IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 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 |
|---|---|---|---|---|---|---|---|
P28482 | O75581 | 1 | phosphorylation | up-regulates | 0.301 | We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. External stimuli, which control the activity of mapks, such as phorbol esters and fibroblast growth factor 2 (fgf2) control the choice of the lrp6-ppps/tp kinase and regulate the amplitude of lrp6 phosphorylation and wnt/beta-catenin-dependent transcription. | SIGNOR-169001 |
Q05655 | P30086 | 1 | phosphorylation | up-regulates | 0.301 | Here we show that the raf kinase inhibitor protein (rkip) is a physiological inhibitor of grk-2. After stimulation of gpcr, rkip dissociates from its known target, raf-1 (refs 6-8), to associate with grk-2 and block its activity. This switch is triggered by protein kinase c (pkc)-dependent phosphorylation of the rkip on serine 153. | SIGNOR-119551 |
Q05655 | P30411 | 1 | phosphorylation | down-regulates activity | 0.301 | In addition, we found a protein kinase C-dependent phosphorylation of Ser(346) that was mutually exclusive with the basal phosphorylation at Ser(348) and therefore may be implicated in differential regulation of B2 receptor activation. Functional analysis of receptor mutants revealed that a low phosphorylation stoichiometry is sufficient to initiate receptor sequestration while a clustered phosphorylation around Ser(346) is necessary for desensitization of the B2 receptor-induced phospholipase C activation. | SIGNOR-249108 |
P25103 | P63096 | 1 | binding | up-regulates activity | 0.301 | 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-257048 |
P61328 | Q9Y5Y9 | 1 | binding | down-regulates activity | 0.301 | 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-253440 |
P53779 | P16949 | 1 | phosphorylation | down-regulates | 0.301 | Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. Here we show that in response to hyperosmotic stress, jnk phosphorylates a key cytoplasmic microtubule regulatory protein, stathmin (stmn), on conserved ser-25 and ser-38 residues. In in vitro biochemical studies, we identified stmn ser-38 as the critical residue required for efficient phosphorylation by jnk and identified a novel kinase interaction domain in stmn required for recognition by jnk. We revealed that jnk was required for microtubule stabilization in response to hyperosmotic stress. | SIGNOR-166690 |
P49841 | Q13950 | 1 | phosphorylation | down-regulates activity | 0.301 | Collectively, these data demonstrate that the kinase activity of GSK-3beta suppresses the Runx2 transcriptional activity.|In vitro kinase assay confirmed that the Runx2 phosphorylation by GSK-3\u03b2 was reduced by the S369-S373-S377 mutation ( xref ). | SIGNOR-279051 |
Q14767 | P35555 | 1 | binding | up-regulates activity | 0.301 | LTBP-2 interacts with fibrillin-1. The association of LTBP-2 with the ECM always coincided with that of fibrillin-1, and in fibroblast cultures the appearance of fibrillar fibrillin-1 structures preceded the assembly of LTBP-2 network. | SIGNOR-251891 |
Q8IYA7 | Q13950 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.301 | MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2). | SIGNOR-267215 |
P29274 | P09471 | 1 | binding | up-regulates activity | 0.301 | 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-257239 |
P17252 | O60869 | 1 | phosphorylation | down-regulates activity | 0.301 | EDF-1 was phosphorylated in vitro by PKC in the presence of Ca2+ and phospholipids | This results shows that introduction of a single negative charge by phosphorylation at Thr-91 inhibited CaM-EDF-1 interactions. | SIGNOR-249041 |
Q02763 | P42224 | 1 | phosphorylation | up-regulates activity | 0.301 | Tie2-R849W induced STAT1 phosphorylation at Y701 independent of ligand stimulation.|Together, Tie2-R849W induced functional activation of STAT1, leading to increased expression of STAT1-responsive gene like IRF1. | SIGNOR-279131 |
P06493 | P26358 | 1 | phosphorylation | up-regulates | 0.3 | We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5 | SIGNOR-173677 |
Q15139 | Q9Y3E5 | 1 | phosphorylation | up-regulates | 0.3 | Overexpression of constitutively active pkd or pkd activation by treatment with phorbol 12-myristate 13-acetate results in phosphorylation of two serine residues (ser5 and ser87) in a form of bit1 that is confined to the cytoplasm and concomitantly increases the apoptotic activity of cytoplasmic bit1 | SIGNOR-180085 |
P18433 | P07948 | 1 | dephosphorylation | down-regulates activity | 0.3 | We found that PTPα and SHP-1 both dephosphorylate Lyn exclusively at Tyr-397|Lyn expressed in CHO cells has a substantially higher specific activity than Lyn in RBL cells because of high levels of phosphorylation at its active site Tyr-397 (Fig. 1). Enhanced Lyn kinase activity in the CHO cells leads to spontaneous phosphorylation of multiple cellular proteins, including FcϵRI | SIGNOR-248436 |
P00519 | Q15746 | 1 | phosphorylation | up-regulates | 0.3 | Nonmuscle myosin light chain kinase (nmmlck), a multi-functional cytoskeletal protein critical to vascular homeostasis, is highly regulated by tyrosine phosphorylation. We identified multiple novel c-abl-mediated nmmlck phosphorylation sites by mass spectroscopy analysis (including y231, y464, y556, y846) and examined their influence on nmmlck function and human lung endothelial cell (ec) barrier regulation. Tyrosine phosphorylation of nmmlck increased kinase activity | SIGNOR-167989 |
P52179 | Q5VST9 | 1 | relocalization | up-regulates quantity | 0.3 | Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins. | SIGNOR-266727 |
P62714 | Q05655 | 1 | dephosphorylation | down-regulates activity | 0.3 | PP2A(c) displayed the highest specific activity towards PKCdelta. The role of PP2A(c) in the dephosphorylation of PKCdelta in cells was supported by the demonstration that these proteins could be co-immunoprecipitated from NIH3T3 cells.|In conclusion, the evidence here indicates that PKCdelta de-phosphorylation and hence inactivation is effected by PP2A with which it forms a complex | SIGNOR-248595 |
Q9UN86 | Q00987 | 1 | binding | down-regulates activity | 0.3 | G3BP2 binds to MDM2 and decreases its E3 ligase activity. The G3BP2 isoform additionally associated with murine double minute 2 (MDM2), a negative regulator of p53. G3BP2 expression resulted in significant reduction in MDM2-mediated p53 ubiquitylation and degradation. | SIGNOR-278892 |
P12931 | P01135 | 1 | cleavage | up-regulates | 0.3 | Ep2 can also promote the transactivation of epidermal growth factor receptor (egfr) expressed in colon cancer cells through src, which activates the proteolytic release of the egfr ligands amphiregulin (ar) and transforming growth factor-alfa (tgfalfa)125, thereby stimulating the egfr- network. | SIGNOR-235888 |
P62837 | Q8IYM9 | 1 | binding | up-regulates activity | 0.3 | It was found that TRIM22 underwent self-ubiquitylation in vitro in combination with the E2 enzyme UbcH5B and the ubiquitylation was dependent on its RING finger domain. Further evidences showed that TRIM22 could also be self-ubiquitylated in vivo. Importantly, TRIM22 was conjugated with poly-ubiquitin chains and stabilized by the proteasome inhibitor in 293T cells, suggesting that TRIM22 targeted itself for proteasomal degradation through the poly-ubiquitylation. We also found that TRIM22 was located in the nucleus, indicating that TRIM22 might function as a nuclear E3 ubiquitin ligase. | SIGNOR-271779 |
P29274 | P50148 | 1 | binding | up-regulates activity | 0.3 | 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-257364 |
P78317 | Q9UGL1 | 1 | sumoylation | down-regulates quantity by destabilization | 0.3 | Hendriks and coworkers showed that, in response to alkylation damage by methyl methanesulfonate (MMS), SUMOylated JARID1B (KDM5B) is ubiquitylated by the SUMOtargeted ubiquitin ligase RNF4 and degraded by the proteasome, whereas JARID1C (KDM5C) is SUMOylated and recruited to the chromatin to demethylate histone H3K4 (Hendriks et al., 2015). | SIGNOR-271575 |
Q9UKV5 | O95140 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.3 | Gp78 induces ubiquitylation and proteasomal degradation of Mfn1 and Mfn2. | SIGNOR-272887 |
P29274 | P63092 | 1 | binding | up-regulates activity | 0.3 | 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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256766 |
Q9NYY3 | P30533 | 1 | phosphorylation | up-regulates activity | 0.3 | Inhibition of Ras and activation of Rap by Plk2.|Plk2 phosphorylation of Ras and Rap regulators controls surface AMPARs. | SIGNOR-279476 |
Q9UBW7 | Q9H9S0 | 1 | binding | down-regulates activity | 0.3 | In this work, we identified ZMYM2/ZFP198, which physically associates with NANOG as a key negative regulator of NANOG-mediated reprogramming of both epiblast stem cells and somatic cells. | SIGNOR-269802 |
P17252 | P29474 | 1 | phosphorylation | down-regulates activity | 0.3 | 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-251620 |
P27361 | P43364 | 1 | phosphorylation | up-regulates | 0.3 | Mage-11 ser-174 appears to be a post-translational regulatory site phosphorylated by erk1, based on the inhibitory effect of the s174a mutation in the context of shorter ar nh2-terminal fragments (19), and the greater transcriptional activity of gal-mage-11 fusion proteins containing the s174d phosphomimetic. | SIGNOR-188466 |
P40763 | P17677 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.3 | In this study, we demonstrated for the first time that growth-associated protein 43 (GAP43), a well known growth cone protein that promotes axonal regeneration, can be induced in rat brain astrocytes by the proinflammatory endotoxin lipopolysaccharide via both nuclear factor-κB and signal transducer and activator of transcription 3-mediated transcriptional activation. | SIGNOR-266772 |
O14980 | Q13485 | 1 | relocalization | down-regulates | 0.3 | We demonstrate that inhibition of crm1-mediated nuclear export by treatment of cells with leptomycin b results in endogenous smad4 accumulating very rapidly in the nucleus. | SIGNOR-84247 |
O15550 | P41212 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.3 | Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase | SIGNOR-260032 |
Q92630 | P10070 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.3 | DYRK2 directly phosphorylated Gli2 sequences and resulted in the loss of coexpressed GLI proteins, indicating that DYRK2 acts by inducing the phosphorylation and degradation of GLI proteins via the ubiquitin and proteasome pathway. | SIGNOR-279034 |
Q8IXJ9 | P42771 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.3 | Modeling ASXL1 mutation revealed impaired hematopoiesis caused by derepression of p16Ink4a through aberrant PRC1-mediated histone modification. These results indicated that loss of protein interaction between Asxl1 mutant and Bmi1 affected the activity of PRC1, and subsequent derepression of p16Ink4a by aberrant histone ubiquitination could induce cellular senescence, resulting in low-risk MDS-like phenotypes in Asxl1G643fs/+ mice. | SIGNOR-260119 |
P07900 | P16591 | 1 | phosphorylation | down-regulates activity | 0.3 | Hsp90 and tyrosine616 are required for Fer tyrosine kinase activity.Taken together, our findings underscore the importance of Hsp90 and the residue, tyrosine616, which resides in the Hsp90 recognition loop, in maintaining Fer tyrosine kinase activity. | SIGNOR-277818 |
P08908 | P50148 | 1 | binding | up-regulates activity | 0.3 | 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-257088 |
Q0VAM2 | P01111 | 1 | binding | up-regulates | 0.299 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-161481 |
Q5VWQ8 | P35222 | 1 | relocalization | down-regulates quantity | 0.299 | DAB2IP prevents β-catenin nuclear translocation. | SIGNOR-254755 |
P27361 | P42702 | 1 | phosphorylation | down-regulates | 0.299 | Thus, our results identify the human lifr as a substrate for mapk and suggest a mechanism of heterologous receptor regulation of lifr signaling occurring at ser-1044. | SIGNOR-32757 |
P50613 | P49736 | 1 | phosphorylation | up-regulates activity | 0.299 | Taken together, these results indicate that Cdc7/Dbf4 phosphorylation of MCM2 is essential for the initiation of DNA replication in mammalian cells. | Because MCM2 was phosphorylated in vivo at Ser27, Ser41, and Ser139, which were phosphorylated by Cdc7/Dbf4 in vitro, the results suggested that Ser27, Ser41, and Ser139 are in vivo Cdc7/Dbf4 phosphorylation sites in MCM2. | SIGNOR-259849 |
Q13153 | P30291 | 1 | phosphorylation | down-regulates | 0.299 | Kinases targeted sequentially to the neck, cla4/pak and cdc5/polo, are responsible for stepwise phosphorylation and down-regulation of swe1. | SIGNOR-123528 |
P27348 | P07196 | 1 | binding | down-regulates activity | 0.299 | These results suggest the important role of 14-3-3 in the dynamic regulation of NF-L assembly, and in the capacity to prevent the formation of NF-L aggregates. all seven isoforms specifically interacted with NF-L, but not NF-M or NF-H. specific interaction of 14-3-3 proteins with phosphorylated NF-L subunits also indicated the role of 14-3-3 and NF-L phosphorylation in the disassembly of neurofilaments. What is more, binding of 14-3-3 to phosphorylated NF-L subunits may prevent the dephosphorylation of these subunits by phosphatases, maintaining the hyperphosphorylation state of the subunits, which facilitates the disassembly of neurofilaments. | SIGNOR-252399 |
P61011 | Q07955 | 1 | binding | up-regulates activity | 0.299 | We have now demonstrated that p54 interacts not only with SC35 and ASF/SF2 but also with U2AF. Pairwise interactions between p54 and other RS domain-containing spliceosomal proteins in comparison with SC35 and ASF/SF2 as detected by the yeast two-hybrid interaction assay. . It is conceivable that p54 can mediate 59 and 39 splice site interaction by interacting directly with U2AF65 associated with the 39 splice site and at the same time interact with other SR proteins, such as ASF/SF2 and SC35, which in turn interact with U1-70K. In this scenario, p54 is different from SC35 or ASF/SF2 in that it cannot directly interact with the 59 component (U1-70K) but can interact with the protein associated with the 39 splice site (U2AF65). | SIGNOR-261161 |
O96017 | Q14457 | 1 | phosphorylation | up-regulates activity | 0.299 | We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1-Bcl-2 autophagy-regulatory complex formation in a ROS-dependent fashion.|CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, promoting autophagy via Beclin 1 release from Bcl‐2 sequestration | SIGNOR-264557 |
P08631 | P08151 | 1 | phosphorylation | up-regulates activity | 0.299 | These results suggest that the interaction between Gli1 and Hck or the phosphorylation of Gli1 by Hck disrupts Sufu-Gli1 interaction.|We showed that tyrosine kinase Hck activates Gli1 and the kinase activity is required for its maximum effect. | SIGNOR-279374 |
Q13555 | P18846 | 1 | phosphorylation | up-regulates activity | 0.299 | Phosphopeptide mapping analysis and Western blotting studies demonstrated that in vitro, CaMK II phosphorylates only Ser63 (corresponding to Ser133 of CREB), which is essential for the activation, and not Ser72 (corresponding to Ser142 of CREB), which is a negative regulation site. | SIGNOR-250692 |
Q13315 | Q9Y297 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.299 | ATM phosphorylates and stabilizes β-TrCP1 upon DNA damage. | SIGNOR-277549 |
P27361 | Q02447 | 1 | phosphorylation | up-regulates | 0.299 | Here, we show that sp3, which, as sp1, belongs to the gc-rich binding transcription factor family, is also phosphorylated by erk in vitro on serine 73. | SIGNOR-157276 |
O00308 | P49281 | 1 | ubiquitination | down-regulates quantity | 0.299 | Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2|This promotes DMT1 ubiquitination and degradation by WWP2. | SIGNOR-268852 |
Q9UBF6 | Q8TB45 | 1 | 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 |
P27361 | P56270 | 1 | phosphorylation | up-regulates | 0.299 | Together, these results show that activation of saf-1 in response to il-1 and -6 is mediated via map kinase-regulated phosphorylation. | SIGNOR-114475 |
P17600 | P60709 | 1 | binding | up-regulates activity | 0.299 | Synapsins, a family of neuron-specific phosphoproteins, have been demonstrated to regulate the availability of synaptic vesicles for exocytosis by binding to both synaptic vesicles and the actin cytoskeleton in a phosphorylation-dependent manner. | SIGNOR-269184 |
P29323 | Q92823 | 1 | phosphorylation | up-regulates activity | 0.298 | EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase. | SIGNOR-262863 |
Q8NG06 | Q13409 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.298 | Trim58 ubiquitinates dynein and promotes its proteasomal degradation. Trim58 binds DIC directly, polyubiquitinates it in vitro, and induces proteasomal degradation of the dynein holocomplex in vivo. | SIGNOR-272841 |
P22681 | Q8TBZ2 | 1 | monoubiquitination | up-regulates activity | 0.298 | We moreover found that AMAP1 is monoubiquitinated, rather than polyubiquitinated, by virtue of Cbl and provide evidence that the ability of AMAP1 to be monoubiquitinated is important for its involvement in invasion. | SIGNOR-272627 |
P07384 | P55085 | 1 | cleavage | down-regulates activity | 0.298 | PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|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-263580 |
P09429 | P14651 | 1 | binding | up-regulates activity | 0.298 | 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. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. 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-219902 |
O95147 | Q15750 | 1 | dephosphorylation | down-regulates activity | 0.298 | DUSP14 directly interacted with TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and dephosphorylated TAB1 at Ser (438), leading to TAB1 and TAK1 complex inactivation in T cells. | SIGNOR-277147 |
Q9NP77 | Q8N3U4 | 1 | dephosphorylation | up-regulates activity | 0.298 | Additional experiments revealed that Ssu72 directly interacts with Rad21 and SA2 in vitro and in vivo, and associates with sister chromatids in human cells. Interestingly, depletion or mutational inactivation of Ssu72 phosphatase activity caused the premature resolution of sister chromatid arm cohesion, whereas the overexpression of Ssu72 yielded high resistance to this resolution.|anti‐phospho SA2 serine 1224 | SIGNOR-275531 |
Q7L7X3 | Q13188 | 1 | phosphorylation | up-regulates | 0.298 | In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2. | SIGNOR-201321 |
O15194 | P06400 | 1 | dephosphorylation | up-regulates activity | 0.298 | ppRB (RB phosphorylated at Ser-807/811|Possible Mechanisms of HYA22 Action in Tumorigenesis: Dephosphorylation of RB by Transient Expression of HYA22 Isoforms. | SIGNOR-248304 |
P01106 | Q8N699 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.298 | MT-MC1 is a widely expressed nuclear protein whose overexpression, unlike that of c-Myc targets reported previously, recapitulates multiple c-Myc phenotypes. These include promotion of apoptosis, alteration of morphology, enhancement of anchorage-independent growth, tumorigenic conversion, promotion of genomic instability, and inhibition of hematopoietic differentiation. The MT-MC1 promoter is a direct c-Myc target; it contains two consensus E-box elements, both of which bind c-Myc. | SIGNOR-261736 |
O60674 | P02647 | 1 | null | up-regulates activity | 0.298 | ApoA-I interactions with ABCA1 and lipid efflux to apoA-I were substantially impaired by inhibiting or abolishing JAK2, whereas ABCA1 protein levels were unaffected, and ABCA1 cholesterol translocase activity was only slightly reduced. The most likely explanation for these findings is that JAK2 promotes apolipoprotein interactions with ABCA1 or a closely proximal site, and this facilitates the removal of cellular lipids. the interaction of apolipoproteins with ABCA1-expressing cells activates JAK2, which in turn activates a process that enhances apolipoprotein interactions with ABCA1 and lipid removal from cells | SIGNOR-252107 |
P23470 | P24941 | 1 | dephosphorylation | down-regulates activity | 0.298 | 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-254695 |
P52306 | P08134 | 1 | binding | up-regulates | 0.298 | Smggds is a guanine nucleotide exchange factor that specifically activates rhoa and rhoc | SIGNOR-171399 |
Q9UM11 | Q96BY2 | 1 | binding | down-regulates quantity by destabilization | 0.298 | MOAP-1 is an APC/CCdh1 substrate. Here, we identify MOAP-1 as a novel APC/CCdh1 substrate. MOAP-1 is degraded during G1 by APC/CCdh1, and this degradation is inhibited by Trim39 acting on the APC/C. | SIGNOR-272913 |
P09429 | P31249 | 1 | binding | up-regulates activity | 0.298 | 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. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. 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-219980 |
P51608 | Q7Z2K8 | 1 | post transcriptional regulation | up-regulates quantity by expression | 0.298 | MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1. | SIGNOR-264679 |
P17655 | P55085 | 1 | cleavage | down-regulates activity | 0.298 | PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|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-263581 |
Q8WU17 | P36956 | 1 | ubiquitination | down-regulates quantity | 0.298 | Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. TRC8 destablizes SREBP precursors in a RING and proteasome-dependent manner | SIGNOR-271957 |
Q13464 | O15530 | 1 | phosphorylation | up-regulates activity | 0.298 | Additional phosphorylation of PDK1 by ROCK-I improves the stability of the ROCK-I and PDK1 complex. | SIGNOR-279758 |
P27361 | Q13322 | 1 | phosphorylation | up-regulates | 0.298 | Phosphorylation of grb10 by mitogen-activated protein kinase: identification of ser150 and ser476 of human grb10zeta as major phosphorylation sitesreplacing ser(150) and ser(476) with alanines reduced the inhibitory effect of human grb10zeta on insulin-stimulated irs1 tyrosine phosphorylation | SIGNOR-138171 |
Q7Z6Z7 | O14757 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.298 | Taken together, these results are consistent with our hypothesis that HUWE1 directly poly-ubiquitinates and targets Chk1 to the proteasome. | SIGNOR-278568 |
P09429 | P09630 | 1 | binding | up-regulates activity | 0.298 | 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. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. 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-219937 |
P49760 | Q07955 | 1 | phosphorylation | up-regulates activity | 0.298 | In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors. | SIGNOR-273858 |
Q92949 | Q71U36 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.298 | FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1). | SIGNOR-266938 |
P51668 | Q6PJ69 | 1 | ubiquitination | up-regulates activity | 0.298 | Ubiquitination assays demonstrate that TRIM65 is an ubiquitin E3 ligase for TNRC6 proteins. The combination of overexpression and knockdown studies establishes that TRIM65 relieves miRNA-driven suppression of mRNA expression through ubiquitination and subsequent degradation of TNRC6. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria. | SIGNOR-272175 |
Q00535 | P12830 | 1 | phosphorylation | down-regulates activity | 0.298 | Using both the Cdk inhibitor roscovitine and an RNA interference strategy, it was also demonstrated that Cdh1 was phosphorylated by Cdk5, an enzyme that can be persistently activated when bound to p25 [ xref ], the proteolytic product of p35 that has previously been shown to accumulate in the neurons of patients with Alzheimer\u2019s disease [ xref ]. | SIGNOR-279679 |
P09429 | P14653 | 1 | binding | up-regulates activity | 0.298 | 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. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. 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-219853 |
P19484 | P10619 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.298 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276549 |
Q9HBT6 | P35222 | 1 | binding | up-regulates activity | 0.297 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265859 |
O75116 | Q09472 | 1 | phosphorylation | up-regulates activity | 0.297 | Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase.|p300 acetyltransferase activity is dependent on its phosphorylation status in cells, and p300 phosphorylation by ROCK2 results in an increase in its acetyltransferase activity in vitro. | SIGNOR-279482 |
O15297 | P53778 | 1 | dephosphorylation | down-regulates | 0.297 | Ppm1d selectively inhibits p38 activation by dephosphorylating thr 180. | SIGNOR-135976 |
O00409 | Q9P1W9 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.297 | CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis. | SIGNOR-261607 |
P53350 | P12830 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.297 | Priming phosphorylation of Cdh1 by the Cdk2/cyclin A kinase complex allows Plk1 to bind to Cdh1 and phosphorylate Cdh1 at Ser138 and Ser146. Phosphorylation of Cdh1 at Ser138 and Ser146 then triggers its interaction with, and subsequent ubiquitination by, SCFbeta-TRCP | SIGNOR-274054 |
P06493 | O00571 | 1 | phosphorylation | down-regulates | 0.297 | Thr204 to glu204 ddx3 mutant protein lost its function, suggesting that phosphorylation at thr204 affects ddx3 function. Thr204 was phosphorylated by cyclin b/cdc2. Thr323 in motif ib was also phosphorylated by cyclin b/cdc2 kinase. We propose a novel function of cyclin b/cdc2 kinase in mitosis, which is to cause a loss of ddx3 function to repress cyclin a expression and to decrease ribosome biogenesis and translation during mitosis. | SIGNOR-141569 |
P12931 | Q969T9 | 1 | phosphorylation | up-regulates activity | 0.297 | Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα. | SIGNOR-273567 |
P34969 | P09471 | 1 | binding | up-regulates activity | 0.297 | 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-257256 |
P12931 | O15259 | 1 | phosphorylation | up-regulates activity | 0.297 | Src-induced tyrosine phosphorylation could be prevented by mutating the tyrosine residue at position 721 to phenylalanine ( C, lane 12) suggesting that Src kinase phosphorylates NPHP1 at tyrosine 721. | SIGNOR-279122 |
P43146 | Q01668 | 1 | null | up-regulates activity | 0.297 | DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER. | SIGNOR-268292 |
P51608 | P61278 | 1 | post transcriptional regulation | up-regulates quantity by expression | 0.297 | MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1. | SIGNOR-264676 |
Q96A56 | Q9GZQ8 | 1 | binding | up-regulates | 0.297 | Tp53inp1-lc3 interaction occurs via a functional lc3-interacting region (lir) | SIGNOR-196673 |
O60674 | Q14457 | 1 | phosphorylation | up-regulates activity | 0.297 | Mechanistically, IL-6 triggers the interaction between JAK2 and BECN1, where JAK2 phosphorylates BECN1 at Y333. We demonstrate that BECN1 Y333 phosphorylation is crucial for BECN1 activation and IL-6-induced autophagy by regulating PI3KC3 complex formation. | SIGNOR-277567 |
Q0VAM2 | P01116 | 1 | binding | up-regulates | 0.297 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-183835 |
Q13315 | Q14738 | 1 | phosphorylation | up-regulates activity | 0.297 | In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth. | SIGNOR-276319 |
P48729 | Q00535 | 1 | phosphorylation | up-regulates activity | 0.297 | We also show that casein kinase I, but not casein kinase II, can phosphorylate and activate cdk5 in vitro. Ser(159) in cdk5 is homologous to the regulatory Thr(160) in cdk2. | SIGNOR-275966 |
Q99608 | O75925 | 1 | binding | down-regulates quantity by destabilization | 0.297 | Necdin bound to PIAS1 central domains that are highly conserved among PIAS family proteins and suppressed PIAS1-dependent sumoylation of the substrates STAT1 and PML (promyelocytic leukemia protein). Remarkably, necdin promoted degradation of PIAS1 via the ubiquitin-proteasome pathway. In transfected HEK293A cells, amino- and carboxyl-terminally truncated mutants of PIAS1 bound to necdin but failed to undergo necdin-dependent ubiquitination. | SIGNOR-253387 |
Q12772 | P27169 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.297 | we conclude that quercetin exhibits its antiatherogenic property by eliciting the translocation of the mature SREBP2 from endoplasmic reticulum to the nucleus, where it binds to SRE-like sequence in the PON1 promoter and up-regulates PON1 gene transcription and PON1 activity. | SIGNOR-255224 |
P15498 | Q13588 | 1 | binding | up-regulates | 0.297 | Here we report that both in cell extracts and within intact mammalian cells vav binds to grb2 (sem-5/ash/drk), an adaptor molecule which plays a key role in ras activation. | SIGNOR-33840 |
Q16665 | O76061 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.297 | With the ChIP assay, we demonstrated the direct binding of HIF-1alpha to STC2 promoter. These findings support the notion that HIF-1 is a potent stimulator of STC2 expression. Collectively, this is the first report to show that STC2 was aberrantly hypermethylated in human cancer cells. The findings demonstrated that STC2 epigenetic inactivation may interfere with HIF-1 mediated activation of STC2 expression. | SIGNOR-260389 |
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