IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q86Y13 | Q9BTM1 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271763 |
Q13976 | Q9NS28 | 1 | phosphorylation | up-regulates activity | 0.332 | Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. S216 phosphorylation might activate PP1 leading to dephosphorylation of both 14-3-3 binding sites, S49 and S218, and detachment of 14-3-3. Removal of 14-3-3 activates RGS18 to turn off Gq signaling thus contributing to platelet inhibition. | SIGNOR-273785 |
Q00535 | Q8NER1 | 1 | phosphorylation | up-regulates activity | 0.2 | TNF-alpha overexpression increased Cdk5-mediated phosphorylation of TRPV1 at T407.|These results suggest that the activation of Cdk5 by p35 enhances the response of TRPV1 to capsaicin, probably by phosphorylation of the channel [34]. | SIGNOR-278437 |
Q16539 | Q6STE5 | 1 | phosphorylation | up-regulates activity | 0.368 | P38 phosphorylates the baf60 subunit of the swi-snf chromatin remodelling complex, and p38 recruits this complex to differentiation-specific loci. | SIGNOR-176557 |
Q5JWF2 | P41968 | 0 | null | up-regulates activity | 0.547 | We hypothesize that XLαs may be involved in this regulatory loop by coupling to melanocortin receptors 3 and 4 in the hypothalamus. | SIGNOR-253068 |
Q12913 | P19174 | 1 | dephosphorylation | down-regulates | 0.369 | Cd148 can dephosphorylate lat and plc?1 In vitro. / plc?1 Undergoes inducible tyrosine phosphorylation following tcr stimulation (46), and this phosphorylation is required to stimulate its catalytic activity | SIGNOR-105790 |
P07101 | P17612 | 0 | phosphorylation | up-regulates activity | 0.368 | HTH1 was phosphorylated at Ser40 by PKA. Tyrosine hydroxylase (TH) has been reported to require binding of 14-3-3 proteins for optimal activation by phosphorylation. phosphorylationof hTH1‚4 at Ser40, to a stoichiometry of up to 1.0 molphosphate per mol TH subunit, dramatically increases their binding to 14-3-3 proteins. | SIGNOR-250061 |
O43318 | Q5SQI0 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we report TGF-beta-activated kinase 1 (TAK1) as a key activator of alphaTAT1. TAK1 directly interacts with and phosphorylates alphaTAT1 at Ser237 to critically enhance its catalytic activity | SIGNOR-272243 |
Q96I25 | P49759 | 0 | phosphorylation | up-regulates activity | 0.317 | In this work, we show that Cdc2-like kinase 1 (Clk1) phosphorylates SPF45 on eight serine residues. | SIGNOR-262710 |
Q9BXL7 | O15530 | 0 | 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 |
P09769 | P41240 | 0 | phosphorylation | down-regulates activity | 0.537 | CSK catalyzed phosphorylation affects Tyr-511 of c-Fgr, homologous to Tyr-527 of c-Src and it prevents the autophosphorylation normally occurring at c-Fgr Tyr-400, homologous to c-Src Tyr-416. | Once phosphorylated at Tyr-511 and down-regulated by CSK, c-Fgr is no more susceptible to polylysine stimulation. | SIGNOR-250779 |
P50542 | P51668 | 0 | ubiquitination | up-regulates activity | 0.388 | Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle. | SIGNOR-253022 |
P51812 | P07101 | 1 | phosphorylation | up-regulates | 0.267 | Mitogen-activated protein-kinase (map) kinase-activated protein kinases 1 and 2 (mapkap kinase-1, mapkap kinase-2), were found to phosphorylate bacterially expressed human tyrosine hydroxylaserecombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation by msk1 induced an increase in vmax | SIGNOR-34682 |
P55211 | P17612 | 0 | phosphorylation | down-regulates | 0.2 | We show that protein kinase a inhibits activation of caspase-9 and caspase-3 downstream of cytochrome c in xenopus egg extracts and in a human cell-free system. Protein kinase a directly phosphorylates human caspase-9 at serines 99, 183, and 195. | SIGNOR-133884 |
Q8IW41 | Q16659 | 0 | phosphorylation | up-regulates activity | 0.69 | ERK3, ERK4 and p38 MAPK can all phosphorylate MK5 at Thr 182 , , , - ], but it is not known whether these enzymes also can phosphorylate Ser 115 and whether this modification contributes to ERK3-, ERK4-, or p38 MAPK -regulated subcellular localization of MK5. | SIGNOR-279073 |
Q9UKT4 | Q9UM11 | 1 | ubiquitination | down-regulates | 0.756 | Emi1 binds cdh1 and inhibits apc-cdh1 activity. | SIGNOR-113385 |
P48729 | Q12778 | 1 | phosphorylation | down-regulates | 0.418 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity | SIGNOR-183658 |
P00533 | Q9Y4L5 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.375 | RNF126 and Rabring7 associate with the EGFR through a ubiquitin-binding zinc finger domain and both E3 ubiquitin ligases promote ubiquitylation of EGFR. In HeLa cells depleted of either RNF126 or Rabring7 the EGFR is retained in a late endocytic compartment and is inefficiently degraded. | SIGNOR-272104 |
Q13148 | Q9UPY3 | 1 | post transcriptional regulation | up-regulates quantity | 0.374 | Molecularly, we observed that TBPH regulates the expression levels of Dicer-2 by direct protein-mRNA interactions in vivo.|In agreement with this idea, we found that the suppression of TDP-43 induces the downregulation of Dicer in human neuroblastoma cell lines signifying that the TDP-43 function is required to prevent defects in Dicer protein expression or stability | SIGNOR-262114 |
Q05086 | P51665 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.271 | Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits. | SIGNOR-265134 |
P68431 | Q92830 | 0 | 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-269602 |
Q6UVK1 | P17252 | 0 | phosphorylation | up-regulates activity | 0.2 | Protein kinase C (PKC)-alpha phosphorylation of recombinant NG2 cytoplasmic domain and phorbol ester-induced PKC-dependent phosphorylation of full-length NG2 expressed in U251 cells are both blocked by mutation of Thr(2256), identifying this residue as a primary phosphorylation site. PKC-alpha-mediated NG2 phosphorylation at Thr(2256) is therefore a key step for initiating cell polarization and motility. | SIGNOR-263162 |
P53355 | Q96RR4 | 1 | phosphorylation | down-regulates | 0.283 | Dapk phosphorylates camkk. S511 was identified as the phosphorylation site . a potential mechanism of action was identified on the basis of the location of s511 near the cam recognition domain of camkk and demonstrated by attenuation of cam-stimulated camkk autophosphorylation after dapk phosphorylation. | SIGNOR-126241 |
P10147 | Q01196 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We show that RUNX1 can specifically bind to both RUNX sites but that only the proximal RUNX site is essential for PMA/ PHA stimulation of the MIP-1a promoter in Jurkat T-cells. We also show that the endogenous MIP-1a promoter is constitutively bound by RUNX1. | SIGNOR-251738 |
P55210 | P49768 | 1 | cleavage | up-regulates activity | 0.342 | Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. | SIGNOR-261757 |
O14490 | Q9BYB0 | 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-264588 |
P10275 | Q8WY64 | 0 | ubiquitination | down-regulates quantity | 0.2 | MYLIP knockdown increased AR protein levels whereas CNPY2 knockdown increased MYLIP and reduced AR protein expression levels.|These results showed that the E3 ligase MYLIP could ubiquitinate lysine 845 and 847 residues of AR. | SIGNOR-278766 |
Q9Y297 | Q15910 | 1 | ubiquitination | down-regulates | 0.376 | _-trcp ubiquitinates ezh2 and jak2-mediated phosphorylation on y641 directs _-trcp-mediated ezh2 degradation. | SIGNOR-204481 |
O75925 | Q13131 | 0 | phosphorylation | up-regulates activity | 0.2 | Mechanically, we found that AMPKα1 directly phosphorylated protein inhibitor of activated STAT-1 (PIAS1), the SUMO E3-ligase of Runx2, at serine 510, to promote its SUMO E3-ligase activity. Finally, mutation of protein inhibitor of activated STAT-1 at serine 510 suppressed m | SIGNOR-259866 |
P12931 | P33151 | 1 | phosphorylation | down-regulates activity | 0.567 | cadherins also act to prevent epithelial cell motilityCadherin-cytoskeletal interactions occur through a number of adaptor proteins that interact with the C-terminal portion of the cadherin cytoplasmic tail, including the _-, _-, and _-catenin (6, 10). Additionally, VE-cadherin stability at the plasma membrane may be regulated by the binding of p120-catenin to the juxtamembrane region of the cytoplasmic tailWe show here that tyrosine phosphorylation of the adherens junction protein VE-cadherin at two critical tyrosines, Tyr-658 and Tyr-731, via tyrosine kinase activation or phosphatase inactivation was sufficient to prevent the binding of p120- and beta-catenin, respectively, to the cytoplasmic tail of VE-cadherinVE-cadherin becomes phosphorylated on Tyr-658 and/or Tyr-731 in response to Src kinase activity. | SIGNOR-246462 |
P53350 | P49137 | 0 | phosphorylation | up-regulates | 0.349 | Here, we have identified mk2 as a major plk1 kinase toward ser326, whose phosphorylation is critical to recruit ?-Tubulin to centrosomes and subsequent establishment of functional bipolar spindles. To our knowledge, this is the first direct evidence to demonstrate that the essential function of plk1 in centrosome maturation and bipolar spindle formation is controlled by its upstream kinase. | SIGNOR-179968 |
O60260 | P00519 | 0 | phosphorylation | down-regulates | 0.2 | Here we show that the nonreceptor tyrosine kinase c-abl phosphorylates tyrosine 143 of parkin, inhibiting parkin's ubiquitin e3 ligase activity and protective function. | SIGNOR-167853 |
P16298 | O95644 | 1 | relocalization | up-regulates | 0.724 | The ca2+ dependent phosphatase calcineurin induces cardiac and skeletal muscle hypertrophy by a process that involves nf-at nuclear translocation, and activation of mef2c. | SIGNOR-84047 |
O14974 | O43293 | 0 | phosphorylation | down-regulates activity | 0.547 | We conclude from our results Par-4 operates through a "padlock" model in which binding of Par-4 to MYPT1 activates MP by blocking access to the inhibitory phosphorylation sites, and inhibitory phosphorylation of MYPT1 by ZIPK requires "unlocking" of Par-4 by phosphorylation and displacement of Par-4 from the MP complex.|We have also demonstrated that Par-4 is required for agonist induced, ZIPK mediated inhibition of MYPT1 and thus is an important amplifier of inputs to MP. | SIGNOR-279030 |
Q92945 | P31749 | 0 | phosphorylation | down-regulates activity | 0.703 | Beta-catenin transcript can be stabilized by either wnt or pi3k-akt signaling activation. Akt phosphorylates ksrp at a unique serine residue akt phosphorylates the mrna decay-promoting factor ksrp at a unique serine residue, induces its association with the multifunctional protein 14-3-3, and prevents ksrp interaction with the exoribonucleolytic complex exosome. | SIGNOR-252497 |
Q9Y6H5 | Q8IUQ4 | 0 | ubiquitination | down-regulates | 0.676 | Siah proteins ubiquitylate synphilin-1 and promote its degradation through the ubiquitin proteasome system | SIGNOR-140612 |
P04637 | P51955 | 0 | phosphorylation | down-regulates | 0.318 | NEK2 Phosphorylates p53 at Ser315 and Reduces Its Stability.|These results are consistent with NEK2 inhibiting p53 transcriptional activation functions. | SIGNOR-278488 |
Q13153 | P63167 | 1 | phosphorylation | down-regulates | 0.378 | Dlc1 phosphorylation on ser(88) by p21-activated kinase 1 (pak1), a signaling nodule, promotes mammalian cell survival by regulating its interaction with bim and the stability of bim. Here we discovered that phosphorylation of ser(88), which juxtapose each other at the interface of the dlc dimer, disrupts dlc1 dimer formation and consequently impairs its interaction with bim | SIGNOR-159995 |
P07949 | P10586 | 0 | dephosphorylation | down-regulates | 0.426 | Lar expression significantly reduced tyrosine-1062 phosphorylation in ret-men2a but not in ret-men2b | SIGNOR-85170 |
P40763 | P17677 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.3 | In this study, we demonstrated for the first time that growth-associated protein 43 (GAP43), a well known growth cone protein that promotes axonal regeneration, can be induced in rat brain astrocytes by the proinflammatory endotoxin lipopolysaccharide via both nuclear factor-κB and signal transducer and activator of transcription 3-mediated transcriptional activation. | SIGNOR-266772 |
Q9Y243 | P04792 | 1 | phosphorylation | down-regulates | 0.286 | First, the akt1, akt2, and akt3 isoforms can bind directly to hsp27 and can be found in a complex with p38 mapk, mk2, and hsp27 [98_100]. Second, rane and colleagues showed that akt could phosphorylate hsp27 at ser-82, but not ser-15 or ser-78, in vitro, while co-expression of an active akt mutant and hsp27 in hek cells resulted in hsp27 phosphorylation at the same residue. | SIGNOR-186780 |
Q02750 | Q6N021 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.247 | TET2 was stabilized by MEK1 phosphorylation at Ser 1107, while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7FBXW11. | SIGNOR-277891 |
Q99250 | P68400 | 0 | 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 |
O43432 | Q6P2M8 | 0 | phosphorylation | up-regulates | 0.2 | Here we report that activity-dependent translational initiation in cultured rat hippocampal neurons is enhanced by camki-mediated phosphorylation of ser1156 in eukaryotic initiation factor eif4gii (4gii). | SIGNOR-197190 |
Q15375 | P31271 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.291 | Analysis of normalized luciferase expression confirmed that wt HOXA13 regulates gene expression through the EphA7 cis-regulatory DNA element | SIGNOR-261631 |
P60953 | O43307 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.834 | 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-260534 |
P08047 | P45983 | 0 | phosphorylation | up-regulates | 0.705 | In addition, for mutation of the jnk-1 phosphorylated residues of sp1, namely, sp1(t278/739a) and sp1(t278/739d), the effect of ga on sp1 stability was reversed. | SIGNOR-184194 |
P31271 | O15550 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.285 | Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters. | SIGNOR-260022 |
P68400 | Q9Y4R8 | 1 | phosphorylation | down-regulates | 0.2 | Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1. ere, we show that tel2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (ck2) | SIGNOR-200202 |
Q15759 | O75928 | 1 | phosphorylation | up-regulates activity | 0.264 | The switch between the coactivating and inhibitory actions of PIASxα is controlled, at least in part, through PIASxα phosphorylation. PIASxα is itself phosphorylated by p38 in vitro and in vivo in response to the activation of stress signaling pathways (Figure 2, Figure 3, Figure 4). We identify Ser113 and Ser 116 as two residues that are phosphorylated by p38 and have important functional roles | SIGNOR-262947 |
P06241 | P43403 | 1 | phosphorylation | up-regulates activity | 0.574 | Subsequently, Lck and Fyn phosphorylate and activate the Syk family kinase ZAP-70 when it is recruited to the phosphorylated ITAM motifs xref . | SIGNOR-279043 |
P49768 | P55212 | 0 | cleavage | up-regulates activity | 0.372 | Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. | SIGNOR-261753 |
Q8NEZ5 | O95863 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | FBXO22 elicits its antimetastatic effects by targeting SNAIL, a master regulator of EMT and breast cancer metastasis, for ubiquitin-mediated proteasomal degradation in a glycogen synthase kinase 3β phosphorylation-dependent manner. | SIGNOR-273446 |
O60260 | P68036 | 0 | ubiquitination | up-regulates activity | 0.2 | Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1). | SIGNOR-272734 |
P15172 | Q8NG27 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | ... chromatin immunoprecipitation (ChIP) analysis showed MYOD binds to a site upstream the Pja1 promoter preferentially in C2C12 cells induced to differentiate (Fig. 2c). In addition, over-expression of MyoD in human fibroblasts is sufficient to up-regulate Pja1 expression | SIGNOR-255718 |
Q14703 | P36956 | 1 | cleavage | up-regulates activity | 0.561 | We present evidence that SKI-1 processes peptides mimicking the cleavage sites of the SKI-1 prosegment, pro-brain-derived neurotrophic factor, and the sterol regulatory element-binding protein SREBP-2 | SIGNOR-267497 |
Q15208 | Q96RD6 | 1 | phosphorylation | up-regulates activity | 0.2 | We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation. | SIGNOR-263032 |
Q6P5Z2 | Q8N392 | 1 | phosphorylation | up-regulates activity | 0.2 | We present strong evidence that PKN3-ARHGAP18 interaction is increased upon ARHGAP18 phosphorylation and that the phosphorylation of ARHGAP18 by PKN3 enhances its GAP domain activity and contributes to negative regulation of active RhoA.|These results support our data from phosphoproteomic screen and suggest that ARHGAP18 can be phosphorylated by PKN3 on Thr154, Ser156 and Thr158. | SIGNOR-264572 |
P28482 | O75582 | 1 | 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 |
Q9BXM7 | Q7KZI7 | 0 | phosphorylation | up-regulates activity | 0.367 | MARK2 phosphorylated and activated the cleaved form of PINK1 (DeltaN-PINK1 | SIGNOR-278975 |
Q9H2X6 | P04637 | 1 | phosphorylation | up-regulates | 0.797 | Based on all these observations, it is legitimate to suggest that axin and daxx seem to adopt both parallel routes and a convergent means to activate p53. In either case, hipk2 seems to be the protein kinase that catalyzes the ser46 phosphorylation. | SIGNOR-151930 |
P27361 | Q15256 | 1 | phosphorylation | up-regulates activity | 0.67 | Specifically, the complex formation between PTP-SL and ERK2 involves an unusual interaction leading to the phosphorylation of PTP-SL by ERK2 at Thr253 and the inactivating dephosphorylation of ERK2 by PTP-SL. | SIGNOR-249477 |
Q9P2J9 | P08559 | 1 | dephosphorylation | up-regulates activity | 0.658 | Pyruvate dehydrogenase phosphatase (PDP) is a mitochondrial serine phosphatase that activates phosphorylated pyruvate dehydrogenase complex by dephosphorylation | SIGNOR-251665 |
P55273 | P17252 | 0 | phosphorylation | up-regulates | 0.2 | Cdk2 and pka were found to participate in p19ink4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19ink4d induced by dna damage was shown to be dependent on serine 76 phosphorylation. | SIGNOR-197285 |
P42224 | P23470 | 0 | dephosphorylation | up-regulates activity | 0.2 | 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-254727 |
Q8WUI4 | O94806 | 0 | phosphorylation | up-regulates activity | 0.2 | Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67]. | SIGNOR-275934 |
O43318 | O75901 | 1 | phosphorylation | up-regulates activity | 0.2 | As expected, increased expression of TAK1 induced by LV-TAK1 stimulated p-RASSF9, whereas p-MEK and p-ERK were reduced.|We further identified RASSF9 as a downstream target of TAK1 which phosphorylates RASSF9 at S284. | SIGNOR-279534 |
P17252 | Q16820 | 1 | phosphorylation | down-regulates quantity | 0.2 | These findings suggest that activation of a protein kinase, presumably PKC, mediates PMA-induced hmeprinβ shedding. By labeling COS-1 cells transfected with mutant constructs lacking the potential phosphorylation sites, we identified Ser687 as the main 32P-acceptor. These data provide evidence that the cytoplasmic domain of hmeprinβ can function as a PKC substrate. | SIGNOR-263172 |
Q16539 | P18850 | 1 | phosphorylation | up-regulates activity | 0.585 | This observation not only confirms the specific role for IFN-γ-induced p38 MAPK-dependent phosphorylation of ATF6 at the T166 site but also indicates a connection between phosphorylation and proteolytic activation. | SIGNOR-276841 |
Q06124 | P21802 | 1 | dephosphorylation | down-regulates activity | 0.622 | In forming this heterotetrameric complex Grb2 inhibits both the dephosphorylation of FGFR2 by Shp2 and the phosphorylation of Shp2 by FGFR2 (XREF_FIG, respectively).|Knockdown of Grb2 elevates Shp2 phosphorylation (XREF_FIG), strongly suggesting that the inability of Shp2 to interact directly with the receptor in the presence of Grb2 prevents FGFR2 kinase activity toward Shp2. | SIGNOR-277030 |
P00734 | P12259 | 1 | null | up-regulates activity | 0.882 | Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind | SIGNOR-263530 |
Q16539 | P47712 | 1 | phosphorylation | up-regulates activity | 0.668 | These results provide the first direct evidence that p38 kinase is responsible for cpla2 phosphorylation in sfllrn-stimulated platelets and is involved in the early phosphorylation of cpla2 in thrombin-stimulated platelets | SIGNOR-44673 |
P08670 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.423 | By identifying eight aurora-b phosphorylation sites on vimentin in vitro, we have demonstrated that vimentin-ser-72 is an in vitrophosphorylation site of aurora-b. in vitro analyses revealed that aurora-b phosphorylates vimentin at approximately 2 mol phosphate/mol of substrate for 30 min and that this phosphorylation dramatically inhibits vimentin filament formation. | SIGNOR-96057 |
P29475 | Q13424 | 0 | relocalization | up-regulates | 0.558 | biochemical studies showed that the N-terminal PDZ domain of nNOS binds to a similar PDZ domain of syntrophin (Fig. 1), a dystrophin-associated protein | SIGNOR-236916 |
Q9NRY4 | Q13464 | 0 | phosphorylation | down-regulates activity | 0.414 | these results indicate that Rho-kinase can phosphorylate p190A RhoGAP at Ser1150 in COS7 cells. Similarly, the immunoblot analysis, through the use of the anti-p190A RhoGAP-pT1226 and -pS1236 antibodies, revealed that Rho-kinase can phosphorylate p190A RhoGAP at Thr1226 and Ser1236 in COS7 cells | SIGNOR-276177 |
Q13485 | P27361 | 0 | phosphorylation | up-regulates | 0.419 | Our results suggest that map kinase can phosphorylate thr276 of smad4 and that phosphorylation can lead to enhanced tgf-beta-induced nuclear accumulation and, as a consequence, enhanced transcriptional activity of smad4. | SIGNOR-101664 |
P50750 | Q96PM5 | 1 | phosphorylation | down-regulates | 0.46 | We showed that cdk9 phosphorylates pirh2 on ser-211 and thr-217 residues through their physical interaction. Phosphorylation of pirh2 renders it inactive and may contribute to p53-inhibition of transcriptional elongation of the hiv-1 ltr. | SIGNOR-201923 |
P35367 | P17612 | 0 | phosphorylation | down-regulates | 0.2 | Two amino acid residues (ser396, ser398) on hr1 were determined to be pkc phosphorylation sites by in vitro phosphorylation studies.Site-directed mutagenesis studies suggests that the ser398 residue was primarily involved in pkc-mediated desensitization. Possibly, phosphorylation of the residues is required for receptor transport from endosomes to lysosomes. | SIGNOR-128411 |
Q9H2X6 | O15379 | 1 | phosphorylation | down-regulates activity | 0.2 | Mechanistically, HIPK2 bound and phosphorylated histone deacetylase 3 (HDAC3) at serine 374 to inhibit its enzymatic activity, thus reducing the deacetylation of p65 at lysine 218 to suppress NF-κB activation. | SIGNOR-277568 |
Q8TD19 | Q8NHV4 | 1 | phosphorylation | up-regulates activity | 0.426 | Nek9 phosphorylates NEDD1 on Ser377 driving its recruitment and thereby that of γ-tubulin to the centrosome in mitotic cells. | SIGNOR-263016 |
P51955 | Q13257 | 1 | phosphorylation | down-regulates activity | 0.845 | We demonstrated that overexpression of Nek2 can enhance the ability of Mad2 to cause delays in cell division.|We have demonstrated that Nek2 can bind and phosphorylate Mad2 and Cdc20. | SIGNOR-278446 |
Q9NTX7 | Q9Y2T1 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.671 | Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation. | SIGNOR-263336 |
P42345 | P06213 | 1 | phosphorylation | up-regulates activity | 0.391 | Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR and InsR. | SIGNOR-280045 |
O14746 | P12931 | 0 | phosphorylation | down-regulates | 0.418 | Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via src kinase family-dependent phosphorylation of tyrosine 707 | SIGNOR-102097 |
Q00534 | P30304 | 0 | dephosphorylation | up-regulates activity | 0.704 | Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs. | SIGNOR-267569 |
Q9H1Y0 | Q92995 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.274 | Here, we identified USP13 as an essential deubiquitinase that stabilizes ATG5 in a process that depends on the PAK1 serine/threonine-protein kinase and which enhances autophagy and promotes IM resistance in GIST cells. | SIGNOR-275838 |
Q13651 | O60674 | 1 | phosphorylation | up-regulates activity | 0.432 | IL10R2 recruits cytoplasmic protein Jak1 followed by phosphorylation of tyrosine at position 705 in the STAT3 (705Y-STAT3) molecule. Phosphorylated STAT3 forms a homodimer, which is then translocated to the nucleus to facilitate transcriptional regulation of target genes. | SIGNOR-249545 |
Q96M98 | O60260 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | In this study, we found that CHIP promotes Parkin-mediated Pael-R ubiquitination and subsequent degradation. In vitro ubiquitination assays suggested that only a combination of both Parkin and its cofactor CHIP function as a ubiquitin ligase, which is able to sufficiently ubiquitinate Pael-R in vivo (Figure 6). | SIGNOR-272889 |
P05412 | P49841 | 0 | phosphorylation | down-regulates activity | 0.712 | The c-jun and c-myc oncogenic transcription factors are highly unstable proteins due to polyubiquitination. Similar to c-myc, we report here that phosphorylation of c-jun by gsk3 creates a high-affinity binding site for the e3 ligase fbw7, which targets c-jun for polyubiquitination and proteasomal degradation similar to c-myc, we report here that phosphorylation of c-jun by gsk3 creates a high-affinity binding site for the e3 ligase fbw7, which targets c-jun for polyubiquitination and proteasomal degradation.Phosphorylation of Thr-239 and Ser-243 is required for Fbw7-mediated c-Jun disappearance | SIGNOR-236717 |
P18146 | Q14774 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.262 | In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells. | SIGNOR-261621 |
Q02750 | P32121 | 1 | phosphorylation | up-regulates activity | 0.587 | Here, we show that activation of serotonin 5-HT2C receptors, which engage Erk1/2 pathway via a _-arrestin-dependent mechanism, promotes MEK-dependent _-arrestin2 phosphorylation at Thr383 | SIGNOR-252027 |
P41091 | Q13144 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.735 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269133 |
P15976 | P31749 | 0 | phosphorylation | up-regulates | 0.514 | We found that akt directly phosphorylates the transcription factor gata-1 at serine 310 and that this site-specific phosphorylation is required for the transcriptional activation of the timp-1 promoter. | SIGNOR-139782 |
Q9UL17 | P01579 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.475 | T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells | SIGNOR-266234 |
P16662 | P12931 | 0 | phosphorylation | up-regulates | 0.343 | Overexpression of regular or active src, but not dominant-negative src, in 2b7-transfected cos-1 cells increased 2b7 activity and phospho-y438-2b7 by 50% | SIGNOR-184613 |
Q9Y2K6 | Q9HAW4 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.508 | USP20 deubiquitinates and stabilizes Claspin. | SIGNOR-272821 |
P11308 | P33151 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.278 | Erg overexpression resulted in an approximate 1.8-fold transactivation of VE-cadherin promoter activity. Thus, our data indicate that Erg drives constitutive VE-cadherin expression in human ECs | SIGNOR-261595 |
Q712K3 | P68400 | 0 | phosphorylation | up-regulates activity | 0.338 | Ck2-dependent phosphorylation of the e2 ubiquitin conjugating enzyme ubc3b induces its interaction with beta-trcp and enhances beta-catenin degradation | SIGNOR-88050 |
P45983 | P41970 | 1 | phosphorylation | down-regulates activity | 0.323 | JNK binds to the J box in the middle of the protein, and binding is required for phosphorylation of the adjacent EXport motif. Both the binding and phosphorylation sites (the JEX element) are important for Net export. | SIGNOR-250139 |
P04234 | O60858 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | RFP2, a gene frequently lost in various malignancies, encodes a protein with RING finger, B-box, and coiled-coil domains that belongs to the RBCC/TRIM family of proteins.Rfp2 Regulates the Stability of the ERAD Substrate CD3-δ. In summary, these experiments demonstrate that Rfp2 functions as a RING-dependent ERAD E3 ubiquitin ligase and regulates the degradation of the ER substrate, CD3-δ. | SIGNOR-271644 |
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