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 |
|---|---|---|---|---|---|---|---|
P17612 | Q14500 | 1 | phosphorylation | down-regulates activity | 0.283 | Phosphorylation of the Kir2.2 C terminus by protein kinase A inhibited the association with SAP97.‚ | SIGNOR-249998 |
P53779 | P30307 | 1 | phosphorylation | down-regulates | 0.245 | Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset. | SIGNOR-164085 |
P31152 | Q8IW41 | 2 | phosphorylation | up-regulates activity | 0.63 | ERK3, ERK4 and p38 MAPK can all phosphorylate MK5 at Thr 182 , , , - ], but it is not known whether these enzymes also can phosphorylate Ser 115 and whether this modification contributes to ERK3-, ERK4-, or p38 MAPK -regulated subcellular localization of MK5. | SIGNOR-279072 |
O75676 | P16220 | 1 | phosphorylation | up-regulates | 0.605 | Msk1 and msk2 directly phosphorilate and activete transcription factors such as creb1, atf1 msk was the kinase responsible for phosphorylation of the transcription factor creb in response to tcr stimulation. | SIGNOR-157158 |
P17861-2 | Q09472 | 0 | acetylation | up-regulates quantity by stabilization | 0.285 | P300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity.. The mRNA encoding the active spliced form of XBP1 (XBP1s) is generated from the unspliced form by IRE1 (inositol-requiring enzyme 1) during the UPR. | SIGNOR-260429 |
Q9HAU4 | O15198 | 1 | ubiquitination | down-regulates | 0.644 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps | SIGNOR-193390 |
P42345 | P19484 | 1 | phosphorylation | down-regulates activity | 0.477 | Our data points to the lysosome as the site where mTORC1-dependent phosphorylation of TFEB occurs. [...]Our study has revealed a specific role for phosphorylation of TFEB S211 in the negative regulation of the nuclear abundance of TFEB. This occurs through the promotion of 14-3-3 binding and the masking of the nearby NLS on TFEB. | SIGNOR-248270 |
P06239 | P09693 | 1 | phosphorylation | up-regulates activity | 0.56 | Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. | SIGNOR-259931 |
P19784 | P13349 | 1 | phosphorylation | up-regulates activity | 0.307 | Here, we report that Myf-5 protein constitutes a substrate for phosphorylation in vitro by protein kinase CK2. We identified two potential phosphorylation sites at serine49 and serine133, both of which seem to be necessary for Myf-5 activity. | SIGNOR-251016 |
Q96PN8 | Q96PN8 | 2 | phosphorylation | up-regulates activity | 0.2 | We elucidated the mechanism of regulation of TSSK3 activity showing that autophosphorylation and PDK1 phosphorylation in the ‘activation loop’ are necessary for activation. | SIGNOR-260785 |
Q00987 | P54253 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.334 | NICD and MDM2 ubiquitinate and degrade ATXN1.|These results suggest that NICD and MDM2 synergistically reduce ATXN1 expression at the posttranscriptional level. | SIGNOR-278823 |
Q92945 | Q13315 | 0 | phosphorylation | up-regulates | 0.423 | The atm kinase directly binds to and phosphorylates ksrp, leading to enhanced interaction between ksrp and pri-mirnas and increased ksrp activity in mirna processing | SIGNOR-172127 |
P61073 | P54578 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.448 | The physical interaction of CXCR4 and USP14 is paralleled by USP14-catalyzed deubiquitination of the receptor|We also observed that ubiquitination of CXCR4 facilitated receptor degradation, whereas overexpression of USP14 or RNAi-induced knockdown of USP14 blocked CXCL12-mediated CXCR4 degradation | SIGNOR-265057 |
Q70Z35 | Q13177 | 0 | phosphorylation | down-regulates activity | 0.359 | P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ. | SIGNOR-277182 |
P35612 | P17252 | 0 | phosphorylation | down-regulates | 0.2 | We now demonstrate that ptn stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (pk) c substrate domain of beta-adducin through activation of either pkc alpha or beta. | SIGNOR-139870 |
Q96GD4 | Q96GD4 | 2 | phosphorylation | up-regulates | 0.2 | We report here that human aurora-b is phosphorylated at thr-232 through interaction with the inner centromere protein (incenp) in vivo. The phosphorylation of thr-232 occurs by means of an autophosphorylation mechanism, which is indispensable for the aurora-b kinase activity. | SIGNOR-121340 |
P10153 | P11678 | 0 | post translational modification | up-regulates activity | 0.476 | Human eosinophils are bone marrow-derived, non-dividing granulocytes of the innate immune system, which store the highly cationic proteins eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) in secondary granules. we demonstrated that Tyr nitration of the eosinophil granule proteins is exclusively mediated by EPO, in the presence of functional NADPH oxidase and minute amounts of NOx. EPO appears to nitrate itself via an autocatalytic mechanism. | SIGNOR-261704 |
Q13233 | P00519 | 0 | phosphorylation | up-regulates activity | 0.258 | Moreover, c-Abl activates MEKK-1 in vitro and in response to DNA damage.|The results demonstrate that the nuclear c-Abl binds to MEKK-1 and that c-Abl phosphorylates MEKK-1 in vitro and in vivo. | SIGNOR-279672 |
O00238 | Q15797 | 1 | phosphorylation | up-regulates | 0.643 | Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression. | SIGNOR-187190 |
P05771 | P19484 | 1 | phosphorylation | up-regulates activity | 0.33 | This occurs following PKCβ phosphorylation of TFEB on three serine residues located in its last 15 amino acids. This post-translational modification stabilizes and increases the activity of this transcription factor. | SIGNOR-255315 |
P30307 | O96017 | 0 | phosphorylation | down-regulates activity | 0.856 | Activated chk2 in turn phosphorylates cdc25c at serine-216 contributing to the g2/m checkpoints. Cds1 phosphorylates and inactivates cdc25 in vitro|CDC25C is phosphorylated on Ser 216 throughout interphase, but not in mitosis. This creates a binding site for 14‐3‐3 proteins | It has been suggested that 14‐3‐3 protein binding is responsible for retaining Cdc25C in the cytoplasm during interphase, thereby contributing to the prevention of premature initiation of mitotic events | SIGNOR-102779 |
O15297 | P06744 | 1 | dephosphorylation | down-regulates activity | 0.24 | The WIP1 mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer binding factor 1 (LEF1), enhancing its interaction with beta-catenin.|Wip1 directly dephosphorylates NLK and increases Wnt activity during germ cell development. | SIGNOR-277155 |
Q9UHD2 | Q04759 | 0 | phosphorylation | up-regulates activity | 0.2 | TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation | SIGNOR-272472 |
Q96FX8 | P19838 | 1 | ubiquitination | down-regulates quantity | 0.2 | We identify KPC1 as the Ub ligase (E3) that binds to the ankyrin repeats domain of p105, ubiquitinates it, and mediates its processing both under basal conditions and following signaling | SIGNOR-255843 |
Q8WY54 | Q13153 | 1 | dephosphorylation | down-regulates activity | 0.303 | The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family|POPX Can Dephosphorylate and Downregulate PAK| To confirm that POPX2 acts on αPAK phospho-Thr422, a key regulator of activity in the kinase activation loop [9], we used phospho-specific antibodies against αPAK P-Thr422 (Figure 3B, lower panel), which proved to be an excellent substrate for POPX2. Similarly, complete loss of αPAK P-Ser57 with 0.2 μg POPX2 contrasts with the slight loss observed with 1.5 μg PP1. On the basis of these results, we suggest PAK is a substrate of POPX. | SIGNOR-248761 |
P18031 | P17252 | 0 | phosphorylation | up-regulates activity | 0.249 | PKC\u03b1 then phosphorylates and activates endothelial cell protein tyrosine phosphatase 1B (PTP1B) , . | SIGNOR-279257 |
P68431 | Q9UGL1 | 0 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264302 |
Q15078 | P17655 | 0 | cleavage | up-regulates activity | 0.565 | Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain | SIGNOR-251610 |
P61586 | Q92888 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.831 | 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-260528 |
Q8NHV4 | P53350 | 0 | phosphorylation | up-regulates activity | 0.619 | Here we report that the function of Nedd1 is regulated by Cdk1 and Plk1. During mitosis, Nedd1 is firstly phosphorylated at T550 by Cdk1, which creates a binding site for the polo-box domain of Plk1. Then, Nedd1 is further phosphorylated by Plk1 at four sites: T382, S397, S637 and S426. The sequential phosphorylation of Nedd1 by Cdk1 and Plk1 promotes its interaction with gamma-tubulin for targeting the gammaTuRC to the centrosome and is important for spindle formation. | SIGNOR-272992 |
P10636 | P33981 | 0 | phosphorylation | up-regulates activity | 0.2 | Fig. 6C-1 shows that the GST-TTK fusion protein phosphorylated both tau and tubulin, but the phosphorylating activity on tau was much higher than that on tubulin. | SIGNOR-279132 |
P07101 | Q99742 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.252 | Overexpression and siRNA experiments revealed that NPAS1, in concert with ARNT, negatively regulates the expression of TH and that this regulation is mediated by a direct binding of NPAS1 on the TH promoter. | SIGNOR-253702 |
P29353 | Q16832 | 2 | binding | up-regulates | 0.393 | Collectively, our findings are consistent with the following mechanism for src-dependent ddr2 activation and signaling: 1) ligand binding promotes phosphorylation of tyr-740 in the ddr2 activation loop by src;2) tyr-740 phosphorylation stimulates intramolecular autophosphorylation of ddr2;3) ddr2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of ddr2 cytosolic domain-shc signaling complexes. | SIGNOR-140724 |
Q01638 | Q9NWZ3 | 2 | binding | up-regulates activity | 0.604 | As shown in Figure 3D, MyD88, IRAK, IRAK4, and TRAF6 are all recruited to ST2 upon IL-33 stimulation. | SIGNOR-277705 |
Q8N431 | P01116 | 2 | binding | up-regulates | 0.2 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-161508 |
Q9Y2J4 | P42345 | 0 | phosphorylation | down-regulates activity | 0.2 | AMOTL2 is phosphorylated at serine 760 by mTORC2. Mutation of AMOTL2 mimicking constitutive Ser(760) phosphorylation blocks its ability to bind and repress YAP leading to increased relative expression of known YAP gene targets. | SIGNOR-272086 |
P07949 | Q05397 | 2 | phosphorylation | up-regulates | 0.639 | The identification of focal adhesion kinase (fak) as a direct substrate for ret kinase revealed (i) a ret-fak transactivation mechanism consisting of direct phosphorylation of fak tyr-576/577 by ret and a reciprocal phosphorylation of ret by fak, which crucially is able to rescue the kinase-impaired ret k758m mutant and (ii) that fak binds ret via its ferm domain. Interestingly, this interaction is abolished upon ret phosphorylation, indicating that ret binding to the ferm domain of fak is a priming step for ret-fak transactivation. | SIGNOR-173013 |
Q07817 | Q96D59 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.385 | As an E3 ligase, RNF183 ubiquitinates Bcl-xL, causing its degradation and subsequent apoptosis. | SIGNOR-278595 |
P28482 | P51812 | 1 | phosphorylation | up-regulates | 0.728 | Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3. | SIGNOR-161518 |
Q9Y6W5 | Q9UQB8 | 2 | binding | up-regulates activity | 0.802 | Here we demonstrate that IRSp53, a substrate for insulin receptor with unknown function, is the 'missing link' between Rac and WAVE. Activated Rac binds to the amino terminus of IRSp53, and carboxy-terminal Src-homology-3 domain of IRSp53 binds to WAVE to form a trimolecular complex. From studies of ectopic expression, we found that IRSp53 is essential for Rac to induce membrane ruffling, probably because it recruits WAVE, which stimulates actin polymerization mediated by the Arp2/3 complex. | SIGNOR-265556 |
Q96SL8 | P54845 | 2 | binding | up-regulates activity | 0.55 | Interaction of Fiz1 and NRL-leucine zipper was validated by GST pulldown assays and co-immunoprecipitation from bovine retinal nuclear extracts. Fiz1 suppressed NRL- but not CRX-mediated transactivation of rhodopsin promoter activity in transiently transfected CV1 cells. | SIGNOR-223796 |
Q15391 | P63096 | 2 | binding | up-regulates activity | 0.403 | 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-256723 |
P51668 | Q8NEG5 | 2 | binding | up-regulates activity | 0.32 | MEX can act as an E3, Ub (ubiquitin) ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c or UbcH6. A region of MEX that contains the RING fingers and the ZZ zinc finger was required for interaction with UbcH5a and MEX self-association, whereas the SWIM domain was critical for MEX ubiquitination. The expression of MEX promoted apoptosis that was induced through Fas, DR (death receptor) 3 and DR4 signalling, but not that mediated by the BH3 (Bcl-2 homology 3)-only protein BimEL or the chemotherapeutic drug adriamycin. | SIGNOR-271554 |
P52292 | O43148 | 2 | binding | down-regulates activity | 0.412 | KPNA2 Inhibits RNMT Activity|We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. | SIGNOR-265502 |
P27708 | P17612 | 0 | phosphorylation | down-regulates | 0.307 | Protein kinase a phosphorylation at thr456 of the multifunctional protein cad antagonizes activation by the map kinase cascade. | SIGNOR-151816 |
P19544 | Q6N021 | 2 | binding | up-regulates activity | 0.447 | In this study, we demonstrate that WT1 binds directly to TET2 and recruits TET2 to specific genomic sites to regulate the expression of WT1 target genes. | SIGNOR-255703 |
P62745 | Q8TD10 | 2 | binding | up-regulates activity | 0.2 | MIPOL1 protein interacts with tumor suppressor RhoB and enhances its cellular activity | SIGNOR-261134 |
O43561 | P43403 | 0 | phosphorylation | up-regulates activity | 0.77 | In the presence of the catalytically inactive LckK273R, the phosphorylation of LAT Y132 and Y191 residues by Zap70K362E were considerably increased | SIGNOR-274562 |
Q9HCE7 | P36894 | 1 | ubiquitination | down-regulates | 0.66 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps. | SIGNOR-153399 |
Q15418 | P19634 | 1 | phosphorylation | up-regulates | 0.452 | The results indicate that p90rsk phosphorylates serine 703 of nhe-1, and this phosphorylation is required for growth factor stimulation of na+/h+ exchange. | SIGNOR-69171 |
P11309 | Q9UNQ0 | 1 | phosphorylation | up-regulates activity | 0.36 | Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug-resistant activity in human prostate cancer cells|This is further corroborated by our finding that the plasma membrane localization and drug-resistant activity of BCRP were compromised by T362A mutation. | SIGNOR-264420 |
O15033 | O43464 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.406 | Furthermore, the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells following apoptotic stimulation, indicating that AREL1 binds to and ubiquitinates cytosolic but not mitochondria-associated forms of IAP antagonists | SIGNOR-267669 |
Q9Y5T5 | P06493 | 0 | phosphorylation | up-regulates | 0.455 | Here, we report that cyclin-dependent kinase 1 (cdk1) phosphorylates the histone h2a deubiquitinase ubp-m at serine 552 (s552p), and, importantly, this phosphorylation is required for cell cycle progression. | SIGNOR-202678 |
Q9NRD5 | P42262 | 2 | binding | up-regulates activity | 0.807 | RAB39B directs GluA2 trafficking in neurons. GTP-bound RAB39B interacts with PICK1. In line with evidence that PICK1 can dimerize, the structural model suggests that dimerization of PICK1 is a prerequisite for simultaneous recognition of both RAB39B and GluA2 each by one of the PICK1 molecules in the PICK1 dimer (Fig. 6a–c). The existence of such complex is supported by our co-immunoprecipitation experiments shown above. | SIGNOR-264046 |
O14595 | Q15796 | 1 | dephosphorylation | down-regulates activity | 0.445 | Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity | SIGNOR-248299 |
Q5JRX3 | P05067 | 1 | cleavage | down-regulates activity | 0.373 | In the present study we have identified and characterized the human PreP homologue, hPreP, in brain mitochondria, and we show its capacity to degrade the amyloid beta-protein (Abeta). PreP belongs to the pitrilysin oligopeptidase family M16C containing an inverted zinc-binding motif. We show that hPreP is localized to the mitochondrial matrix. In situ immuno-inactivation studies in human brain mitochondria using anti-hPreP antibodies showed complete inhibition of proteolytic activity against Abeta. | SIGNOR-260661 |
O15534 | P49674 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.842 | We show here that mPer proteins, negative limbs of the autoregulatory loop, are specific substrates for CKIepsilon and CKIdelta. The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway. | SIGNOR-267997 |
Q9NV58 | P41180 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.381 | Coexpression with dorfin decreased the amount of total CaR protein and increased CaR ubiquitination, whereas a dominant negative fragment of dorfin had opposite effects. dorfin-mediated proteasomal degradation of immature CaR occurs from the endoplasmic reticulum. Because endogenous CaR in Madin-Darby canine kidney cells is also subject to degradation from the endoplasmic reticulum, dorfin-mediated ubiquitination may contribute to a general mechanism for CaR quality control during biosynthesis. | SIGNOR-271456 |
P07948 | Q16827 | 0 | dephosphorylation | down-regulates activity | 0.325 | Both Lyn and ZAP70 were dephosphorylated by wild-type PTPROt, but not by its catalytic site mutant.|Lyn kinase and ZAP70 are substrates of PTPROt in B-cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF-R inhibitor pazopanib. | SIGNOR-277144 |
Q99698 | P51148 | 2 | binding | down-regulates activity | 0.2 | Mauve interacts with Rab5, Msps, and gamma-tubulin|Mauve/LYST opposes Rab5, which promotes vesicle fusion affecting PCM recruitment | SIGNOR-266003 |
P25800 | P17542 | 2 | binding | up-regulates | 0.736 | Transcriptional activity of tal1 in t cell acute lymphoblastic leukemia (t-all) requires rbtn1 or -2 | SIGNOR-46114 |
P35346 | P08754 | 2 | binding | up-regulates activity | 0.45 | 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-256833 |
P09874 | O14647 | 2 | binding | up-regulates quantity | 0.2 | Non-homologous end-joining (NHEJ) is the dominant DSB repair pathway in human cells, but our understanding of how it operates in chromatin is limited. Here, we define a mechanism that plays a crucial role in regulating NHEJ in chromatin. This mechanism is initiated by DNA damage-associated poly(ADP-ribose) polymerase 1 (PARP1), which recruits the chromatin remodeler CHD2 through a poly(ADP-ribose)-binding domain. CHD2 in turn triggers rapid chromatin expansion and the deposition of histone variant H3.3 at sites of DNA damage. | SIGNOR-264526 |
Q14469 | P09471 | 0 | null | down-regulates | 0.2 | GNAO1 overexpression enhances GSC differentiation by downregulating neural progenitor gene HES1 | SIGNOR-278092 |
Q6ZMU5 | Q05397 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.326 | Because RING disrupted MG53 mutants (C14A and DeltaR) did not induce FAK ubiquitination and degradation, the RING domain was determined to be required for MG53 induced FAK ubiquitination. | SIGNOR-278648 |
Q9H2X6 | Q9H2X6 | 2 | phosphorylation | up-regulates activity | 0.2 | Here, we deciphered the molecular mechanism of HIPK2 activation and show its relevance for DNA damage-induced apoptosis in cellulo and in vivo. HIPK2 autointeracts and site-specifically autophosphorylates upon DNA damage at Thr880/Ser882. Autophosphorylation regulates HIPK2 activity and mutation of the phosphorylation-acceptor sites deregulates p53 Ser46 phosphorylation and apoptosis in cellulo. | SIGNOR-276601 |
O95166 | Q96A56 | 2 | binding | up-regulates | 0.345 | Tp53inp1 is also able to interact with atg8-family proteins | SIGNOR-196664 |
P05067 | P55212 | 0 | cleavage | up-regulates activity | 0.724 | Inhibition of caspase-6 activity prevents serum deprivation-mediated increase of Ab. Caspase-6 directly cleaves APP at the C terminus and generates a C-terminal fragment of 3 kDa (Capp3) and an Ab-containing 6.5-kDa fragment, Capp6.5, that increases in serum-deprived neurons | SIGNOR-261762 |
P17612 | Q07955 | 1 | phosphorylation | up-regulates | 0.2 | Here, we show that pka phosphorylates srsf1 on serine 119 in vitro. Phosphorylation of srsf1 on this site enhanced the rna binding capacity of srsf1 in vivo | SIGNOR-196397 |
P09769 | Q9Y6K9 | 1 | phosphorylation | down-regulates activity | 0.327 | Either IKKγ/NEMO WT or the Y374F mutant was coexpressed with each member of the Src family protein tyrosine kinases (SF-PTKs) in HEK 293T cells. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation. | SIGNOR-276368 |
P10275 | O96028 | 2 | binding | up-regulates | 0.2 | In this study, we discovered that nsd2 specifically interacts with the dna-binding domain of androgen receptor (ar) via its hmg domain, and the nuclear translocation of both nsd2 and ar is enhanced in the presence of ligand / the histone methyltransferase, nsd2, enhances androgen receptor-mediated transcription. | SIGNOR-186045 |
P14416 | P09471 | 2 | binding | up-regulates activity | 0.518 | 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-256980 |
Q9UKT6 | P49841 | 0 | phosphorylation | up-regulates activity | 0.2 | GSK-3beta phosphorylates FBXL21 and TCAP to activate FBXL21-mediated, phosphodegron-dependent TCAP degradation.|These results show direct GSK-3beta phosphorylation of TCAP S157 and FBXL21 T33 sites. | SIGNOR-264851 |
P68431 | Q7LBC6 | 0 | demethylation | down-regulates activity | 0.2 | We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation. | SIGNOR-266634 |
Q14457 | Q16644 | 0 | phosphorylation | up-regulates activity | 0.425 | Taken together, these data indicate that MK2 and MK3 directly phosphorylate Beclin 1 S90 in vitro, and that MK2 like kinase activity also mediates starvation induced Beclin 1 S90 phosphorylation in cultured cells. | SIGNOR-279342 |
Q13224 | P29323 | 0 | phosphorylation | up-regulates quantity | 0.443 | In addition, EPHB2 signaling leads to phosphorylation of GluN2B at tyrosine residue 1472 preventing clathrin dependent endocytosis, and increasing the surface retention of GluN2B containing NMDARs. | SIGNOR-279710 |
P46937 | P28347 | 2 | binding | up-regulates | 0.905 | When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14. | SIGNOR-201465 |
Q8NFA2 | P17252 | 0 | phosphorylation | up-regulates | 0.2 | Phosphorylation of thr341 allows noxo1 to sufficiently interact with noxa1, an interaction that participates in nox1 activation. | SIGNOR-202482 |
O14920 | P20749 | 1 | phosphorylation | up-regulates activity | 0.365 | Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA. | SIGNOR-277364 |
Q8N884 | O00743 | 0 | dephosphorylation | down-regulates activity | 0.2 | In this study, we found that PPP6C suppressed phosphorylation of human cGAS (hcGAS) at S435 or mouse cGAS (mcGAS) at S420 in its substrate-binding pocket, thus preventing its binding to GTP and inhibiting the synthesis of cGAMP.|These data suggest that PPP6C inhibits cGAS activity. | SIGNOR-276990 |
Q99685 | Q7KZF4 | 2 | binding | down-regulates quantity by destabilization | 0.2 | Interaction of SND1 with MGLL resulted in ubiquitination and proteosomal degradation of MGLL. We demonstrate that interaction of SND1 with MGLL results in increased ubiquitination and subsequent proteosomal degradation of MGLL. This down-regulation of MGLL is required for SND1 to exert its pro-tumorigenic activity because forced overexpression of MGLL markedly abrogates cell proliferation. | SIGNOR-259138 |
Q15796 | P35813 | 0 | dephosphorylation | down-regulates | 0.668 | Ppm1a dephosphorylates and promotes nuclear export of tgfbeta-activated smad2/3; these results suggest that phospho-smad2 is a direct substrate of mg2+-dependent ppm1a. in conclusion, ppm1a is a bona fide phosphatase that directly dephosphorylates the critical sxs motif of r-smads. | SIGNOR-146919 |
Q96J02 | P16403 | 1 | polyubiquitination | up-regulates activity | 0.2 | ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. The results indicated that ITCH-mediated K46-Ubn is essential for the binding of histone H1.2 to chromatin. | SIGNOR-272926 |
Q16512 | O15530 | 0 | phosphorylation | up-regulates | 0.567 | It is shown that activation in vitro and in vivo involves the activation loop phosphorylation of prk1/2 by 3-phosphoinositide-dependent protein kinase-1 (pdk1) /pdk1 phosphorylates the prks at their conserved activation loop threonines (thr-774 and thr-816 for prk1 and prk2, respectively) | SIGNOR-76640 |
Q13635 | P98164 | 2 | binding | up-regulates quantity | 0.493 | LRP2 Promotes SHH Activity in Neurogenic Niches of the Developing and Adult Brain. In the RDVM, LRP2 forms a co-receptor complex with PTCH1 facilitating SHH binding and internalization of SHH/PTCH1 complexes, a prerequisite for pathway activation (Fig. 3B). | SIGNOR-265257 |
Q96A26 | P21796 | 2 | binding | up-regulates activity | 0.2 | HGTD-P was coprecipitated with VDAC but not with ANT or cyclophilin D (Fig. 7A, left upper panel).|However, it is not clear at present whether HGTD-P participates directly in channel formation in association with VDAC or modulates its channel-forming activity. | SIGNOR-260293 |
P30307 | P45984 | 0 | phosphorylation | down-regulates | 0.376 | Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset. | SIGNOR-164093 |
Q12913 | P27986 | 1 | dephosphorylation | down-regulates | 0.261 | As reduction of pi3k activity by cd148 or shp-1 [32] is not large (2540%), it is likely that these ptps may function as modulators of the pi3k pathway rather than suppressors. | SIGNOR-178049 |
P30679 | P51582 | 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-257214 |
O43463 | Q00987 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.4 | A recent report showed that the p53 inducible E3 ligase MDM2 causes SUV39H1 degradation.|Furthermore, it was reported that MDM2 can ubiquitinate and degrade SUV39H1. | SIGNOR-278631 |
Q16816 | P11217 | 1 | phosphorylation | up-regulates activity | 0.684 | It is well-characterized that GP is activated by PhK-mediated serine phosphorylation at Ser-15 | SIGNOR-267398 |
P37840 | P62714 | 0 | dephosphorylation | down-regulates activity | 0.276 | α-Synuclein (α-Syn) is a key protein that accumulates as hyperphosphorylated aggregates in pathologic hallmark features of Parkinson's disease (PD) and other neurodegenerative disorders. Phosphorylation of this protein at serine 129 is believed to promote its aggregation and neurotoxicity, suggesting that this post-translational modification could be a therapeutic target. Here, we demonstrate that phosphoprotein phosphatase 2A (PP2A) dephosphorylates α-Syn at serine 129 | SIGNOR-248592 |
P51812 | P32314 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Importantly, we identified RSK2 kinase as the upstream kinase for the FOXN2 phosphodegron. The Ser365 and Ser369 sites in a conserved DSGYAS motif are responsible for the ubiquitination of FOXN2 by β-Trcp. | SIGNOR-273841 |
O95831 | Q16611 | 0 | relocalization | up-regulates | 0.297 | First, bax/bak-mediated momp leads to the release of a significant part of the cyt c, smac/diablo and htra2/omi proteins. in a third step, cyt c, smac/diablo and htra2/omi, which were released into the cytosol, trigger caspase activation. This is necessary to alter the physical association of aif and endog with the im to enable their relocation to the cytosol. | SIGNOR-192092 |
Q9BYF1 | P0DTC2 | 2 | binding | down-regulates activity | 0.2 | SARS-CoV and likely SARS-CoV-2 lead to downregulation of the ACE2 receptor, but not ACE, through binding of the spike protein with ACE2. This leads to viral entry and replication, as well as severe lung injury. | SIGNOR-260742 |
A6NFN3 | Q14938 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268913 |
P45985 | Q9UPT6 | 2 | binding | up-regulates | 0.629 | Overexpression of full-length jsap1 in cos-7 cells led to a considerable enhancement of jnk3 activation, and modest enhancement of jnk1 and jnk2 activation, by the mekk1-sek1 pathwaythe regions of jsap1 that bound jnk, sek1, and mekk1 were distinct from one another. Jnk and mekk1 also bound jsap1 in vitro, suggesting that these interactions are direct. | SIGNOR-71468 |
Q15652 | P84243 | 1 | demethylation | down-regulates activity | 0.2 | We now determine that JMJD1C is recruited by USF-1 to various lipogenic genes for H3K9 demethylation to enhance chromatin accessibility in the fed state. | SIGNOR-265169 |
Q5S007 | Q05397 | 1 | phosphorylation | down-regulates activity | 0.2 | LRRK2 inhibits FAK activation in a kinase dependent manner, meaning that the G2019S gain-of-function mutation results in the excessive inhibition of FAK activation and microglial motility.|Taken together, these results suggest that LRRK2 directly phosphorylate FAK at T474. | SIGNOR-278281 |
P09471 | Q5NUL3 | 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 |
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