IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q96L34 | P10636-5 | 1 | phosphorylation | down-regulates activity | 0.419 | AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A). | SIGNOR-273932 |
Q14457 | P49137 | 0 | phosphorylation | up-regulates activity | 0.432 | Beclin 1 S90 is phosphorylated by MAPKAPK2 (MK2) and MAPKAPK3 (MK3). | SIGNOR-278342 |
Q99418 | P05771 | 0 | phosphorylation | down-regulates activity | 0.307 | ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'. | SIGNOR-249024 |
P04637 | Q7Z6Z7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.495 | HUWE1 directly binds and ubiquitinates p53 to target it for proteasomal degradation, independently of MDM2 [ xref ]. | SIGNOR-278547 |
P00519 | P23759 | 1 | phosphorylation | up-regulates activity | 0.272 | Furthermore, we show that c-Abl interacts with and phosphorylates Pax7 protein.|Indeed, reporter gene assays indicate that c-Abl inhibition decreases Pax7 dependent activation of the 6xPRS9-luc reporter. | SIGNOR-279773 |
P36873 | P51955 | 0 | phosphorylation | down-regulates | 0.488 | Pp1 is a substrate for nek2 and phosphorylation of pp1gamma(1) on two c-terminal sites reduces its phosphatase activity. | SIGNOR-78603 |
P42345 | Q96B36 | 1 | phosphorylation | down-regulates activity | 0.904 | We propose that after mtorc1 kinase activation by upstream regulators, pras40 is phosphorylated directly by mtor, thus contributing to the relief of pras40-mediated substrate competitionwe also find that mutation of ser-221 to ala increases the inhibitory activity of pras40 toward mtorc1. | SIGNOR-178128 |
O60260 | P53350 | 0 | phosphorylation | up-regulates activity | 0.2 | Parkin Is Phosphorylated by Plk1 at Ser378 and Activated during Mitosis | SIGNOR-276938 |
Q05655 | P04792 | 1 | phosphorylation | down-regulates activity | 0.515 | Radioactive kinase assays confirmed that PKC\u03b4 phosphorylated Hsp27 at Ser78 and Ser82 ( Fig. 3 B). | SIGNOR-278425 |
Q15468 | P06493 | 0 | phosphorylation | down-regulates activity | 0.32 | Importantly, we show that CDK1 and CyclinB phosphorylates the N-terminal domain of STIL, but not the region encompassing the CC or STAN motifs. | SIGNOR-279145 |
P23443 | P04792 | 1 | phosphorylation | down-regulates | 0.309 | Ser-15, ser-78, and ser-82 in hsp27 (ser-15 and ser-86 in hsp25) are part of the rxxs motif, a known recognition site for p70rsk. | SIGNOR-186959 |
O95644 | Q03405 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Inducible podocyte-specific expression of constitutively active NFATc1 increased podocyte uPAR expression by binding to the Plaur gene promoter (encoding uPAR) in chromatin immunoprecipitation assays. | SIGNOR-253336 |
Q92830 | Q71DI3 | 1 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269601 |
Q13237 | Q9UL51 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we show for the first time that in the HCN2 channel cGMP can also exert an inhibitory effect on gating via cGMP-dependent protein kinase II (cGKII)-mediated phosphorylation.We identify the proximal C-terminus of HCN2 as binding region of cGKII and show that cGKII phosphorylates HCN2 at a specific serine residue (S641) in the C-terminal end of the CNBD. The cGKII shifts the voltage-dependence of HCN2 activation to 2-5 mV more negative voltages and, hence, counteracts the stimulatory effect of cGMP on gating. | SIGNOR-263185 |
P0DPK5 | 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-265416 |
O60825 | P17252 | 0 | phosphorylation | up-regulates activity | 0.439 | The phosphorylation sites for both cAMP-dependent protein kinase and protein kinase C were located in a single peptide whose sequence was Arg-Arg-Asn-Ser-(P)-Phe-Thr-Pro-Leu-Ser-Ser-Ser-Asn-Thr(P)-Ile-Arg-Arg-Pro. The seryl residue nearest the N terminus was the residue specifically phosphorylated by cAMP-dependent protein kinase, whereas the threonine residue nearest the C terminus was phosphorylated by protein kinase C. | Phosphorylation of bovine heart Fru-6-P,B-kinase by either protein kinase C or CAMP-dependent protein kinase results in activation of the enzyme. | SIGNOR-248844 |
Q92918 | O75791 | 1 | phosphorylation | down-regulates activity | 0.834 | Serine/threonine phosphorylation of the T cell adaptor proteins SLP76 and GADS by HPK1 induces their release from signaling microclusters and subsequent termination of the T cell response. | SIGNOR-279421 |
Q96KB5 | Q06830 | 1 | phosphorylation | up-regulates | 0.26 | We report that prx1 is newly discovered direct target of topk. Our results demonstrate that topk phosphorylation of prx1 at ser-32 inhibits uvb-induced apoptosis in rpmi7951 melanoma cells by increasing prx1 peroxidase activity and decreasing the intracellular accumulation of h2o2. | SIGNOR-166901 |
P78527 | P16403 | 1 | phosphorylation | down-regulates activity | 0.2 | Similarly, DNA-PK-mediated phosphorylation of H1.2 at T146 enhances p53 transcriptional activity by impeding H1.2 binding to p53 and thereby attenuating its suppressive effects on p53 transactivation. | SIGNOR-273834 |
O14929 | Q13131 | 0 | phosphorylation | up-regulates activity | 0.2 | Together, these results indicate that AMPK phosphorylated DNMT1-Ser730, RBBP7-Ser314, and HAT1-Ser190|AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314 | SIGNOR-264782 |
O94901 | P06493 | 0 | phosphorylation | down-regulates activity | 0.358 | Here, we show that SUN1, located in the INM, undergoes mitosis-specific phosphorylation on at least 3 sites within its nucleoplasmic N-terminus. We further identify Cdk1 as the kinase responsible for serine 48 and 333 phosphorylation, while serine 138 is phosphorylated by Plk1. Together, these data support a model whereby mitotic phosphorylation of SUN1 disrupts interactions with nucleoplasmic binding partners, promoting disassembly of the nuclear lamina and, potentially, its chromatin interactions. | SIGNOR-263099 |
P31749 | Q9Y3C5 | 1 | phosphorylation | down-regulates quantity | 0.456 | Upon inhibition of the AKT pathway or mutation of T135, the phosphorylation at one of these sites is virtually eliminated, suggesting that AKT may phosphorylate RNF11 at T135. Moreover, RNF11 is phosphorylated by AKT in vitro and is recognized by phospho-AKT substrate antibodies. RNF11 shows enhanced binding to 14-3-3 in WM239 cells compared with that seen in the parental WM35 cells which have low AKT activity | SIGNOR-252558 |
P28482 | P23469 | 0 | dephosphorylation | down-regulates activity | 0.39 | The effect of PTP epsilon on ERKs is at least in part indirect because phosphorylation of the threonine residue in the ERK activation loop is reduced in the presence of PTP epsilon. Nonetheless, PTP epsilon is present in a molecular complex with ERK, providing PTP epsilon with opportunity to act on ERK proteins also directly. We conclude that PTP epsilon is a physiological inhibitor of ERK signaling|These enzymes are joined by the large family of dual-specificity phosphatases, which are structurally similar to tyrosine phosphatases but which can dephosphorylate both residues of the activation loop | SIGNOR-248448 |
P30086 | P05129 | 0 | phosphorylation | up-regulates activity | 0.381 | Here we report that one mechanism involves dissociation of Raf kinase inhibitory protein (RKIP) from Raf-1. Classic and atypical but not novel PKC isoforms phosphorylate RKIP at serine 153 (Ser-153). RKIP Ser-153 phosphorylation by PKC either in vitro or in response to 12-O-tetradecanoylphorbol-13-acetate or epidermal growth factor causes release of RKIP from Raf-1, whereas mutant RKIP (S153V or S153E) remains bound. I | SIGNOR-249190 |
P40259 | P07948 | 0 | phosphorylation | up-regulates activity | 0.678 | Y182 of CD79a appears to be the initial and preferred site of Ag receptor phosphorylation by Src family kinases. In vitro, Src family Lyn and Fyn predominantly phosphorylate this residue in CD79a, and Y195 does so in CD79b | SIGNOR-251398 |
P18031 | P78337 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.354 | PTP1B dephosphorylates PITX-1 at Y160, 175 and Y179.|Through directly dephosphorylating PITX-1 at Y160, Y175 and Y179, PTP1B promoted proteasomal degradation of PITX-1, thus leaded in downregulating p120RasGAP and CRC cell survival. | SIGNOR-276973 |
P28482 | Q15788 | 1 | phosphorylation | up-regulates | 0.364 | Furthermore, erk-2 phosphorylated threonine 1179 and serine 1185 (and to a lesser extent, serine 395) in vitro, suggesting the importance of this pathway for src-1 regulation. Treatment of cells expressing src-1 with epidermal growth factor enhanced the ligand-dependent, progesterone receptor-mediated activation of a target reporter gene. | SIGNOR-74880 |
O15111 | P42345 | 1 | phosphorylation | up-regulates activity | 0.511 | In those studies, we found that IKKalpha interacts with and phosphorylates mTOR in the mTORC1 complex to activate mTORC1, and that Akt signaling drives the IKKalpha-mTORC1 interaction.|We then studied whether IKKalpha promotes Akt and mTOR activity in other mammalian cancer cell lines. | SIGNOR-279607 |
P07195 | Q9NXA8 | 0 | deacetylation | up-regulates activity | 0.2 | In colorectal cancer, SIRT5 binds to lactate dehydrogenase B (LDHB) to deacetylate it at Lysine 329, thereby increasing its enzymatic activity. | SIGNOR-267645 |
Q96K19 | Q14643 | 1 | polyubiquitination | down-regulates activity | 0.431 | In summary, here we present evidence that RNF170 is an E3 ligase that mediates IP3 receptor ubiquitination and processing by the UPP and that it is recruited to activated IP3 receptors by the erlin1/2 complex to which it is constitutively bound. | SIGNOR-271913 |
O95140 | Q7Z6Z7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.42 | AMBRA1 regulates mitophagy at two critical steps. Upon mitophagy stimulation, AMBRA1 mediates the HUWE1 E3 ubiquitin ligase translocation from cytosol to mitochondria (light blue). AMBRA1 acts as a cofactor for HUWE1 E3 ubiquitin ligase activity, favouring its binding to its substrate MFN2 (and maybe other OMM substrates) and targeting it to the proteasome | SIGNOR-272978 |
Q16650 | Q8TBJ5 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.486 | We found that TBR1 promotes the identity of corticothalamic neurons and represses subcerebral fates through reducing expression of Fezf2 and CTIP2.|(3) Chromatin immunoprecipitation analysis using TBR1 antibodies showed that TBR1 bound to a conserved region in the Fezf2 gene. | SIGNOR-268967 |
O43561 | P06241 | 0 | phosphorylation | up-regulates | 0.749 | Both lck and syk, phosphorylate the itam-like motifs on lat at y171y191, which is essential for induction of the interaction of lat with downstream signaling molecules such as grb2, plc-gamma1 and c-cbl, and for activation of mapk-erk. | SIGNOR-149174 |
O14777 | P51955 | 0 | phosphorylation | up-regulates | 0.592 | Phosphorylation of the mitotic regulator protein hec1 by nek2 kinase is essential for faithful chromosome segregation.Hec1 (highly expressed in cancer) plays essential roles in chromosome segregation by interacting through its coiled-coil domains with several proteins that modulate the g(2)/m phase.Nek2 phosphorylates hec1 on serine residue 165, both in vitro and in vivo. | SIGNOR-94322 |
P68400 | Q92915 | 1 | phosphorylation | up-regulates activity | 0.269 | Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents. | SIGNOR-275738 |
O15530 | Q9BXL7 | 1 | phosphorylation | up-regulates | 0.55 | We demonstrate that 3-phosphoinositide-dependent kinase 1 (pdk1) has an essential role in this pathway by regulating the activation of pkc and through signal-dependent recruiting of both pkc and card11 to lipid rafts. | SIGNOR-134866 |
P09619 | P06241 | 1 | phosphorylation | up-regulates activity | 0.58 | PDGF-induced phosphorylation of Tyr28 in the N-terminus of Fyn affects Fyn activation. We show here that Fyn, a member of the Src family, is phosphorylated on Tyr28 in the unique N-terminal part of the molecule after interaction with the intracellular domain of the PDGF beta-receptor. Activated Fyn furthermore undergoes autophosphorylation on Tyr30, Tyr39 and Tyr420. When Fyn mutants with Tyr28, Tyr30 or Tyr39 replaced with phenylalanine residues were transfected into NIH3T3 cells a decreased activation after PDGF stimulation was seen, suggesting a functional importance of the N-terminal tyrosine phosphorylation of Fyn. | SIGNOR-250253 |
Q16539 | Q9BUB5 | 1 | phosphorylation | up-regulates | 0.672 | Mnk1, but not mnk2, also binds strongly to the stress-activated kinase, p38. | SIGNOR-48346 |
Q9H4A3 | O95747 | 1 | phosphorylation | up-regulates | 0.484 | Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1) | SIGNOR-151659 |
P23470 | P35968 | 1 | dephosphorylation | down-regulates activity | 0.253 | 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-254707 |
O95831 | P98170 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.434 | Notably, cotransfection of XIAP along with AIF resulted in the complete inhibition of DNA degradation (21.2% degraded nuclei), suggesting that XIAP directly abrogates the ability of AIF to induce chromatin degradation.|XIAP binds and ubiquitinates AIF, and in this study, we determined the functional consequences of XIAP-mediated AIF ubiquitination. | SIGNOR-278537 |
P17612 | Q15831 | 1 | phosphorylation | up-regulates activity | 0.502 | Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell growth. | SIGNOR-250055 |
Q05655 | P35222 | 1 | phosphorylation | down-regulates activity | 0.269 | Moreover, protein kinase Cδ, which directly phosphorylates β-catenin at Ser715, is required for the TRIM33–β-catenin interaction. | Phosphorylation of β-catenin Ser715 is critical for TRIM33-induced β-catenin degradation | SIGNOR-260897 |
Q9UGM6 | Q2TAL8 | 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-269411 |
P01106 | P45983 | 0 | phosphorylation | up-regulates activity | 0.556 | The jnk pathway is selectively involved in the c-myc-mediated apoptosis and that the apoptotic function of c-myc is directly regulated by jnk pathway through phosphorylation at ser-62 and ser-71. | SIGNOR-236018 |
P53671 | P60484 | 1 | phosphorylation | down-regulates activity | 0.274 | LIMK2 inhibits PTEN phosphatase activity in vitro and in cells.|PTEN phosphorylation and downregulation by LIMK2 promotes tumorigenesis and EMT in vivo. | SIGNOR-278363 |
P53779 | P05067 | 1 | phosphorylation | up-regulates | 0.582 | Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in sh-sy5y neuroblastoma cells. is regulated by jnk3 via phosphorylation of app at thr668 | SIGNOR-204671 |
P53350 | P52565 | 1 | phosphorylation | up-regulates activity | 0.2 | PLK1 phosphorylates RhoGDI1 at Thr7/91 residue in vitro and in vivo. Collectively, we demonstrate that the phosphorylation of RhoGDI1 by PLK1 promotes cancer cell migration and invasion through RhoA activation. | SIGNOR-277882 |
P61586 | Q8N5V2 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.675 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260562 |
P25963 | P06239 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.586 | Loss of tyrosine kinase p56lck in Jurkat cells abolished NFkappaB activation and partially suppressed and delayed phosphorylation of Tyr-42 of IkappaB upon pervanadate treatment. |Transfection of these cells with wild type Lck but not with mutant Lck F394 followed by H/R induces the tyrosine phosphorylation of inhibitor of nuclear factor kappaB (IkappaBalpha) and transcriptional activation of NFkappaB, and these are inhibited by Lck inhibitors | SIGNOR-249374 |
P52565 | P12931 | 0 | phosphorylation | down-regulates | 0.399 | We show here that src kinase binds and phosphorylates rhogdi both in vitro and in vivo at tyr156. analysis of rho gtpase-rhogdi complexes using in vitro assays of complexation and in vivo by coimmunoprecipitation analysis indicates that src-mediated phosphorylation of tyr156 causes a dramatic decrease in the ability of rhogdi to form a complex with rhoa, rac1, or cdc42. | SIGNOR-149282 |
P08670 | P41743 | 0 | phosphorylation | up-regulates activity | 0.2 | Results suggest that aPKCs target multiple activation sites (Ser33/39/56) on Vimentin and therefore is essential for VIF dynamics regulation during the metastasis of prostate cancer cells. | SIGNOR-277623 |
Q9NZM5 | Q13315 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PICT-1 S233 and T289 were identified as the key phosphorylation sites in this pathway, as mutating both to alanine abolished UVB-induced increase of PICT-1 phosporylation. Inhibition of PIKKs or ATM (with wortmannin and KU55933, respectively) prevented the agglomeration and degradation of PICT-1, suggesting that ATM is a key regulator of PICT-1. | SIGNOR-273506 |
P22087 | Q92793 | 0 | acetylation | down-regulates activity | 0.27 | Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. |Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206) | SIGNOR-275897 |
P78527 | P07948 | 0 | phosphorylation | down-regulates activity | 0.466 | The interaction between Lyn and DNA-PKcs inhibits DNA-PKcs activity and the ability of DNA-PKcs to form a complex with Ku/DNA.|We also show that Lyn phosphorylates DNA-PKcs but not Ku in vitro. | SIGNOR-279061 |
Q5FBB7 | O43683 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Bub1 phosphorylates Sgo1 in the vicinity of its APC/C degrons in vitro.|On the other hand, Bub1 targets PP2A to centromeres, which in turn maintains Sgo1 at centromeres by counteracting Plk1 mediated chromosome removal of Sgo1. | SIGNOR-278915 |
Q16566 | Q92793 | 1 | phosphorylation | up-regulates activity | 0.635 | Ser301 of CBP was identified as a major target of CaMKIV phosphorylation in vitro and in vivo. CaM kinase inhibitors attenuated phosphorylation at Ser301 and blocked CBP-dependent transcription. Additionally, mutation of Ser301 impaired NMDA- and CaMKIV-stimulated transcription. These findings demonstrate that activity-induced CaMKIV signaling contributes to CREB/CBP-dependent transcription by phosphorylating CBP at Ser301. | SIGNOR-250710 |
Q9NXR1 | P17612 | 0 | phosphorylation | up-regulates | 0.4 | Here, we demonstrate that disc1 and pde4 modulate nde1 phosphorylation by camp-dependent protein kinase a (pka) and identify a novel pka substrate site on nde1 at threonine-131 (t131).Since phosphorylated t131 is detectable at multiple subcellular locations (centrosome, nucleus, postsynaptic density, proximal axon), there is potential for disc1/pde4 to influence several important brain processes that critically depend on the nde1/ndel1/lis1 comple | SIGNOR-174410 |
Q92953 | O95292 | 1 | 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-262123 |
Q8TBJ5 | Q16650 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.486 | We found that TBR1 promotes the identity of corticothalamic neurons and represses subcerebral fates through reducing expression of Fezf2 and CTIP2.|(3) Chromatin immunoprecipitation analysis using TBR1 antibodies showed that TBR1 bound to a conserved region in the Fezf2 gene. | SIGNOR-268967 |
Q06710 | Q92911 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.408 | Pax8 has an essential role in thyroid organogenesis and differentiation, being the main mediator of thyroid gene transcription, including the NIS gene. | SIGNOR-251990 |
Q5JSP0 | P60953 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.648 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260553 |
P41240 | P07948 | 1 | phosphorylation | down-regulates | 0.538 | Lyn tyr507 kinase, csk, is recruited by pag, which targets lipid rafts by palmitoylation.Thus, our data suggest that il-6 treatment induces the translocation of cd45 to lipid rafts sequentially, followed by the association of cd45 with lyn and pag;dephosphorylation of lyn tyr507 and pag tyr314;lyn activation;and csk release from lipid rafts | SIGNOR-132912 |
P12931 | P53396 | 1 | phosphorylation | up-regulates activity | 0.265 | We demonstrate the binding of PIP2 to the CoA-binding domain of ACLY and identify the six tyrosine residues of ACLY that are phosphorylated by Lyn. Three of them (Y682, Y252, Y227) can be also phosphorylated by Src and they are located in catalytic, citrate binding and ATP binding domains, respectively. PI3K and Lyn inhibitors reduce the ACLY enzyme activity, ACLY-mediated Acetyl-CoA synthesis, phospholipid synthesis, histone acetylation and cell growth. Thus, PIP2/PIP3 binding and Src tyrosine kinases-mediated stimulation of ACLY links oncogenic pathways to Acetyl-CoA-dependent pro-growth and survival metabolic pathways in cancer cells. | SIGNOR-274107 |
Q05655 | P05787 | 1 | phosphorylation | up-regulates | 0.322 | The present study showed that shear stress, but not stretch, activates PKC delta and phosphorylates K8 Ser-73, which then mediates the disassembly/reorganization of keratin IF in AEC. | SIGNOR-260887 |
P84243 | Q9H3R0 | 0 | demethylation | down-regulates activity | 0.2 | As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation | SIGNOR-263869 |
P42574 | Q9UBF6 | 0 | ubiquitination | down-regulates activity | 0.2 | SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. | SIGNOR-271448 |
O95835 | Q9GZV5 | 1 | phosphorylation | down-regulates | 0.791 | In response to high cell densities, activated LATS1/2 phosphorylates the WW-domain containing transcriptional co-activators YAP at Ser127 and TAZ at Ser89, promoting 14-3-3 binding and thereby inhibiting their translocation into the nucleus. | SIGNOR-197643 |
O00308 | Q9P2A4 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | The AIP2 E3 ligase acts as a novel negative regulator of ABA signaling by promoting ABI3 degradation. Here, we show that ABI3 is an unstable protein and that an ABI3-interacting protein (AIP2), which contains a RING motif, can polyubiquitinate ABI3 in vitro. | SIGNOR-272656 |
Q01167 | P57073 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.288 | We showed for the first time that Aurora-A interacts directly with SOX8 and phosphorylates the protein at Ser327 to further regulate the SOX8/FOXK1 axis, which modulates cell senescence and glycolysis, ultimately leading to cisplatin resistance.. Our results showed that SOX8 targets FOXK1, thereby regulating its transcription, which has significant impacts on senescence, glycolysis and chemoresistance in ovarian cancer. | SIGNOR-273613 |
P63104 | P49137 | 0 | phosphorylation | down-regulates activity | 0.625 | We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. Mutation analysis showed that MAPKAPK2 phosphorylated 14-3-3zeta at Ser-58. S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1. | SIGNOR-250151 |
Q8N140 | Q4FZB7 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Here we show that, when over-expressed, FRG1 binds and interferes with the activity of the histone methyltransferase Suv4-20h1 both in mammals and Drosophila. Accordingly, FRG1 over-expression or Suv4-20h1 knockdown inhibits myogenesis. The novel inhibitor of differentiation Eid3 is an FRG1/Suv4-20h1 target involved in the myogenic defects caused by FRG1 over-expression. Eid3 is down-regulated upon muscle differentiation and behaves as a myogenic inhibitor gene. | SIGNOR-266640 |
Q99683 | P11309 | 0 | phosphorylation | down-regulates | 0.28 | Pim1 phosphorylates and negatively regulates ask1-mediated apoptosispim1 phosphorylation of ask1 on ser83 inhibited ask1-mediated c-jun n-terminal kinase phosphorylation | SIGNOR-187905 |
O95835 | P06493 | 0 | phosphorylation | up-regulates | 0.389 | Warts is a serine/threonine kinase and a dynamic component of the mitotic apparatus. We have found that cdc2/cyclin b forms a complex with a fraction of warts in the centrosome and phosphorylates the ser613 site of warts during mitosisit can be speculated that phosphorylation of warts by cdc2/cyclin b promotes a protein complex formation on the mitotic apparatus at early mitosis, which may be required for subsequent activation of warts kinase at the metaphase-anaphase transition. | SIGNOR-94160 |
P04637 | P51948 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.351 | Collectively, these results indicate that MNAT1 increases p53 ubiquitination, thus promoting its proteasomal degradation.|These suggest that MNAT1 decreases p53 expression by the proteasome. | SIGNOR-278831 |
O14965 | Q99661 | 1 | phosphorylation | down-regulates activity | 0.584 | In addition, we found that MCAK localization at spindle poles was regulated through another Aurora A phosphorylation site (S719), which positively enhances bipolar spindle formation. | SIGNOR-279139 |
P60953 | Q9P2F6 | 0 | gtpase-activating protein | down-regulates activity | 0.447 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260474 |
Q13153 | Q13418 | 1 | phosphorylation | up-regulates | 0.41 | We found that pak1 phosphorylates ilk at threonine-173 and serine-246 in vitro and in vivo. together, these results suggest that ilk is a pak1 substrate, undergoes phosphorylation-dependent shuttling between the cell nucleus and cytoplasm, and interacts with gene-regulatory chromatin. | SIGNOR-154303 |
P10071 | Q15915 | 0 | relocalization | up-regulates | 0.358 | Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels | SIGNOR-105497 |
P06493 | Q9NQR1 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | We found that PR-Set7 is phosphorylated at Ser 29 (S29) specifically by the cyclin-dependent kinase 1 (cdk1)/cyclinB complex, primarily from prophase through early anaphase, subsequent to global accumulation of H4K20me1. While S29 phosphorylation did not affect PR-Set7 methyltransferase activity, this event resulted in the removal of PR-Set7 from mitotic chromosomes. S29 phosphorylation also functions to stabilize PR-Set7 by directly inhibiting its interaction with the anaphase-promoting complex (APC), an E3 ubiquitin ligase. | SIGNOR-259832 |
P04626 | P15514 | 0 | phosphorylation | up-regulates | 0.628 | Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor | SIGNOR-31199 |
O14965 | Q9ULW0 | 1 | phosphorylation | up-regulates activity | 0.965 | Here we show that TPX2, a microtubule-bundling protein and activator of Aurora A, plays an important role. TPX2 was phosphorylated by Aurora A during mitosis. Its phospho-null mutant caused short metaphase spindles coupled with low microtubule flux rate. Interestingly, phosphorylation of TPX2 regulated its interaction with CLASP1 but not Kif2a.|This suggests that TPX2 phosphorylation positively regulates the function of CLASP1.| This is in accord with a phosphoproteomics study that identified S121 and S125 as potential phosphorylation sites for Aurora A in mitotic HeLa cells | SIGNOR-265089 |
O14920 | P42574 | 0 | cleavage | down-regulates | 0.364 | Ikappab kinase (ikk) beta was specifically proteolyzed by caspase-3-related caspases at aspartic acid residues 78, 242, 373, and 546 during tumor necrosis factor (tnf)-alpha-induced apoptosis. | SIGNOR-112792 |
P31751 | O43464 | 1 | phosphorylation | down-regulates | 0.2 | Akt attenuation of the serine protease activity of htra2/omi through phosphorylation of serine 212 | SIGNOR-153327 |
Q53GL7 | Q13283 | 1 | post translational modification | up-regulates activity | 0.2 | Further, we pinpoint the core SG component, G3BP1, as a PARP10 substrate and find that PARP10 regulates SG assembly driven by both G3BP1 and its modeled mechanism. Intriguingly, while PARP10 only adds a single ADP-ribose unit to proteins, G3BP1 is PARylated, suggesting its potential role as a scaffold for protein recruitment. PARP10 knockdown alters the SG core composition, notably decreasing translation factor presence. | SIGNOR-273727 |
P42224 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.72 | All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below). | SIGNOR-154779 |
Q13164 | Q92886 | 1 | phosphorylation | up-regulates activity | 0.35 | Activation of ERK5 potentiates while inhibition of ERK5 attenuates Neurog1 stimulated neurogenesis.|ERK5 directly phosphorylated Neurog1 in vitro and modulated the transcriptional and pro-neural activity of Neurog1 in cortical progenitors. | SIGNOR-278364 |
Q15910 | P06493 | 0 | phosphorylation | down-regulates | 0.575 | Cdk1, which phosphorylates ezh2 at threonines 345 and 487.Phosphorylation of thr-345 and thr-487 promotes ezh2 ubiquitination and subsequent degradation by the proteasome | SIGNOR-174058 |
Q96S53 | P60981 | 1 | phosphorylation | down-regulates activity | 0.422 | The present study provides evidence that TESK2 can phosphorylate cofilin and ADF specifically at Ser-3. Since actin-depolymerizing and -severing activities of cofilin/ADF are abrogated by phosphorylation at Ser-3, TESK2 seems to play an important role in actin filament dynamics by inhibiting cofilin/ADF activity. | SIGNOR-246707 |
Q9UKE5 | P35240 | 1 | phosphorylation | up-regulates activity | 0.2 | Consistently with TNIK modulating Merlin, we also observed reduced YAP levels following TNIK knockdown in LK2 and NCI-H520 cells (Supplementary Fig. S7B).|Using in vitro kinase assays followed by phosphopeptide mapping, and mass spectrometry analysis on Merlin isolated from cells co-expressing TNIK and Merlin, we determined that TNIK could phosphorylate Merlin at S13, T272, S315, and T576 (Fig. 4B, Supplementary Fig. S4D, and Supplementary Table S3). | SIGNOR-278386 |
P00533 | P63096 | 1 | phosphorylation | up-regulates activity | 0.464 | RTKs directly phosphorylate Gαi on Y154, 155, and Y320. | SIGNOR-277227 |
P08236 | P19484 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.249 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276553 |
P29350 | P23458 | 1 | dephosphorylation | down-regulates | 0.646 | We find, for the first time, that shp-1 down-regulates the level of tyk2 kinase in h9 cells and of jak1 kinase in htb26 cells, by accelerating their degradation. | SIGNOR-119197 |
Q13315 | Q03112 | 1 | phosphorylation | up-regulates activity | 0.2 | To investigate to what extent EVI1 function might be regulated by post-translational modifications we carried out mass spectrometry- and antibody-based analyses and uncovered an ATM-mediated double phosphorylation of EVI1 at the carboxy-terminal S858/S860 SQS motif. | SIGNOR-273433 |
P06241 | Q9UK17 | 1 | phosphorylation | up-regulates activity | 0.2 | These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels. | SIGNOR-276396 |
P31749 | Q9UGI0 | 1 | phosphorylation | up-regulates activity | 0.2 | Our findings also identify an essential role for activation of Trabid by AKT-mediated phosphorylation at Ser78/Thr117 in negatively regulating Twist1 signaling, which further provides insights into the mechanisms by which Trabid regulates Twist1 ubiquitination. | SIGNOR-273484 |
P12931 | O43255 | 1 | phosphorylation | up-regulates activity | 0.334 | In human breast cancer cell lines, the protein kinase Src has been shown to activate Siah2 by phosphorylation of tyrosines 86, 140, and 263.|This function is promoted by Src phosphorylation of Siah2, which increases C/EBPdelta binding, ubiquitination, and degradation. | SIGNOR-279555 |
P45983 | P14618 | 1 | phosphorylation | up-regulates activity | 0.371 | Active JNK1 specifically activates PKM2 but not PKM1. Mechanistically, PARP14 inhibits the pro-apoptotic kinase JNK1, which results in the activation of PKM2 through phosphorylation of Thr365. | SIGNOR-276933 |
P10915 | P09237 | 0 | cleavage | down-regulates quantity by destabilization | 0.322 | Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix. | SIGNOR-256329 |
Q13131 | O43524 | 1 | phosphorylation | up-regulates activity | 0.517 | Phosphorylation by AMPK leads to the activtion of FOXO3 transcriptional activity without affecting FOXO3 subcellular localization. | SIGNOR-249684 |
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