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 |
|---|---|---|---|---|---|---|---|
O00206 | P09429 | 2 | binding | up-regulates activity | 0.802 | Here we show that Toll-like receptor 4 (TLR4), a pivotal receptor for activation of innate immunity and cytokine release, is required for HMGB1-dependent activation of macrophage TNF release. | SIGNOR-252057 |
P11802 | P06400 | 1 | phosphorylation | down-regulates | 0.929 | Cyclin d1 is known to activate cdk4, which then phosphorylates the rb protein, leading to cell cycle progression. | SIGNOR-200487 |
O95229 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.651 | Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores|During prometaphase, AurB phosphorylation of zwint-1 is required for recruitment of ZW10-, pT89 dynein-, and RZZ-dependent proteins to kinetochores. This is defective after AurB inhibition or after expression of the triple-A zwint-1 mutant. Triple-E mutant zwint-1 mimics phospho–zwint-1 in RZZ recruitment, even after AurB inhibition | SIGNOR-265010 |
Q9UI10 | P20042 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.754 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269132 |
O43896 | Q9H0N0 | 1 | relocalization | up-regulates quantity | 0.245 | Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation. | SIGNOR-266879 |
O60716 | Q9HCE7 | 0 | monoubiquitination | down-regulates activity | 0.2 | Upon TGFβ treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. TGFβ promotes monoubiquitination of p120-catenin through Smurf1 to induce junction dissociation. | SIGNOR-277507 |
O94763 | P23443 | 0 | phosphorylation | down-regulates activity | 0.344 | Here we report that the prefoldin chaperone URI represents a mitochondrial substrate of S6K1. In growth factor-deprived or rapamycin-treated cells, URI forms stable complexes with protein phosphatase (PP)1gamma at mitochondria, thereby inhibiting the activity of the bound enzyme. Growth factor stimulation induces disassembly of URI/PP1gamma complexes through S6K1-mediated phosphorylation of URI at serine 371. | SIGNOR-262943 |
Q00987 | Q96GD0 | 0 | dephosphorylation | down-regulates activity | 0.2 | Considering the roles of NF2 in actin dynamics and Mdm2 regulation - , , , it is noteworthy to elucidate whether interaction of PLPP and CIN with NF2 modulates actin dynamics and Mdm2 degradation in neuronal excitability.|Recently, we have reported that PLPP and CIN dephosphorylates Mdm2 at S166 site in activity dependent manners, which inhibits Mdm2 mediated PSD95 degradation by facilitating Mdm2 ubiquitination 38. | SIGNOR-277151 |
Q13153 | P04049 | 1 | phosphorylation | up-regulates | 0.602 | P21-activated protein kinases (paks) are serine/threonine protein kinases that phosphorylate raf-1 at ser-338 and ser-339. | SIGNOR-180808 |
P17174 | P17676 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In cotransfection experiments, the C/EBP beta protein trans-activated 10-15-fold the cAspAT gene promoter in HepG2 cells. Deletion studies revealed that regions P2 and P4 are critical for promoter activity. In gel retardation experiments, the P4 region bound different C/EBP-related proteins in different tissues | SIGNOR-254051 |
Q13485 | P35658 | 2 | binding | up-regulates | 0.561 | We demonstrate that smad3 and smad4 are capable of interaction with the nucleoporin can/nup214, and this interaction is required for nuclear import | SIGNOR-117647 |
P50281 | P02671 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-14 27YVATRDN g-chain| 105XDAATLKSR g-chain | 92LTYNPDES g-chain |105LTTNIXEXL a-chain|433LVTSKGDKE a-chain| 117FXSANNRD a-chain | SIGNOR-263620 |
Q00535 | P48730 | 0 | phosphorylation | up-regulates activity | 0.555 | We also show that casein kinase I, but not casein kinase II, can phosphorylate and activate cdk5 in vitro. | SIGNOR-250798 |
Q8WWY8 | Q9HBW0 | 2 | binding | up-regulates | 0.293 | When overexpressed in jurkat t cells, the edg4 protein mediated lpa-induced activation of a serum response element reporter gene with lpa concentration dependence (ec50 of 10 nm) and specificity. | SIGNOR-56093 |
Q13541 | O75582 | 0 | phosphorylation | down-regulates activity | 0.671 | In response to UV-B irradiation, the translation factor 4E-BP1 (eukaryotic initiation factor 4E [eIF4E]-binding protein 1) was phosphorylated at Thr36, Thr45, Ser64 and Thr69. Using either p38 MAPK inhibitors or the MSK inhibitor H89, UV-B-irradiation-induced phosphorylation was blocked [43]. 4E-BP1 binds to eIF4E in resting cells to prevent formation of a functional eIF4F complex, which is essential for cap-dependent initiation of translation. Phosphorylation of 4E-BP1 leads to dissociation from eIF4E | SIGNOR-262992 |
Q7Z419 | P38936 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.359 | P53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1. Here we report the isolation of a novel transcriptional target of p53, designated p53RFP (p53-inducible RING-finger protein), whose product has E3 ubiquitin ligase activity. Its expression was negatively correlated to that of p21(WAF1) protein; p53RFP is likely to play a role in the regulation of this protein, probably through interaction with, and ubiquitination of, p21(WAF1). | SIGNOR-271478 |
P30305 | P06493 | 2 | dephosphorylation | up-regulates activity | 0.829 | CDC25B facilitates dephosphorylation of the key cell cycle regulator CDC2 (also called CDK1) at Tyr15 or Thr14, thereby initiating the G 2 /M transition ( xref ).|CDC25B facilitates dephosphorylation of the key cell cycle regulator CDC2 (also called CDK1) at Tyr15 or Thr14, thereby initiating the G2/M transition ( ). | SIGNOR-276969 |
Q13322 | P42345 | 0 | phosphorylation | up-regulates | 0.412 | The adaptor protein grb10 was identified as an mtorc1 substrate that mediates the phosphoinositide 3-kinase. | SIGNOR-174071 |
P00734 | O00254 | 2 | binding | up-regulates | 0.653 | as noted previously, the human form of par-3 activated phosphoinositide signaling in response to thrombin when overexpressed in cos-7 cells | SIGNOR-108225 |
Q13362 | P23443 | 2 | binding | down-regulates | 0.341 | The human homolog of pp2a-b', ppp2r5c, also counteracts s6k1 phosphorylation, indicating a conserved mechanism in mammals | SIGNOR-165224 |
P00533 | Q6UW88 | 2 | binding | up-regulates | 0.619 | Remarkably, three members of the epidermal growth factor (egf) family (ereg, areg, and epgn) showed increased expression that was associated with elevated epidermal activation of the egf receptor (egfr) and stat3, a downstream effector of egfr signaling. | SIGNOR-165779 |
Q8WXH5 | O75553 | 2 | binding | down-regulates quantity by destabilization | 0.2 | 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-272139 |
Q13627 | P40763 | 1 | phosphorylation | up-regulates activity | 0.265 | DYRK1A overexpression promotes STAT3 activity by phosphorylating STAT3 at Ser727 and contributes to reduced neuronal production and increased astroglial generation in DS. | SIGNOR-279992 |
Q00535 | Q12879 | 1 | phosphorylation | up-regulates activity | 0.525 | Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs. | SIGNOR-250666 |
Q14980 | Q9UJT1 | 2 | binding | up-regulates | 0.2 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-117159 |
P41743 | Q9NPB6 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.866 | APKC associates and phosphorylates Par6 on S345. aPKC expression stabilizes Par6 protein levels. We show that the aPKC, PKCι, interacts with TGF-β receptors through Par6 and that these proteins localize to the leading edge of migrating cells. Furthermore, Par6 phosphorylation on serine 345 by TGF-β receptors is enhanced in the presence of aPKC. aPKC kinase activity, as well as an association with Par6, were found to be important for Par6 phosphorylation. | SIGNOR-276432 |
P49910 | Q9HAU4 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.268 | ZNF165 drives the unrestrained activation of transforming growth factor β (TGFβ) signalling by directly inactivating the expression of negative feedback pathway regulators, SMURF2, SMAD7 and PMEPA1. | SIGNOR-266095 |
P50219 | P49841 | 0 | phosphorylation | down-regulates | 0.295 | Here we show that gsk-3_ inactivates the proapoptotic activity of hlxb9 by phosphorylating hlxb9 at ser-78/ser-80 (phlxb9). | SIGNOR-203657 |
O43187 | Q07955 | 1 | phosphorylation | down-regulates activity | 0.348 | IRAK2 phosphorylates SRSF1 and thereby reduces SRSF1 binding to the target mRNAs. | SIGNOR-278406 |
Q9P2F6 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.709 | 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-260472 |
Q8TCU6 | P62136 | 0 | dephosphorylation | up-regulates activity | 0.2 | MS analysis of wild-type P-Rex1 and a PP1\u03b1-binding-deficient mutant revealed that endogenous PP1\u03b1 dephosphorylates P-Rex1 on at least three residues, Ser834, Ser1001 and Ser1165.|The phosphatase activity of PP1\u03b1 is required for P-Rex1 activation. | SIGNOR-277024 |
Q16549 | P18850 | 1 | phosphorylation | up-regulates | 0.2 | We discovered that azc, an agent that causes the formation of abnormal proteins, stimulates the stress-activated kinase p38 mapk, which phosphorylates atf6 | SIGNOR-89813 |
Q12809 | P17612 | 0 | phosphorylation | up-regulates | 0.307 | Deletion of protein kinase a phosphorylation sites in the herg potassium channel inhibits activation shift by protein kinase afour consensus pka phosphorylation sites (s283a, s890a, t895a, s1137a) | SIGNOR-70726 |
Q12772 | P01130 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.772 | Recent studies have demonstrated that PCSK9 mRNA expression was upregulated to a greater extent than that of the LDL receptor in human hepatocytes in primary culture. Our findings also support the role of SREBP-2 as a transcriptional regulator of both the LDL receptor and PCSK9 in human enterocytes. | SIGNOR-254453 |
O96017 | Q13972 | 1 | phosphorylation | down-regulates | 0.405 | During interphase, cdc25 is inhibited by ser287 phosphorylation (xenopus cdc25;ser 216 in human cdc25c) and this inhibitory phosphorylation is maintained by dna-responsive checkpoints / s287 is targeted by many kinases, including chk1, chk2, ctak-1, pka, p38 and mapkap kinase-2 suggesting that phosphorylation of this site may integrate multiple signaling inputs. | SIGNOR-150843 |
O14965 | Q9NWT8 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.681 | AIP is phosphorylated on Serine 70 by Aurora‐A but not Aurora‐B and expression of phosphorylation mimic mutant of AIP results in prolonged protein stability compared to unphosphorylatable mutant. Phosphorylation of AIP Prolongs its Protein Stability | SIGNOR-262648 |
P28482 | P40763 | 1 | phosphorylation | down-regulates activity | 0.75 | ERK2 phosphorylates Stat3 on three serine-containing peptides and decreases its tyrosine phosphorylation induced by EGF treatment.|Here, we report that ERK2 activated by its upstream kinase, MEK1, represses Stat3 transcriptional activity induced by Src or Jak-2. | SIGNOR-279635 |
Q7LG56 | Q13315 | 0 | phosphorylation | up-regulates | 0.512 | Atm-mediated serine 72 phosphorylation stabilizes ribonucleotide reductase small subunit p53r2 protein against mdm2 to dna damage | SIGNOR-182423 |
Q00535 | P27695 | 1 | phosphorylation | up-regulates activity | 0.377 | Apurinic/apyrimidinic endonuclease-1 (APE1) is a multifunctional DNA repair/gene regulatory protein in mammalian cells, and was recently reported to be phosphorylated at Thr233 by CDK5. | SIGNOR-276337 |
P14618 | P36956 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.29 | Well-described targets of srebp-1 and the carbohydrate response element binding protein (chrebp), which include the following: fatty acid synthase (fas), acetyl coa carboxylase (acc1), and liver pyruvate kinase (l-pk) | SIGNOR-166381 |
Q06187 | Q9UJV9 | 1 | phosphorylation | up-regulates activity | 0.406 | The kinase and SH3/SH2 interaction domains of BTK bind, respectively, the DEAD-box domain of DDX41 and transmembrane region of STING. BTK phosphorylates DDX41, and its kinase activities are critical for STING-mediated IFN-β production. We show that Tyr364 and Tyr414 of DDX41 are critical for its recognition of AT-rich DNA and binding to STING, and tandem mass spectrometry identifies Tyr414 as the BTK phosphorylation site. | SIGNOR-266404 |
P07766 | Q9UJZ1 | 2 | binding | up-regulates activity | 0.2 | We observed that SLP-2 steadily associated with the CD3-epsilon chain of the TCR complex under resting conditions and during the 60 min of stimulation|The SLP-2-associated pool of these molecules became phosphorylated/activated in a sequential manner, a profile compatible with their temporal involvement in early TCR signalling. | SIGNOR-260375 |
Q12968 | P35354 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.279 | NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration | SIGNOR-264028 |
P55060 | Q13490 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.333 | We find that TRAIL induces up-regulation of CAS in a posttranscriptional, caspase-8-dependent manner through degradation of cIAP1, an E3 ligase that targets CAS for ubiquitin-dependent proteasomal degradation. | SIGNOR-272812 |
Q8TDI7 | O75838 | 2 | binding | up-regulates activity | 0.352 | Furthermore, we report that calcium and integrin-binding protein 2 binds to the components of the hair cell mechanotransduction complex, TMC1 and TMC2, and these interactions are disrupted by deafness-causing Cib2 mutations. We conclude that calcium and integrin-binding protein 2 is required for normal operation of the mechanotransducer channels and is involved in limiting the growth of transducing stereocilia. | SIGNOR-269665 |
Q13309 | P11309 | 0 | phosphorylation | up-regulates activity | 0.34 | We found that expression of Pim-1 increases the level of Skp2 through direct binding and phosphorylation of multiple sites on this protein. Along with known Skp2 phosphorylation sites including Ser(64) and Ser(72), we have identified Thr(417) as a unique Pim-1 phosphorylation target. Phosphorylation of Thr(417) controls the stability of Skp2 and its ability to degrade p27. | SIGNOR-259819 |
P07949 | Q6PKX4 | 2 | binding | up-regulates | 0.647 | These data identify dok-6 as a novel dok-4/5-related adaptor molecule that may function in vivo to transduce signals that regulate ret-mediated processes such as axonal projection. | SIGNOR-127382 |
P08754 | P28566 | 2 | binding | up-regulates activity | 0.448 | 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-256848 |
P15391 | P00519 | 0 | phosphorylation | up-regulates activity | 0.533 | The results revealed that only tyrosine (Y)490 of CD19 was phosphorylated by c-Abl. | SIGNOR-245283 |
Q96Q15 | Q92900 | 1 | phosphorylation | up-regulates | 0.971 | Smg-1 directly phosphorylates upf1 helicase, another key component of nmd, upon recognition of ptc on postspliced mrna during the initial round of translation. Phosphorylated-upf1 recruits the smg-5/smg-7 complex to induce ribosome dissociation and decapping-mediated decay. T28 and s1096 are responsible for phospho-specific recruitment of smg-6 to the n-terminal conserved region, and the smg-5/smg-7 heterodimer complex to the c-terminal sq-rich region of upf1, respectively | SIGNOR-200785 |
P09884 | P27694 | 2 | binding | up-regulates activity | 0.687 | In our studies, we have shown that T antigen, DNA polymerase R, and the activation domain of VP16 all interact with overlapping regions of the 70-kDa subunit of RPA.| In the latter, both the direct protein-protein interaction and ssDNA-binding activities of RPA were needed for RPA to modulate polymerase processivity. We also found that SV40 T antigen inhibited the ability of RPA to increase processivity of DNA polymerase alpha, suggesting that this activity of RPA may be important for elongation but not during the initiation of DNA replication. | SIGNOR-261272 |
P67809 | Q8IUQ4 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.244 | Here, we identified that SIAH1 which was downregulated in chemoresistant EOC samples and cell lines functioned as novel E3 ligases to trigger degradation of YBX-1 at cytoplasm by RING finger domain.|SIAH1 ubiquitinated YBX-1 at its K304 through the RING domain. | SIGNOR-278780 |
O60502 | Q01813 | 1 | deglycosylation | up-regulates activity | 0.2 | Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267606 |
P12931 | P04083 | 1 | phosphorylation | up-regulates | 0.389 | The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].Finally in 2013 caron et al. showed the relevance of y21 phosphorylation for the anxa1 stability. In fact the authors demonstrated that the tyrosine 21 phosphorylation is crucial for anxa1 sumoylation induced by egf | SIGNOR-202796 |
Q14938 | P54764 | 1 | 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-268908 |
P25025 | P37231 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.264 | EMSA, ChIP, and transient transfection assays indicate that PPAR-gamma activates the CXCR2 promoter by binding to a PPAR response element (PPRE). | SIGNOR-271682 |
P52757 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.64 | 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-260500 |
P06493 | P27361-3 | 1 | phosphorylation | up-regulates activity | 0.314 | We found that CDK1 phosphorylates Ser343 of ERK1c, thereby allowing the binding of phosphorylated ERK1c to a complex that consists of PI4KIIIβ (also known as PI4KB) and the 14-3-3γ dimer (encoded by YWHAB). | SIGNOR-277185 |
P55085 | P63092 | 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 ‚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-256752 |
P28482 | P15336 | 1 | phosphorylation | up-regulates | 0.733 | Here, we show that in fibroblasts, insulin, epidermal growth factor (egf) and serum activate atf2 via a so far unknown two-step mechanism involving two distinct ras effector pathways: the raf-mek-erk pathway induces phosphorylation of atf2 thr71, whereas subsequent atf2 thr69 phosphorylation requires the ral-ralgds-src-p38 pathway. | SIGNOR-90517 |
Q71U36 | Q14980 | 2 | binding | up-regulates | 0.433 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-116640 |
Q15831 | P04637 | 1 | phosphorylation | up-regulates | 0.756 | We show that lkb1 physically associates with p53 in the nucleus and directly or indirectly phosphorylates p53 ser15 (previously shown to be phosphorylated by amp-dependent kinase) and p53 ser392 | SIGNOR-150830 |
Q14653 | Q13043 | 0 | phosphorylation | up-regulates activity | 0.2 | Beyond that, another investigation demonstrated that MST1 directly phosphorylated IRF3 at T75 and T253, which disrupted the dimerization of IRF3 and restrained RLRs and cGAS-mediated innate antiviral response. | SIGNOR-280145 |
Q9P0J1 | P00519 | 0 | phosphorylation | down-regulates activity | 0.268 | Here we report that phosphorylation at another tyrosine residue, Tyr-94, inhibits PDP1 by reducing the binding ability of PDP1 to lipoic acid, which is covalently attached to the L2 domain of dihydrolipoyl acetyltransferase (E2) to recruit PDP1 to PDC. We found that multiple oncogenic tyrosine kinases directly phosphorylated PDP1 at Tyr-94, and Tyr-94 phosphorylation of PDP1 was common in diverse human cancer cells and primary leukemia cells from patients. | SIGNOR-276641 |
Q9NRY4 | P12931 | 0 | phosphorylation | up-regulates | 0.772 | Phosphorylation of y1105, but not the minor site, was modulated in vivo to a greater extent by overexpression of c-src than by the egf receptor and was efficiently catalyzed by c-src in vitro. Mutation of y1105 from tyr to phe resulted in complete loss of p-tyr-dependent complex formation, indicating that p-y1105 was the sole p-tyr residue mediating binding to p120 | SIGNOR-61670 |
Q99814 | Q9H3R0 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271585 |
P17252 | P30622 | 1 | phosphorylation | down-regulates | 0.2 | Furthermore, by using phosphoproteomic analysis, we determined that s309 and s311 of clip-170 are phosphorylated in cells and mapped s311 as a protein kinase a (pka) phosphorylation site.phosphorylation of s311 may be critical for establishing the ?folded Back? Conformation of clip-170clip-170 open and folded back conformations represent active and inactive modes of the protein, respectively | SIGNOR-165857 |
P07948 | P53396 | 1 | phosphorylation | up-regulates activity | 0.2 | We demonstrate the binding of PIP2 to the CoA-binding domain of ACLY and identify the six tyrosine residues of ACLY that are phosphorylated by Lyn. Three of them (Y682, Y252, Y227) can be also phosphorylated by Src and they are located in catalytic, citrate binding and ATP binding domains, respectively. PI3K and Lyn inhibitors reduce the ACLY enzyme activity, ACLY-mediated Acetyl-CoA synthesis, phospholipid synthesis, histone acetylation and cell growth. Thus, PIP2/PIP3 binding and Src tyrosine kinases-mediated stimulation of ACLY links oncogenic pathways to Acetyl-CoA-dependent pro-growth and survival metabolic pathways in cancer cells. | SIGNOR-274105 |
P68400 | Q8TEA8 | 1 | phosphorylation | up-regulates activity | 0.285 | Here we show that DUE-B is de-phosphorylated in M phase and phosphorylated in G1/S phase. Phosphorylated DUE-B forms homodimers, whereas de-phosphorylated DUE-B interacts with the Mcm2–7 complex and aminoacyl-tRNA synthetases. We find that CKII can prime DUE-B for Cdc7 phosphorylation. Confirming the importance of DUE-B phosphorylation in replication initiation, a C-terminal Ser/Thr to Ala mutant blocks Cdc45 and RPA loading on sperm chromatin and inhibits DNA replication. DUE-B C-terminal phosphorylation sites (serine 179, 181, 182, 194, 196, 197, 204, 205, and threonine 187) were mutated to unphosphorylatable alanine (DUE-B(S/T)-A) or phosphomimic aspartic acid (DUE-B(S/T)-D). | SIGNOR-273970 |
P29590 | P63165 | 0 | sumoylation | up-regulates | 0.78 | We have shown previously that wild type PML, but not PML-RARalpha, is covalently modified by the sentrin family of ubiquitin-like proteins|We show that Lys65 in the RING finger domain, Lys160 in the B1 Box, and Lys490 in the nuclear localization signal contributes three major sentrinization sites| Furthermore, the triple substitution mutant is localized predominantly to the nucleoplasm, in contrast to wild type PML, which is localized to the nuclear bodies. Thus, sentrinization of PML, in the context of the RING finger and the B1 box, regulates nuclear body formation. | SIGNOR-261786 |
P31751 | Q9GZV1 | 1 | phosphorylation | up-regulates | 0.414 | In vitro and in vivo studies confirmed that akt phosphorylates ankrd2 at ser-99. moreover, the forced expression of a phosphorylation-defective mutant form of ankrd2 in c2c12 myoblasts promoted a faster differentiation program, implicating akt-dependent phosphorylation at ser-99 in the negative regulation of myogenesis in response to stress conditions. | SIGNOR-236978 |
O75116 | Q9UBR4 | 1 | phosphorylation | up-regulates activity | 0.2 | Rok-\u03b1 phosphorylates and activates LIM kinase, which in turn phosphorylates and inactivates cofilin. | SIGNOR-280110 |
P16591 | P07900 | 0 | phosphorylation | down-regulates activity | 0.3 | Hsp90 and tyrosine616 are required for Fer tyrosine kinase activity.Taken together, our findings underscore the importance of Hsp90 and the residue, tyrosine616, which resides in the Hsp90 recognition loop, in maintaining Fer tyrosine kinase activity. | SIGNOR-277818 |
P60891 | O95835 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness. | SIGNOR-276505 |
P06493 | Q8IZP0 | 1 | phosphorylation | down-regulates activity | 0.419 | We identified serine 216 of Abi1 as a target of CDK1/cyclin B kinase that is phosphorylated in cells at the onset of mitosis.|Bcr-Abl-induced actin polymerization requires the Abi1 pathway, as the blockade of the signal transduction from Bcr-Abl to Abi1 abolishes the F-actin assembly|serine phosphorylation of Abi1 by CDK1/cyclin B serves as a cell cycle-dependent regulatory mechanism that inhibits actin assembly | SIGNOR-264421 |
Q92785 | Q01196 | 2 | binding | down-regulates activity | 0.2 | The interaction between RUNX1 and DPF2 is dependent on the RUNX1 methylation status | SIGNOR-261966 |
P56703 | O75581 | 2 | binding | up-regulates | 0.649 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131823 |
Q9UJD0 | P20336 | 1 | relocalization | up-regulates activity | 0.282 | N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle | SIGNOR-264379 |
P27695 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.377 | Apurinic/apyrimidinic endonuclease-1 (APE1) is a multifunctional DNA repair/gene regulatory protein in mammalian cells, and was recently reported to be phosphorylated at Thr233 by CDK5. | SIGNOR-276337 |
Q05923 | P28482 | 1 | dephosphorylation | down-regulates | 0.745 | Pac1 and mkp-1 previously have been implicated in the in vivo inactivation of erk or of erk and jnk, respectively. | SIGNOR-40915 |
P49662 | P57764 | 1 | cleavage | up-regulates activity | 0.647 | Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence | | SIGNOR-256417 |
P49959 | P09874 | 0 | relocalization | up-regulates activity | 0.2 | PARP1 collaborates with Mre11 to promote replication fork restart after release from replication blocks, most likely by recruiting Mre11 to the replication fork to promote resection of DNA. | SIGNOR-272478 |
Q9BXL7 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.309 | NF-kappaB activation is triggered by PKCtheta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCtheta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane|we demonstrate that PP2A removes PKCtheta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation. | SIGNOR-248650 |
P27708 | P27708 | 2 | phosphorylation | up-regulates activity | 0.2 | Autophosphorylation resulted in a 2-fold increase in CPSase activity, an increased sensitivity to the feedback inhibitor UTP, and decreased allosteric activation by 5-phosphoribosyl-1-pyrophosphate | SIGNOR-250610 |
O14965 | P16949 | 1 | phosphorylation | down-regulates activity | 0.388 | Inhibition of AURKA activity activates stathmin function via reduced phosphorylation and facilitates microtubule destabilization in RB1 -/- cells, heavily impacting the bipolar spindle formation and inducing mitotic cell death selectively in RB1 -/- cells.|Two serine phosphorylation sites, Ser16 and Ser63, in stathmin contain a consensus sequence for AURKA phosphorylation and the mutations in these two serine sites abolished stathmin phosphorylation by AURKA, suggesting that stathmin is a substrate of AURKA for phosphorylation xref , xref . | SIGNOR-278913 |
P06493 | Q8NFH5 | 1 | phosphorylation | down-regulates activity | 0.563 | Collectively, these data show that mitotic hyperphosphorylation of Nup53 by CDK1 and PLK1 contributes to its removal from NPCs.|The combined mutation of the CDK1 and PLK1 sites to phosphomimetic residues almost completely abolished NPC integration of Nup53, indicating that hyperphosphorylation of Nup53 might be incompatible with its NPC association. | SIGNOR-278917 |
Q8NA31 | P54274 | 1 | relocalization | up-regulates activity | 0.2 | The shelterin complex has six proteins, containing TRF1, TRF2, POT1, RAP1, TIN2, and TPP1. The shelterin complex is localized to the chromosome end and protects telomeric DNA (Palm and de Lange, 2008). The TTM complex acts as a “linker” and bridges the LINC and shelterin complexes together. The connection between TTM and shelterin complexes is well-known, which is mediated by TERB1 and TRF1 | SIGNOR-263315 |
O75385 | P14373 | 0 | ubiquitination | down-regulates quantity | 0.2 | STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination | SIGNOR-270349 |
P17275 | P45984 | 2 | binding | down-regulates | 0.673 | Jnk targets junb ubiquitination | SIGNOR-53827 |
Q9BS16 | P35712 | 2 | binding | up-regulates activity | 0.47 | Here we report the cloning of a novel cDNA, termed Solt, from a mouse testis cDNA library. Its gene product, Solt, interacts with the leucine zipper region of SoxLZ/Sox6. In transient transfection assays with SoxLZ/Sox6 containing the transactivation domain of herpes simplex virus VP16, the expression of a luciferase reporter gene under the control of a promoter containing a synthetic cis element that is bound by the HMG box of SoxLZ/Sox6 was poorly enhanced in the presence of Solt. | SIGNOR-221820 |
P42574 | P55211 | 2 | cleavage | up-regulates activity | 0.639 | Active caspase-3 itself is able to process its upstream , caspase-8 and caspase-9, establishing a self-amplifying loop of caspase activation | SIGNOR-90397 |
O60346 | Q9Y243 | 1 | dephosphorylation | down-regulates activity | 0.648 | The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells. | SIGNOR-248330 |
Q9UI40 | Q96CW1 | 2 | binding | down-regulates quantity | 0.2 | we report that the first tyrosine motif of NCKX2 interacts with AP2M1 and that the interaction is required for endocytosis of NCKX2 from the dendritic surface. Furthermore, we show that a Src family kinase (SFK) modulates the endocytosis of NCKX2 by tyrosine-phosphorylation of the AP-2 recognition motif in NCKX2. | SIGNOR-264388 |
P13639 | P41240 | 0 | phosphorylation | down-regulates quantity | 0.264 | C-terminal Src kinase (Csk)-mediated phosphorylation of eukaryotic elongation factor 2 (eEF2) promotes proteolytic cleavage and nuclear translocation of eEF2.|In this report, we show that eukaryotic elongation factor 2 (eEF2) is a new protein substrate of Csk and could locate in the nucleus. | SIGNOR-279698 |
P27361 | P10828 | 1 | phosphorylation | down-regulates activity | 0.428 | We concluded that serine 142 of the tr dbd is the likely site of phosphorylation by t(4)-activated mapk and that the docking site on tr for activated mapk includes residues 128-133 (kgffrr), a basic amino acid-enriched motif novel for mapk substrates. Tr mutations in the proposed mapk docking domain and at residue 142 modulated t(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of tr in a thyroid hormone response element-luciferase reporter assay. | SIGNOR-102224 |
P26718 | Q9BZM5 | 2 | binding | up-regulates | 0.586 | Here we describe a family of gpi-anchored cell surface proteins that function as ligands for the mouse activating nkg2d receptor. These molecules are encoded by the retinoic acid early inducible (rae-1) and h60 minor histocompatibility antigen genes on mouse chromosome 10 and show weak homology with mhc class i. | SIGNOR-79233 |
P50148 | P35348 | 2 | binding | up-regulates activity | 0.585 | 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-257084 |
P28482 | P38936 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.364 | Extracellular signal-regulated kinase 2-dependent phosphorylation induces cytoplasmic localization and degradation of p21cip1.|Phosphopeptide analysis of in vitro ERK2-phosphorylated p21(Cip1) revealed two phosphorylation sites, Thr57 and Ser130. | SIGNOR-185215 |
O14625 | P25106 | 2 | binding | up-regulates activity | 0.637 | This paper characterizes an alternate receptor, CXCR7, which binds with high affinity to SDF-1 and to a second chemokine, interferon-inducible T cell alpha chemoattractant (I-TAC; also known as CXCL11) | SIGNOR-268415 |
P35354 | P15172 | 1 | null | up-regulates | 0.264 | Furthermore, COX-2 inhibition reduced MyoD expression in regenerating muscle, suggesting a role for COX-2 in modulating muscle differentiation, as well as growth | SIGNOR-256214 |
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