity | 0.588 | Src dependent phosphorylation of TLR4 is significantly increased in Cftr-KO cholangiocytes.|TLR4 can be activated through the phosphorylation of its TIR domains by Src, a non receptor tyrosine kinase 28. | SIGNOR-279658 |
Q9NP71 | Q13131 | 0 | phosphorylation | down-regulates | 0.451 | Ampk has also been suggested to phosphorylate the glucose-sensitive transcription factor chrebpthe dna binding activity, as assayed in a gel-shift assay of the truncated chrebp, was gradually inactivated with time by treatment with ampk | SIGNOR-176494 |
P53671 | Q05655 | 0 | phosphorylation | down-regulates | 0.256 | Activation of pkc by phorbol ester treatment of endothelial cells stimulated limk2 phosphorylation at ser-283 and inhibited nuclear import of limk2 | SIGNOR-137927 |
O75144 | P17252 | 0 | phosphorylation | up-regulates activity | 0.2 | PKCα and PKCβ are required for phosphorylation of ICOSL and ICOSL-mediated cytokine induction. Therefore, S285 is required for PKC substrate (serine) phosphorylation of ICOSL, and each of the upstream arginines is similarly required for this phosphorylation. | SIGNOR-273798 |
Q15303 | Q99075 | 2 | binding | up-regulates | 0.75 | It was concluded that her4 is a newly described receptor for hb-egf and that hb-egf can activate two egf receptor subtypes, her1 and her4, but with different biological response. | SIGNOR-67009 |
P06493 | Q96GX5 | 1 | phosphorylation | up-regulates activity | 0.513 | We propose a model in which the initiating event for Gwl activation is phosphorylation by MPF of the proline-directed sites T193 and T206 in the presumptive activation loop | SIGNOR-249653 |
P28223 | P50148 | 2 | binding | up-regulates activity | 0.608 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257137 |
Q9HBH9 | P28482 | 0 | phosphorylation | up-regulates | 0.6 | We have identified a new subfamily of murine serine/threonine kinases, whose members, map kinase-interacting kinase 1 (mnk1) and mnk2, bind tightly to the growth factor-regulated map kinases, erk1 and erk2erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity | SIGNOR-48338 |
P21854 | P29350 | 0 | dephosphorylation | down-regulates | 0.623 | Our work clearly identifies cd72 as both an shp-1 binding protein (figure 1,figure 2) and a direct substrate for shp-1 in vivo (figure 3). As tyrosine phosphorylation of cd72 strongly correlates with the ability of the bcr to deliver growth-inhibitory/apoptosis-inducing signals (figure 4), our results suggest that shp-1-catalyzed dephosphorylation of cd72 may antagonize these signals. | SIGNOR-60155 |
Q15672 | P53671 | 0 | phosphorylation | up-regulates quantity | 0.2 | LIMK2 directly phosphorylated TWIST1, indicating that LIMK2 also regulates TWIST1 post-translationally (XREF_FIG).|LIMK2 positively regulates TWIST1 protein levels. | SIGNOR-278952 |
O95644 | P48454 | 0 | relocalization | up-regulates | 0.704 | The ca2+ dependent phosphatase calcineurin induces cardiac and skeletal muscle hypertrophy by a process that involves nf-at nuclear translocation, and activation of mef2c. | SIGNOR-179796 |
Q13118 | P24941 | 0 | phosphorylation | up-regulates quantity | 0.329 | In this study we have shown that CDK2 phosphorylates KLF10 at residue Ser 206 in vivo and in vitro .|In this study, we have shown that KLF10 protein has tightly controlled expression and that the expression level varies in a cell cycle dependent manner whereby CDK2 up-regulates activity the protein level of KLF10 through interference with the protein 's association with SIAH1. | SIGNOR-278394 |
P45983 | Q06481 | 1 | phosphorylation | up-regulates | 0.362 | Phosphorylation at the thr(668) residue of app (with respect to the numbering conversion for the app 695 isoform) and the thr(736) residue of aplp2 (with respect to the numbering conversion for the aplp2 763 isoform) in their cytoplasmic domains acts as a molecular switch for their protein-protein interaction and is implicated in neural function(s) and/or alzheimer's disease pathogenesis. Here we demonstrate that both app and aplp2 can be phosphorylated by jnk at the thr(668) and thr(736) residues, respectively, in response to cellular stress. | SIGNOR-122196 |
P38405 | P30968 | 2 | binding | up-regulates activity | 0.274 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256935 |
Q14289 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.725 | We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. |We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. Moreover, overexpression of dominant negative SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and suggest SHP2 as a novel therapeutic target in MM..... 1) RAFTK is a substrate of SHP2 in vitro and 2) dephosphorylation of RAFTK by SHP2 inhibits its kinase activity. | SIGNOR-277084 |
O00141 | O15530 | 0 | phosphorylation | up-regulates activity | 0.65 | PDK1 activates SGK in vitro by phosphorylating Thr256. | SIGNOR-250275 |
Q13131 | P04406 | 1 | phosphorylation | up-regulates activity | 0.293 | Under glucose starvation, but not amino acid starvation, cytoplasmic GAPDH is phosphorylated on Ser122 by activated AMPK. This causes GAPDH to redistribute into the nucleus. Inside the nucleus, GAPDH interacts directly with Sirt1, displacing Sirt1's repressor and causing Sirt1 to become activated. | SIGNOR-259857 |
Q9Y5H9 | Q9UN70 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265674 |
P04035 | Q9UKV5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.492 | Gp78 mediates the sterol regulated ubiquitination of HMGCR. | SIGNOR-278622 |
P05771 | Q8IWA4 | 1 | phosphorylation | down-regulates activity | 0.2 | Here we report that βIIPKC accumulates on the mitochondrial outer membrane and phosphorylates mitofusin 1 (Mfn1) at serine 86. Mfn1 phosphorylation results in partial loss of its GTPase activity and in a buildup of fragmented and dysfunctional mitochondria in heart failure. | SIGNOR-273826 |
P27361 | O60716 | 1 | phosphorylation | down-regulates activity | 0.293 | Upon TGFβ treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. TGFβ promotes monoubiquitination of p120-catenin through Smurf1 to induce junction dissociation. | SIGNOR-277506 |
Q9UGL1 | Q9H9S0 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.308 | Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes. | SIGNOR-273451 |
P35575 | Q53ET0 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB | SIGNOR-256103 |
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