IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q92831 | P04150 | 0 | relocalization | up-regulates activity | 0.549 | NR3C1 impaired GLI1 function by dynamically modulating the recruitment of PCAF acetyltransferase | SIGNOR-269233 |
P78527 | Q9H4A6 | 1 | phosphorylation | up-regulates activity | 0.318 | In response to DNA damage, DNA-PK phosphorylates GOLPH3, resulting in increased interaction with MYO18A, which applies a tensile force to the Golgi. Interference with the Golgi DNA damage response by depletion of DNA-PK, GOLPH3, or MYO18A reduces survival after DNA damage, whereas overexpression of GOLPH3, as is observed frequently in human cancers, confers resistance to killing by DNA-damaging agents | SIGNOR-253558 |
P01106 | Q13177 | 0 | phosphorylation | down-regulates activity | 0.649 | Here we demonstrate that Pak2 phosphorylates Myc at three sites (T358, S373, and T400) and affects Myc functions both in vitro and in vivo. | SIGNOR-278489 |
Q8WU20 | P06213 | 0 | phosphorylation | up-regulates activity | 0.371 | We found that insulin receptor can directly phosphorylate FRS2. | SIGNOR-278945 |
O00635 | Q9Y4K3 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.43 | As an E3 ligase, TRIM38 bound to TRAF6 and promoted K48-linked polyubiquitination, which led to the proteasomal degradation of TRAF6. | SIGNOR-272009 |
P78347 | P27361 | 0 | phosphorylation | up-regulates | 0.374 | Tfii-i can be phosphorylated in vitro by erk and mutation of consensus map kinase substrate sites at serines 627 and 633 impairs the phosphorylation of tfii-i by erk and its activity on the c-fos promoter. These results suggest that erk regulates the activity of tfii-i by direct phosphorylation. | SIGNOR-74308 |
P24941 | Q8WYH8 | 1 | phosphorylation | up-regulates quantity | 0.401 | We report that ING5 is phosphorylated in a cell cycle dependent manner by CDK2 at T152 (Figs 1 and 3). | SIGNOR-279447 |
P17752 | P17612 | 0 | phosphorylation | up-regulates activity | 0.35 | The activation of tryptophan hydroxylase by protein kinase A is mediated by the phosphorylation of serine-58 within the regulatory domain of the enzyme. | SIGNOR-250062 |
P54756 | Q04760 | 1 | phosphorylation | up-regulates activity | 0.2 | We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D). | SIGNOR-276183 |
P49790 | Q92973 | 0 | relocalization | up-regulates activity | 0.499 | TNPO1 only mediates the nuclear import of a subset of proteins.|Among TNPO1 cargos, the most extensively characterized is the RNA binding protein heterogeneous nuclear ribonucleoprotein 1 (hnRNPA1) (27), which functions in several processes including mRNA biogenesis and promotion of transcription factor activity (28–30). NPC protein NUP153 is also a target for TNPO1-mediated nuclear import | SIGNOR-262100 |
P17252 | Q01844 | 1 | phosphorylation | down-regulates activity | 0.331 | Here we report thatews, a nuclearrna-bindingprooncoprotein, contains an iq domain, is phosphorylated byproteinkinase c, and interacts with calmodulin. Interestingly, pkc phosphorylation of ews inhibits its binding to rna homopolymers, and conversely,rna binding to ews interferes with pkc phosphorylation./ these data indicate that ews contains an iq domain with ser266 acting as the primary site for pkc phosphorylation. | SIGNOR-52850 |
Q99704 | P06213 | 0 | phosphorylation | up-regulates activity | 0.562 | Insulin receptor-mediated p62dok tyrosine phosphorylation at residues 362 and 398. p62(dok) is a direct substrate for the IR tyrosine kinase and that phosphorylation at Tyr(362) and Tyr(398) plays an essential role for p62(dok) to interact with its effectors and negatively regulate the insulin signaling pathway. | SIGNOR-251307 |
P31947 | P53779 | 0 | phosphorylation | down-regulates | 0.2 | Here we demonstrate that activated jnk promotes bax translocation to mitochondria through phosphorylation of 14-3-3, a cytoplasmic anchor of bax. Phosphorylation of 14-3-3 led to dissociation of bax from this protein.Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-191 | SIGNOR-124005 |
Q9NRM7 | P46937 | 1 | phosphorylation | down-regulates | 0.821 | Lats1/2 inhibit yap by direct phosphorylation at s127, which results in yap binding to 14-3-3 and cytoplasmic sequestration | SIGNOR-198514 |
Q15797 | Q9P2J9 | 0 | dephosphorylation | down-regulates | 0.243 | We show that the mammalian pdps are important in dephosphorylation of bmp-activated smad1 but not tgf-beta-activated smad2 or smad3. Thus, pdps specifically inactivate smads in the bmp/dpp pathway. [...] These observations suggest that pdp1 and pdp2 are important for dephosphorylation of smad1. | SIGNOR-144909 |
O95863 | Q9UNE7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.289 | These results indicate that CHIP can ubiquitylate and degrade Snail in a GSK\u20103\u03b2\u2010independent manner.|These results suggest that CHIP negatively regulates the stability of Snail through inducing its proteasomal degradation. | SIGNOR-278545 |
P49137 | P42574 | 1 | phosphorylation | up-regulates activity | 0.311 | MK2 Phosphorylates Caspase-3, Facilitates Nuclear Translocation of Caspase 3, and Regulates Apoptosis.|Over-expression of MK2 led to an increase in nuclear caspase-3 activity. | SIGNOR-278960 |
Q9UNE7 | P04626 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.627 | The ErbB2 kinase domain is required for GA-induced and CHIP-dependent ErbB2 ubiquitination and degradation . | SIGNOR-278645 |
Q7L7X3 | Q13188 | 1 | phosphorylation | up-regulates | 0.298 | In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2. | SIGNOR-201321 |
Q05655 | P31946 | 1 | phosphorylation | down-regulates | 0.493 | We provide a mechanism for these observations through the phosphorylation of 14-3-3 by ikk and pkc on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm. | SIGNOR-138612 |
P17252 | Q9UQ13 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PKCalpha/delta phosphorylate Sur8 at Thr-71 and Ser-297, respectively. This phosphorylation is essential for polyubiquitin-dependent degradation of Sur8. | SIGNOR-275568 |
P68400 | P55957 | 1 | phosphorylation | up-regulates activity | 0.286 | Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. | These results suggest that residues S61, S64, and to a much lesser extent T58 are sites of phosphorylation of Bid. | SIGNOR-250831 |
P07355 | P12931 | 0 | phosphorylation | up-regulates | 0.547 | Translocation requires the presence of the annexin 2 binding partner p11 (s100a10) and the phosphorylation of annexin 2 at tyr23 through a src-like tyrosine kinase-dependent mechanism both in vitro and in vivo. | SIGNOR-127872 |
Q02156 | P29474 | 1 | phosphorylation | down-regulates activity | 0.331 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251632 |
Q03468 | P00519 | 0 | phosphorylation | up-regulates activity | 0.271 | N-terminal region of CSB interacts with the SH3 domain of c-Abl in vitro and in vivo. In addition, c-Abl kinase phosphorylates CSB at Tyr932. our results suggest that c-Abl interacts with and tyrosine phosphorylates CSB. This interaction may play an important role in the response to oxidative stress, resulting in activation of c-Abl, tyrosine phosphorylation of CSB and more efficient BER of oxidative DNA damage. Tyrosine-phosphorylated CSB may serve as a signal for repair proteins to localize to DNA damage and may help maintain active transcription in the nucleolus. | SIGNOR-251933 |
P40424 | P55075 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.271 | Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription | SIGNOR-265803 |
Q9BXM7 | P99999 | 1 | null | down-regulates quantity | 0.382 | There is a strong cyto-protective role of PINK1 in maintaining mitochondrial homeostasis via different mechanisms. Overexpression of wild-type PINK1 in SH-SY5Y neuroblastoma cells stabilizes respiring mitochondrial networks through various mechanisms that include maintaining mitochondrial membrane potential, reducing basal and neurotoxin-induced ROS, suppression of cytochrome c release, reversal of toxin-induced fission, and suppression of autophagy | SIGNOR-249704 |
P17302 | P12931 | 0 | phosphorylation | down-regulates | 0.588 | The oncogenic tyrosine kinase, v-src, phosphorylates connexin43 (cx43) on y247 and y265 and inhibits cx43 gap junctional communication (gjc), the process of intercellular exchange of ions and metabolites. | SIGNOR-148913 |
O15194 | Q15796 | 1 | dephosphorylation | down-regulates activity | 0.498 | Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity | SIGNOR-248310 |
P00390 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.405 | NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy | SIGNOR-279871 |
P42345 | Q9Y4K3 | 0 | ubiquitination | up-regulates activity | 0.438 | Together, these results demonstrate that mTOR polyubiquitination by TRAF6 modulates its activation in response to amino acids and point to a role for K63 ubiquitin modification as a sensor of nutrient status. | SIGNOR-278789 |
Q92686 | P05129 | 0 | phosphorylation | up-regulates activity | 0.429 | Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM. | SIGNOR-248915 |
Q53EL6 | Q9UBS0 | 0 | phosphorylation | down-regulates | 0.438 | Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation. | SIGNOR-160992 |
O60674 | P04626 | 1 | phosphorylation | up-regulates activity | 0.623 | Our results indicate that autocrine secretion of PRL stimulates tyrosine phosphorylation of ErbB-2 by Jak2, provides docking sites for Grb2 and stimulates Ras-MAP kinase cascade, thereby causing unrestricted cellular proliferation. | SIGNOR-279197 |
Q16777 | 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-265398 |
P06493 | P27816 | 1 | phosphorylation | down-regulates activity | 0.497 | We have shown that MAP4 is phosphorylated in vivo in mitotic HeLa cells at eight sites. Five of these were phosphorylated by p34cdc2 kinase. Two of the five p34cdc2 kinase phosphorylation sites were shown to be Ser696 and Ser787 in the proline-rich region. Mutation of Ser787 to Glu strikingly reduced the MAP4's MT-polymerization activity, while Glu-mutation at Ser696 did not. These results suggest that Ser787 could be the critical phosphorylation site causing MTs to be dynamic at mitosis. | SIGNOR-277459 |
P49840 | Q14449 | 1 | phosphorylation | down-regulates activity | 0.264 | Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor| In vitro kinase assay using the motif-derived peptides showed that the serine residues located in N-terminal (Ser358, Ser362 and Ser366) and C-terminal (Ser419 and Ser423) regions of the BPS domain were phosphorylated by GSK-3. | SIGNOR-264871 |
P24941 | P15172 | 1 | phosphorylation | down-regulates | 0.522 | Cyclin e/cdk2 can phosphorylate myod at serine 200, which causes ubiquitination and degradation of this transcription factor during g1, preventing its accumulation and a commitment to differentiation. | SIGNOR-176509 |
P60520 | Q9Y4P1 | 0 | cleavage | up-regulates activity | 0.844 | In mammals, at least three atg8 homologs, lc3, gabarap, and gate-16, have been identified (fig. 1a), all of which have structural ubiquitin folds (1416). In vivo and in vitro biochemical analyses have shown that human atg4b is an authentic cysteine protease essential for cleavage of the c terminus of each atg8 homolog to expose the c-terminal gly | SIGNOR-141932 |
P41440 | P17676 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Collectively, these results identify transcriptionally important regions in the hRFC-C minimal promoter that include a GC-box and CCAAT-box, and suggest that cooperative interactions between Sp1 and C/EBP beta are essential for hRFC-C transactivation. | SIGNOR-254053 |
P18031 | P42229 | 1 | dephosphorylation | down-regulates activity | 0.676 | A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b | SIGNOR-248428 |
Q16539 | P08151 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.27 | Here, we show that SHH inactivates p38α (MAPK14) in a smoothened-dependent manner, conversely, p38α directly phosphorylates GLI1 on Ser937/Ser941 (human/mouse) to induce GLI1's proteasomal degradation and negates the transcription of SHH signaling. | SIGNOR-277916 |
Q13291 | Q86YJ5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271537 |
Q15465 | P35398 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.251 | RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice. | SIGNOR-266846 |
O75582 | P28482 | 0 | phosphorylation | up-regulates | 0.617 | Together, our in vivo and in vitro studies indicate that the pkc/c-raf/mek/erk pathway plays a major role in the s6k1 activation in hypertrophic cardiac growth. | SIGNOR-131311 |
P62993 | Q92529 | 0 | relocalization | up-regulates | 0.819 | In addition to direct binding of grb2 to phosphotyrosine residues of receptor kinases, grb2 can also be recruited to the receptor by binding to shc when shc is tyrosine phosphorylated as a result of receptor stimulation. | SIGNOR-146897 |
Q86YJ5 | P31994 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271541 |
O00755 | P03956 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.261 | Because MMP1 is also another direct target of the canonical Wnt pathway (22), Wnt7a overexpression upregulated MMP1/10 to degrade the extracellular matrix and to facilitate UBC cell invasion. | SIGNOR-278868 |
P23528 | P60484 | 0 | dephosphorylation | up-regulates activity | 0.441 | Unexpectedly, cofilin-1 activation by PGE 2 was mediated by the protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10), with which it directly associated.|Unexpectedly, cofilin-1 dephosphorylation and activation in our model was mediated by the protein phosphatase activity of PTEN. | SIGNOR-276980 |
O43187 | Q07955 | 1 | phosphorylation | down-regulates activity | 0.348 | IRAK2 phosphorylates SRSF1 and thereby reduces SRSF1 binding to the target mRNAs. | SIGNOR-278406 |
P08047 | P07288 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We characterized four Sp1/Sp3 binding sites in the proximal promoter of the PSA gene. In a luciferase assay, these sites contributed to the basal promoter activity in prostate cancer cells. In an electrophoretic mobility shift assay and chromatin immunoprecipitation assay, we confirmed that Sp1 and Sp3 bind to these sites. Overexpression of wild-type Sp1 and Sp3 further upregulated the promoter activity, whereas overexpression of the Sp1 dominant-negative form or addition of mithramycin A significantly reduced the promoter activity and the endogenous mRNA level of PSA. | SIGNOR-253664 |
O95271 | P53350 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.427 | Here, we report that Plk1 forms a complex with TNKS1 in vitro and in vivo, and phosphorylates TNKS1. Phosphorylation of TNKS1 by Plk1 appears to increase TNKS1 stability and telomeric poly(ADP-ribose) polymerase (PARP) activity. By contrast, targeted inhibition of Plk1 or mutation of phosphorylation sites decreased the stability and PARP activity of TNKS1, leading to distort mitotic spindle-pole assembly and telomeric ends. | SIGNOR-276245 |
Q13485 | Q9UKB1 | 0 | ubiquitination | up-regulates | 0.2 | We have identified scf(beta-trcp1), a ubiquitin (e3) ligase, as a critical determinant for the protein degradation of smad4 protein. | SIGNOR-123060 |
O43255 | Q9Y6H5 | 1 | ubiquitination | down-regulates | 0.62 | Siah proteins ubiquitylate synphilin-1 and promote its degradation through the ubiquitin proteasome system | SIGNOR-140651 |
O60346 | P04049 | 1 | dephosphorylation | down-regulates activity | 0.272 | PHLPP1 and PHLPP2 dephosphorylate RAF1 to reduce its signaling, increase the invasive and migratory activities of CRC cells, and activate the epithelial-mesenchymal transition. In Apc(Min) mice, loss of PHLPP1 promotes tumor progression. | SIGNOR-237449 |
P06493 | P78344 | 1 | phosphorylation | up-regulates activity | 0.339 | To test whether CDK1 phosphorylates T508, Flag-DAP5 was purified from dox-induced HEK293 cells and incubated with active recombinant JNK2 or CDK1 in the presence of ATP (Fig. 3G). DAP5(T508) was phosphorylated only upon incubation with CDK1 (Fig. 3G). | SIGNOR-266387 |
Q05397 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.346 | The focal adhesion kinase (FAK) is a key regulator of cell migration. Phosphorylation at Tyr-397 activates FAK |The dephosphorylation at Tyr-397 in FAK triggered by wild-type alpha-actinin and PTP 1B caused a significant increase in cell migration. | SIGNOR-248431 |
P10070 | O43791 | 0 | ubiquitination | down-regulates quantity | 0.71 | RNAi knockdown of Spop (a substrate-binding adaptor for the cullin3-based ubiquitin E3 ligase) in Sufu mutant mouse embryonic fibroblasts (MEFs) can restore the levels of Gli2 and Gli3 full-length proteins | SIGNOR-268860 |
P48775 | P43694 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.252 | GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes. | SIGNOR-268994 |
Q13485 | O75925 | 0 | sumoylation | up-regulates | 0.394 | These data demonstrate that pias1 protein positively modulates tgf-beta responses as a sumo e3 ligase for smad4 | SIGNOR-123462 |
P06213 | P53004 | 1 | phosphorylation | up-regulates activity | 0.479 | Human BVR (hBVR) also reduces the hemeoxygenase activity product biliverdin to bilirubin and is directly activated by insulin receptor kinase (IRK).|in addition to Y198 in the YMKM motif, 2 other tyrosines, Y228 in the YLSF motif and Y291 in the C-terminus of the protein, are directly phosphorylated by IRK | SIGNOR-275514 |
P55089 | P10275 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | When cells were treated with DHT alone, AR was upregulated and translocated into the nuclei, which might repress UCN1 expression via a potential androgen-responsive element found in human CRF family promoter|These data suggest that DHT differentially influences UCN1 levels under normal and inflammatory conditions in human umbilical vein endothelial cells, which involves AR-dependent and -independent mechanisms respectively. | SIGNOR-253688 |
P31751 | Q9Y4I1 | 1 | phosphorylation | up-regulates activity | 0.458 | Here we identify an Akt consensus phosphorylation motif in the actin-based motor protein myosin 5a and show that insulin stimulation leads to phosphorylation of myosin 5a at serine 1650. This Akt-mediated phosphorylation event enhances the ability of myosin 5a to interact with the actin cytoskeleton.Taken together, these data indicate that myosin 5a is a newly identified direct substrate of Akt2 and, upon insulin stimulation, phosphorylated myosin 5a facilitates anterograde movement of GLUT4 vesicles along actin to the cell surface. | SIGNOR-262632 |
Q13285 | P49675 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.472 | The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes. | SIGNOR-271788 |
P05114 | O75582 | 0 | phosphorylation | down-regulates activity | 0.62 | HMGN1 (formerly known as HMG-14) phosphorylation at Ser6 occurs concomitantly with IE gene expression. | MSK2 seems to be the most important kinase responsible for this modification |Accordingly, it was suggested that HMGN1 phosphorylation reduces binding of the protein to the nucleosomes | SIGNOR-262988 |
O94761 | P06493 | 0 | phosphorylation | up-regulates activity | 0.355 | During S/G2 phases, CDK1 and CDK2 (CDK1/2) phosphorylate RECQL4 on serines 89 and 251, enhancing MRE11/RECQL4 interaction and RECQL4 recruitment to DSBs. | SIGNOR-277375 |
P24941 | P08047 | 1 | phosphorylation | up-regulates activity | 0.423 | Mutation of Sp1 Ser59 abrogates the cyclin ACDK augmentation of Sp1-dependent transcriptional transactivation | SIGNOR-248232 |
P17252 | Q8WZ42 | 1 | phosphorylation | up-regulates activity | 0.271 | In summary, titin is a PKC substrate with PKCalpha phosphorylating predominately the full-length titin molecule.|Mechanical experiments with skinned LV myocardium revealed that PKCalpha significantly increases titin based passive tension, an effect that is reversed by PP1. | SIGNOR-278382 |
P27361 | P16949 | 1 | phosphorylation | down-regulates activity | 0.577 | Stress-induced stathmin phosphorylation is not de- pendent on ERK. Stathmin is also known to be phos- phorylated by ERK on Ser-25 and Ser-38 (17). Thus, it is possible that ERK phosphorylates stathmin in 293 cells|In subsequent reports (28, 29) it was shown that phosphorylation of stathmin blocks its ability to destabilize MTs. | SIGNOR-249483 |
P55036 | Q05086 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.463 | S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. Surprisingly, the same four Lys residues on S5a, Lys-74, Lys-122, Lys-262, and Lys-365 were ubiquitinated by MuRF1 and E6AP (Fig. 10). Two additional Lys residues (Lys-126 and -135) were ubiquitinated by E6AP. | SIGNOR-272746 |
P22736 | P28482 | 0 | phosphorylation | up-regulates activity | 0.669 | NGFI-B is an inducible orphan nuclear receptor that initiates apoptosis. Growth factors such as EGF activate the MAP kinase ERK, whose activity may determine if a cell survives or undergoes apoptosis. EGF stimulation of cells leads to phosphorylation of threonine in NGFI-B. Thr-142 of NGFI-B is comprised in a consensus MAP kinase site and was identified as a preferred substrate for ERK2 (but not ERK1) in vitro. | SIGNOR-249430 |
Q7Z570 | O43451 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3). | SIGNOR-269466 |
P12931 | Q9UKW4 | 1 | phosphorylation | up-regulates | 0.325 | Activation of rac1 and the exchange factor vav3 are involved in npm-alk signaling in anaplastic large cell lymphomas. | SIGNOR-159240 |
Q9P286 | P15923 | 1 | phosphorylation | up-regulates activity | 0.2 | The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the transcription factor E47 is a direct repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). |In this study, we found that PAK5-mediated E47 phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47 and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation | SIGNOR-275653 |
Q9H0M0 | P04637 | 1 | ubiquitination | up-regulates activity | 0.319 | Unlike other E3 ligases, WWP1 increases p53 stability; inhibition of WWP1 expression or expression of a ligase-mutant form results in decreased p53 expression.|WWP1 associates with p53 and induces p53 ubiquitylation. | SIGNOR-278649 |
P49815 | O00141 | 0 | phosphorylation | down-regulates activity | 0.579 | SGK1, which is activated by PDK1, contributes to the maintenance of residual mTORC1 activity through direct phosphorylation and inhibition of TSC2. | SIGNOR-277266 |
P24941 | P54198 | 1 | phosphorylation | up-regulates activity | 0.326 | Hira bound to and was phosphorylated by cyclin a- and e-cdk2 in vitrohira became phosphorylated on threonine 555 in s phase when cyclin-cdk2 kinases are active.ectopic expression of hira in cells caused arrest in s phase and this is consistent with the notion that it is a cyclin-cdk2 substrate that has a role in control of the cell cycle. | SIGNOR-105548 |
P06493 | Q08050 | 1 | phosphorylation | up-regulates | 0.762 | A conserved phosphorylation site within the forkhead domain of foxm1b is required for its activation by cyclin-cdk1further analysis reveals that the leu-641 residue within an lxl motif is required for the recruitment of the cyclin-cdk complex, and the thr-596 residue is a critical cdk1 phosphorylation site within the activation domain of foxm1b. Cdk-dependent phosphorylation stimulates the foxm1b transcriptional activity | SIGNOR-187880 |
P28482 | P17535 | 1 | phosphorylation | up-regulates | 0.529 | Menin binds the jun family transcription factor jund and inhibits its transcriptional activity. The menin-jund interaction blocks jun n-terminal kinase (jnk)-mediated jund phosphorylation and suppresses jund-induced transcription. We found a role for phosphorylation of the ser100 residue of jund;jund phosphorylation were prevented by inhibitors of calcium, calmodulin, or erk1/2 kinase. | SIGNOR-196030 |
P42684 | P17931 | 1 | phosphorylation | up-regulates | 0.2 | The sh (src homology)3 domains of c-abl/arg bind to a p(80)gppsgp motif of gal3, and tyr79 and tyr118 are the major tyrosine phosphorylation sites. A consequence of this interaction and phosphorylation is the significant impairment of chaperone-mediated autophagy of gal3. | SIGNOR-163747 |
P24390 | P17612 | 0 | phosphorylation | up-regulates | 0.309 | We conclude that pka phosphorylation of serine 209 is required for the retrograde transport of the kdel receptor from the golgi complex to the er from which the retrieval of proteins bearing the kdel signal depends. | SIGNOR-118257 |
Q9UQM7 | P17676 | 1 | phosphorylation | up-regulates activity | 0.326 | These studies implicate Ser276 of CIEBPP as the major in vim phosphorylation site for CaMKII. | Phosphorylation of serine at position 276 within the leucine zipper of C/EBP beta appeared to confer calcium-regulated transcriptional stimulation of a promoter that contained binding sites for C/EBP beta. | SIGNOR-250617 |
P06748 | P09467 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | For instance, nucleophosmin (NPM1) and zinc-finger protein X-linked (ZFX) bind to the E-box and ZFX binding site on the FBP1 promoter, respectively, and restrain FBP1 expression to facilitate aerobic glycolysis in PDAC and melanoma | SIGNOR-267594 |
P56192 | Q9P2K8 | 0 | phosphorylation | down-regulates | 0.2 | Here we demonstrate that aimp3 is released from mrs by uv irradiation-induced stress. Dissociation was induced by phosphorylation of mrs at ser662 by general control nonrepressed-2 (gcn2) following uv irradiation. Substitution of ser662 to asp (s662d) induced a conformational change in mrs and significantly reduced its interaction with aimp3. This mutant possessed significantly reduced mrs catalytic activity because of loss of trna(met) binding, resulting in down-regulation of global translation. | SIGNOR-177648 |
Q9BYB0 | P12814 | 1 | relocalization | up-regulates activity | 0.2 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264585 |
P0DP24 | P06213 | 0 | phosphorylation | down-regulates | 0.352 | The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule. | SIGNOR-266320 |
O14746 | Q9UHC7 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.475 | MKRN1 functions as an E3 ubiquitin-ligase for hTERT in vitro and in vivo. Furthermore, we have used the yeast two-hybrid method to identify a novel RING finger gene (MKRN1) encoding an E3 ligase that mediates ubiquitination of hTERT. Overexpression of MKRN1 in telomerase-positive cells promotes the degradation of hTERT and decreases telomerase activity and subsequently telomere length. | SIGNOR-271529 |
P62987 | Q93008 | 0 | cleavage | up-regulates quantity | 0.611 | Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors. | SIGNOR-270825 |
P11309 | P27448 | 1 | phosphorylation | down-regulates | 0.418 | Here we show that the protein kinase cdc25 c-associated kinase 1 (c-tak1) is a binding partner and a substrate of pim-1. | SIGNOR-128264 |
Q13153 | O15344 | 1 | phosphorylation | up-regulates activity | 0.2 | Pak1 phosphorylates the N-terminus of Mid1 to promote its association with cortical nodes.|Pak1 promotes Mid1 localization to cortical nodes. | SIGNOR-279307 |
P19784 | Q9UD71 | 1 | phosphorylation | up-regulates activity | 0.375 | Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. | Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase | SIGNOR-251018 |
Q15154 | O95613 | 1 | relocalization | up-regulates | 0.688 | Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome | SIGNOR-95117 |
O14733 | Q13158 | 1 | phosphorylation | down-regulates activity | 0.497 | The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells | SIGNOR-123164 |
P18031 | P06493 | 0 | phosphorylation | up-regulates activity | 0.502 | Cdk1-cyclin B1 directly phosphorylates PTP1B at serine 386 in a kinase assay. Recombinant Plk1 phosphorylates PTP1B on serine 286 and 393 in vitro, however, it requires a priming phosphorylation by Cdk1 at serine 386 highlighting a novel co-operation between Cdk1 and Plk1 in the regulation of PTP1B.|Finally, phosphorylation on serine 286 enhanced PTP1B phosphatase activity. | SIGNOR-272970 |
Q8IZL8 | P24941 | 0 | phosphorylation | up-regulates | 0.367 | We identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we conclude that pelp1 is a novel substrate of interphase cdks and that its phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression and also for optimal e2f transactivation function. | SIGNOR-167766 |
P60484 | O75365 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.296 | As expected, PRL3 clearly reduced PTEN phosphorylation at the tyrosine residue and PTEN protein in PRL3 overexpressing LO2 and HepG2 cell lines, with no significant changes in PRL3 (C104S) mutant cells.|PRL3 down-regulates PTEN expression, a negative regulator of the Akt pathway.11 Phosphorylation of PTEN at Tyr336 is required for maintenance of PTEN protein stability and prevention of PTEN degradation.17 We therefore speculated that PRL3 might dephosphorylate PTEN at tyrosine sites and consequently reduce the PTEN protein level. | SIGNOR-277010 |
P00519 | O15350 | 1 | phosphorylation | up-regulates | 0.754 | C-abl phosphorylates p73 on a tyrosine residue at position 99 both in vitro and in cells that have been exposed to ionizing radiation. Our results show that c-abl stimulates p73-mediated transactivation and apoptosis. | SIGNOR-68931 |
Q14289 | Q14247 | 1 | phosphorylation | up-regulates activity | 0.365 | In conclusion, these data suggest that Pyk2 phosphorylates cortactin on tyrosine residues Y421, Y466, and Y482.|To confirm the direct and indirect effects of Pyk2 on cortactin phosphorylation, we used cells overexpressing Arg YFP and treated with Pyk2 siRNA or a nonsilencing siRNA. | SIGNOR-278344 |
P49418 | P27361 | 0 | phosphorylation | down-regulates activity | 0.274 | Thus, we propose that mapk phosphorylation of amphiphysin1 controls ngf receptor/trka-mediated endocytosis by terminating the amphiphysin1-ap-2 interaction.Our results indicate that phosphorylation of amphiphysin 1 at ser-285 and/or ser-293 affects the function of amphiphysin1.Mapk phosphorylation of ser-285 and ser-293 could modulate the interaction between prd and ap-2, resulting in the dissociation of amphiphysin1 from ap-2. | SIGNOR-126867 |
P46527 | Q00534 | 0 | phosphorylation | up-regulates | 0.855 | Phosphorylation on ser-10 is the major site of phosphorylation in resting cells, takes place at the g(0)-g1 phase and leads to protein stability.p27(kip1) was phosphorylated by v-cyclin-cdk6 predominantly on ser10, which enhances its cytoplasmic localization. | SIGNOR-140401 |
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