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 |
|---|---|---|---|---|---|---|---|
Q14680 | Q12778 | 1 | phosphorylation | down-regulates quantity | 0.257 | Direct phosphorylation of FOXO1 and FOXO3 by MELK.|Our findings revealed that siRNA mediated MELK knockdown increased protein levels of FOXO1 and FOXO3, which might increase p21 transcriptional level in a p53 independent manner. | SIGNOR-279543 |
P19086 | P35462 | 2 | binding | up-regulates activity | 0.315 | 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-257097 |
Q9NPG1 | P56703 | 2 | binding | up-regulates | 0.632 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131820 |
P09471 | Q9Y5N1 | 2 | binding | up-regulates activity | 0.261 | 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-256968 |
P16949 | Q00535 | 0 | phosphorylation | down-regulates | 0.376 | Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. The kinases involved in phosphorylating stmn ser-16 and ser-63 include camp-dependent protein kinase (pka) and pak1, whereas stmn ser-25 and ser-38 have been shown to be targets for proline-directed serine/threonine kinases such as cyclin-dependent kinases, erk1/2, and members of the p38 mapk subfamily. | SIGNOR-166682 |
P49593 | Q13177 | 1 | dephosphorylation | down-regulates | 0.261 | Pop x2, a pp 2c serine/threonine phosphatase, is known to dephosphorylate pak and downregulate its activity. | SIGNOR-162149 |
P60484 | P51149 | 1 | dephosphorylation | up-regulates activity | 0.373 | PTEN dephosphorylates Rab7 on two conserved residues S72 and Y183, which are necessary for GDP dissociation inhibitor (GDI)-dependent recruitment of Rab7 on to late endosomes and subsequent maturation. | SIGNOR-276960 |
P10275 | P12931 | 0 | phosphorylation | up-regulates activity | 0.76 | In addition to the ability of Src to promotes castration resistant progression and AR activation, Src is involved in regulating prostate cancer cell migration, invasion, and metastasis and affects bone remodeling.|These data suggest that downstream of cell surface receptors, Ack1 mediates AR tyrosine phosphorylation at Tyr 267 and Src mediates AR tyrosine phosphorylation at Tyr 534. | SIGNOR-278168 |
Q2Q1W2 | Q6ZN17 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.527 | In cells, TRIM71 negatively regulates Lin28B protein stability by catalyzing polyubiquitination. | SIGNOR-272054 |
P12814 | Q9Y566 | 0 | 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 |
P02741 | P08603 | 2 | binding | down-regulates activity | 0.551 | In this study, we provide mechanistic insight into how CRP contributes to the development of AMD. In particular, we show that monomeric CRP (mCRP) but not the pentameric form (pCRP) upregulates IL-8 and CCL2 levels in retinal pigment epithelial cells. Further, we show that complement factor H (FH) binds mCRP to dampen its proinflammatory activity. FH from AMD patients carrying the “risk” His402 polymorphism displays impaired binding to mCRP, and therefore proinflammatory effects of mCRP remain unrestrained. | SIGNOR-252145 |
P04150 | P20962 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.328 | Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner | SIGNOR-268460 |
P11387 | P38398 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.463 | Here, we show that the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is subsequently ubiquitinated by BRCA1. Taken together, we conclude that BRCA1 is the E3 ligase for topoI, and the rate of topoI proteasomal degradation determines CPT response. | SIGNOR-277353 |
Q9Y4H4 | P49840 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Co-immunoprecipitation of endogenous GPSM3 and 14-3-3 proteins from the human monocytic cell line THP-1 suggests basal phosphorylation of GPSM3 at serine 35 as potentially mediated by GSK3alpha. The GPSM3/14-3-3 interaction is seen to stabilize GPSM3 from degradation and also support the nuclear exclusion of both proteins. | SIGNOR-264863 |
P07477 | P55085 | 1 | cleavage | up-regulates activity | 0.388 | Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3. | SIGNOR-263602 |
O14965 | P38398 | 1 | phosphorylation | up-regulates | 0.677 | Previous studies have shown that the brca1 breast cancer tumor suppressor also localizes to the centrosome and that brca1 inactivation results in loss of the g(2)-m checkpoint. We demonstrate here that aurora-a physically binds to and phosphorylates brca1. We propose that brca1 phosphorylation by aurora-a plays a role in g(2) to m transition of cell cycle | SIGNOR-123065 |
P31629 | P30874 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.411 | Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain. | SIGNOR-261617 |
P19544 | Q9Y6K1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.379 | Here, we show that Wilms' tumour 1 (WT1), a developmental master regulator that can also act as a tumour suppressor or oncoprotein, transcriptionally regulates the de novo DNA methyltransferase 3A (DNMT3A) and that cellular WT1 levels can influence DNA methylation of gene promoters genome-wide. we demonstrate that depletion of WT1 by short-interfering RNAs leads to reduced DNMT3A in Wilms' tumour cells and human embryonal kidney-derived cell lines. Chromatin immunoprecipitation assays demonstrate WT1 recruitment to the DNMT3A promoter region and reporter assays confirm that WT1 directly transactivates DNMT3A expression. | SIGNOR-255904 |
Q9BW92 | P18848 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269428 |
P17612 | Q9UH17 | 1 | phosphorylation | down-regulates activity | 0.2 | Here we show that protein kinase A (PKA) physically binds to A3B and phosphorylates Thr214. | SIGNOR-277455 |
P04004 | P05771 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.303 | Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin. | SIGNOR-248963 |
Q14493 | P84243 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265418 |
P28482 | P14598 | 1 | phosphorylation | up-regulates | 0.45 | Erk1/2 are the kinases involved in p47phox_ phosphorylation on ser345 in gm-csfprimed human neutrophils._ Phosphorylation of ser345 is required for the priming of nadph oxidase activity in neutrophil-like cells | SIGNOR-147170 |
Q5NUL3 | P38405 | 2 | binding | up-regulates activity | 0.25 | 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-256916 |
P08754 | Q9Y271 | 2 | binding | up-regulates activity | 0.2 | 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-256883 |
P53350 | Q15208 | 1 | phosphorylation | down-regulates activity | 0.316 | Here, we identified a conserved signaling axis in which NDR1 kinase activity is regulated by PLK1 in mitosis. PLK1 phosphorylates NDR1 at three putative threonine residues (T7, T183 and T407) at mitotic entry, which elicits PLK1-dependent suppression of NDR1 activity and ensures correct spindle orientation in mitosis. | SIGNOR-276914 |
O75553 | P46531 | 2 | binding | up-regulates | 0.378 | The induction of disabled-1 (dab-1) tyrosine phosphorylation, and the subsequent activation of src family kinases, were found to be essential steps for the activation of notch-1 signaling by reelin | SIGNOR-196438 |
P31749 | P42574 | 0 | cleavage | down-regulates activity | 0.602 | P53 can inhibit the survival function of integrins by inducing the caspase-dependent cleavage and inactivation of the serine/threonine kinase akt/pkb;the involvement of caspase 3 in akt/pkb regulation was indicated by the ability of z-devd-fmk, a caspase 3 inhibitor, to block the alpha6beta4-associated reduction in akt/pkb levels in vivo, and by the ability of recombinant caspase 3 to promote the cleavage of akt/pkb in vitro | SIGNOR-252624 |
Q9H6R7 | P49959 | 2 | binding | up-regulates activity | 0.2 | PLK1 Phosphorylates MMAP to Promote Its Interaction with KIF2A and MRE11. | SIGNOR-273733 |
P08034 | P17252 | 0 | phosphorylation | up-regulates activity | 0.362 | Phosphorylation of connexin-32 by protein kinase C prevents its proteolysis by mu-calpain and m-calpain. |In agreement with other authors (see Saez et al., 1990b), we have found that phosphorylation of connexin-32 by protein kinase A and protein kinase C occurs in serine residues, although we have detected trace amounts of phosphothreonine in connexin-32 phosphorylated by protein kinase C (results not shown). Indeed, Se233 has been shown to be the major phosphorylation site catalyzed by protein kinase A. However, Ser233, Ser239, and perhaps other serines are phosphorylated by protein kinase C (Saez et al., 1990b). | SIGNOR-248919 |
Q9Y2U5 | Q02750 | 1 | phosphorylation | up-regulates | 0.414 | Both mekk2 and mekk3 are able to activate the jun kinase pathway in vivo. However, following routine immunoprecipitation in triton x-100, mekk2 but not mekk3 is able to effectively phosphorylate both sek-1 and mek-1 and to undergo autophosphorylation | SIGNOR-107692 |
P29371 | Q03113 | 2 | binding | up-regulates activity | 0.283 | 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-257389 |
Q9UGI9 | O75385 | 0 | phosphorylation | down-regulates | 0.406 | Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity phosphorylation of ampk by ulk1 represents a negative feedback circuit. | SIGNOR-173053 |
Q5VTB9 | O75182 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.429 | Here we identify RNF220 (RING finger protein 220) as a novel ubiquitin ligase for Sin3B. RNF220 specifically interacts with Sin3B both in vitro and in vivo. Sin3B can be regulated by the ubiquitin-proteasome system. Co-expression of RNF220 promotes the ubiquitination and proteasomal degradation of Sin3B. | SIGNOR-271943 |
O60341 | P84243 | 1 | demethylation | up-regulates activity | 0.2 | Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. | SIGNOR-264509 |
Q9UBY5 | P63096 | 2 | binding | up-regulates activity | 0.458 | 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-256890 |
Q14498 | Q66K64 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.377 | Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation. | SIGNOR-272203 |
Q13586 | Q9Y478 | 0 | phosphorylation | down-regulates activity | 0.2 | STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE | SIGNOR-277298 |
Q13490 | Q13490 | 2 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Ciap1 and ciap2 undergo autoubiquitination and degradation upon binding to the iap antagonist second mitochondrial activator of caspases (smac)/direct iap-binding protein with low pi (diablo), which is released from the mitochondria. | SIGNOR-121877 |
Q8NHZ8 | Q9NRM7 | 0 | phosphorylation | up-regulates activity | 0.46 | LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C|Overall, these results suggest that LATS1/2 are novel kinases involved in APC/C phosphorylation and indicate a direct regulatory link between LATS1/2 and APC/C | SIGNOR-275474 |
O15146 | O14904 | 2 | binding | up-regulates | 0.399 | we provide evidence that wnt9a and wnt11 bind directly to the extracellular domain of musk, to induce musk dimerization and subsequent tyrosine phosphorylation of the kinase | SIGNOR-195975 |
P63096 | P35372 | 2 | binding | up-regulates activity | 0.603 | 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-256711 |
P60953 | Q7Z6J4 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.483 | 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-260552 |
P30874 | O95837 | 2 | binding | up-regulates activity | 0.353 | 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-256963 |
P18669 | Q16512 | 0 | phosphorylation | down-regulates | 0.254 | Activated pak1 inhibits glycolysis by association of its catalytic domain with pgam-b and subsequent phosphorylation of the enzyme on serine residues 23 and 118, thereby abolishing pgam activity. | SIGNOR-91602 |
Q02535 | P15884 | 2 | binding | down-regulates activity | 0.458 | All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo. | SIGNOR-241379 |
Q16539 | P19419 | 1 | phosphorylation | up-regulates | 0.526 | We demonstrate here that elk-1 is barely activated by a third subclass of map kinases (p38), most likely because the critical residues ser383 and ser389 are poorly phosphorylated by p38 map kinase. | SIGNOR-47630 |
O75096 | O15146 | 2 | binding | up-regulates activity | 0.73 | AGRN is released by the nerve and binds to LRP4, which then binds to MuSK. This interaction leads to MuSK autophosphorylation and activation of its kinase function, leading to anterograde signalling by subsequent phosphorylation of DOK7 (not shown), which binds MuSK as a dimer. | SIGNOR-273850 |
P17612 | P55064 | 1 | phosphorylation | up-regulates activity | 0.2 | AQP5 can be directly phosphorylated by PKA at Ser 156 |Our data hint at a mechanism whereby phosphorylation of Ser 156 in AQP5 increases its membrane localization, thereby enhancing cancer cell proliferation. | SIGNOR-272088 |
Q9BXW9 | O94782 | 0 | deubiquitination | down-regulates activity | 0.761 | The deubiquitinating enzyme USP1 controls the cellular levels of the DNA damage response protein Ub-FANCD2|The level of monoubiquitinated FANCD2 protein increases in response to various types of DNA damage in mammalian cells | SIGNOR-263273 |
Q14934 | P45984 | 0 | phosphorylation | up-regulates activity | 0.419 | Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose-dependent manner by JNK1 or JNK2. | SIGNOR-280036 |
Q06187 | Q04206 | 1 | phosphorylation | up-regulates activity | 0.403 | Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ ].|Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ xref ]. | SIGNOR-280197 |
P84022 | P28482 | 0 | phosphorylation | down-regulates activity | 0.746 | Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3 | SIGNOR-161613 |
P17612 | O43566 | 1 | phosphorylation | up-regulates activity | 0.338 | RGS14 is phosphorylated in vitro at Ser258 and Thr494 by PKA. cAMP-induced phosphorylation as an important modulator of RGS14 function since phosphorylation could enhance RGS14 binding to Galpha(i)-GDP | SIGNOR-250045 |
Q06787 | Q9Y566 | 1 | post transcriptional regulation | up-regulates quantity | 0.4 | These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets. | SIGNOR-262109 |
Q9UQB3 | P49841 | 0 | phosphorylation | down-regulates quantity | 0.347 | Therefore, our data which supports that partial inhibition of GSK-3beta increases delta-catenin expression, raises an interesting possibility that delta-catenin may be an important downstream target of GSK-3beta signaling that participates in modulating neuronal morphology.|We demonstrate that GSK-3beta forms a stable complex with delta-catenin and phosphorylates delta-catenin in neurons, an event that mediates ubiquitination and subsequent proteasome degradation of delta-catenin. | SIGNOR-279719 |
O94811 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.403 | Here we show that TPPP induces tubulin self-assembly into intact frequently bundled microtubules, and that the phosphorylation of specific sites distinctly affects the function of TPPP. The phosphorylation sites Thr(14), Ser(18), Ser(160) for Cdk5; Ser(18), Ser(160) for ERK2, and Ser(32) for PKA were identified by mass spectrometry. The phosphorylation by ERK2 or Cdk5 resulted in the loss of microtubule-assembling activity of TPPP. | SIGNOR-262931 |
P09429 | P28358 | 2 | binding | up-regulates activity | 0.292 | We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein. | SIGNOR-240556 |
P17612 | Q01094 | 1 | phosphorylation | up-regulates activity | 0.2 | We confirmed the phosphorylation of T130, S235, and S364 by developing monoclonal antibodies against phospho-specific forms of these sites and showed that their phosphorylation is cell cycle-dependent. According to our results, PKA-mediated phosphorylation of E2F1 by PKA inhibits proliferation and glucose uptake and induces caspase-3 activation and senescence. | SIGNOR-277537 |
Q9H4L7 | Q13547 | 2 | binding | up-regulates activity | 0.319 | SMARCAD1 interacts with HDAC1 and KAP1 and is required for their binding to heterochromatin | SIGNOR-239835 |
P40763 | P48357 | 2 | binding | up-regulates activity | 0.759 | LRb signaling is initiated by leptin binding to the extracellular domain of the LRb dimer, leading to Jak2 transphosphorylation and activation. Activated Jak2 mediates the tyrosine phosphorylation of Tyr985 and Tyr1138of LRb. These phosphotyrosine residues immediately function as binding sites (double-ended lines) for SHP-2 and STAT3, both of which quickly become tyrosine-phosphorylated by Jak2. | SIGNOR-263495 |
Q9H4B6 | O00506 | 0 | phosphorylation | down-regulates activity | 0.28 | STK25 inhibits the ability of SAV1 to counteract STRIPAK.|Using this antibody, we confirmed that SAV1 WT was indeed phosphorylated by STK25 at T26 in human cells (XREF_FIG). | SIGNOR-278369 |
P50613 | P10275 | 1 | phosphorylation | down-regulates | 0.377 | Here, we show that the transcription factor tfiih, via its cdk7 kinase, phosphorylates the androgen receptor (ar) at position ar/s515. Strikingly, this phosphorylation is a key step for an accurate transactivation that includes the cyclic recruitment of the transcription machinery, the mdm2 e3 ligase, the subsequent ubiquitination of ar at the promoter of target genes and its degradation by the proteasome machinery | SIGNOR-170599 |
P35240 | Q9NRM7 | 2 | binding | up-regulates | 0.693 | As expected, the nf2-/- fc-912 cells were defective in lats1/2 phosphorylation (figure s2e-f). Subcellular fractionation revealed a significant increase of endogenous lats1/2 in the cytoplasmic relative to the membrane fraction in the nf2-/- fc-912 schwann cells compared to the nf2+/+ fh-912 schwann cells (figure 2e). This localization defect was rescued by re-expression of nf2 | SIGNOR-202607 |
P06493 | Q9H8V3 | 1 | phosphorylation | down-regulates | 0.577 | We show that phosphorylation of ect2 at threonine-341 (t341) affects the autoregulatory mechanism of ect2. In g2/m phase, ect2 was phosphorylated at t341 most likely by cyclin b/cyclin-dependent kinase 1 (cdk1) ect2 is biologically active even when it is not phosphorylated at t341 | SIGNOR-140549 |
P42224 | O00141 | 0 | phosphorylation | up-regulates activity | 0.252 | Notably, A\u03b2-activated SGK1 or JAK2 kinase phosphorylates STAT1 and induces its association with Tau(1\u2013368). | SIGNOR-279281 |
Q8IYT4 | Q9BVA0 | 2 | binding | up-regulates activity | 0.585 | Katanin, a heterodimeric microtubule-severing ATPase, is found localized at mitotic spindle poles. In this paper we demonstrate that human p60 katanin and the C-terminal domain of human p80 katanin both bind microtubules in vitro. Association of these two proteins results in an increased microtubule affinity and increased microtubule-severing activity in vitro. Association of these subunits in transfected HeLa cells increases microtubule disassembly activity and targeting to spindle poles. | SIGNOR-267180 |
P02511 | P05549 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.259 | Aberrant expression of CRYAB has been shown to be associated with several neurological diseases and malignant neoplasms. To identify transcriptional regulators of CRYAB expression, we examined its promoter for binding sites of transcription factors and identified four potential AP-2 binding sites in addition to a p53 binding site reported previously|Taken together, our results indicate that AP-2_ up-regulates the transcription of the CRYAB gene through stabilizing p53 | SIGNOR-253636 |
P37231 | O00327 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.399 | Rosiglitazone treatment induced aortic expression of Bmal1 mRNA, and ChIP and promoter assays revealed that Bmal1 is a direct PPARgamma target gene. These studies have uncovered a role for vascular PPARgamma as a peripheral factor participating in regulation of cardiovascular rhythms. | SIGNOR-268026 |
P45984 | P35568 | 1 | phosphorylation | down-regulates | 0.706 | Map kinases and mtor mediate insulin-induced phosphorylation ofinsulinreceptor substrate-1 on serine residues 307, 612 and 632 | SIGNOR-118877 |
Q8TB45 | Q9UBF6 | 0 | ubiquitination | down-regulates activity | 0.299 | SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. | SIGNOR-271449 |
O15525 | P35452 | 2 | binding | down-regulates activity | 0.376 | Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf. | SIGNOR-221958 |
O00141 | O00213 | 1 | phosphorylation | down-regulates activity | 0.345 | In the present study, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 attenuates the interaction between FE65 and APP (XREF_FIG).|In this regard, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 abolishes the effect of FE65 on APP processing and the amount of secreted Abeta is comparable to APP + Mock control (XREF_FIG). | SIGNOR-278220 |
P06241 | P09619 | 0 | phosphorylation | up-regulates activity | 0.58 | PDGF-induced phosphorylation of Tyr28 in the N-terminus of Fyn affects Fyn activation. We show here that Fyn, a member of the Src family, is phosphorylated on Tyr28 in the unique N-terminal part of the molecule after interaction with the intracellular domain of the PDGF beta-receptor. Activated Fyn furthermore undergoes autophosphorylation on Tyr30, Tyr39 and Tyr420. When Fyn mutants with Tyr28, Tyr30 or Tyr39 replaced with phenylalanine residues were transfected into NIH3T3 cells a decreased activation after PDGF stimulation was seen, suggesting a functional importance of the N-terminal tyrosine phosphorylation of Fyn. | SIGNOR-250253 |
Q00987 | Q13761 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.579 | RUNX3 protein is ubiquitinated by MDM2 at Lys-94 and Lys-148.|RUNX3 protein is ubiquitinated by MDM2 at Lys 94 and Lys 148.|MDM2 suppresses the transcriptional activity of RUNX3. | SIGNOR-278557 |
P56945 | P51813 | 0 | phosphorylation | up-regulates quantity | 0.506 | Recombinant Bmx kinase was found to effectively phosphorylate the wt CAS SH3 domain on Tyr-12 (Figure 2B). A novel phosphorylation site on CAS, Tyr-12 (Y12) within the ligand-binding hydrophobic pocket of the CAS SH3 domain, was identified and found to be enriched in Src-transformed cells and invasive human carcinoma cells. | SIGNOR-276384 |
Q12929 | Q13882 | 0 | phosphorylation | up-regulates activity | 0.357 | Eps8 which was identified by this method is phosphorylated by Myr-PTK6 in HEK293 cells. Mouse Eps8 expressed in HEK293 cells is phosphorylated by Myr-PTK6 at residues Tyr497, Tyr524, and Tyr534. These results indicate that plasma-membrane-associated PTK6 phosphorylates Eps8, which promotes cell proliferation, adhesion, and migration and, thus, tumorigenesis. | SIGNOR-263191 |
P51532 | Q92922 | 2 | binding | up-regulates | 0.95 | The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added. | SIGNOR-65441 |
P35367 | P08754 | 2 | binding | up-regulates activity | 0.2 | 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-257163 |
P59634 | P78406 | 2 | binding | down-regulates activity | 0.2 | Orf6 of SARS-CoV antagonizes host interferon signaling by perturbing nuclear transport, and the NUP98-RAE1 interaction with Orf6 may perform the same function for SARS-CoV-2. | SIGNOR-260975 |
P30530 | P30530 | 2 | phosphorylation | up-regulates activity | 0.2 | Our data showed that various receptor substrates are at least associated with the C-terminal tyrosine pY821. Two additional potential autophosphorylation sites (pY866 and pY779) may play a minor role in binding of eector proteins | SIGNOR-250593 |
P17081 | Q9UPT5 | 2 | binding | up-regulates | 0.636 | Here we show that tc10 interacts with one of the components of the exocyst complex, exo70. | SIGNOR-100486 |
Q9UGP8 | P68400 | 0 | phosphorylation | up-regulates activity | 0.291 | Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62. | SIGNOR-265267 |
Q13131 | Q9GZT9 | 1 | phosphorylation | down-regulates activity | 0.373 | Mechanistically, AMPKα1 directly phosphorylated prolyl hydroxylase domain-containing (PHD)2 at serines 61 and 136, which suppressed PHD2-dependent hydroxylation of hypoxia-inducible factor (HIF)1α and subsequent regulation of hepatic hepcidin-related iron signalling. | SIGNOR-277592 |
Q8IVH8 | Q13434 | 0 | ubiquitination | down-regulates quantity | 0.2 | MKRN4 ubiquitinated GLK at Lys650 residue.|Remarkably, MKRN4 overexpression induced GLK protein degradation in HEK293T cells and Jurkat T cells (figure 5A and B). | SIGNOR-278658 |
Q13485 | Q9Y297 | 0 | ubiquitination | down-regulates | 0.388 | Here we show that beta-trcp1, a f-box protein in the scf e3 ligase complex, interacts with smad4 and induces the degradation of smad4 | SIGNOR-123057 |
P07949 | P42224 | 1 | phosphorylation | up-regulates activity | 0.275 | In detail, RET and PTC3 induced STAT1 overexpression and phosphorylation at Ser 727 and Tyr 701. | SIGNOR-279276 |
P27448 | P30305 | 1 | phosphorylation | up-regulates activity | 0.26 | In addition, our results showed that MARK3 phosphorylated serine 323 of CDC25B, which is a phosphorylation site of another checkpoint kinase, MAPKAPK2, to induce cytoplasmic translocation of CDC25B .|In addition, our results showed that MARK3 phosphorylated serine 323 of CDC25B, which is a phosphorylation site of another checkpoint kinase, MAPKAPK2, to induce cytoplasmic translocation of CDC25B xref . | SIGNOR-279223 |
Q14191 | P78527 | 0 | phosphorylation | up-regulates | 0.641 | Here, we identify ser-440 and -467 in wrn as major phosphorylation sites mediated by dna-pk our findings indicate that phosphorylation of ser-440 and -467 in wrn are important for relocalization of wrn to nucleoli, and that it is required for efficient dsb repair. | SIGNOR-203737 |
P04040 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.266 | Endothelin-1 stimulates catalase activity through the PKCδ-mediated phosphorylation of serine 167. | SIGNOR-260904 |
P08912 | P09471 | 2 | binding | up-regulates activity | 0.2 | 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-257009 |
Q13464 | P53667 | 1 | phosphorylation | up-regulates activity | 0.617 | Rho-associated kinase rock activates lim-kinase 1 by phosphorylation at threonine 508 within the activation loop. | SIGNOR-74569 |
P16284 | P07332 | 0 | phosphorylation | up-regulates activity | 0.276 | PECAM-1 Is Phosphorylated by Fer and, To a Lesser Extent, by Fes. These results suggest that Fer not only functions as a tyrosine kinase for PECAM-1 but also that Fer modulates the downstream signaling of PECAM-1 by inducing phosphorylation of SHP-2 and Gab1. | SIGNOR-262868 |
P80370 | Q9Y261 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.332 | Taken together, these data suggest that Foxa-2 is a direct transcriptional activator of the Pref-1 gene. | SIGNOR-254971 |
Q99081 | P41134 | 2 | binding | down-regulates activity | 0.583 | All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo. | SIGNOR-241104 |
Q99879 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265390 |
P15173 | P33076 | 2 | binding | down-regulates | 0.2 | During early stages of myogenesis, CIITA binds directly to myogenin (MYOG) and inactivates it, preventing MYOG-mediated induction of myogenic genes that are required for muscle differentiation and function | SIGNOR-255111 |
P03200 | P20023 | 2 | binding | up-regulates activity | 0.2 | The binding of the Epstein-Barr virus glycoprotein gp350 by complement receptor type 2 (CR2) is critical for viral attachment to B lymphocytes. | SIGNOR-266624 |
P30408 | O14641 | 2 | binding | up-regulates activity | 0.2 | TM4SF1 is a partner of DVL2 and positively modulates Wnt/beta-catenin signaling by enhancing DVL2-Axin interaction. | SIGNOR-272402 |
Q92990 | P08581 | 0 | relocalization | down-regulates | 0.331 | Significantly, nonphosphorylated hgf receptor prevents fap68 from stimulating p70s6k. fap68 binding to met requires the last 30 amino acids of the c-terminal tail, which are unique to the hgf receptor. | SIGNOR-110726 |
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