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 |
|---|---|---|---|---|---|---|---|
O43597 | Q9BUB5 | 0 | phosphorylation | down-regulates | 0.531 | The spry2/nedd4 association involves the ww domains of nedd4 and requires phosphorylation of the mnk2 kinase sites, ser(112) and ser(121), on spry2. mnk2 silencing decreased spry2-nedd4 interactions and also augmented the ability of spry2 to inhibit fibroblast growth factor signaling. endogenous and overexpressed nedd4 polyubiquitinate spry2 via lys(48) on ubiquitin and decrease its stability. | SIGNOR-188889 |
P38936 | O14757 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.531 | Responsible for this degradation is the checkpoint kinase Chk1, which phosphorylates p21(Waf1) on T145 and S146 residues and induces its proteasome-dependent proteolysis. | SIGNOR-279325 |
P41208 | Q15154 | 0 | relocalization | up-regulates | 0.531 | Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome | SIGNOR-94990 |
P16144 | P17252 | 0 | phosphorylation | down-regulates | 0.531 | Egf stimulates a pkc-?-Dependent pathway that results in the phosphorylation of the ?4 Integrin subunit on serine residues and its redistribution to actin-rich structures together, these results highlight the importance of serine phosphorylation in regulating type ii hemidesmosome disassembly, implicate a cluster of serine residues within the connecting segment of ?4, and argue for a key role for pkc-? In regulating these structures | SIGNOR-124494 |
Q9UQ26 | O15034 | 0 | binding | down-regulates activity | 0.531 | 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-264366 |
Q8N9B5 | Q8N0Z6 | 0 | binding | up-regulates activity | 0.531 | DNA damage activates ATM kinase which then phosphorylates Strap at Ser 203 (red circles). Phosphorylated Strap is stabilized and undergoes nuclear accumulation where it assembles into a co-activator complex, which includes p300 and cofactors such as JMY | SIGNOR-262647 |
Q96N67 | P04626 | 0 | phosphorylation | up-regulates | 0.531 | We show that the nrg1 receptor erbb2 directly binds and activates dock7 by phosphorylating tyr-1118. thus, dock7 functions as an intracellular substrate for erbb2 to promote schwann cell migration. This provides an unanticipated mechanism through which ligand-dependent tyrosine phosphorylation can trigger the activation of rho gtpase-gefs of the dock180 family. | SIGNOR-178348 |
P60953 | Q96P48 | 0 | gtpase-activating protein | down-regulates activity | 0.531 | 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-260452 |
P27540 | P81133 | 0 | binding | up-regulates activity | 0.531 | We demonstrate that both SIM1 and SIM2 can heterodimerize via their helix-loop-helix·PAS regions with ARNT, but not with AHR, and that they do not form homodimers. Furthermore, SIM1 may have a dual role, both negatively affecting AHR·ARNT binding to the XRE and also acting in concert with ARNT as a novel DNA-binding heterodimer. | SIGNOR-240759 |
O95630 | Q9Y3C5 | 0 | binding | down-regulates quantity by destabilization | 0.531 | RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome. | SIGNOR-272953 |
Q13151 | P49137 | 0 | phosphorylation | up-regulates activity | 0.531 | MAPKAP-K2 phosphorylated hnRNP A0 at Ser84 in vitro and this residue became phosphorylated in LPS-stimulated cells. The simplest explanation for these findings is that the phosphorylation of hnRNP A0 at Ser84 by MAPKAP-K2 enhances binding to the AREs of these mRNAs or allows hnRNP A0 to displace another protein(s) from the AREs. | SIGNOR-262951 |
Q07955 | P49761 | 0 | phosphorylation | up-regulates activity | 0.531 | 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-273859 |
O15379 | P68400 | 0 | phosphorylation | up-regulates activity | 0.531 | A protein kinase CK2 phosphoacceptor site in the HDAC3 protein was identified at position Ser424, which is a nonconserved residue among the class I HDACs. Mutation of this residue was found to reduce deacetylase activity. | SIGNOR-250889 |
P67775 | Q01105 | 0 | binding | down-regulates | 0.531 | Here we report that both the amino terminal fragment (i(2ntf);aa 1-175) and the carboxy terminal fragment (i(2ctf);aa 176-277) of i(2)(pp2a) inhibit pp2a by binding to its catalytic subunit pp2ac | SIGNOR-175719 |
P35222 | P46937 | 0 | binding | up-regulates | 0.531 | Additionally, the hippo and wnts also cooperate in the nucleus, where yap interacts with beta-catenin and induces the expression of canonical wnt target genes, such as sox2 and snai2 in mouse heart tissue. | SIGNOR-201939 |
P10636 | O15264 | 0 | phosphorylation | down-regulates activity | 0.531 | Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in the ability of tau to promote microtubule assembly. | SIGNOR-278313 |
P07315 | P02511 | 0 | binding | up-regulates activity | 0.531 | Human gamma-crystallins are long-lived, unusually stable proteins of the eye lens exhibiting duplicated, double Greek key domains. The lens also contains high concentrations of the small heat shock chaperone alpha-crystallin, which suppresses aggregation of model substrates in vitro. Mature-onset cataract is believed to represent an aggregated state of partially unfolded and covalently damaged crystallins. The alphaB-crystallin oligomers formed long-lived stable complexes with their gammaD-crystallin substrates. These in vitro results provide support for protein unfolding/protein aggregation models for cataract, with alpha-crystallin suppressing aggregation of damaged or unfolded proteins through early adulthood but becoming saturated with advancing age. | SIGNOR-253622 |
P16220 | P51608 | 0 | post transcriptional regulation | up-regulates quantity by expression | 0.531 | Interestingly, Creb1 was one of the activated MeCP2 targets that we validated by quantitative real-time RT-PCR (Fig. 1C), and using ChIP analysis we found that in vivo MeCP2 binds to the promoter region of Creb1, with significantly enhanced binding in MECP2-Tg samples compared to WT (p < 0.05) | In addition, Sst and CREB1 protein levels were increased in MECP2-Tg hypothalami compared to WT, indicating that MeCP2 indeed enhances expression of Sst and Creb1 | SIGNOR-264682 |
Q92831 | Q8IXJ6 | 0 | binding | down-regulates | 0.53 | Sir2 forms a complex with the acetyltransferase pcaf and myod and, when overexpressed, retards muscle differentiation. | SIGNOR-104248 |
P14921 | P04637 | 0 | binding | down-regulates activity | 0.53 | We demonstrate that p53 and ets-1 coregulate TXSA in an antagonistic and inter-related manner, with ets-1 being a potent transcriptional activator and p53 inhibiting ets-1-dependent transcription. We show that ets-1 and p53 associate physically in vitro and in vivo and that their interaction, rather than a direct binding of p53 to the TXSA promoter, is required for transcriptional repression of TXSA by wild-type p53. | SIGNOR-254087 |
O94761 | Q8IWV8 | 0 | binding | up-regulates | 0.53 | The isolated recql4, assayed as a complex with ubr1 and ubr2, exhibited dna-stimulated atpase activity but was inactive as either dna helicase or dna translocase / the discovery, in the present work, that these ub ligases, ubr1 and ubr2, interact with the putative helicase recql4 (fig. 2), and that recql4 is a long-lived, non-ubiquitylated protein in hela cells | SIGNOR-128214 |
P11532 | Q01484 | 0 | relocalization | up-regulates quantity | 0.53 | We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4. | SIGNOR-266712 |
Q8IUC6 | Q6SZW1 | 0 | binding | down-regulates | 0.53 | SARM utilizes its TIR domain to negatively regulate TRIF | SIGNOR-252068 |
P50148 | O95136 | 0 | binding | up-regulates activity | 0.53 | 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-257215 |
P43403 | Q12959 | 0 | phosphorylation | up-regulates activity | 0.53 | Immunoblot analysis showed that phosphorylation of the activating ZAP70 kinase domain residue Tyr 493 was decreased in the DLG1 KD cells. Similarly, the Tyr 319 residue of ZAP70 and Tyr 83 residue of TCR- ζ also showed reduced phosphorylation. | SIGNOR-274142 |
P10275 | P06493 | 0 | phosphorylation | up-regulates | 0.53 | At first, the data show that cdk5 enables phosphorylation of ar at ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of ar proteins although ar was reported as substrates for cdk9 (5) as well as cdk1 | SIGNOR-175692 |
P63092 | P43119 | 0 | binding | up-regulates activity | 0.53 | 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-256806 |
P56545 | O95600 | 0 | binding | up-regulates activity | 0.53 | Here we report the characterisation of KLF8/ZNF741/BKLF3 (KLF8). We demonstrate that this protein is able to bind CACCC-boxes in DNA and can repress gene expression by associating with CtBP co-repressors. | SIGNOR-236962 |
Q03393 | Q13237 | 0 | phosphorylation | up-regulates | 0.53 | Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps. Addition of cgmp stimulated phosphotransferase activity 2-fold. Extracts from transfected cos-1 cells overexpressing cgkii stimulated ser(19) phosphorylation more than 100-fold.In assays with purified enzymes, wild-type but not ptps-s19a was a specific substrate for the cgmp-dependent protein kinase (cgk) type i and ii. Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps | SIGNOR-71751 |
Q14596 | Q9BXW4 | 0 | binding | down-regulates | 0.53 | We performed glutathione s-transferase (gst) pull-down assays using extracts from hek293 cells overexpressing an ha-tagged nbr1(d50r) mutant, which lacks the ability to bind p62 (lamark et al., 2003) (figures s1a and s1b, available online), and gst fusions of six human atg8 homologs: gabarap, gabarapl1, gabarapl2, lc3a, lc3b, and lc3c. Indeed, nbr1 interacted with all these members of the mammalian atg8 protein family. . downregulation of either lc3 or gabarap (or both) family members leads to stabilization and p62-dependent aggregation of nbr1. | SIGNOR-184258 |
P42229 | P04150 | 0 | 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 |
Q99814 | Q9Y2N7 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.53 | None of the long HIF-3α variants was capable of efficient induction of an HRE reporter in overexpression experiments, but instead inhibited the transcriptional activation of the reporter by HIF-1 and HIF-2. | SIGNOR-261616 |
P15923 | Q02535 | 0 | binding | down-regulates activity | 0.53 | 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-241134 |
P46527 | P31751 | 0 | phosphorylation | down-regulates | 0.53 | Akt-induced t157 phosphorylation causes retention of p27(kip1) in the cytoplasm, precluding p27(kip1)-induced g1 arrest.[__]Thus, cytoplasmic relocalization of p27(kip1), secondary to akt-mediated phosphorylation, is a novel mechanism whereby the growth inhibitory properties of p27(kip1) are functionally inactivated and the proliferation of breast cancer cells is sustained. | SIGNOR-93122 |
Q9C0F0 | Q92560 | 0 | binding | up-regulates activity | 0.53 | We report a critical link between BAP1 complex and BRD4, which is bridged by the physical interaction between ASXL3 and BRD4 in an SCLC subtype (SCLC-A), which expresses a high level of ASCL1. We further showed that ASXL3 functions as an adaptor protein, which directly interacts with BRD4's extra-terminal (ET) domain via a novel BRD4 binding motif (BBM), and maintains chromatin occupancy of BRD4 to active enhancers. | SIGNOR-266761 |
Q15303 | P04626 | 0 | binding | up-regulates | 0.53 | Most breast, skin, lung, ovary, and gastrointestinal tract tumors express erbb-4, and heterodimerization of this receptor with erbb-2, may be involved in some cancer | SIGNOR-43844 |
P06493 | Q9H4X1 | 0 | binding | up-regulates activity | 0.53 | RGC-32 was physically associated with cyclin-dependent kinase p34CDC2 and increased the kinase activity in vivo and in vitro. In addition, RGC-32 was phosphorylated by p34CDC2-cyclin B1 in vitro. Mutation of RGC-32 protein at Thr-91 prevented the p34CDC2-mediated phosphorylation and resulted in loss of p34CDC2 kinase enhancing activity. | SIGNOR-262726 |
Q15796 | Q9NYA4 | 0 | dephosphorylation | down-regulates | 0.53 | Here we demonstrate that myotubularin-related protein 4 (mtmr4), a fyve domain-containing dual-specificity protein phosphatase (dsp), attenuates tgfbeta signaling by reducing the phosphorylation level of r-smads in early endosomes. | SIGNOR-163031 |
P50148 | Q99705 | 0 | binding | up-regulates activity | 0.529 | 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-257302 |
P17535 | P28482 | 0 | phosphorylation | up-regulates | 0.529 | Menin binds the jun family transcription factor jund and inhibits its transcriptional activity. The menin-jund interaction blocks jun n-terminal kinase (jnk)-mediated jund phosphorylation and suppresses jund-induced transcription. We found a role for phosphorylation of the ser100 residue of jund;jund phosphorylation were prevented by inhibitors of calcium, calmodulin, or erk1/2 kinase. | SIGNOR-196030 |
O15111 | P31751 | 0 | phosphorylation | up-regulates | 0.529 | Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta | SIGNOR-187010 |
P15311 | P00533 | 0 | phosphorylation | up-regulates | 0.529 | Ezrin was initially identified as a substrate for tyrosine phosphorylation by egfr (bretscher, 1989) and phosphorylation of residues y145 and y353 were detected to high stoichiometry after egf treatment . Phosphorylation of ezrin at y353 has been delineated to signal survival during epithelial cell differentiation via the phosphatidylinositol 3-kinase (pi3k)/akt pathway. | SIGNOR-133215 |
P61586 | Q2M1Z3 | 0 | gtpase-activating protein | down-regulates activity | 0.529 | 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-260488 |
P23588 | Q15418 | 0 | phosphorylation | up-regulates | 0.529 | S6k1/s6k2 specifically phosphorylate ser422 in vitro. Substitution of ser422 with ala results in a loss of activity in an in vivo translation assay, indicating that phosphorylation of this site plays an important role in eif4b function. | SIGNOR-123993 |
P01100 | Q15418 | 0 | phosphorylation | up-regulates activity | 0.529 | We now provide evidence that two growth-regulated, nucleus- and cytoplasm-localized protein kinases, 90-kda ribosomal s6 kinase (rsk) and mitogen-activated protein kinase (map kinase), contribute to the serum-induced phosphorylation of c-fos. The major phosphopeptides derived from biosynthetically labeled c-fos correspond to phosphopeptides generated after phosphorylation of c-fos in vitro with both rsk and map kinase. The phosphorylation sites identified for rsk (ser-362) and map kinase (ser-374) are in the transrepression domain. Cooperative phosphorylation at these sites by both enzymes was observed in vitro and reflected in vivo by the predominance of the peptide phosphorylated on both sites, as opposed to singly phosphorylated peptides. This study suggests a role for nuclear rsk and map kinase in modulating newly synthesized c-fos phosphorylation and downstream signaling. | SIGNOR-37154 |
P63000 | Q7Z5H3 | 0 | gtpase-activating protein | down-regulates activity | 0.529 | 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-260477 |
P31273 | O43541 | 0 | binding | up-regulates activity | 0.529 | Smad6 interacts with hox transcription factors as part of the negative feedback circuit in the bmp signaling pathway | SIGNOR-75823 |
O95630 | Q9HAU4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.529 | RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome. | SIGNOR-272951 |
Q14344 | Q99500 | 0 | binding | up-regulates | 0.529 | Edg-3 and edg-5 couple not only to gibut also to gqand g13. | SIGNOR-70710 |
P11717 | Q8IWJ2 | 0 | relocalization | up-regulates activity | 0.529 | Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector | SIGNOR-253085 |
Q06187 | P12931 | 0 | phosphorylation | up-regulates activity | 0.529 | This interaction of BTK with SRC kinases transphosphorylated BTK on tyrosine at residue 551, which led to BTK activation. | SIGNOR-251100 |
Q15797 | P27361 | 0 | phosphorylation | down-regulates | 0.528 | Ras signaling was shown previously to induce the phosphorylation of the bmp mediator smad1 at four erk consensus sites in the linker domain (kretzschmar et al. 1997a). Phosphorylation of these four sites inhibits smad1 accumulation in the nucleus | SIGNOR-66755 |
O95863 | Q9NRM7 | 0 | phosphorylation | up-regulates | 0.528 | Lats2 kinase potentiates snail1 activity by promoting nuclear retention upon phosphorylation. during tgf_-induced emt lats2 is activated and snail1 phosphorylated at t203. | SIGNOR-176647 |
P12931 | P29320 | 0 | binding | up-regulates | 0.528 | We propose src kinase as a downstream effector that mediates the neuron's response to eph receptor activation. | SIGNOR-58139 |
P37173 | Q9UER7 | 0 | binding | up-regulates | 0.528 | Tgf-beta-induced apoptosis is mediated by the adapter protein daxx that facilitates jnk activation | SIGNOR-109542 |
Q96EB6 | P06493 | 0 | phosphorylation | up-regulates | 0.528 | We identified cyclinb/cdk1 as a cell cycle-dependent kinase that forms a complex with and phosphorylates sirt1. Mutation of two residues phosphorylated by cyclin b/cdk1 (threonine 530 and serine 540) disturbs normal cell cycle progression and fails to rescue proliferation defects in sirt1-deficient cells | SIGNOR-182863 |
P15036 | Q15131 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.528 | Altogether, these results suggest that CDK10/cyclin M directly controls ETS2 degradation through the phosphorylation of these two serines. | SIGNOR-260914 |
P55211 | P31751 | 0 | phosphorylation | down-regulates | 0.528 | Akt phosphorylated recombinant casp9 in vitro on serine-196 and inhibited its protease activity | SIGNOR-61561 |
P17947 | P49715 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.528 | Activation of C/EBPα induces PU.1 expression, cell cycle arrest, and differentiation in 32D cells expressing FLT3/ITD | SIGNOR-261531 |
P23528 | Q15569 | 0 | phosphorylation | down-regulates activity | 0.528 | Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin | SIGNOR-246723 |
P63000 | Q96HP0 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.528 | Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton. | SIGNOR-275670 |
P10636 | Q5S007 | 0 | phosphorylation | down-regulates | 0.528 | Lrrk2 directly phosphorylates tubulin-associated tau, but not free tau;(iii) lrrk2 phosphorylates tau at thr181 as one of the target sites;. furthermore, we revealed that lrrk2-mediated phosphorylation of tau reduces its tubulin-binding ability. | SIGNOR-195756 |
P26358 | P51608 | 0 | binding | up-regulates activity | 0.528 | Thus, these results indicate that MeCP2-interacting Dnmt1 has significant maintenance DNA methyltransferase activity and that MeCP2 does not vanish Dnmt1 enzymatic activity. | SIGNOR-264541 |
P31431 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.528 | The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant. | SIGNOR-116265 |
O43353 | Q96J02 | 0 | binding | up-regulates activity | 0.528 | ITCH preferentially binds to RIPK2, promoting its K63-linked ubiquitination while simultaneously protecting YAP protein levels and maintaining its nuclear localization in CRC cells. | SIGNOR-280458 |
P51532 | P15172 | 0 | binding | up-regulates | 0.528 | Myod targets brg1 to the myogenin promoter during the initiation of myogenesis in tissue culture models for skeletal muscle differentiation /initiation of myogenin transcription is dependent upon myod, the pbx homeodomain factor, and swi/snf chromatin-remodeling enzymes | SIGNOR-151685 |
P29597 | P23458 | 0 | phosphorylation | up-regulates | 0.527 | These results indicate that tyk2 is activated by phosphorylation on tyr-1054 and/or tyr-1055 and that this phosphorylation requires another kinase, most likely jak1. | SIGNOR-43080 |
P11166 | P27105 | 0 | binding | down-regulates activity | 0.527 | Similar to the results obtained in the RBC, Glut1 and stomatin immunoprecipitated with each other in lysates of Clone 9 cells. The above results suggest that stomatin is closely associated with Glut1 in the plasma membrane and that overexpression of stomatin results in a depression in the basal rate of glucose transport. | SIGNOR-261278 |
P46821 | P49841 | 0 | phosphorylation | down-regulates activity | 0.527 | GSK-3beta phosphorylates MAP1B and the adenomatous polyposis coil gene product (APC; Grimes and Jope 2001; Frame and Cohen 2001). The phosphorylation of MAP1B by GSK-3beta suppresses detyrosination of microtubules and decreases the numbers of stable microtubules | SIGNOR-264843 |
P06241 | P54829 | 0 | dephosphorylation | down-regulates | 0.527 | Wild-type step(61) dephosphorylates fyn at tyr(420) but not at tyr(531). These results suggest that step regulates the activity of fyn by specifically dephosphorylating the regulatory tyr(420) and may be one mechanism by which fyn activity is decreased within psds. | SIGNOR-86791 |
Q99816 | Q6UWE0 | 0 | monoubiquitination | down-regulates quantity | 0.527 | Tal increases ubiquitylation of Tsg101 and affects its solubility in a RING- and PTAP-dependent manner. Tal-mediated ubiquitylation of Tsg101 inactivates this sorting function and concomitantly translocates Tsg101 from relatively insoluble membrane subdomains. Presumably, the coordinated action of Tal and a deubiquitylation enzyme (DUB) enables recycling of Tsg101 and reloading of cargo. | SIGNOR-271509 |
P08700 | Q16649 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.527 | NF-IL3A transactivates the IL-3 promoter through the A region sequences. | SIGNOR-266222 |
Q07820 | P28482 | 0 | phosphorylation | up-regulates | 0.527 | We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage. | SIGNOR-92593 |
P05556 | O75365 | 0 | dephosphorylation | down-regulates activity | 0.527 | In this study, we demonstrate that PRL-3 directly binds to integrin \u03b21 and dephosphorylates integrin \u03b21-Y783, a key residue for integrin \u03b21 function [ ].|These results indicate that PRL-3 dephosphorylates integrin \u03b21 in vitro and in vivo. | SIGNOR-277050 |
P63092 | P08588 | 0 | binding | up-regulates activity | 0.527 | 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-256758 |
P26358 | P31749 | 0 | phosphorylation | up-regulates | 0.527 | Akt1 kinase colocalizes and directly interacts with dnmt1 and phosphorylates ser143. Phosphorylated dnmt1 peaks during dna synthesis, before dnmt1 methylation. Depletion of akt1 or overexpression of dominant-negative akt1 increases methylated dnmt1, resulting in a decrease in dnmt1 abundance. In mammalian cells, phosphorylated dnmt1 is more stable than methylated dnmt1. | SIGNOR-170530 |
Q92731 | P03372 | 0 | binding | up-regulates | 0.527 | It was recently shown that er? And er? Could form a heterodimer complex both in vitro and in vivo | SIGNOR-64427 |
P37231 | P45983 | 0 | phosphorylation | down-regulates activity | 0.527 | The a/b domain of human ppargamma1 was phosphorylated in vivo, and this was abolished either by mutation of serine 84 to alanine (s84a) or coexpression of a phosphoprotein phosphatase. In vitro, this domain was phosphorylated by erk2 and jnk, and this was markedly reduced in the s84a mutant. Thus, phosphorylation of a mitogen-activated protein kinase site in the a/b region of ppargamma inhibits both ligand-independent and ligand-dependent transactivation functions. | SIGNOR-46518 |
Q9ULB1 | P61764 | 0 | binding | up-regulates activity | 0.527 | We propose that all these neurexin complexes can interact with Munc18. Both Mint1 and Mint2 could function as direct adaptors of Munc18 to neurexins, whereas Mint1 in addition could recruit Munc18 to CASK-neurexin (Fig. 5 B). | SIGNOR-264040 |
P35222 | P55283 | 0 | binding | up-regulates activity | 0.527 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265866 |
P52735 | P12931 | 0 | phosphorylation | up-regulates activity | 0.527 | Since we find that Vav2 is necessary for cell spreading and Src activity is necessary for Vav2 activation of Rac and lamellipodia formation, our data suggest a model of Rac activation by integrins that depends on Src phosphorylation of Vav2.|We did not detect increased Rac activation when Vav2 was cotransfected with activated Src, although Vav2 tyrosine phosphorylation was increased (data not shown), indicating that endogenous Src activity is sufficient to fully activate Vav2. | SIGNOR-280138 |
Q6ZN17 | Q2Q1W2 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.527 | In cells, TRIM71 negatively regulates Lin28B protein stability by catalyzing polyubiquitination. | SIGNOR-272054 |
P06396 | Q14289 | 0 | phosphorylation | down-regulates activity | 0.527 | Our results demonstrate that PYK2 inhibits this EGTA stable gelsolin-actin monomer association.|PYK2 phosphorylates gelsolin at tyrosine residues and regulates gelsolin bioactivity, including decreasing gelsolin binding to actin monomer and increasing gelsolin binding to phosphatidylinositol lipids. | SIGNOR-278325 |
Q9Y6Q9 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.526 | P38 MAPK and JNK can phosphorylate multiple sites on SRC-3, including S505, S543, S860, and S867. Our results suggest that several kinases are important for phosphorylating SRC-3 and enhancing its interaction with DNA-dependent transcription factors and other coactivators. | SIGNOR-250103 |
P05412 | P00519 | 0 | phosphorylation | up-regulates activity | 0.526 | Active nuclear Abl efficiently phosphorylate c-Jun. After phosphorylation of c-Jun by Abl on Tyr170, both proteins interacted via the SH2 domain of Abl. | SIGNOR-251428 |
P55085 | P08311 | 0 | cleavage | down-regulates activity | 0.526 | 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-263585 |
Q07820 | P45983 | 0 | phosphorylation | up-regulates | 0.526 | We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage. | SIGNOR-92597 |
P55273 | P24941 | 0 | phosphorylation | up-regulates | 0.526 | Cdk2 and pka were found to participate in p19ink4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19ink4d induced by dna damage was shown to be dependent on serine 76 phosphorylation. | SIGNOR-197270 |
P19419 | Q16539 | 0 | 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 |
P14923 | P16591 | 0 | phosphorylation | up-regulates activity | 0.526 | The tyrosine kinase Fer, which modifies beta-catenin Tyr142, lessening its association with alpha-catenin, phosphorylates plakoglobin Tyr549 and exerts the contrary effect: it raises the binding of plakoglobin to alpha-catenin. Fer stimulation, through modification of Tyr549, causes diminished binding of plakoglobin to components of desmosomes (desmoplakin) and increased interaction with adherens junction proteins (α-catenin) | SIGNOR-251134 |
P16333 | Q13191 | 0 | binding | up-regulates activity | 0.526 | Activated Cbl and Cbl-b interacted with Crk-L, Zap-70, Nck, PLC-gamma | SIGNOR-236054 |
P84022 | Q92830 | 0 | binding | up-regulates | 0.526 | Gcn5 functions like pcaf, in that it binds to tgf-beta-specific r-smads, and enhances transcriptional activity induced by tgf-beta. In addition, gcn5, but not pcaf, interacts with r-smads for bone morphogenetic protein (bmp) signalling pathways, and enhances bmp-induced transcriptional activity, suggesting that gcn5 and pcaf have distinct physiological functions in vivo. | SIGNOR-123318 |
Q05655 | P06239 | 0 | phosphorylation | up-regulates activity | 0.526 | The tyrosine phosphorylation sites of PKC delta in the H(2)O(2)-treated cells were identified as Tyr-311, Tyr-332, and Tyr-512 by mass spectrometric analysis with the use of the precursor-scan method and by immunoblot analysis with the use of phosphorylation site-specific antibodies. Tyr-311 was the predominant modification site among them. In an in vitro study, phosphorylation at this site by Lck, a non-receptor-type tyrosine kinase, enhanced the basal enzymatic activity and elevated its maximal velocity in the presence of diacylglycerol. phosphorylation at Tyr-311 between the regulatory and catalytic domains is a critical step for generation of the active PKC delta in response to H(2)O(2). | SIGNOR-251386 |
O15455 | P12931 | 0 | phosphorylation | up-regulates activity | 0.526 | Markedly, Src mediated late TLR3 Pi-Tyr759 leads to the nuclear accumulation of IRF3 and IRF7 and the increase of IFN-beta production.|Src can directly phosphorylate TLR3 Tyr759 in\nvitro and in vivo . | SIGNOR-279657 |
P62820 | P06493 | 0 | phosphorylation | down-regulates activity | 0.526 | We now present biochemical evidence for a mitosis-specific p34cdc2 phosphorylation of RablAp and Rab4p.We also show that the distribution of RablAp and Rab4p between cytosolic and membrane-bound forms is different in interphase and mitotic cells. | SIGNOR-261284 |
O95622 | P04899 | 0 | binding | down-regulates activity | 0.526 | Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3 | SIGNOR-278075 |
Q02750 | Q9BRX9 | 0 | binding | up-regulates | 0.526 | Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex. | SIGNOR-124470 |
P51530 | O96017 | 0 | phosphorylation | up-regulates activity | 0.526 | We later observed that Dna2 phosphorylation by Cds1 is necessary for Dna2 association with chromatin in HU treated cells. | SIGNOR-279729 |
P54132 | O96017 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.526 | We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3β- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates.Phosphorylation on BLM Thr171 and Ser175 depends on prior phosphorylation at Thr182 by Chk1/Chk2. Thr182 phosphorylation not only controls BLM ubiquitylation and degradation during mitosis but is also a determinant for its localization on the ultrafine bridges. | SIGNOR-276908 |
P17655 | P12931 | 0 | phosphorylation | up-regulates activity | 0.525 | CAPN2 itself was a bone fide substrate of SRC that was primarily phosphorylated at Y625 by SRC and exhibited increased proteolysis activity upon phosphorylation. | SIGNOR-277598 |
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