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 |
|---|---|---|---|---|---|---|---|
P67775 | O43318 | 1 | dephosphorylation | down-regulates | 0.329 | Our results demonstrate that pp6 specifically down-regulates tak1 through dephosphorylation of thr-187 in the activation loop, which is likely important for suppressing inflammatory responses via tak1 signaling pathways. | SIGNOR-150369 |
P68400 | Q92598 | 1 | phosphorylation | down-regulates activity | 0.329 | Protein kinase CK2 phosphorylates Hsp105 alpha at Ser509 and modulates its function. | the phosphorylation of Hsp105 alpha at Ser(509) abolished the inhibitory activity of Hsp105 alpha in vitro. | SIGNOR-250901 |
P07948 | Q13568 | 1 | phosphorylation | down-regulates activity | 0.329 | Lyn Kinase Suppresses the Transcriptional Activity of IRF5. Here, we found that Lyn physically interacted with IRF5 to inhibit ubiquitination and phosphorylation of IRF5 in the TLR-MyD88 pathway, thereby suppressing the transcriptional activity of IRF5 in a manner independent of Lyn's kinase activity. | SIGNOR-277247 |
P53350 | Q8N122 | 1 | phosphorylation | up-regulates activity | 0.329 | Of note, MYC-PLK1 (WT) overexpression strongly enhanced MTOR and RPTOR signals in PLK1 IPs, whereas the LAMP2 signal was strongly decreased (XREF_FIG).|Thus, we conclude that PLK1 can directly phosphorylate RPTOR in vitro. | SIGNOR-279346 |
P54132 | Q96RL1 | 1 | binding | up-regulates activity | 0.329 | Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of . | SIGNOR-272116 |
P36873 | Q13422 | 1 | dephosphorylation | up-regulates | 0.329 | Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway | SIGNOR-174865 |
Q9Y371 | Q07812 | 1 | binding | up-regulates | 0.329 | Here, we provide evidence that bif-1 plays a regulatory role in apoptotic activation of not only bax but also bak and appears to be involved in suppression of tumorigenesis. while bif-1 did not directly interact with bak, it heterodimerized with bax on mitochondria in intact cells, and this interaction was enhanced by apoptosis induction and preceded the bax conformational change. | SIGNOR-141166 |
P08253 | P20742 | 2 | cleavage | down-regulates quantity by destabilization | 0.329 | The complex formation was confirmed by the use of 125I-labeled matrix metalloproteinase-2. The cleavage sites in the "bait" regions following formation of high-molecular-weight complexes of matrix metalloproteinases with the alpha-macroglobulins were determined by protein sequence analysis. Pregnancy zone protein was cleaved at Thr693-Tyr694 and alpha2-macroglobulin at Gly679-Leu680 and Arg696-Leu697 by matrix metalloproteinase-2. Matrix metalloproteinase-9 cleaved alpha2-macroglobulin at the same site as matrix metalloproteinase-2, but cleavage of pregnancy zone protein was at Leu753-Ser754.|MMP-2 and MMP-9 cause a significant degradation of these bands and the background, a degradation which is prevented by both a2M and PZP. | SIGNOR-261796 |
P26232 | P46937 | 1 | binding | down-regulates | 0.329 | The trimeric complex of alfa-catenin, 14-3-3, and yap sequesters yap at ajs and prevents yap dephosphorylation/activation. | SIGNOR-201245 |
Q05655 | P05107 | 1 | phosphorylation | up-regulates | 0.329 | In this study, we present evidence that pkc isoforms are the major protein kinases that phosphorylate the c terminus of the integrin cd18 chain in leukocytes. Ser-745 is identified as a novel phosphorylation site in the integrin cytoplasmic domain. Additionally, we show that a thr-758-phosphorylated integrin peptide can interact with 14-3-3 proteins in leukocyte lysates | SIGNOR-178897 |
Q7Z6J0 | O14733 | 1 | binding | up-regulates | 0.329 | We confirmed that posh binds activated rac1 and find that it also binds all mlk family members tested and interacts with mkk4/7 as well as jnk1 and jnk2. | SIGNOR-96955 |
Q5S007 | P10415 | 1 | phosphorylation | up-regulates activity | 0.329 | Thus, we propose that Thr56 phosphorylation of Bcl-2 by LRRK2 G2019S might be a crucial step of mitochondrial disorder, which initiates the subsequent cellular damage in the context of PD relevant to G2019S.|We found that LRRK2 G2019S induced loss of the MMP was recovered in both GFP-Bcl-2 and GFP-M-Bcl-2 stable cells (XREF_FIG -lower panel). | SIGNOR-279531 |
O94916 | P80188 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.329 | As expected, the depletion of NFAT5 decreased the S100A4 and LCN2 mRNA levels (Figure 3a). In addition, chromatin immunoprecipitation (ChIP) assay using NFAT5 antibody indicated that NFAT5 was bound to the S100A4 and LCN2 promoters (Figure 3b, Supplementary Figure S3), as expected (Chen et al., 2009). | SIGNOR-274114 |
P49841 | P30291 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.329 | Serine 211 phosphorylation occurred under control conditions in the absence of CK1δ and in the presence of GSK3-β (Fig. 5, D and E). | SIGNOR-276632 |
Q02156 | Q9H9S0 | 1 | phosphorylation | up-regulates activity | 0.329 | Taken together, our results demonstrate that PKC\u03b5-mediated phosphorylation at T200 and T280 enhances Nanog protein stability in head and neck squamous cell carcinoma.|These observations confirm that PKCepsilon modulates Nanog transcriptional activity and demonstrate that Nanog is phosphorylated by PKCepsilon at T200 and T280 in vivo. | SIGNOR-278203 |
P24941 | O94761 | 1 | phosphorylation | up-regulates activity | 0.329 | During S/G2 phases, CDK1 and CDK2 (CDK1/2) phosphorylate RECQL4 on serines 89 and 251, enhancing MRE11/RECQL4 interaction and RECQL4 recruitment to DSBs. | SIGNOR-277374 |
P20742 | P08253 | 2 | binding | down-regulates activity | 0.329 | Both PZP and a2M collagenase complexes incubated with gelatin demonstrated a significant inhibition of the catalytic activity| MMP-2 and MMP-9 cause a significant degradation of these bands and the background, a degradation which is prevented by both a2M and PZP. | SIGNOR-261804 |
P12931 | Q9UQB3 | 1 | phosphorylation | up-regulates activity | 0.329 | Furthermore, according to our data from immunoprecipitation to py20 antibody, c-Src can phosphorylate delta-catenin on Y1073, Y1176, Y1179 and Y1112, with the predominant sites being Y1073, Y1112 and Y1176.|Interestingly, we found that c-Src can increase the stability of delta-catenin in MEF cells. | SIGNOR-278327 |
P17252 | Q14469 | 1 | phosphorylation | down-regulates activity | 0.329 | Endogenous HES-1 DNA-binding activity is post-translationally inhibited during NGF signaling in vivo, and phosphorylation of PKC consensus sites in the HES-1 DNA-binding domain inhibits DNA binding by purified HES-1 in vitro. | SIGNOR-248993 |
Q14680 | Q15910 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.329 | We observed a MELK-mediated increase of EZH2 S220 phosphorylation along with a concomitant loss of EZH2 K222 ubiquitination, suggesting a phosphorylation-dependent regulation of EZH2 ubiquitination. | SIGNOR-277480 |
P43405 | Q13261 | 1 | phosphorylation | up-regulates activity | 0.329 | Mutation of a defined region of the intracellular signaling portion of IL-15Ralpha (Tyr227) abrogates both the IL-15Ralpha/Syk association and IL-15Ralpha phosphorylation. Taken together, this suggests that Syk kinase physically and functionally associates with the IL-15Ralpha chain in B cells and that Syk plays a key role in mediating IL-15-induced signal transduction, thus accounting for the distinct functional consequences of IL-15 vs IL-2 binding to B cells | SIGNOR-246556 |
Q8IYT8 | Q9Y478 | 1 | phosphorylation | down-regulates | 0.329 | Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity | SIGNOR-173092 |
Q9UQM7 | P23677 | 1 | phosphorylation | up-regulates | 0.329 | D-myo-inositol 1,4,5-trisphosphate 3-kinase a is activated by receptor activation through a calcium:calmodulin-dependent protein kinase ii phosphorylation mechanism. the phosphorylated residue was thr311. | SIGNOR-48387 |
P62136 | P40763 | 1 | dephosphorylation | down-regulates activity | 0.329 | Avicins dephosphorylate Stat3 in a variety of human tumor cell lines, leading to a decrease in the transcriptional activity of Stat3.| However, PD98059, an inhibitor of MEK1/2, had no significant effects on avicin-induced dephosphorylation of Stat3 (Ser 727) | SIGNOR-248563 |
P67870 | Q9UBF6 | 1 | phosphorylation | up-regulates activity | 0.329 | In the present study, we show the evidence that CKBBP1 is phosphorylated on threonine residue at position 10 by CKII in vitro and in vivo. Most importantly, disruption of this phosphorylation in CKBBP1 results in accumulation of IκBα and p27Kip1 in HeLa cells and inhibits cell proliferation that appears to be linked to defects in G1/S transition. | SIGNOR-251081 |
Q05655 | P18433 | 1 | phosphorylation | up-regulates activity | 0.328 | In this process, PTPalpha Ser-180 and Ser-204 phosphorylation is critical for the induction of phosphatase activity, which is required for dephosphorylation of pp60(c-src). Taken together, we demonstrate the physical and functional association between PI 3-kinase, PKCdelta and PTPalpha in a signaling complex that mediates the antitumor activity of the somatostatin analogue TT-232. | SIGNOR-249113 |
Q6ZVD8 | P05771 | 1 | dephosphorylation | down-regulates quantity | 0.328 | Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle | SIGNOR-237039 |
P19525 | Q15172 | 1 | phosphorylation | up-regulates | 0.328 | Phosphorylation of serine 28 by pkr promotes mitochondrial localization of b56alpha, because wild-type but not mutant s28a b56alpha promoted mitochondrial pp2a activity. | SIGNOR-181793 |
Q04759 | Q8IV61 | 1 | phosphorylation | up-regulates | 0.328 | Activation of rasgrp3 by phosphorylation of thr-133 is required for b cell receptor-mediated ras activation. our data suggest that pkc, after being activated by diacylglycerol, phosphorylates rasgrp3, thereby contributing to its full activation. | SIGNOR-130490 |
Q9BV68 | P00533 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.328 | RNF126 and Rabring7 associate with the EGFR through a ubiquitin-binding zinc finger domain and both E3 ubiquitin ligases promote ubiquitylation of EGFR. In HeLa cells depleted of either RNF126 or Rabring7 the EGFR is retained in a late endocytic compartment and is inefficiently degraded. | SIGNOR-272103 |
O00743 | Q9UKV8 | 1 | dephosphorylation | up-regulates activity | 0.328 | Our experiments demonstrated that target engagement by AGO2 stimulates its hierarchical, multi-site phosphorylation by CSNK1A1 on a series of highly conserved residues (S824-S834).Although this impairs target binding, dephosphorylation by ANKRD52-PPP6C allows AGO2 to engage new targets. Inactivation of this cycle strongly inhibits global miRNA-mediated repression. | SIGNOR-276515 |
Q06547 | P51610 | 1 | binding | down-regulates activity | 0.328 | The C1 factor interacts with the GABP_ transactivation domain.The domain of the C1 factor required for C1GABP interaction can inhibit GABP_dependent transcriptional activation | SIGNOR-221377 |
Q9H6Y7 | Q15836 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.328 | Here, we show that Godzilla/RNF167 regulates endosome recycling by the ubiquitylation of VAMP3 on Lys66, Lys68 and Lys77; namely, two adjacent Lys residues on the both sides of the critical interface of SNARE complex are ubiquitylated. In agreement with VAMP3 being a target for Goliath family ubiquitin ligases, we show that recycling endosome trafficking is abrogated in response to their activity. While we observed ubiquitylation of VAMP3 by Godzilla, we are unable to describe the nature of this ubiquitination, be it mono-ubiquitin or extended ubiquitin chains. | SIGNOR-272093 |
O14757 | P62745 | 1 | phosphorylation | up-regulates activity | 0.328 | We identified that Thr173 and Thr175 of RhoB was phosphorylated by Chk1 using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) (Supplementary Fig.\u00a06f). | SIGNOR-279727 |
Q5EBL8 | Q86UF1 | 1 | binding | up-regulates activity | 0.328 | Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11. The PLEKHA7-PDZD11 Complex Clusters ADAM10 at Junctions through Tspan33 | SIGNOR-261252 |
Q9UNE7 | Q15797 | 1 | ubiquitination | down-regulates | 0.328 | These results suggest that chip can interact with the smad1/smad4 proteins and block bmp signal transduction through the ubiquitin-mediated degradation of smad proteins. | SIGNOR-120731 |
P19525 | P06493 | 1 | phosphorylation | down-regulates | 0.328 | Our findings demonstrate that (i) pkr, ser/thr kinase, phosphorylates its new substrate cdc2 at the tyr 4 residue, (ii) pkr-mediated tyr 4-phosphorylation facilitates cdc2 ubiquitination and proteosomal degradation | SIGNOR-164809 |
P05771 | Q9P2D0 | 1 | phosphorylation | down-regulates | 0.328 | We found that ibtk_ is phosphorylated at serines 87 and 90 by pkc on bcr engagement;this phosphorylation causes the dissociation of the btk:ibtk_ complex and allows btk to translocate to the plasma membrane. | SIGNOR-173387 |
P49711 | O14746 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.328 | CTCF binds the proximal exonic region of hTERT and inhibits its transcription | SIGNOR-253832 |
P51812 | Q9H6Z4 | 1 | phosphorylation | up-regulates quantity | 0.328 | RSK phosphorylates RanBP3 at Serine 58 residue in vitro and in vivo.RanBP3 phosphorylation increases its affinity towards Ran | SIGNOR-276148 |
P68400 | Q14493 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.328 | Phosphorylation of Thr61 is necessary for subsequent phosphorylation of Thr60 by CK2 in vitro. Inhibitors of CK2 also prevent degradation of SLBP at the end of S phase. Thus, phosphorylation of Thr61 by cyclin A/Cdk1 primes phosphorylation of Thr60 by CK2 and is responsible for initiating SLBP degradation. | SIGNOR-265260 |
Q00535 | O15516 | 1 | phosphorylation | up-regulates | 0.328 | Cdk5 phosphorylates clock at the thr-451 and thr-461 residues in association with transcriptional activation of clock. | SIGNOR-203227 |
P48730 | P35968 | 1 | phosphorylation | down-regulates activity | 0.328 | CKIdelta phosphorylates VEGFR2 at both DSG and DDTD phosphodegrons to promote its interaction with beta-TRCP1.|In a reciprocal set of experiments, we found that overexpression of CKIdelta markedly decreased the half-life of VEGFR2 (XREF_FIG). | SIGNOR-280235 |
P68400 | P04004 | 1 | phosphorylation | up-regulates activity | 0.328 | Therefore, we expressed Vn in a baculovirus system and show (i) that the CKII phosphorylation of wt-Vn enhances the adhesion of bovine aorta endothelial cells; (ii) that the double mutant T50E/T57E (in which the neutral Thr residues are replaced by the negatively charged Glu residues considered analogs of Thr-P) has a significantly enhanced capacity to promote cell adhesion and to accelerate cell spreading when compared with either wild-type Vn or to the neutral T50A/T57A mutant | SIGNOR-250971 |
P20962 | P04150 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.328 | Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner | SIGNOR-268460 |
P54257 | Q13562 | 1 | binding | up-regulates activity | 0.328 | We identified two proteins that interact with ND, huntingtin-associated protein 1 (HAP1) and mixed-lineage kinase 2 (MLK2). Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2 | SIGNOR-234602 |
P27361 | Q15672 | 1 | phosphorylation | up-regulates | 0.328 | Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness. this ser 68 is phosphorylated by p38, c-jun n-terminal kinases (jnk), and extracellular signal-regulated kinases1/2 in vitro | SIGNOR-173413 |
P54646 | P36956 | 1 | phosphorylation | down-regulates | 0.328 | Here we demonstrate that ampk interacts with and directly phosphorylates sterol regulatory element binding proteins (srebp-1c and -2). Ser372 | SIGNOR-173031 |
P27361 | P09917 | 1 | phosphorylation | up-regulates activity | 0.328 | Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells. | SIGNOR-264440 |
P17612 | P15924 | 1 | phosphorylation | down-regulates activity | 0.328 | HeLa cells treated with forskolin indicated that stimulation of protein kinase A in transfected cells could decrease the interaction of DP.AN.SerC23 with keratin IF networks. phosphorylation of Ser-C23 could destabilize interactions that occur either directly through this 20 residue sequence or that are dependent on its correct conformation | SIGNOR-250353 |
Q92934 | P04637 | 1 | binding | up-regulates activity | 0.328 | We also demonstrate that bad physically interacts with cytoplasmic p53. bad is able to direct p53 to the mitochondria and forms a p53/bad complex at the mitochondria. the mitochondrial p53/bad complex promotes apoptosis | SIGNOR-149815 |
P50570 | P29033 | 1 | binding | down-regulates | 0.328 | This study identifies dynamin 2 (dyn2) as a cx26 interactor in yeast and mammalian cells / we demonstrate that dyn2 regulates cx26 endocytosis and ubiquitination | SIGNOR-205372 |
P17252 | P35240 | 1 | phosphorylation | down-regulates activity | 0.328 | PKC\u03b1\nnormally phosphorylates and inactivates NF2.|PKCalpha normally phosphorylates and inactivates NF2. | SIGNOR-280081 |
O43164 | P13861 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.328 | Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits | SIGNOR-271856 |
P31749 | P24941 | 1 | phosphorylation | up-regulates | 0.328 | Akt phosphorylates cdk2 at threonine 39 residue both in vitro and in vivo. Although cdk2 threonine 39 phosphorylation mediated by akt enhances cyclin-a binding, it is dispensable for its basal binding and the kinase activity. | SIGNOR-178058 |
O60674 | P78347 | 1 | phosphorylation | up-regulates activity | 0.328 | Jak2 activates tfii-i and regulates its interaction with extracellular signal-regulated kinase the interaction between tfii-i and erk, which is essential for its activity, can be regulated by jak2 through phosphorylation of tfii-i at tyrosine 248 | SIGNOR-235313 |
P46934 | O15399 | 1 | ubiquitination | down-regulates activity | 0.328 | Nedd4 coexpression with GluN2D enhances GluN2D ubiquitination and reduces GluN1/GluN2D NMDA receptor responses.|This suggests that Nedd4 association reduces GluN2D function, mostly likely by promoting GluN2D ubiquitination and internalization. | SIGNOR-278636 |
O76064 | O95999 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.328 | Phosphorylated and ubiquitinated BCL10 is stabilized on the damage sites through binding to and presenting UBC13 to RNF168.|We thus concluded that BCL10 is ubiquitinated mainly with K63-linked ubiquitination by RNF8. | SIGNOR-278778 |
O14757 | O00716 | 1 | phosphorylation | up-regulates | 0.328 | These results suggest that e2f3a is directly phosphorylated by chk kinases and that the phosphorylation of serine 124 is required for the posttranslational induction of e2f3a protein by chemotherapy. | SIGNOR-161758 |
Q13191 | P10721 | 1 | ubiquitination | down-regulates activity | 0.328 | KIT binds to and induces the phosphorylation of Cbl proteins, which in turn act as E3 ligases, mediating the ubiquitination and degradation of KIT and themselves. Tyrosine kinase binding and RING finger domains of Cbl are essential for Cbl-mediated ubiquitination and degradation of KIT. | SIGNOR-260105 |
P98161 | Q6IE81 | 1 | binding | down-regulates quantity by destabilization | 0.328 | Full-length PC1 bound, stabilized and colocalized with Jade-1 and inhibited Jade-1 ubiquitination. Jade-1 ubiquitination was mediated by Siah-1, an E3 ligase that binds PC1. | SIGNOR-272917 |
O43303 | P0DP25 | 1 | binding | up-regulates activity | 0.328 | We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis. | SIGNOR-266348 |
P17612 | Q05086 | 1 | phosphorylation | down-regulates activity | 0.328 | These data suggest that PKA phosphorylation at T485 inhibits UBE3A ubiquitin ligase activity in cells. | SIGNOR-236899 |
Q5VWQ8 | P10275 | 1 | binding | down-regulates activity | 0.328 | DAB2IP acts as a scaffold protein for PP2A to suppress DHT-elicited S81 phosphorylation of the AR, preventing its nuclear translocation and binding to androgen response elements. In addition, DAB2IP can compete with the AR for binding to c-Src, thus blocking the non-genomic AR pathway | SIGNOR-254758 |
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 |
P68400 | Q9UER7 | 1 | phosphorylation | up-regulates | 0.327 | Daxx-sim is phosphorylated by ck2 kinase at residues s737 and s739. Phosphorylation promotes daxx-sim binding affinity toward sumo-1 over sumo-2/3, causing daxx preference for sumo-1 conjugation and interaction with sumo-1-modified factors. | SIGNOR-173105 |
P19784 | Q92598 | 1 | phosphorylation | down-regulates activity | 0.327 | Protein kinase CK2 phosphorylates Hsp105 alpha at Ser509 and modulates its function. | the phosphorylation of Hsp105 alpha at Ser(509) abolished the inhibitory activity of Hsp105 alpha in vitro. | SIGNOR-251008 |
O00192 | P22223 | 1 | binding | up-regulates quantity by stabilization | 0.327 | 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-252127 |
P17612 | P23677 | 1 | phosphorylation | up-regulates activity | 0.327 | Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328 | SIGNOR-249994 |
Q05513 | P47712 | 1 | phosphorylation | up-regulates activity | 0.327 | To further evaluate cPLA2 as a candidate substrate for PKCζ, we developed a custom antibody recognizing the cPLA2 T376 phosphorylation site. Specificity was validated in both serum starved/stimulated samples | SIGNOR-277518 |
P35240 | Q13188 | 1 | binding | up-regulates activity | 0.327 | NF2 is activated by oxidative stress in cardiomyocytes and mouse myocardium and facilitates apoptosis. NF2 promotes I/R injury through activation of Mst1 and inhibition of Yap, thereby regulating Hippo signaling in the adult heart. | SIGNOR-261955 |
Q969H0 | Q5VWQ8 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.327 | DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1 | SIGNOR-254774 |
P31751 | Q09472 | 1 | phosphorylation | up-regulates | 0.327 | We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity | SIGNOR-148987 |
Q86YT6 | P34925 | 1 | ubiquitination | down-regulates | 0.327 | We discovered that ryk both physically and functionally interacts with the e3 ubiquitin ligase mind bomb 1 (mib1).We Found that overexpressed ryk and mib1 colocalized and that the overexpression of mib1 leads to the loss of surface ryk expression. In addition, biochemical studies revealed that mib1 promotes the ubiquitination and degradation of ryk. Endogenous ryk and mib1 were required for the wnt-dependent activation of wnt/ctnnb1 signaling | SIGNOR-176282 |
P48730 | O43312 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.327 | Mechanistically, we defined that Casein Kinase Iδ (CKIδ) phosphorylates Ser322 to trigger MTSS1's interaction with β-TRCP for subsequent ubiquitination and degradation. | SIGNOR-276611 |
P49137 | Q9NY61 | 1 | phosphorylation | up-regulates | 0.327 | Upon genotoxic stress, aatf is phosphorylated by the checkpoint kinase mk2. Phosphorylation results in the release of aatf from cytoplasmic mrlc3 and subsequent nuclear translocation where aatf binds to the puma, bax and bak promoter regions to repress p53-driven expression of these pro-apoptotic genes. | SIGNOR-191935 |
Q9UNE7 | Q9BXL7 | 1 | ubiquitination | up-regulates activity | 0.327 | Subsequently, the ubiquitination of CARMA1 catalyzed by STUB1 was identified as Lys 27 linked, which is important for CARMA1 mediated NF-kappaB activation. | SIGNOR-278720 |
P45983 | P85298 | 1 | phosphorylation | up-regulates activity | 0.327 | Furthermore, we identify that BPGAP1 (a BCH domain-containing, Cdc42GAP-like Rho GTPase-activating protein) promotes MEK partner 1 (MP1)-induced ERK activation on late endosome through scaffolding MP1/MEK1 complex. This regulatory function requires phosphorylation of BPGAP1 by JNK at its C terminal tail (Ser424) to unlock its autoinhibitory conformation. | SIGNOR-275550 |
Q05655 | Q01995 | 1 | phosphorylation | down-regulates activity | 0.327 | Of the three consensus protein kinase C or casein kinase II phosphorylation sites in SM22, only Ser-181 was readily phosphorylated by protein kinase C in vitro, and such phosphorylation greatly decreased actin binding. | SIGNOR-249061 |
P06241 | Q15831 | 1 | phosphorylation | down-regulates activity | 0.327 | Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine 261 and 365 residues and mutations of these sites resulted in LKB1 export into the cytoplasm and increased AMPK phosphorylation. | SIGNOR-278477 |
Q14765 | O43504 | 1 | binding | up-regulates activity | 0.327 | It suggests that HBXIP is able to activate S100A4 promoter via interacting with STAT4 in breast cancer cells, leading to the up-regulation of S100A4. here we first report that the transcription factor STAT4 plays a role in regulating S100A4 mediated by HBXIP in breast cancer. | SIGNOR-255247 |
P67870 | Q9Y5B0 | 1 | phosphorylation | down-regulates activity | 0.327 | We found that only phosphorylated FCP1 can physically interact with TFIIF. We set out to purify an FCP1 kinase from HeLa cells and identified casein kinase 2, which, surprisingly, displayed a negative effect on FCP1-associated activities.| Phosphorylation of FCP1 by CK2 Inhibits the Transcription Elongation Activity of FCP1. | Two in vivo phosphorylation sites within the C terminus of FCP1 at Ser-575 and Ser-740 were identified | SIGNOR-251064 |
O43541 | O95947 | 1 | binding | down-regulates quantity by destabilization | 0.327 | Smad6 mediates Tbx6 ubiquitination and proteasomal degradation. Tbx6 forms a ternary complex with Smad6 and Smurf1. Here, we report that Tbx6 interacts directly with Smad6, an inhibitory Smad that antagonizes the BMP signal. This interaction is mediated through the Mad homology 2 (MH2) domain of Smad6 and residues 90-180 of Tbx6. We demonstrate that Smad6 facilitates the degradation of Tbx6 protein through recruitment of Smurf1, a ubiquitin E3 ligase. | SIGNOR-272785 |
Q99576 | Q00653 | 1 | binding | down-regulates activity | 0.327 | GILZ inhibits NF-kappaB nuclear translocation and DNA binding due to a direct protein-to-protein interaction of GILZ with the NF-kappaB subunits. | SIGNOR-253298 |
Q00535 | Q9UQB3 | 1 | phosphorylation | up-regulates activity | 0.327 | Cdk5 mediated delta-catenin phosphorylation regulates delta-catenin subcellular localization into two distinct pools : a cytoplasmic or intraneurite state as well as a pool that is localized to the membrane.|Cdk5 phosphorylates delta-catenin on serines 300 and 357. | SIGNOR-279323 |
Q14814 | Q9UKX2 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.327 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238712 |
P17252 | Q13769 | 1 | phosphorylation | up-regulates | 0.327 | We conclude m-csf-mediated activation of pkcalpha can potentiate fmip action to initiate survival/differentiation signaling. | SIGNOR-126572 |
Q93034 | O75553 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.327 | SOCS7 promotes Dab1 polyubiquitylation and degradation. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. SOCS7, a CRL5 substrate adaptor protein, is also required for neocortical layering. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. | SIGNOR-272140 |
Q9UBC3 | P42658 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.327 | Dnmt3b was responsible for transcriptional silencing of Dpp6 gene as depletion of Dnmt3b resulted in increased mRNA and protein expression of Dpp6. | SIGNOR-268963 |
P05771 | P49840 | 1 | phosphorylation | down-regulates | 0.327 | Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway. | SIGNOR-115718 |
P01106 | P08237 | 1 | transcriptional regulation | up-regulates quantity | 0.327 | C-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway. | SIGNOR-259988 |
P18031 | P42226 | 1 | 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 |
Q9UBE8 | Q8N122 | 1 | phosphorylation | down-regulates activity | 0.327 | NLK inhibits mTORC1 lysosomal localization and thereby suppresses mTORC1 activation. Mechanistically, NLK phosphorylates Raptor on S863 to disrupt its interaction with the Rag GTPase, which is important for mTORC1 lysosomal recruitment. | SIGNOR-273908 |
P17612 | P13796 | 1 | phosphorylation | up-regulates | 0.327 | Phosphorylation on ser5 increases the f-actin-binding activity of l-plastin and promotes its targeting to sites of actin assembly in cells. L-plastin phosphorylation require protein kinase a. | SIGNOR-146287 |
Q7Z6Z7 | Q13105 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.327 | Previously, we reported that K48 linked polyubiquitination of Miz1 by Mule triggers its proteasomal degradation, thereby relieving Miz1 suppression on TNF induced JNK activation and apoptosis. | SIGNOR-278697 |
Q04912 | P35222 | 1 | phosphorylation | up-regulates activity | 0.327 | Ron and beta-catenin associate and Ron kinase activity leads to tyrosine phosphorylation of beta-catenin.|We also show that tyrosine residues 654 and 670 of beta-catenin are important in mediating Ron induced beta-catenin transcriptional activation and cell growth. | SIGNOR-279376 |
P68400 | Q9Y237 | 1 | phosphorylation | down-regulates activity | 0.326 | As proved by MALDI-TOF mass spectrometry and MS/MS fragmentation, hPar14 is phosphorylated at Ser19 in vitro and in vivo. In human HeLa cells the protein is most likely modified by casein kinase 2 (CK2). |In contrast to wild-type hPar14, the in vitro DNA-binding affinity of the Glu19 mutant is strongly reduced, suggesting that only the dephosphorylated protein is the active DNA-binding form of hPar14 in the nucleus. | SIGNOR-265753 |
P17542 | P62256 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.326 | Tal1 expression activated UBE2H expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin transfer activity.|Binding of Tal1 to UBE2H was confirmed by chromatin immunoprecipitation. | SIGNOR-269000 |
P51452 | Q05397 | 1 | dephosphorylation | down-regulates activity | 0.326 | Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration.|In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. | SIGNOR-277033 |
P52954 | P37275 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.326 | Compared with the empty vector, LBX1 induced increased promoter activity of threefold to fourfold and fivefold to sixfold for ZEB1 and Snail1, respectively | SIGNOR-266054 |
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