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 |
|---|---|---|---|---|---|---|---|
P42773 | Q13351 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.266 | Thus, EKLF is a direct regulator of p18INK4c gene expression, and much of EKLF's role in driving erythroid cell differentiation may occur via p18INK4c. | SIGNOR-266046 |
Q00987 | Q8N6T7 | 1 | ubiquitination | down-regulates quantity | 0.415 | These results suggest that MDM2 degrades SIRT6 in a proteasome dependent manner.|USP10 has been shown to deubiquitinate and stabilize p53, a well-known substrate of MDM2, suggesting a mechanism whereby SIRT6 is ubiquitinated and destabilized by MDM2, which could be reversed by USP10 mediated deubiquitination. | SIGNOR-278702 |
Q13118 | Q13526 | 2 | binding | down-regulates quantity by destabilization | 0.2 | RAF1 phosphorylates the Thr93 site of KLF10 in vivo. Since the phosphorylation of Thr93 enables KLF10 and PIN1 to bind, it seems likely that RAF-1 will have an effect on KLF10 stability that is similar to that of PIN1.PIN1 facilitates KLF10 protein degradation. ( | SIGNOR-276503 |
Q9UQF2 | Q06330 | 2 | binding | down-regulates | 0.2 | Here, we show that jip1 suppresses notch1 activity. Jip1 was found to physically associate with either intracellular domain of notch1 or rbp-jk and interfere with the interaction between them. | SIGNOR-165713 |
Q9H2X6 | P29590 | 1 | phosphorylation | up-regulates | 0.438 | In response to dna damage, hipk2 phosphorylates pml at serines 8 and 38. he n-terminal phosphorylation sites contribute to the dna damage-induced pml sumoylation and are required for the ability of pml to cooperate with hipk2 for the induction of cell death. | SIGNOR-182428 |
Q9UQB3 | P33151 | 2 | binding | up-regulates quantity by stabilization | 0.316 | To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member. | SIGNOR-252132 |
Q8IZJ0 | Q8IU57 | 2 | binding | up-regulates | 0.71 | Il-28 and il-29 interacted with a heterodimeric class ii cytokine receptor that consisted of il-10 receptor beta (il-10rbeta) and an orphan class ii receptor chain, designated il-28ralpha. | SIGNOR-96206 |
P19634 | Q99558 | 0 | phosphorylation | up-regulates activity | 0.307 | The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor.|We now show that NIK binds to and divergently activates the plasma membrane Na(+)-H(+) exchanger NHE1. | SIGNOR-279632 |
O95628 | Q96T37 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.359 | We demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578, leading to its degradation via ubiquitylation by an E3 ligase (CNOT4). | SIGNOR-271466 |
Q9H0K1 | Q9H0K1 | 2 | phosphorylation | up-regulates activity | 0.2 | SIK2 S358 Autophosphorylation Is a Marker of SIK2 Activity | SIGNOR-277268 |
P33151 | O60716 | 2 | binding | up-regulates quantity by stabilization | 0.776 | To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member. | SIGNOR-252126 |
P58012 | Q9UHI6 | 2 | binding | up-regulates | 0.445 | Dp103 further increased the cell killing effect induced by foxl2 probably due to the direct association of dp103 with foxl2 protein. | SIGNOR-140388 |
Q9UQ26 | Q96E17 | 1 | relocalization | up-regulates activity | 0.558 | N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle | SIGNOR-264378 |
Q13464 | P63000 | 2 | binding | up-regulates activity | 0.404 | Although there are other activators of PCP, Wnt5a can activate the PCP pathway by forming a complex with Fzd and Ror2 receptors, activating DVL, which in turn activates Rho-family small GTPases, including RhoA and Rac, and their downstream effectors, Rho-associated protein kinase (ROCK), the actin-binding protein, Filamin A and c-Jun N-terminal protein kinase (JNK) | SIGNOR-258972 |
P29965 | P25942 | 2 | binding | up-regulates activity | 0.929 | Ramos cells were mixed with increasing numbers of transfected cells that expressed cd70 (cd27l) or cd154 (cd40l), both of which are expressed by activated T cells, in the presence of anti-igm ab. Cd27 ligation as well as cd40 ligation inhibited bcr-mediated apoptosis in a dose-dependent manner. cd40 binds its ligand cd40l. | SIGNOR-93432 |
Q16512 | P04049 | 1 | phosphorylation | up-regulates | 0.2 | Interaction between active pak1 and raf-1 is necessary for phosphorylation and activation of raf-1. | SIGNOR-112549 |
P16671 | P25098 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We, therefore, propose a pathway by which inhibition of GRK2 in the failing heart prevents CD36 phosphorylation, ubiquitination, and, in turn, induces its proteasomal degradation.|Our data reveal direct phosphorylation of CD36 by GRK2. | SIGNOR-279524 |
P49840 | P17655 | 0 | cleavage | up-regulates activity | 0.2 | Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase | SIGNOR-251612 |
O43561 | O00459 | 2 | binding | up-regulates activity | 0.2 | By substituting these tyrosine residues in LAT with phenylalanine and by utilizing phosphorylated peptides derived from these sites, we mapped the tyrosine residues in LAT required for the direct interaction and activation of Vav, p85/p110alpha and phospholipase Cgamma1 (PLCgamma1). Our results indicate that Tyr(226) and Tyr(191) are required for Vav binding, whereas Tyr(171) and Tyr(132) are necessary for association and activation of phosphoinositide 3-kinase activity and PLCgamma1 respectively. | SIGNOR-246055 |
Q9Y222 | P17275 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.265 | Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated. | SIGNOR-261585 |
P53671 | Q5VT25 | 0 | phosphorylation | up-regulates activity | 0.395 | These results indicate that mrckalpha phosphorylates and activates lim kinases downstream of cdc42, which in turn regulates the actin cytoskeletal reorganization through the phosphorylation and inactivation of adf/cofilin. | SIGNOR-107584 |
Q92793 | P10242 | 2 | binding | up-regulates activity | 0.807 | the nuclear co-activator CREB binding protein (CBP). This protein interacts directly with both c-Myb and v-Myb and potentiates Myb-specific transcription | SIGNOR-240994 |
P49674 | P15923 | 1 | phosphorylation | up-regulates | 0.2 | Tcf3 is a substrate for both glycogen synthase kinase (gsk) 3 and casein kinase (ck) 1epsilon, and phosphorylation of tcf3 by ckiepsilon stimulates its binding to beta-catenin, an effect reversed by gsk3. | SIGNOR-110056 |
Q96PU5 | P35498 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.292 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253457 |
Q8TDY2 | O75385 | 0 | phosphorylation | up-regulates | 0.913 | Ulk1 and ulk2 are the kinase phosphorylating their binding proteins atg13 and fip200. Atg13 directly binds fip200 and mediates the interaction between fip200 and ulks. | SIGNOR-186992 |
Q15831 | Q05513 | 0 | phosphorylation | up-regulates | 0.321 | Here, we have identified s307 as a novel phosphorylation site in lkb1 and provide evidence that, in multiple cell types, phosphorylation of this site by protein kinase c ? (pkc-?) Induces nucleocytoplasmic transport of lkb1. | SIGNOR-185640 |
P49674 | O14641 | 1 | phosphorylation | up-regulates | 0.693 | We demonstrated that dvl2 is phosphorylated at s143 and t224 in a manner that requires both non-canonical wnt5a ligand and casein kinase 1 epsilon (ck1_), and that this event is critical to interact with plk1 in early stages of the cell cycle | SIGNOR-197555 |
Q9Y275 | Q96RJ3 | 2 | binding | up-regulates activity | 0.785 | Baff specifically binds baff receptor | SIGNOR-135713 |
Q5NUL3 | P09471 | 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-257246 |
P41146 | P09471 | 2 | binding | up-regulates activity | 0.347 | 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-257001 |
Q12888 | Q8TAQ5 | 2 | binding | down-regulates activity | 0.2 | These results indicate that Apak is a genuine substrate of ATM kinase. Apak phosphorylation on Ser 68 is critical for p53-mediated apoptosis. in response to DNA damage, ATM is rapidly activated by autophosphorylation and mediates p53 activation through disruption of the Apak–p53 complex by phosphorylating Apak on Ser 68. | SIGNOR-273512 |
P42229 | P04150 | 2 | binding | up-regulates | 0.53 | We show here that the glucocorticoid receptor can act as a transcriptional co-activator for stat5 and enhance stat5-dependent transcription. Stat5 forms a complex with the gluco-corticoid receptor which binds to dna independently of the gre. This complex formation between stat5 and the glucocorticoid receptor diminishes the glucocorticoid response of a gre-con-taining promoter. | SIGNOR-44376 |
O75688 | Q9UHD2 | 1 | dephosphorylation | down-regulates activity | 0.352 | PPM1B dephosphorylates TBK1 in vivo and in vitro.|These results demonstrate that PPM1B inhibits TBK1 mediated antiviral signaling by directly dephosphorylating TBK1 at Ser172. | SIGNOR-276985 |
P53350 | Q9UBB4 | 1 | phosphorylation | down-regulates | 0.353 | Phosphorylation of ataxin-10 by polo-like kinase 1 is required for cytokinesis. Plk1 phosphorylates ataxin-10 at s77 and t82 in vitro. we found that ataxin-10 is ubiquitinated, and is subject to proteasome-dependent degradation, which is delayed in the 2a mutant. We propose a model in which plk1 phosphorylation of ataxin-10 influences its degradation and cytokinesis | SIGNOR-176122 |
Q03113 | O14843 | 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-256957 |
Q92851 | Q13158 | 2 | binding | up-regulates | 0.794 | The death-effector domains ofcasp8and -10 bothinteractwith the death-effector domain offadd. Therefore, caspase-10 is recruited into the fas signaling complex and becomes activated like caspase-8 | SIGNOR-112058 |
Q05655 | P04792 | 1 | phosphorylation | down-regulates activity | 0.515 | Radioactive kinase assays confirmed that PKC\u03b4 phosphorylated Hsp27 at Ser78 and Ser82 ( Fig. 3 B). | SIGNOR-278425 |
P04908 | 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-265397 |
P22681 | P08581 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.732 | Tyrosine y1001, which when phosphorylated upon met activation, is involved in cbl recruitment, allowing receptor ubiquitination and down regulation | SIGNOR-185680 |
Q9Y297 | Q13485 | 1 | 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 |
Q99683 | P31751 | 0 | phosphorylation | down-regulates activity | 0.646 | Akt2 interacts with and phosphorylates ask1 at ser-83 resulting in inhibition of its kinase activity | SIGNOR-100588 |
Q8WXE1 | Q96PY6 | 2 | binding | up-regulates activity | 0.282 | It was reported that NEK1 associates with ATR/ATRIP and primes it for activation in response to a variety of genotoxic agents | SIGNOR-275842 |
Q9BXK1 | Q96ST3 | 2 | binding | up-regulates activity | 0.464 | detailed biochemical and functional analyses have demonstrated that the TIEG2 _-HRM domain interacts specifically with the PAH2 domain of mSin3A to repress transcription. our data suggest the presence of a conserved _-helical repression motif (_-HRM) in the TIEG and BTEB subfamilies of Sp1-like proteins that mediates transcriptional repression activity through interaction with the corepressor mSin3A. | SIGNOR-222460 |
Q13526 | Q13118 | 2 | binding | down-regulates quantity by destabilization | 0.2 | RAF1 phosphorylates the Thr93 site of KLF10 in vivo. Since the phosphorylation of Thr93 enables KLF10 and PIN1 to bind, it seems likely that RAF-1 will have an effect on KLF10 stability that is similar to that of PIN1.PIN1 facilitates KLF10 protein degradation. ( | SIGNOR-276503 |
Q9Y4K3 | O95551 | 2 | ubiquitination | up-regulates activity | 0.378 | TTRAP is ubiquitylated by TRAF6 and promotes TRAF6 dependent ubiquitylation of TAK1.|In addition, we noted that the presence of TRAF6 strengthened the interaction between TTRAP and the TGF-\u03b2 receptor complex (see also later). | SIGNOR-278717 |
Q8N2H9 | O43353 | 1 | ubiquitination | up-regulates activity | 0.374 | Pellino3 directly bound to the kinase RIP2 and catalyzed its ubiquitination | SIGNOR-280452 |
Q16665 | P01584 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.336 | We finally confirmed that in the absence of HIF-1α there was a significant reduction at the protein level in pro-caspase-1, activated caspase-1, pro-IL-1β, and ultimately active IL-1β (Fig. 4g and h). These data show that adenosine induced up-regulation of IL-1β is dependent on a CREB/HIF-1α pathway which is distinct from the NF-kB pathway used for initial production of IL-1β in response to LPS. | SIGNOR-251718 |
O60216 | P53350 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.737 | We suspected that the observed enhancement of Scc1's cleavability in the presence of Plk1 might be due to phosphorylation at two sites that are directly adjacent to the cleavage sites, Ser175 and Ser454, which we had found to be phosphorylated in mitosis in vivo (Table 1). We therefore mutated these two residues to alanine, thereby creating mutant Scc1-S175A/S454A (see Figure 1C), and tested the cleavability of this mutant in the absence or presence of Plk1 in vitro. |Scc1 phosphorylation is dispensable for cohesin dissociation from chromosomes in early mitosis but enhances the cleavability of Scc1 by separase. | SIGNOR-275535 |
P52888 | P17612 | 0 | phosphorylation | up-regulates activity | 0.307 | PKA phosphorylation is suggested to play a regulatory role in EP24.15 enzyme activity. Mutation analysis of each putative PKA site, in vitro phosphorylation, and phosphopeptide mapping indicated serine 644 as the phosphorylation site. The most dramatic change upon PKA phosphorylation was a substrate-specific, 7-fold increase in both K(m) and k(cat) for GnRH. | SIGNOR-250060 |
P38405 | Q99500 | 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-256933 |
Q02880 | Q13315 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.411 | Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.ATM binds with and phosphorylates TOP2β at Ser1134 to promote its degradation by VM-26. | SIGNOR-277510 |
P27361 | Q9NZQ3 | 1 | phosphorylation | up-regulates | 0.422 | Spin90 was phosphorylated by erk1, which was, itself, activated by cell adhesion and platelet-derived growth factor. Such phosphorylation of spin90 likely promotes the interaction of the spin90.betapix.wasp complex and nck | SIGNOR-118747 |
Q14790 | P12931 | 0 | phosphorylation | down-regulates | 0.453 | Src kinase phosphorylates caspase-8 on tyr380: a novel mechanism of apoptosis suppressionwe identified caspase-8 as a new substrate for src kinase. Phosphorylation occurs on tyr380, situated in the linker region between the large and the small subunits of human procaspase-8, and results in downregulation of caspase-8 proapoptotic function | SIGNOR-146127 |
P05231 | Q14653 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.406 | Recent reports show that in mice the microbiome, comprising commensal microorganisms that colonize body surfaces, promotes a partial and low-grade M1-like phenotype in macrophages throughout the body, including those in lymphoid organs (119, 120). This M1-like priming of macrophages induces chromatin remodeling with increased H3K4me3 marks at Ifnb, Il6, and Tnf promoters, which is associated with increased binding of NF-κB p65, IRF3, and Pol II upon cell stimulation | SIGNOR-251721 |
O75015 | Q05481 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Thus, these results indicate that these cloned ZNF140 and ZNF91 proteins function as repressors for the human Fc gamma RIIB transcription. | SIGNOR-266215 |
P10915 | P08253 | 0 | cleavage | down-regulates quantity by destabilization | 0.339 | Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix. | SIGNOR-256333 |
P17861 | O75460 | 0 | phosphorylation | up-regulates activity | 0.647 | IRE1\u03b1 phosphorylates and activates the XBP1 transcription factor XBP1 via its kinase activity. | SIGNOR-279712 |
P29317 | P22681 | 2 | binding | down-regulates quantity by destabilization | 0.638 | In our present study, we demonstrate that ligand-mediated stimulation causes EphA2 to be internalized and degraded. The mechanism of this response involves ligand-mediated autophosphorylation of EphA2, which promotes an association between EphA2 and the c-Cbl adaptor protein. We also show that c-Cbl promotes stimulation-dependent EphA2 degradation. | SIGNOR-272590 |
Q9H8V3 | P53350 | 0 | phosphorylation | up-regulates activity | 0.75 | Phosphorylation of Ect2 by Plk1 during anaphase might alleviate this intramolecular inhibition by dissociating the Ect2 amino from the carboxyl terminus.|Together with the presence of a prominent microtubule array at the midzone, these data suggest that Plk1 is not essential for the formation of the central spindle at anaphase.The specific failure of Ect2 to localize to the midzone raised the interesting possibility that Plk1 might trigger the initiation of cytokinesis by promoting the interaction of Ect2 with centralspindlin and, thereby, Ect2 activation and recruitment to the central spindle. | SIGNOR-279553 |
P08047 | P10645 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation. | SIGNOR-254273 |
P27635 | P07947 | 2 | binding | down-regulates | 0.388 | Several c-yes kinase activity assays indicated that the qm protein reduced c-yes kinase activity by 70% | SIGNOR-90805 |
P15927 | Q9UMS4 | 0 | polyubiquitination | up-regulates activity | 0.48 | PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). PRP19 ubiquitylates RPA and promotes ATRIP recruitment. | SIGNOR-272075 |
P60484 | P42229 | 1 | dephosphorylation | down-regulates | 0.439 | The forced expression of pten in the eol-1r cells dephosphorylated akt, erk and stat5 /eol-1r cells showed epigenetic silencing of the phosphatase and tensin homolog deleted on chromosome ten (pten) gene. Exposure of eol-1r cells to imatinib failed to dephosphorylate akt, erk and stat5, although pdgfr? Was effectively inactivated. The forced expression of pten negatively regulated these signal pathways and sensitized eol-1r cells to imatinib. | SIGNOR-166481 |
P12931 | Q14693 | 1 | phosphorylation | up-regulates activity | 0.2 | Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride. | SIGNOR-277291 |
Q02790 | P68400 | 0 | phosphorylation | down-regulates activity | 0.343 | Thr-143 in the hinge I region was identified as the major phosphorylation site for CK2. | Most importantly, CK2-phosphorylated FKBP52 did not bind to HSP90 | SIGNOR-250865 |
P22681 | P16234 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.478 | Cbl overexpression in nih3t3 cells enhanced the ubiquitination and degradation of the platelet-derived growth factor receptor-alpha (pdgfralpha) | SIGNOR-68024 |
Q13009 | Q15835 | 0 | phosphorylation | down-regulates activity | 0.2 | For example, RhoK phosphorylates and inhibits TIAM1, STEF, and PAR3; disrupts the polarity complex; and prevents Rac activation ( xref ). | SIGNOR-279995 |
Q6PJ69 | Q8NDV7 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.445 | 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. | SIGNOR-272174 |
Q969H4 | P04049 | 2 | binding | up-regulates | 0.71 | Here we demonstrate that the connector enhancer of ksr1, cnk1, mediates src-dependent tyrosine phosphorylation and activation of raf-1. Cnk1 binds preactivated raf-1 and activated src and forms a trimeric complex. | SIGNOR-135674 |
Q9H0Z9 | O15297 | 0 | dephosphorylation | up-regulates activity | 0.363 | Interestingly, we showed that PPM1D directly interacts with and dephosphorylates RBM38 at serine 195. | SIGNOR-277020 |
P42226 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.327 | Phosphorylated STAT6 may also serve as a cytoplasmic substrate for PTP1B since overexpression of PTP1B leads to STAT6 dephosphorylation and the suppression of STAT6 transcriptional activity, whereas PTP1B deficiency increases IL-4-induced STAT6 signaling in B-cells. | SIGNOR-277122 |
Q9UKB1 | Q9UMX1 | 2 | binding | up-regulates | 0.292 | We found that in vitro-translated 35s- labeled slimb indeed specifically bound to su(fu) in the gst pull-down assay. In our functional gli reporter assay, slimb alone did not alter gli-induced reporter expression;however, when cotransfected with hsu(fu), slimb significantly potentiated the inhibitory effect of su(fu) on gli activity. | SIGNOR-72240 |
P10909 | P10244 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.274 | Here we show that the human ApoJ/Clusterin gene contains a Myb binding site in its 5' flanking region, which interacts with bacterially synthesized B-MYB protein and mediates B-MYB-dependent transactivation of the ApoJ/Clusterin promoter in transient transfection assays. Endogenous ApoJ/Clusterin expression is induced in mammalian cell lines following transient transfection of a B-MYB cDNA. | SIGNOR-269800 |
Q92911 | P16220 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.267 | CREB recognized and bound to the promoter of SLC5A5 to facilitate its transcription. | SIGNOR-267137 |
P50549 | Q15418 | 0 | phosphorylation | up-regulates activity | 0.35 | Here we describe that the 90-kDa ribosomal S6 kinase 1 (RSK1), a protein kinase downstream of the extracellular signal-regulated kinase (ERK) subclass of MAPKs, binds to ER81, phosphorylates it, and enhances ER81-dependent transcription. Two in vivo RSK1 phosphorylation sites within ER81, Ser(191) and Ser(216), were identified, whose mutation to alanine reduces ER81 activity upon ERK-MAPK stimulation. | SIGNOR-249163 |
Q6NUN9 | O60260 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | . Parkin ubiquitinates and regulates the ubiquitin proteasomal degradation of PARIS | SIGNOR-272758 |
P01215 | Q9UBR4 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.387 | Transcription of pituitary alpha-glycoprotein hormone subunit (alpha-GSU) and thyrotropin beta subunit (TSH-beta) genes is stimulated by thyrotropin-releasing hormone (TRH). P-Lim binds to CBP in TRH-dependent manner on this site and that these proteins synergistically activate the human α-GSU promoter during TRH stimulation. | SIGNOR-267207 |
P54646 | O00763 | 1 | phosphorylation | down-regulates activity | 0.649 | The results suggest that the decrease in ACC activity during muscle contraction is caused by an increase in its phosphorylation, most probably due, at least in part, to activation of the alpha2 isoform of AMPK. | SIGNOR-250318 |
Q4FZB7 | Q8N140 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Here we show that, when over-expressed, FRG1 binds and interferes with the activity of the histone methyltransferase Suv4-20h1 both in mammals and Drosophila. Accordingly, FRG1 over-expression or Suv4-20h1 knockdown inhibits myogenesis. The novel inhibitor of differentiation Eid3 is an FRG1/Suv4-20h1 target involved in the myogenic defects caused by FRG1 over-expression. Eid3 is down-regulated upon muscle differentiation and behaves as a myogenic inhibitor gene. | SIGNOR-266640 |
Q8N100 | Q12837 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.474 | Thus, these data suggest that the expression of Brn3b can be activated directly by Math5 and that it is also subject to positive feedback regulation by Brn3 proteins. | SIGNOR-261567 |
P20336 | Q15042 | 0 | gtpase-activating protein | down-regulates activity | 0.439 | Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP). | SIGNOR-265580 |
O60281 | P01241 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Rat Zn-15 is a transcription factor activating GH gene expression by synergistic interactions with Pit-1, named for 15 DNA-binding zinc fingers, including fingers IX, X, and XI that are responsible for GH promoter binding. | SIGNOR-268969 |
A6NNM3 | Q9UQ26 | 2 | binding | down-regulates activity | 0.358 | SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins. | SIGNOR-264369 |
P52732 | P60484 | 0 | dephosphorylation | up-regulates activity | 0.455 | PTEN significantly reduces EG5 phosphorylation at Thr926 (XREF_FIG), suggesting PTEN may target this EG5 site for dephosphorylation. | SIGNOR-277000 |
P63000 | Q9P2F6 | 0 | gtpase-activating protein | down-regulates activity | 0.436 | 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-260473 |
P78352 | Q5JU85 | 0 | relocalization | up-regulates activity | 0.472 | Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1.IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6. | SIGNOR-264907 |
Q7KZI7 | Q9NQT8 | 1 | phosphorylation | down-regulates activity | 0.415 | We report here the identification of GAKIN/KIF13B as a novel in vivo substrate for Par1b and present evidence that GAKIN/KIF13B plays a critical role in axon formation in neurons, which is negatively regulated by Par1b-mediated phosphorylation. Par1b phosphorylates GAKIN/KIF13B at both Ser1381 and Ser1410. | SIGNOR-262956 |
Q9GZY8 | Q9BZL6 | 0 | phosphorylation | up-regulates activity | 0.2 | The mitochondrial fission factor (MFF), the main mitochondrial receptor for the Dynamin-related protein 1 (DRP1), is directly phosphorylated by Protein Kinase D (PKD) specifically during mitosis. PKD-dependent MFF phosphorylation is required and sufficient for mitochondrial fission in mitotic but not in interphasic cells.|PKD directly phosphorylates MFF on serines 155, 172, and 275 | SIGNOR-275947 |
P31749 | P36873 | 0 | dephosphorylation | down-regulates activity | 0.383 | Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells | SIGNOR-252605 |
Q6ZNE5 | Q8NEB9 | 2 | binding | up-regulates activity | 0.881 | Characterization of the new proteins revealed that atg14l enhances vps34 lipid kinase activity and upregulates autophagy, | SIGNOR-235448 |
Q00535 | Q9UD71 | 1 | phosphorylation | up-regulates activity | 0.777 | We find that DARPP-32 is converted into an inhibitor of PKA when phosphorylated at threonine 75 by cyclin-dependent kinase 5 (Cdk5). Cdk5 phosphorylates DARPP-32 in vitro and in intact brain cells. Phospho-Thr 75 DARPP-32 inhibits PKA in vitro by a competitive mechanism. | SIGNOR-250671 |
Q9UQ80 | P19525 | 0 | phosphorylation | up-regulates activity | 0.243 | Ebp1 itself is phosphorylated by the PKR protein kinase, suggesting that the effects of Ebp1 overexpression evidenced in vivo on eIF2alpha phosphorylation could be achieved by competition between Ebp1 and eIF2alpha for PKR kinase activity. | SIGNOR-279170 |
P52961 | P16066 | 0 | phosphorylation | down-regulates activity | 0.2 | Art1 is a substrate for the kinase Npr1, which phosphorylates Art1 and, thereby, causes its inactivation by limiting its plasma membrane association. | SIGNOR-279239 |
P36888 | Q9NTG7 | 1 | phosphorylation | down-regulates activity | 0.2 | We also hypothesize that, besides activating ACAT1 through Y407 phosphorylation (Fan et al., 2016), FLT3 might simultaneously phosphorylate and regulate SIRT3. Our mutational studies on all of the seven tyrosine sites of SIRT3 revealed that purified rFLT3 directly phosphorylated purified rSIRT3 in an in vitro kinase assay, leading to decreased SIRT3 deacetylase activity that was assessed by ability to deacetylate K413 of mIDH2 (Figure 4H, first three samples in left, middle, and right panels), whereas replacement of Y226 completely abolished inhibition of SIRT3 by FLT3 (Figure 4H, right). | SIGNOR-267631 |
O95837 | P08912 | 2 | binding | up-regulates activity | 0.385 | 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-257291 |
Q05516 | Q8WXG1 | 1 | 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 |
P62714 | P31314 | 2 | binding | down-regulates activity | 0.301 | HOX11 also inhibited PP2A serine/threonine phosphatase activity concomitant with stimulation of the AKT/PKB signaling cascade. | SIGNOR-240722 |
Q99684 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | GSK3β-mediated GFI1 S94/S98 phosphorylation triggered its interaction with FBXW7, resulting in SCFFBXW7-mediated ubiquitination and degradation. | SIGNOR-277465 |
O43524 | O00141 | 0 | phosphorylation | down-regulates activity | 0.794 | We show here that sgk1, like akt, promotes cell survival and that it does so in part by phosphorylating and inactivating fkhrl1. However, sgk and akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on fkhrl1. While both kinases can phosphorylate thr-32, sgk displays a marked preference for ser-315 whereas akt favors ser-253. | SIGNOR-236607 |
P21462 | P08754 | 2 | binding | up-regulates activity | 0.454 | 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-256825 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.