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 |
|---|---|---|---|---|---|---|---|
P29317 | O43921 | 2 | binding | up-regulates | 0.816 | Ephrin-a ligands (named ephrin-a1_ephrin-a5) are anchored in the plasma membrane through a gpi-linkage, and each can bind any of the epha subclass of receptors (epha1_epha8) | SIGNOR-65413 |
Q9UMX1 | P10071 | 2 | binding | up-regulates quantity by stabilization | 0.889 | We show that loss of suppressor of fused (Sufu; an inhibitory effector for Gli proteins) results in destabilization of Gli2 and Gli3 full-length activators but not of their C-terminally processed repressors, whereas overexpression of Sufu stabilizes them. | SIGNOR-268868 |
P48426 | Q15139 | 0 | phosphorylation | down-regulates | 0.2 | We conclude that the type ii pip kinases are physiological targets for pkd phosphorylation, and that this modification is likely to regulate inositol lipid turnover by inhibition of these lipid kinases. | SIGNOR-145370 |
Q15904 | P51149 | 2 | binding | up-regulates activity | 0.29 | We found that Ac45 colocalized with Rab7 in resorbing osteoclasts cultured on bone slices (Fig. 6A). In addition, a co-immunoprecipitation assay revealed that Ac45 directly interacted with Rab7| Therefore, Ac45’s role in extracellular acidification, lysosomal trafficking, and cathepsin K exocytosis may be through the Rab7 pathway. | SIGNOR-261484 |
P45983 | Q14653 | 1 | phosphorylation | up-regulates | 0.533 | In this study, we show that another kinase, c-jun-nh(2)-terminal kinase (jnk), phosphorylates irf3 on its n-terminal serine 173 residuejnk1 can synergize the action of irf3(5d), but not the s173a-irf3(5d) mutant | SIGNOR-183489 |
O43516 | Q04759 | 0 | phosphorylation | up-regulates activity | 0.324 | TCR engagement also causes PKCtheta-dependent phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP complex, thereby releasing it from WIP inhibition. These results suggest that the ZAP-70-CrkL-WIP pathway and PKCtheta link TCR to WASP activation. | These results suggest that phosphorylation at S488 disrupts WIP binding to WASP. | SIGNOR-249181 |
Q9NQ66 | O14640 | 0 | null | up-regulates activity | 0.275 | Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin | SIGNOR-258978 |
Q49A26 | O43791 | 2 | binding | down-regulates quantity by destabilization | 0.274 | Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. | SIGNOR-272824 |
Q03721 | P05771 | 0 | phosphorylation | down-regulates | 0.2 | We found that pkc specifically eliminates rapid inactivation of a cloned human a-type k+ channel (hkv3.4), converting this channel from a rapidly inactivating a type to a noninactivating delayed rectifier type. | SIGNOR-35626 |
P06239 | P52757 | 1 | phosphorylation | down-regulates activity | 0.2 | We now demonstrate Lck-dependent phosphorylation of beta2-chimaerin in response to TCR triggering. We identify Tyr-153 as the Lck-dependent phosphorylation residue and show that its phosphorylation negatively regulates membrane stabilization of beta2-chimaerin, decreasing its GAP activity to Rac. | SIGNOR-276240 |
P17252 | P41180 | 1 | phosphorylation | down-regulates | 0.351 | Casr(t888) is a protein kinase c (pkc) phosphorylation site in the receptor's intracellular domain that has previously been identified as a critical negative regulator of casr downstream signaling in vitro, thus, casr(t888) represents a functionally important, inhibitory phosphorylation site that contributes to the control of pth secretion. | SIGNOR-170334 |
P45984 | P63000 | 2 | binding | up-regulates | 0.523 | We show that rac1 activates jnk2 that in turn phosphorylates beta-catenin on critical residues and controls its nuclear translocation. | SIGNOR-178265 |
Q86U44 | Q9UHD2 | 0 | phosphorylation | up-regulates activity | 0.2 | TBK1 also promotes METTL3 activation and m 6 A modification to stabilize IRF3 mRNA .|We here find TBK1, a key kinase of antiviral pathways, phosphorylates the core m 6 A methyltransferase METTL3 at serine 67. | SIGNOR-279299 |
Q13526 | P45983 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.272 | Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation. | SIGNOR-277562 |
O00444 | Q9UPN4 | 1 | phosphorylation | up-regulates activity | 0.534 | We conclude that PLK4 phosphorylates CEP131 at Ser 78 to maintains centriolar satellite integrity. | SIGNOR-280075 |
P35659 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.437 | These data suggest that the E3 ligase SCFFbxw7-α degrades p-DEK in a GSK-3β–dependent manner.Therefore, the phosphorylation of DEK by GSK-3β is a crucial step to mediate Tpm RNA splicing. | SIGNOR-276303 |
O60936 | P68400 | 0 | phosphorylation | up-regulates activity | 0.324 | Phosphorylation of ARC at T149 Is Required for Its Antiapoptotic Effect. Here we report that the function of ARC is regulated by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm. | SIGNOR-262837 |
P34981 | P29992 | 2 | binding | up-regulates activity | 0.485 | Binding of TRH to TRH-R1 receptor, which is coupled to Gq/11 protein, activates phospholipase C, mobilizes calcium and activates protein kinase C. | SIGNOR-267201 |
P20138 | P06239 | 0 | phosphorylation | up-regulates | 0.271 | Human cd33 has two tyrosine residues in its cytoplasmic domain (y340 and y358). When phosphorylated, these tyrosines could function as docking sites for the phosphatases, shp-1 and/or shp-2, enabling cd33 to function as an inhibitory receptor. Lck is effective at phosphorylating y340 | SIGNOR-78960 |
Q13617 | Q9Y4X5 | 2 | binding | up-regulates activity | 0.31 | Here, we provide evidence that Ariadne RBR E3 ubiquitin ligases such as TRIAD1 and HHARI can bind and be activated by CRL complexes. Whereas TRIAD1 specifically associates with CUL5–RBX2, HHARI is more promiscuous towards cullin types and associates with RBX1-associated cullins 1, 2, 3, and 4A. Interestingly, both TRIAD1 and HHARI show a strong preference for binding the neddylated form of the cullin. Our data suggest a novel function of NEDD8 in directing specific CRLs to Ariadne RBR ligases, which in turn exert influence on the levels of their cognate neddylated cullin. | SIGNOR-268845 |
O43915 | P35916 | 2 | binding | up-regulates | 0.2 | Vegf-d is a ligand for both vegf receptors (vegfrs) vegfr-2 (flk1) and vegfr-3 (flt4) and can activate these receptors. | SIGNOR-55065 |
Q13115 | Q16539 | 1 | dephosphorylation | down-regulates | 0.665 | This result suggests that dusp4 represses gluconeogenesis through dephosphorylation of p38 | SIGNOR-147958 |
P62873 | Q99835 | 2 | binding | up-regulates | 0.385 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling. | SIGNOR-199174 |
P08069 | P25098 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting β-arrestin1 association. Using immunoprecipitation, confocal microscopy, and FRET analysis, we demonstrated β-arrestin/IGF-1R association to be transient for GRK2 and stable for GRK6. Using bioinformatic studies we identified serines 1248 and 1291 as the major serine phosphorylation sites of the IGF-1R. Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 effects on IGF-1R signaling/degradation | SIGNOR-276413 |
Q9Y2J4 | P12931 | 2 | binding | up-regulates activity | 0.259 | These data support an idea that Amotl2 Tyr-103 can be phosphorylated by FGF receptor tyrosine kinase activity. We then determined whether Amotl2 Tyr-103 is required for its interaction with c-Src. |Amotl2 promotes MAPK/ERK activation via c-Src, which is dependent on phosphorylation of tyrosine residue at position 103 but independent of the C-terminal PDZ-binding domain. | SIGNOR-271870 |
P62805 | Q92585 | 0 | acetylation | down-regulates activity | 0.2 | We speculated that maml1, in addition to recruiting p300, might directly interact with histones to facilitate histone acetylation. We had observed acetylation of the histones h3 and h4. | SIGNOR-153041 |
O00444 | Q8NHV4 | 1 | phosphorylation | up-regulates activity | 0.593 | We found that PLK4-mediated phosphorylation of NEDD1 at its S325 amino acid residue directly promotes both NEDD1 binding to SAS-6 and recruiting SAS-6 to the centrosome. |Collectively, our results demonstrate that PLK4-regulated NEDD1 facilitates initiation of the cartwheel assembly and of daughter centriole biogenesis in mammals. | SIGNOR-272996 |
O95238 | Q9UQ88 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.356 | In this study we provide evidence that the cell cycle kinase CDK11p58, a protein involved in G2/M transition and degradation of several transcription factors, directly interacts with and phosphorylates SPDEF on serine residues|Western blot analysis demonstrated that only one of the mutant constructs, consisting of mutations of serine 238, 242 and 243, resulted in increased levels of SPDEF protein expression as compared to wild type SPDEF, leading to subsequent ubiquitination and degradation of SPDEF through the proteasome pathway.| | SIGNOR-273022 |
O75460 | P11021 | 2 | binding | down-regulates activity | 0.82 | Besides being activated like PERK via dissociation of GRP78, IRE1 is also activated by direct binding of the unfolded protein to its N-terminal luminal domain | SIGNOR-260176 |
P07355 | Q75N03 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | By immunoprecipitation, we present evidence that Hakai interacts with Hsp90 chaperone complex in several epithelial cells and demonstrate that is a novel Hsp90 client protein. Interestingly, by overexpressing and knocking-down experiments with Hakai, we identified Annexin A2 as a Hakai-regulated protein. Interestingly, geldanamycin-induced Hakai degradation is accompanied by an increased expression of E-cadherin and Annexin A2. | SIGNOR-271473 |
Q13315 | Q00987 | 1 | phosphorylation | down-regulates activity | 0.756 | Dephosphorylation stabilizes mdm2 and increases its affinity for p53, inducing p53 degredation. ;phosphorylated s260 and s395 ands260d and s395d mutant peptides inhibited binding of binding of a specific monoclonal antibody raised to mdm2. Phosphorylation of mdm2 regulates p53 degradation. | SIGNOR-94268 |
O00571 | Q9UHD2 | 0 | phosphorylation | up-regulates activity | 0.721 | Coexpression of TBK1 strongly increased the activity of DDX3X.|This suggests that DDX3X is rather specifically phosphorylated by TBK1 and IKK-i. | SIGNOR-278997 |
P19086 | Q13153 | 0 | phosphorylation | up-regulates | 0.2 | Phosphorylation of either ser(16) by pak1 or ser(27) by pkc decreased the affinity of galpha(z) for gbetagamma;phosphorylation of both residues by pkc caused no further effect. Pak1 thus regulates galpha(z) function by attenuating the inhibitory effects of both gaps and gbetagamma. | SIGNOR-48673 |
P12318 | P07948 | 0 | phosphorylation | up-regulates activity | 0.608 | Phosphorylation of FcgammaRIIa/c by Lyn is clearly dependent on the presence of Y-298, since all mutants lacking this residue are not phosphorylated by this PTK. This result suggests that Y-298 might be the only tyrosine residue of FcgammaRIIa/c phos- phorylated by Lyn. | SIGNOR-249379 |
Q9BXM7 | Q8IXI1 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.719 | PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. in Miro1, Ser156 (homologous to Ser182 in Drosophila) and Thr298, 299 (homologous to Ser324, 325 in Drosophila, Figure 6C). | SIGNOR-272727 |
P38435 | P00742 | 1 | carboxylation | up-regulates activity | 0.615 | This report describes the expression, purification, and characterization of a series of recombinant factor Xa variants bearing aspartate substitutions for each of the glutamate residues which normally undergo gamma-carboxylation. |We have produced fully active recombinant human factor Xa and demonstrated that gla residues 16, 26, and 29 are critical for normal activity of factor Xa.|This observation suggests that, for wild-type r-fX expressed in HEK cells, carboxylation by the gamma-glutamyl carboxylase proceeds to completion once initiated; | 11 amino terminal glutamic acid residues of fX which normally undergo gamma-carboxylation (glas 6, 7, 14, 16, 19, 20, 25, 26, 29, 32, 39). | SIGNOR-263667 |
P79483 | Q8TCQ1 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination. | SIGNOR-271410 |
O43889 | P51610 | 2 | binding | up-regulates activity | 0.566 | We also show that while interaction with HCF is not required for the ability of Luman to activate transcription when tethered to the GAL4 promoter, it appears to be essential for Luman to activate transcription through CRE sites. | SIGNOR-241372 |
O00308 | P49281 | 1 | ubiquitination | down-regulates quantity | 0.299 | Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2|This promotes DMT1 ubiquitination and degradation by WWP2. | SIGNOR-268852 |
Q9HCN8 | O75096 | 2 | binding | up-regulates activity | 0.2 | Here, we show that the chaperon Mesdc2 binds to the intracellular form of Lrp4 and promotes its glycosylation and cell-surface expression. These results suggest that Mesdc2 plays an essential role in NMJ formation by promoting Lrp4 maturation. | SIGNOR-237942 |
P06493 | P30291 | 2 | phosphorylation | down-regulates | 0.858 | We have found also that the major M-phase kinases polo-like kinase 1 (Plk1) and Cdc2 are responsible for the phosphorylation of S53 and S123, respectively, and that in each case phosphorylation generates an unconventional phospho-degron (signal for degradation) that can be recognized by beta-TrCP | SIGNOR-123824 |
P35222 | P29350 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.558 | Because SHP-1 can dephosphorylate residues Y86 and Y654 on the \u03b2-catenin protein, these residues were therefore mutated into phenylalanine and the transcriptional activity of the subsequent \u03b2-catenin mutants analyzed: \u03b2-catenin/Y86F, \u03b2-catenin/Y654F and \u03b2-catenin/Y86F/Y654F. As shown in Fig.\u00a03 B, the mutants \u03b2-catenin/Y86F, \u03b2-catenin/Y654F and \u03b2-catenin/Y86F/Y654F had a significantly reduced transcriptional activity in comparison to wild-type \u03b2-catenin.|SHP-1 inhibits \u03b2-catenin function by inducing its degradation and interfering with its association with TATA-binding protein. | SIGNOR-277014 |
Q13627 | Q13627 | 2 | phosphorylation | up-regulates | 0.2 | Mirk kinase is activated by autophosphorylation on tyrosine at the y271/y273 site | SIGNOR-79760 |
P62140 | Q9UD71 | 2 | binding | down-regulates activity | 0.445 | DARPP-32 (dopamine and cyclic AMP-regulated phospho-protein, relative molecular mass 32,000) is converted into an inhibitor of protein phosphatase 1 when it is phosphorylated by protein kinase A (PKA) at threonine 34.‚ | SIGNOR-264959 |
Q9NPB6 | O14641 | 2 | binding | up-regulates | 0.643 | In pcp , dvl binds to proteins such as pkc, atypical pkc (apkc), dvl-associated activator of morphogenesis 1 (daam1), dvl-associating protein with a high frequency of leu residues (daple) and partitioning defective 6 (par6), which are important for the regulation of small gtpases such as rho and rac and, consequently, the cytoskeleton and cell polarity58. | SIGNOR-199500 |
Q9H2P9 | P13639 | 1 | methylation | down-regulates activity | 0.747 | Analysis of EF2 in the mutant cells revealed a novel form of diphthamide with an additional methyl group that prevented ADP-ribosylation and inactivation of EF2. The abnormal methylation appeared to be catalyzed by DPH5. | SIGNOR-261146 |
Q92769 | P24385 | 2 | binding | up-regulates | 0.469 | Cyclin d1 bound hdac in vivo and preferentially physically associated with hdac1, hdac2, hdac3, and hdac5. | SIGNOR-134062 |
P14635 | P30304 | 0 | dephosphorylation | up-regulates activity | 0.855 | Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1 [4,5] . | SIGNOR-277137 |
Q9NRM6 | Q9UHF5 | 2 | binding | up-regulates | 0.748 | Here we report on the discovery of a novel il-17 homolog (il-17b), together with the identification of a novel cell surface receptor that specifically binds to it. We detail the molecular cloning, tissue distribution, and expression of both il-17b and il-17br, describe thein vivo activity of il-17b, and demonstrate binding to il-17br. | SIGNOR-76544 |
Q9H1J5 | O75197 | 2 | binding | up-regulates | 0.633 | 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-131987 |
P23560 | P51608 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.471 | We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. | SIGNOR-264540 |
O00429 | Q9NX47 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | We found that MITOL associated with and ubiquitinated mitochondrial fission protein hFis1 and Drp1.Pulse–chase experiment also indicated that MITOL overexpression promoted Drp1 turnover. | SIGNOR-271894 |
Q9UKV8 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.2 | Taken together, our results indicate that Tyr 393 of AGO2 is hyperphosphorylated in response to PTP1B inactivation and may contribute to H-RAS V12 -induced development of senescence.|We identified phospho-Tyr 393 of argonaute 2 (AGO2) as a direct substrate of PTP1B. | SIGNOR-277120 |
Q13469 | P48454 | 0 | dephosphorylation | up-regulates activity | 0.408 | NFAT1 is phosphorylated on fourteen conserved phosphoserine residues in its regulatory domain, thirteen of which are dephosphorylated upon stimulation. Dephosphorylation of all thirteen residues is required to mask a nuclear export signal (NES), cause full exposure of a nuclear localization signal (NLS), and promote transcriptional activity | SIGNOR-248512 |
P07814 | Q00535 | 0 | phosphorylation | down-regulates | 0.2 | Ser(886) phosphorylation is required for the interaction of nsap1, which blocks eprs binding to target mrnas. The same phosphorylation event induces subsequent binding of ribosomal protein l13a and gapdh and restores mrna binding. Ifn-_ activates cdk5 to phosphorylate ser(886) in the linker domain of glutamyl-prolyl trna synthetase (eprs), the initial event in assembly of the gait complex. Cdk5/p35 also induces, albeit indirectly via a distinct kinase, phosphorylation of ser(999), the second essential event in gait pathway activation | SIGNOR-187383 |
Q15349 | P49959 | 1 | phosphorylation | down-regulates activity | 0.2 | Rsk can phosphorylate the Mre11 protein directly at S676 both in vitro and in intact cells and thereby can inhibit the binding of Mre11 to DNA with DSBs.|ribosomal s6 kinase can phosphorylate the Mre11 protein directly at S676 both in vitro and in intact cells and thereby can inhibit the binding of Mre11 to DNA with double-stranded breaks. | SIGNOR-280116 |
Q9Y4B6 | P35240 | 2 | binding | down-regulates quantity by destabilization | 0.2 | VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. In this study, we provide evidence to show that Merlin is regulated in a Roc1-Cullin4A-DDB1-dependent manner. Following serum stimulation, Merlin is recruited to the E3 ligase complex through a direct interaction with the WD40-containing adaptor protein VprBP. Loading of Merlin to the E3 ubiquitin ligase complex resulted in its polyubiquitination, and consequently its proteasome-mediated degradation. | SIGNOR-271673 |
Q15119 | Q9H300 | 1 | phosphorylation | up-regulates activity | 0.2 | As expected, knocking down PDK2 in HEK293 cells that overexpress PARL resulted in a significant increase in beta cleavage in comparison to the control cells.|Furthermore, we show that PDK2, a key regulator in metabolic plasticity, phosphorylates PARL and regulates \u03b2 cleavage. | SIGNOR-280018 |
P05771 | Q03721 | 1 | phosphorylation | down-regulates | 0.2 | We found that pkc specifically eliminates rapid inactivation of a cloned human a-type k+ channel (hkv3.4), converting this channel from a rapidly inactivating a type to a noninactivating delayed rectifier type. | SIGNOR-35626 |
Q9Y4G8 | P48729 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here, we report that in response to factors that promote cell motility, the Rap guanine exchange factor RAPGEF2 is rapidly phosphorylated by I-kappa-B-kinase-β and casein kinase-1α and consequently degraded by the proteasome via the SCF(βTrCP) ubiquitin ligase. | SIGNOR-276604 |
P01106 | Q8TEK3 | 2 | binding | up-regulates activity | 0.334 | Our data suggest that the c-Myc-dependent transcriptional switch is modulated by DOT1L, as in the presence of DOT1L c-Myc preferentially forms an active complex with p300 rather than a repressive complex containing HDAC1 and DNMT1 | SIGNOR-239362 |
P06400 | O14757 | 0 | phosphorylation | up-regulates activity | 0.422 | These results suggest that ser612 is phosphorylated by chk1/2 after dna damage, leading to the formation of prb-e2f-1. phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1 | SIGNOR-153904 |
P17252 | P31431 | 1 | phosphorylation | up-regulates activity | 0.732 | The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant. | SIGNOR-249149 |
Q9UM47 | P00533 | 0 | phosphorylation | up-regulates activity | 0.593 | Here, we report that treatment of EGFR mutated lung cancer cell lines with erlotinib, while showing robust cell death, enriches the ALDH+ stem like cells through EGFR dependent activation of Notch3.|We also find a kinase-dependent physical association between the Notch3 and EGFR receptors and tyrosine phosphorylation of Notch3. | SIGNOR-280002 |
O95837 | P30411 | 2 | binding | up-regulates activity | 0.387 | 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-257199 |
Q9P0L0 | Q14721 | 0 | relocalization | up-regulates quantity | 0.2 | Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions. | SIGNOR-262122 |
P12931 | P17706 | 0 | dephosphorylation | down-regulates | 0.72 | We found that tcptp dephosphorylates and inactivates src family kinases to regulate t cell responses._ | SIGNOR-177116 |
P41212 | P28482 | 0 | phosphorylation | down-regulates | 0.317 | Tel became phosphorylated by erk on two serine residues, ser213 and ser257, in the internal domain between the hlh and ets domains. Tel lost its abilities to repress transcription through the phosphorylation. | SIGNOR-260086 |
Q9BY84 | P42345 | 1 | dephosphorylation | down-regulates activity | 0.274 | MKP7 represses mTOR function.|These results suggest that MKP7 could directly dephosphorylate pmTOR and pPRAS40 and forming complexes with these two proteins ( xref ). | SIGNOR-277067 |
P27540 | Q14190 | 2 | binding | up-regulates activity | 0.497 | We demonstrate that both SIM1 and SIM2 can heterodimerize via their helix-loop-helix·PAS regions with ARNT, but not with AHR, and that they do not form homodimers. Furthermore, SIM1 may have a dual role, both negatively affecting AHR·ARNT binding to the XRE and also acting in concert with ARNT as a novel DNA-binding heterodimer. | SIGNOR-240808 |
P29376 | P35568 | 1 | phosphorylation | up-regulates | 0.314 | Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells. | SIGNOR-49531 |
Q8IWJ2 | P20645 | 1 | relocalization | up-regulates activity | 0.532 | Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector | SIGNOR-253086 |
Q9UMX1 | Q99835 | 2 | binding | down-regulates activity | 0.64 | In addition to activating g(i), smo signals through its c-terminal tail to inhibit suppressor of fused, resulting in stabilization and activation of the gli family of transcription factors, which execute a transcriptional response to so-called canonical hh signaling. | SIGNOR-177656 |
P56524 | Q04206 | 2 | binding | up-regulates | 0.316 | P65 and histone deacetylases 4 cooperate to inhibit the ability of mef2 factors to induce the klf2 promoter | SIGNOR-138368 |
Q13426 | P78527 | 0 | phosphorylation | up-regulates activity | 0.907 | In response to ionizing radiation, ATM phosphorylates FBXW7 at serine 26 to recruit it to DNA double-strand break (DSB) sites, whereas activated DNA-PKcs phosphorylates XRCC4 at serines 325/326, which promotes binding of XRCC4 to FBXW7. SCF(FBXW7) E3 ligase then promotes polyubiquitylation of XRCC4 at lysine 296 via lysine 63 linkage for enhanced association with the Ku70/80 complex to facilitate NHEJ repair. | SIGNOR-277198 |
Q14995 | O00327 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.467 | A retinoic acid receptor-related orphan receptor (ROR) response element within the BMAL1 promoter is responsive to both ROR and REV-ERB (encoded by the genes NR1D1 and NR1D2); ROR activates the transcription of BMAL1, whereas REV-ERB suppresses its transcription. | SIGNOR-268006 |
Q9H4P4 | P21860 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.691 | Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3 | SIGNOR-272599 |
P15153 | P52306 | 2 | binding | up-regulates | 0.5 | Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob | SIGNOR-171421 |
P17612 | Q9Y6X9 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Mechanistically, GPER1 activates PRKACA (protein kinase cAMP-activated catalytic subunit alpha), which in turn phosphorylates MORC2 at threonine 582 (T582). Phosphorylated MORC2 decreases its interaction with HSPA8 (heat shock protein family A [Hsp70] member 8) and LAMP2A (lysosomal associated membrane protein 2A), two core components of the chaperone-mediated autophagy (CMA) machinery, thus protecting MORC2 from lysosomal degradation by CMA. | SIGNOR-273781 |
P05771 | P41594 | 1 | phosphorylation | up-regulates activity | 0.354 | Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839. | SIGNOR-249286 |
Q16665 | Q8NHM5 | 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-271567 |
Q00536 | P04637 | 1 | phosphorylation | down-regulates activity | 0.386 | In this study, we demonstrated that CDK16 phosphorylates p53 at Ser315 and promotes ubiquitination and subsequent degradation of p53.|Together, these results suggest that CDK16 negatively regulates p53 stability at the post-translational level. | SIGNOR-278354 |
P63279 | P59595 | 1 | sumoylation | up-regulates activity | 0.2 | In this study, we identified Ubc9 as a host protein that interacts specifically with SARS-CoV N protein. This interaction was verified both in vivo and in vitro. Furthermore, we showed that, in addition to phosphorylation, the N protein was modified by covalent attachment of SUMO to its lysine 62 residue. Evidence provided demonstrated that sumoylation may promote homo-oligomerization of the protein. | SIGNOR-260263 |
Q9HAU4 | P53804 | 0 | ubiquitination | down-regulates quantity | 0.2 | Tribbles homolog 3 ( TRB3 ) and Tetratricopeptide Repeat Domain 3 ( TTC3 ) directly ubiquitinate Smurf2 , thereby mediating Smurf2 degradation in a proteasome-dependent manner .|Tribbles homolog 3 (TRB3) and Tetratricopeptide Repeat Domain 3 (TTC3) directly ubiquitinate Smurf2, thereby mediating Smurf2 degradation in a proteasome dependent manner. | SIGNOR-278739 |
P62993 | Q92835 | 2 | binding | up-regulates activity | 0.583 | An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling. | SIGNOR-268449 |
P11387 | Q15233 | 2 | binding | up-regulates | 0.373 | We show that the psf/p54 dimer has pronounced stimulatory effect on dna catalysis by topoisomerase i | SIGNOR-60557 |
Q13188 | Q9H2K8 | 0 | phosphorylation | up-regulates | 0.291 | In addition, the thousand-and-one (tao) amino acids kinase or taok1 3 has been shown to directly phosphorylate and activate hpo or mst1/2 | SIGNOR-201333 |
Q9UHD2 | Q13546 | 2 | phosphorylation | down-regulates activity | 0.373 | Our data clearly indicate that TBK1 can directly phosphorylate RIPK1 at T189.|TBK1 inhibits RIPK1 by direct phosphorylation. | SIGNOR-279388 |
P09471 | Q9GZQ6 | 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-256987 |
Q96BF3 | O14920 | 0 | phosphorylation | up-regulates activity | 0.2 | Manipulating the IκB kinase β activity coupled with in vivo and in vitro kinase assays demonstrated that IκB kinase β is a key serine/threonine kinase activated by autophagy stimuli and that it catalyzes phosphorylation of IGPR-1 at Ser220 The subsequent activation of IGPR-1, in turn, stimulates phosphorylation of AMP-activated protein kinase, which leads to phosphorylation of the major pro-autophagy proteins ULK1 and Beclin-1 (BECN1), increased LC3-II levels, and accumulation of LC3 punctum. | SIGNOR-273642 |
P18848 | P41250 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269426 |
Q13418 | P31749 | 1 | phosphorylation | up-regulates | 0.779 | Ilk can phosphorylate pkb-akt on serine-473, whereas kinase-deficient ilk severely inhibits endogenous phosphorylation of pkb-akt on serine-473, demonstrating that ilk is involved in agonist stimulated, pi(3)k-dependent, pkb-akt activation. | SIGNOR-252597 |
O43524 | P48729 | 0 | phosphorylation | down-regulates | 0.2 | Casein kinase (ck) 1 mediates the hierarchical phosphorylation of foxo3a at s318 and s321, which like foxo1 (rena et al., 2002 blue right-pointing triangle, 2004 blue right-pointing triangle), is probably to enhance its rate of nuclear export | SIGNOR-163676 |
O60260 | Q99719 | 1 | ubiquitination | down-regulates quantity | 0.2 | Furthermore, Parkin ubiquitinates and promotes the degradation of CDCrel-1.|Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. | SIGNOR-278711 |
P00533 | P21860 | 1 | phosphorylation | up-regulates | 0.67 | The erbb3 protein which possesses little or no intrinsic protein tyrosine kinase activiity is phosphorylated by the activated egf receptor protein tyrosine kinase on tyrosine residues within the yxxm sequence motif. These phosphorylated tyrosine residues interact with the p85 regulatory subunit of pi 3-kinase, which could result in the activation of the p110 catalytic subunit via a conformational mechanism. | SIGNOR-34748 |
Q13469 | Q9Y625 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.354 | NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype. | SIGNOR-264021 |
P51812 | P05204 | 1 | phosphorylation | down-regulates activity | 0.29 | We report here that the NBD of the HMGN1 and -N2 protein family is highly and specifically phosphorylated during mitosis and that this phosphorylation has a major functional consequence: it abolishes the interaction of the proteins with its chromatin targets. | SIGNOR-249102 |
Q99877 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265392 |
P54753 | P52799 | 2 | binding | up-regulates | 0.883 | Lerk-5 is a ligand for both elk and hek and induces receptor phosphorylation | SIGNOR-52583 |
Q16539 | Q15910 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.372 | Here, we show that p38α kinase promotes EZH2 degradation in differentiating muscle cells through phosphorylation of threonine 372 | SIGNOR-255663 |
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