IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P42224 | P22607 | 0 | phosphorylation | up-regulates activity | 0.671 | Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3. | SIGNOR-251138 |
P53350 | Q9BQQ3 | 1 | phosphorylation | down-regulates quantity | 0.729 | As GRASP65 is a substrate of cdc2 and polo-like kinase, manipulation of GRASP65 level may affect the localization and activity of these kinases in cell cycle progression, as suggested by a previous study ( ).|During mitosis, GRASP65 is phosphorylated by two mitotic kinases, cdc2 and polo-like kinase (plk), which leads to GRASP65 deoligomerization and thus Golgi unstacking ( xref , xref ). | SIGNOR-279554 |
P12931 | P42680 | 1 | phosphorylation | up-regulates activity | 0.32 | The proximal event following T cell-APC synapse formation is immediate activation of several signaling molecules: The Src kinase phosphorylates and activates Tec tyrosine kinases, which then activate PLC-\u03b3 that is required for IP 3 generation to sustain intracellular calcium flux. | SIGNOR-280135 |
P04070 | P08709 | 1 | cleavage | down-regulates activity | 0.237 | Activated protein C (APC), which cleaves and inactivates both FVIIIa and FVa, thereby shutting down both the tenase and prothrombinase complexes | SIGNOR-263527 |
Q8NET8 | P27361 | 0 | phosphorylation | up-regulates activity | 0.2 | We observed that ERK-mediated phosphorylation of TRPV3 alters its responsiveness to repeated chemical stimuli. Among several putative ERK phosphorylation sites, we identified threonine 264 in the N-terminal ankyrin repeat domain as the most critical site for the ERK-dependent modulation of TRPV3 channel activity. Of note, Thr264 is in close vicinity to a structurally and functionally important TRPV3 region comprising an atypical finger 3 and oxygen-dependent hydroxylation site. In summary, our findings indicate that Thr264 in TRPV3 is a key ERK phosphorylation site mediating EGFR-induced sensitization of the channel to stimulate signaling pathways involved in regulating skin homeostasis. | SIGNOR-273672 |
Q99683 | P51812 | 0 | phosphorylation | down-regulates activity | 0.2 | We provide evidence to show that RSK2 inhibits ASK1 by phosphorylating S83, T1109, and T1326 through a novel mechanism in which phospho-T1109/T1326 inhibits ATP binding to ASK1, while phospho-S83 attenuates ASK1 substrate MKK6 binding. | SIGNOR-276463 |
Q14524 | Q13131 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | AMPK was found to phosphorylate Nav1.5 at threonine (T) 101, which then regulates the interaction between Nav1.5 and the autophagic adaptor protein, microtubule-associated protein 1 light chain 3 (LC3), by exposing the LC3-interacting region adjacent to T101 in Nav1.5. | SIGNOR-277432 |
A7KAX9 | Q9UQC2 | 0 | relocalization | up-regulates | 0.374 | Gc-gap, a rho family gtpase-activating protein that interacts with signaling adapters gab1 and gab2we propose that gab1 and gab2 in cooperation with other adapter molecules might regulate the cellular localization of gc-gap under specific stimuli. | SIGNOR-102628 |
P56704 | P11308 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression. | SIGNOR-261598 |
Q14012 | Q92974 | 1 | phosphorylation | up-regulates activity | 0.389 | In this study, we found that CaMKI phosphorylated GEF-H1 at Thr103, which is located close to the C1 domain. | SIGNOR-279359 |
Q15349 | P27361 | 0 | phosphorylation | up-regulates | 0.719 | Several lines of investigation have suggested that rsk is phosphorylated and activated by erk1/2 mapk isoforms | SIGNOR-44949 |
Q6NXT1 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.2 | The mechanism by which phosphorylation of Ankrd54 by PKC\u03b4 enhances cytoplasmic accumulation of Ankrd54 and its interaction with Lyn remains to be determined.|This revealed, in agreement with the biochemical analysis, that PKCdelta significantly promotes cytoplasmic accumulation of Ankrd54. | SIGNOR-279259 |
P14136 | Q9UQM7 | 0 | phosphorylation | down-regulates activity | 0.427 | On the other hand, GFAP was phosphorylated to approximately 1.9 mol of phosphate/mol of GFAP by Ca(2+)-CaM-dependent protein kinase II, and this phosphorylation did induce disassembly of the filament. Sequential analysis of the purified phosphopeptides revealed that only Ser8 on GFAP was phosphorylated by cdc2 kinase, whereas Ser13, Ser17, Ser34, and Ser389 on GFAP were phosphorylated by Ca(2+)-CaM-dependent protein kinase II. | SIGNOR-250626 |
P41594 | Q02156 | 0 | phosphorylation | up-regulates activity | 0.396 | 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-249288 |
Q16584 | Q16539 | 0 | phosphorylation | down-regulates | 0.304 | Jnk and p38 mapk activation have antagonistic effects in many cases. From a mechanicistic point of view, the p38 mapk pathway can negatively regulate jnk activity at the level of map3ks, either by phosphorylating mlk3 or the tak1 regulatory subunit tab2 | SIGNOR-166605 |
P23528 | P12931 | 0 | phosphorylation | down-regulates | 0.553 | Tyrosine phosphorylation of cofilin at y68 by v-src leads to its degradation through ubiquitin-proteasome pathway | SIGNOR-188352 |
P23381 | P18848 | 0 | 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-269429 |
Q9UBS0 | Q15633 | 1 | phosphorylation | up-regulates activity | 0.333 | We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. | SIGNOR-274066 |
P30530 | Q8NB16 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | TAM kinases phosphorylate MLKL to promote necroptosis. MLKL is then recruited to the plasma membrane, where TAM kinases phosphorylate MLKL at Tyr376 (Figure 5G, step 5), promoting its oligomerization and formation of membrane-rupturing pores that result in necrotic cell death (Figure 5G, step 6). | SIGNOR-274119 |
Q7L9L4 | Q13188 | 0 | phosphorylation | up-regulates | 0.817 | Mob1, when phosphorylated by MST1/2, binds to the autoinhibitory motif in Lats1/2, which in turn leads to the phosphorylation of the Lats activation loop (Lats1 S909 and Lats2 S872) and thereby an increase of their kinase activity | SIGNOR-201290 |
P12931 | Q13017 | 1 | phosphorylation | up-regulates activity | 0.607 | Phosphotyrosine (p-Tyr)-dependent and -independent mechanisms of p190 RhoGAP-p120 RasGAP interaction: Tyr 1105 of p190, a substrate for c-Src, is the sole p-Tyr mediator of complex formation. 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, indicating that Y1105 is a selective and preferential target of c-Src both in vitro and in vivo. | SIGNOR-276170 |
P04150 | P28562 | 1 | null | up-regulates quantity | 0.58 | Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1|Both induction of MKP-1 expression and inhibition of its degradation are necessary for glucocorticoid-mediated inhibition of Erk-1/2 activation. In NIH-3T3 fibroblasts, although glucocorticoids up-regulate the MKP-1 level, they do not attenuate the proteasomal degradation of this protein and consequently they are unable to inhibit Erk-1/2 activity. | SIGNOR-253546 |
P06493 | P60510 | 0 | dephosphorylation | down-regulates activity | 0.397 | PP4c efficiently dephosphorylates Cdk1 sites of NDEL1 but does not dephosphorylate the Aurora A site.|We also found that PP4c negatively regulates Cdk1 activity in interphase. | SIGNOR-277162 |
P12931 | P61586 | 1 | phosphorylation | down-regulates activity | 0.668 | When these RhoA mutants were coexpressed with Bcr-Abl, phosphorylation levels of Y34F and Y66F RhoA mutants dramatically decreased to 32% and 17%, respectively. As expected, when Y34 and Y66 were both mutated to phenylalanine, phosphorylation was completely abolished. Together, these observations indicate that Y34 and Y66 are the two predominant phosphorylation sites, and that the Src kinase and Bcr-Abl are the two candidate kinases that may phosphorylate these sites.|In contrast to active RhoA, RhoAQ63L(Y34,66E) had a dramatic decrease in RBD binding. This binding fraction was even lower than that of WT RhoA, suggesting phosphorylation at these sites could have a negative effect on RhoA activity | SIGNOR-271701 |
Q05513 | O43315 | 1 | phosphorylation | up-regulates | 0.2 | Wt-pkc_-mediated phosphorylation of wt aqp9 in vitro. In the experiments, substitution of ser11 to ala markedly inhibited phosphorylation. the s11a mutation in fibroblasts caused a smoother cell periphery with fewer aqp9-induced filopodia | SIGNOR-176278 |
O96004 | P17612 | 0 | phosphorylation | down-regulates activity | 0.296 | In vitro and in vivo phosphorylation studies show that both PKA and PKC can phosphorylate HAND1 and -2. T107; S109 within helix I and S98 within the basic domain, are the phosphorylated residues. We determined that modification of HAND1 at residues 107 and 109 affects dimerization affinities with E-proteins, thus changing the bHLH dimer equilibrium within the cell. These modifications also affect HAND1 function. | SIGNOR-249991 |
O94782 | Q9NVI1 | 1 | deubiquitination | down-regulates activity | 0.666 | Phosphorylation of FANCI may also turn the ubiquitinated ID complex into a poor substrate for deubiquitination by the USP1–UAF1 complex, resulting in increased levels of monoubiquitinated FANCD2. | SIGNOR-263272 |
P49841 | P57059 | 1 | phosphorylation | up-regulates activity | 0.2 | Glycogen synthase kinase-3beta (GSK-3beta) phosphorylates Ser/Thr residues located at the fourth position ahead of the pre-phosphorylated Ser/Thr residues, and inhibitors of GSK-3beta reduce the phosphorylation at Thr182. The results of an in vitro reconstitution assay also indicate that GSK-3beta could be the SIK1 kinase. However, overexpression and knockdown of GSK-3beta in LKB1-defective HeLa cells suggests that GSK-3beta alone may not be able to phosphorylate or activate SIK1, indicating that LKB1 may play a crucial role by phosphorylating SIK1 at Thr182, possibly as an initiator of the autophosphorylation cascade, and GSK-3beta may phosphorylate SIK1 at Thr182 by recognizing the priming-autophosphorylation at Ser186 in cultured cells. | SIGNOR-279742 |
P19429 | P05771 | 0 | phosphorylation | down-regulates | 0.2 | Pkc-betaii sensitizes cardiac myofilaments to ca2+ by phosphorylating troponin i on threonine-144. | SIGNOR-149957 |
P42226 | O60674 | 0 | phosphorylation | up-regulates activity | 0.67 | Downstream intracellular signaling from the IL-4IL-4Rc complex involves activation of the Jak1 and Jak3 kinases, phosphorylation of the Stat6 transcription factor, and activation of the insulin receptor substrate (IRS)-2 and Dok2-signaling intermediates. IL-13 initially binds to IL-13R1 with intermediate affinity, and then heterodimerizes with IL-4R. The IL-13IL-13R1IL-4R complex activates the Tyk2, Jak2, and Jak1 kinases and Stat6. | SIGNOR-249532 |
P53805 | P27361 | 0 | phosphorylation | up-regulates activity | 0.38 | Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively |Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin. | SIGNOR-249478 |
Q99558 | Q96JP5 | 0 | ubiquitination | up-regulates | 0.5 | Zfp91 interacts with and promotes the lys(63)-linked ubiquitination of nik and subsequent processing of p100 to p52. | SIGNOR-167331 |
P28482 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.621 | P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3).Mapk activity is tightly regulated by phosphorylation and dephosphorylation. The activation of the mapk activity requires the dual phosphorylation of the ser/thr and tyr residues in the txy kinase activation motif (1113), and deactivation occurs through the action of either ser/thr protein phosphatase | SIGNOR-103159 |
P48729 | P01106 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.282 | Together, our findings provide evidence for CK1α-mediated destruction of c-Myc and identify c-Myc S252 as a crucial CK1α phosphorylation site for c-Myc degradation. | SIGNOR-276387 |
Q9NZW4 | Q9Y222 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In addition, our in vitro analyses showed that DMP1 and its 57-kDa C-terminal fragment significantly up-regulated the Dspp promoter activities in a mesenchymal cell line. | SIGNOR-271685 |
Q16539 | P15923 | 1 | phosphorylation | up-regulates activity | 0.48 | Here we show that p38 mapk, whose activity is essential for myogenesis, regulates myod/e47 heterodimerization. Phosphorylation of e47 at ser140 by p38 induces myod/e47 association and activation of muscle-specific transcription | SIGNOR-134194 |
Q96ST3 | P07288 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Chromatin immunoprecipitation (ChIP) and DNA affinity precipitation analysis demonstrated that Ebp1 and Sin3A associate at the PSA and E2F1 promoters. Functionally, Sin3A enhanced the ability of Ebp1 to repress transcription of androgen receptor (AR) and E2F1 regulated genes. | SIGNOR-253663 |
P53350 | Q6IBW4 | 1 | phosphorylation | up-regulates activity | 0.444 | Plk1 phosphorylation of CAP-H2 at Ser288 is required for the accumulation of CAP-H2 and accurate chromosomal condensation during prophase. | SIGNOR-278419 |
Q9UBE8 | Q9NQB0 | 1 | phosphorylation | down-regulates quantity | 0.772 | NLK Augments the Ubiquitylation Activity of NARF against TCF/LEF. ctivation of NLK induced by unknown ligands leads to the phosphorylation of TCF/LEF. NARF then acts on TCF/LEF as an E3 ubiquitin-ligase and, together with E1 and E2 ubiquitylation enzymes, catalyze the ubiquitylation of TCF/LEF. Finally, ubiquitylated TCF/LEF is degraded by the 26 S proteasome. | SIGNOR-271597 |
P23771 | P24941 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.362 | Phosphorylation of GATA3 Thr-156 was detected in mouse thymocytes, and cyclin-dependent kinase 2 (CDK2) was identified as a respondent for phosphorylation at Thr-156. | SIGNOR-276634 |
P49715 | Q05655 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We next demonstrated by immunoprecipitation that IL-32\u03b2 interacted with PKC\u03b4 and C/EBP\u03b1, thereby mediating C/EBP\u03b1 Ser-21 phosphorylation by PKC\u03b4. | SIGNOR-279427 |
Q9UBW7 | P53350 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.376 | PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis|Similar analyses with ZNF198 identified two clusters of putative Plk1 phosphorylation sites in vitro. A cluster of serine residues at the N-terminus of ZNF198, S303, S305, and S309, and a cluster at the C-terminus, S1056 and S1064. The triple Ser to Ala mutant, S303A/S305A/S309A, consistently exhibited the lowest level of phosphorylation in vitro, in comparison to the double S1056A/S1064A mutant | SIGNOR-275560 |
P42345 | P55895 | 0 | relocalization | up-regulates | 0.267 | Rag gtpases, together with a multi-protein complex called ragulator, mediate amino acid-mediated mtor recruitment to the lysosome surface where mtor becomes activated. | SIGNOR-198245 |
P01106 | P24385 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.496 | C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation | SIGNOR-102731 |
P23458 | Q9NZJ5 | 1 | phosphorylation | up-regulates activity | 0.2 | JAK1 interacts with and phosphorylates PERK. PERK-dependent activation of JAK1 and STAT3 contributes to endoplasmic reticulum stress-induced inflammation. Similarly, PERK is associated with and phosphorylated by JAK1 at Y585 and Y619 (and possibly other JAKs) during ER stress, resulting in PERK- and JAK1-dependent activation of STAT3. | SIGNOR-276677 |
Q13105 | Q7Z6Z7 | 0 | 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 |
O95297 | P12931 | 0 | phosphorylation | up-regulates | 0.468 | Indeed, our studies indicated that cross-linking of pzr by cona lead to activation of c-src, which may be responsible for phosphorylation of pzr and possibly other proteins. Phosphorylation of pzr in turn recruits shp-2, which by itself is an essential signal transducertyrosine residues 241 and 263 embedded in the itims are responsible for the tyrosine phosphorylation of pzr | SIGNOR-113410 |
Q9UMS4 | P15927 | 1 | polyubiquitination | up-regulates activity | 0.48 | PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). PRP19 ubiquitylates RPA and promotes ATRIP recruitment. | SIGNOR-272075 |
O15021 | Q12778 | 1 | phosphorylation | down-regulates activity | 0.334 | MAST4 phosphorylation of FOXO1 regulates RTKN2 expression. | SIGNOR-279079 |
Q6U7Q0 | Q9H9S0 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays revealed that Zfp322a binds to Pou5f1 and Nanog promoters and regulates their transcription. | SIGNOR-264899 |
P01106 | P26599 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.438 | We also demonstrate that the oncogenic transcription factor c-Myc upregulates transcription of PTB, hnRNPA1 and hnRNPA2, | SIGNOR-268689 |
P46060 | P68400 | 0 | phosphorylation | up-regulates | 0.31 | Phosphorylation of rangap1 stabilizes its interaction with ran and ranbp1. Serine-358 (358s) was identified as the major phosphorylation site. Experiments using purified recombinant kinase and specific inhibitors such as drb and apigenin strongly suggest that casein kinase ii (ck2) is the responsible kinase | SIGNOR-143948 |
Q12913 | O60674 | 1 | dephosphorylation | down-regulates activity | 0.323 | These results support PTPRJ preferentially dephosphorylating Y813 and Y868 in JAK2.|We revealed that PTPRJ negatively regulates leptin signaling by dephosphorylating specific tyrosine residues (Y813 and Y868) in JAK2, the simultaneous phosphorylation of which plays a pivotal role in JAK2 activation. | SIGNOR-277094 |
Q92547 | Q8IYD8 | 0 | relocalization | up-regulates | 0.418 | The enzymatic activity of fan cm is then required to remodel and stabilize the fork to allow topbp1 access to activate atr , in a 9-1-1-independent manner. | SIGNOR-164765 |
P23470 | P43403 | 1 | dephosphorylation | up-regulates activity | 0.26 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254733 |
Q13315 | O43683 | 1 | phosphorylation | up-regulates | 0.461 | We also demonstrate that mitotically activated atm phosphorylates bub1, a critical kinetochore protein, on ser314. Atm-mediated bub1 ser314 phosphorylation is required for bub1 activity and is essential for the activation of the spindle checkpoint | SIGNOR-177276 |
P31431 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.528 | The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant. | SIGNOR-116265 |
P12931 | Q92558 | 1 | phosphorylation | up-regulates | 0.407 | The wave/scar proteins regulate actin polymerisation at the leading edge of motile cells via activation of the arp2/3 complex in response to extracellular cues.Src-dependent phosphorylation of scar1 promotes its association with the arp2/3 complex | SIGNOR-142724 |
Q9NQC7 | Q96LD4 | 0 | ubiquitination | down-regulates quantity | 0.2 | CYLD is progressively degraded upon interaction with the E3 ligase TRIM47 in proportion to NASH severity | SIGNOR-266443 |
Q9UKV5 | P04114 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.29 | In physiological condition, the unnecessary apoB is usually ubiquitinated by E3 ligase AMFR, and subsequently degraded by ubiquitination proteasomes. | SIGNOR-278685 |
Q9UHB6 | P28482 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Mechanistic study revealed that EGF could activate the phosphorylation, ubiquitination, and degradation of EPLIN through an extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent signaling cascade. Pharmacological inhibition of the ERK1/2 pathway effectively antagonized EGF-induced EPLIN degradation. Two serine residues, i.e. serine 362 and serine 604, were identified as putative ERK1/2 phosphorylation sites in human EPLIN, whose point mutation rendered resistance to EGF-induced protein turnover. | SIGNOR-263054 |
P17612 | P17600 | 1 | phosphorylation | down-regulates activity | 0.338 | Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I | SIGNOR-250058 |
Q8WZ73 | Q6MZQ0 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.261 | RFFL is an E3 ligase for PRR5L. | SIGNOR-271495 |
P63000 | Q14185 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.735 | We found in this study that AUTS2 is involved in Rac1 activation via P-Rex1 and the Elmo2/Dock180 complex, but not STEF or Tiam1, for the lamellipodia formation in N1E-115 cells. However, the enhancement of neurite elongation in primary neurons by AUTS2 expression is specifically mediated by the Elmo2/Dock180 complex. These results suggested that several Rac-GEFs differentially or cooperatively participate in Rac1 activation to promote neuronal migration and neurite outgrowth. | SIGNOR-266822 |
Q14457 | P19484 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.409 | As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes; | SIGNOR-276558 |
O95155 | O95997 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | We further demonstrate that Ufd2 directly and efficiently ubiquitylates securin in vitro and is required for securin polyubiquitylation in vivo. This is the first description of a physiologic substrate for Ufd2, establishing this E4 enzyme as an important regulator of chromosome condensation and separation during mitosis in human cells. | SIGNOR-271523 |
P24941 | Q92698 | 1 | phosphorylation | down-regulates activity | 0.347 | Effect of CDK2 phosphorylation on the RAD54 activities. We find that the RAD54 N-terminal domain (NTD) is responsible for initiation of BM through two coupled, but distinct steps; specific binding to Holliday junctions and RAD54 oligomerization. Furthermore, we find that the RAD54 oligomeric state can be controlled by NTD phosphorylation at S49, a CDK2 consensus site, which inhibits RAD54 oligomerization and, consequently, BM. | SIGNOR-273599 |
P20823 | Q9NPD5 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.251 | Farnesoid X receptor, hepatocyte nuclear factors 1alpha and 3beta are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene.|This study demonstrated that the transcription of the LST-2 gene is regulated by three transcription factors, FXR, HNF1alpha, and HNF3beta. | SIGNOR-268988 |
P49137 | P15923 | 1 | phosphorylation | up-regulates | 0.52 | Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2 | SIGNOR-166643 |
Q6NUN9 | O60260 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | . Parkin ubiquitinates and regulates the ubiquitin proteasomal degradation of PARIS | SIGNOR-272758 |
Q99523 | O75914 | 0 | phosphorylation | down-regulates activity | 0.2 | PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction. | SIGNOR-273719 |
P60484 | O00308 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.632 | We have shown that WWP2 interacts with and ubiquitylates PTEN, promoting its degradation. | SIGNOR-278650 |
P30305 | P68400 | 0 | phosphorylation | up-regulates activity | 0.338 | Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. | Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo. | SIGNOR-250836 |
Q13153 | P51114 | 1 | phosphorylation | up-regulates activity | 0.271 | Identification of Ser420 in FXR1 as a PAK1 Kinase Target. During zebrafish muscle development, FXR1 Ser420 phosphorylation is needed for protein function. | SIGNOR-273713 |
P27361 | Q9NQ66 | 1 | phosphorylation | up-regulates activity | 0.412 | Plc beta1 could be efficiently phosphorylated by activated mitogen-activated protein kinase but not by pka. The erk phosphorylation site was mapped to serine 982 | SIGNOR-106565 |
O14672 | Q15717 | 0 | post transcriptional regulation | up-regulates quantity | 0.2 | Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure | SIGNOR-266862 |
P05412 | Q00526 | 0 | phosphorylation | up-regulates | 0.443 | Egf-induced cdk3 activation caused c-jun phosphorylation at ser63 and ser73, resulting in increased ap-1 transactivation. | SIGNOR-183013 |
P06213 | Q8TCQ1 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH1 ubiquitinates INSR to decrease cell surface INSR levels, but unlike other INSR ubiquitin ligases, MARCH1 acts in the basal state rather than after insulin stimulation. | SIGNOR-278819 |
Q96RR4 | P54646 | 1 | phosphorylation | up-regulates | 0.619 | These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo. | SIGNOR-138364 |
P49841 | P54252 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.465 | Phosphorylation of ataxin-3 by glycogen synthase kinase 3beta at serine 256 regulates the aggregation of ataxin-3| | SIGNOR-264821 |
P55210 | P12931 | 0 | phosphorylation | up-regulates activity | 0.395 | Src enhances caspase-7 activity in vitro and in cells.|When all four sites were mutated to phenylalanine, the in vitro kinase assay results showed that phosphorylation of the Mut-caspase-7 protein by Src decreased dramatically compared with Wt-caspase-7, suggesting that these four sites, Tyr58, Tyr151, Tyr229 and Tyr230, are the most important sites of caspase-7 to be phosphorylated by Src (XREF_FIG). | SIGNOR-278455 |
P42566 | Q16539 | 0 | phosphorylation | up-regulates | 0.345 | Tnf-_ induces phosphorylation of eps15 at ser-796eps15 is a substrate for p38_these results suggest an attractive model in which p38 phosphorylates both eps15 and egfr to trigger efficient endocytosis | SIGNOR-203315 |
Q9H0Z9 | P49841 | 0 | phosphorylation | down-regulates | 0.2 | Here, we showed that rnpc1 is phosphorylated at ser195 by glycogen synthase kinase 3 (gsk3). We also provided evidence that ser195 phosphorylation converts rnpc1 from a repressor to an activator of p53. | SIGNOR-203011 |
Q9NZJ5 | Q15084 | 0 | null | down-regulates activity | 0.2 | Protein disulfide isomerase A6 (PDIA6) interacts with protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol requiring enzyme (IRE)-1 and inhibits their unfolded protein response signaling. | SIGNOR-256537 |
Q99986 | O75531 | 1 | phosphorylation | down-regulates | 0.877 | We demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. Coexpression of vrk1 and gfp-baf greatly diminishes the association of baf with the nuclear chromatin/matrix and leads to its dispersal throughout the cell | SIGNOR-144783 |
Q14498 | Q66K64 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.377 | Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation. | SIGNOR-272203 |
Q9NRC8 | Q96LA8 | 0 | methylation | down-regulates activity | 0.259 | Protein arginine methyltransferase 6 (PRMT6) directly interacts with and methylates SIRT7 at R388 in vitro and in vivo R388 methylation suppresses the H3K18 deacetylase activity of SIRT7 without modulating its subcellular localization. | SIGNOR-275888 |
Q8N6F7 | P43405 | 0 | phosphorylation | up-regulates activity | 0.356 | Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. Y148 (in black) was already phosphorylated before the addition of kinases. We demonstrate that Grb2 facilitates HGAL and Syk binding following BCR stimulation but does not affect the HGAL-mediated increase in Syk kinase activity. Previous studies showed that Grb2 inhibits BCR signaling by decreasing the activation of Syk by Lyn.11 Thus, while HGAL and Grb2 oppositely affect Syk kinase activity, this is not due to direct Grb2 effects on HGAL-mediated Syk kinase activation. | SIGNOR-273570 |
Q06413 | P68400 | 0 | phosphorylation | up-regulates activity | 0.333 | We show that serine 59 located between the MADS and MEF2 domains of MEF2C is phosphorylated in vivo and can be phosphorylated in vitro by casein kinase-II (CKII). Phosphorylation of this site enhanced the DNA binding and transcriptional activity of MEF2C by increasing its DNA binding activity 5-fold. | SIGNOR-250914 |
Q00978 | Q92793 | 0 | acetylation | up-regulates activity | 0.361 | CBP was also the most effective one among the acetyltransferases tested for catalyzing IRF9 acetylation in 293T cells. [²] Figure 5 (F) K81 acetylation is required for IRF9 dimerization between the N-terminal 1-118 and the C-terminal 340-393 regions. In the left panel, Myc-DBD (1- 118) of IRF9 was cotransfected with 118-393, 118-339, or 1-393 (FL) of IRF9 in 293T cells. Anti-IRF9 (C-terminal region) precipitates were analyzed with anti-Myc or anti-IRF9. Anti-IRF9 precipitates, prepared from 293T cells cotransfected with the C-terminal fragment 118-393 of IRF9 and Myctagged DBD of different forms, were analyzed with anti-Myc or anti-IRF9 (right panel). | SIGNOR-217787 |
P08151 | P28482 | 0 | phosphorylation | up-regulates activity | 0.323 | We conclude that multisite phosphorylation of GLI1 by ERK2 or other MAP kinases weakens GLI1-SUFU binding, thereby facilitating GLI1 activation and contributing to both physiological and pathological crosstalk. | SIGNOR-277601 |
P68400 | Q99250 | 1 | phosphorylation | up-regulates activity | 0.2 | We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. | SIGNOR-275761 |
Q9UNE7 | Q99828 | 1 | ubiquitination | down-regulates quantity | 0.2 | All those were suggesting that CHIP promotes CIB1 ubiquitination via the Lys 48 residue of ubiquitin.|K10 and K65 were the Lysine (K) residues for CHIP mediated CIB1 degradation. | SIGNOR-278721 |
O00429 | Q14012 | 0 | phosphorylation | up-regulates activity | 0.333 | For example, protein kinase A (PKA) phosphorylation of Drp1S600 has been reported to decrease Drp1 GTPase activity in vitro (23, 24), whereas phosphorylation of the same conserved serine residue by Ca2+-calmodulin–dependent protein kinase Iα (CaMKIα) in Drp1 isoform 3 has been reported to cause a significant increase in mitochondrial fission | SIGNOR-262552 |
P48431 | Q99986 | 0 | phosphorylation | up-regulates activity | 0.468 | VRK1, but not kinase-dead VRK1 (K179E), phosphorylated Sox2 (XREF_FIG). | SIGNOR-279578 |
P31751 | P98177 | 1 | phosphorylation | down-regulates activity | 0.606 | FOXO4 transcription factor, also referred to AFX, contains three putative phosphorylation motif sites for protein kinase B (PKB), Thr32, Ser197, and Ser262, and it is proposed that phosphorylated FOXO4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression.[...]These results indicate that phosphorylation at Thr32 and Ser197 is indispensable, whereas that at Ser262 is not critical, for regulation of the nuclear localization and transcriptional activity of FOXO4 | SIGNOR-248055 |
Q15118 | Q16513 | 1 | phosphorylation | up-regulates activity | 0.338 | PDK1 phosphorylates the PRKs at their conserved activation loop threonines (Thr-774 and Thr-816 for PRK1 and PRK2, respectively) both in vitro and in vivo. | SIGNOR-250265 |
P35573 | Q6VVB1 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.56 | The E3 ubiquitin ligase Malin interacts with and promotes the ubiquitination of AGL. | SIGNOR-271669 |
Q05086 | Q6IAA8 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator. Ube3a ubiquinates p18, resulting in its proteasomal degradation, and Ube3a deficiency in the hippocampus of AS mice induces increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity | SIGNOR-256145 |
P46108 | P08069 | 0 | phosphorylation | down-regulates activity | 0.722 | On activation of the IGF-I receptor, Crk-II binds to phosphorylated tyrosine residues, especially in the juxtamembrane region. As a result of this binding, the IGF-I receptor kinase phosphorylates Tyr-221 of Crk-II, resulting in a change in intramolecular folding and binding of the SH2 domain to the phosphorylated Tyr-221, which causes rapid disassociation of the Crk-II-IGF-I receptor complex. | SIGNOR-251273 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.