IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q5JR12 | P53779 | 0 | phosphorylation | down-regulates | 0.2 | Specific phosphorylation of pp2czeta at ser (92) by stress-activated jnk attenuates its phosphatase activity in cells. | SIGNOR-178926 |
Q04912 | P35222 | 1 | phosphorylation | up-regulates activity | 0.327 | Ron and beta-catenin associate and Ron kinase activity leads to tyrosine phosphorylation of beta-catenin.|We also show that tyrosine residues 654 and 670 of beta-catenin are important in mediating Ron induced beta-catenin transcriptional activation and cell growth. | SIGNOR-279376 |
P78352 | Q8NFZ4 | 0 | relocalization | up-regulates activity | 0.759 | Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions. | SIGNOR-264193 |
P68400 | Q04206 | 1 | phosphorylation | up-regulates activity | 0.443 | We demonstrate that casein kinase II (CKII) interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A CKII inhibitor (PD144795) inhibited TNFalpha-induced p65 phosphorylation in vivo. Furthermore, our results indicate that the association between IkappaBalpha and p65 inhibits p65 phosphorylation by CKII and that degradation of IkappaBalpha allows CKII to phosphorylate p65 to increase NF-kappaB transactivation potential. | SIGNOR-250942 |
Q7Z6Z7 | P04198 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.423 | HUWE1 ubiquitinates and directs MYCN degradation to the proteasome. | SIGNOR-278750 |
Q9Y2I7 | P31749 | 0 | phosphorylation | up-regulates | 0.491 | Here we report that serine318 on the fyve domain-containing ptdins3p 5-kinase (pikfyve) is a novel substrate for pkb, and show that phosphorylation stimulates the ptdins3p 5-kinase activity of the enzyme. | SIGNOR-252474 |
Q71U36 | Q92949 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.298 | FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1). | SIGNOR-266938 |
P12931 | P06396 | 1 | phosphorylation | up-regulates | 0.572 | Identification of tyr438 as the major in vitro c-src phosphorylation site in human gelsolin recently | SIGNOR-67014 |
P05771 | P09211 | 1 | phosphorylation | up-regulates activity | 0.2 | Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently | SIGNOR-276023 |
O14757 | P12931 | 1 | phosphorylation | up-regulates activity | 0.338 | In this study, we show that Chk1 phosphorylates human Src at the newly identified site serine 51 to fully induce Src kinase activity. | SIGNOR-278332 |
P12931 | P31645 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.258 | We found that 1) SERT exists in a tyrosine-phosphorylated form, 2) inhibition of tyrosine kinase(s) reduces SERT expression levels by facilitating SERT protein degradation, 3) Src-kinase activity up-regulates SERT protein expression with a concomitant increase in 5-HT uptake and tyrosine phosphorylation, and 4) mutation of Tyr47 or Tyr142 abolishes src-induced increases in transport function and phosphorylation of SERT. | SIGNOR-276386 |
P05106 | P12931 | 0 | phosphorylation | down-regulates activity | 0.661 | The phosphorylation level of beta(3) integrin was modulated using a temperature-sensitive v-Src kinase. Increased beta(3) phosphorylation abolished alpha(v)beta(3)- but not alpha(5)beta(1)-mediated adhesion to fibronectin. Thus, phosphorylation of the cytoplasmic domain of beta(3) is a negative regulator of alpha(v)beta(3)-fibronectin binding strength. | SIGNOR-247207 |
P36873 | P31749 | 1 | dephosphorylation | down-regulates activity | 0.383 | Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells | SIGNOR-252605 |
P10636-2 | P05129 | 0 | phosphorylation | down-regulates activity | 0.27 | We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs. | SIGNOR-275445 |
Q99719 | O60260 | 0 | ubiquitination | down-regulates quantity | 0.2 | Furthermore, Parkin ubiquitinates and promotes the degradation of CDCrel-1.|Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. | SIGNOR-278711 |
P49840 | P52630 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.263 | GSK3α/β are critical kinases to regulate STAT2 protein stability mediated by FBXW7.The 4-point mutant (STAT2-4A) of STAT2 at S381A/T385A/E389A/S393A inhibited GSK3α/β-mediated STAT2 phosphorylation. | SIGNOR-276761 |
Q9NYA1 | P19525 | 0 | phosphorylation | up-regulates activity | 0.2 | This suggests that PKR is critical in the phosphorylation of SPHK1 at Ser225.|We confirmed that phosphorylated PKR activates SPHK1 kinase activity, but it remained necessary to determine whether there has mutual correlation or any reciprocal effect between these two kinases in stressed cells. | SIGNOR-278514 |
Q93034 | O75553 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.327 | SOCS7 promotes Dab1 polyubiquitylation and degradation. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. SOCS7, a CRL5 substrate adaptor protein, is also required for neocortical layering. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. | SIGNOR-272140 |
P31749 | P31152 | 0 | phosphorylation | up-regulates activity | 0.271 | Mechanistically, MAPK4 directly bound and activated AKT by phosphorylation of the activation loop at threonine 308. | SIGNOR-275450 |
Q9Y5B0 | P06493 | 1 | dephosphorylation | down-regulates activity | 0.333 | Thus, Fcp1 coordinates Cdk1 and Gwl inactivation to derepress PP2A-B55, generating a dephosphorylation switch that drives mitosis progression.|We can not exclude that, in addition to S90 and S453, other Cdk1 phosphorylation sites in Gwl are dephosphorylated by Fcp1; nevertheless, assaying S67-Ensa kinase activity of V5-GwlS90A and V5-GwlS453A mutant proteins, isolated from transfected and prometaphase arrested HeLa cells, revealed that both mutants had significantly reduced S67-Ensa kinase activity compared to V5-GwlWT (XREF_FIG).|We show here that activation of PP2A-B55, a major mitosis exit phosphatase, required the phosphatase Fcp1 downstream Cdk1 inactivation in human cells. | SIGNOR-277141 |
O14974 | O60285 | 0 | phosphorylation | down-regulates | 0.507 | Phosphorylation of ser(445), ser(472), and ser(910) of mypt1 by nuak1 promoted the interaction of mypt1 with 14-3-3 adaptor proteins, thereby suppressing phosphatase activity. | SIGNOR-164747 |
P06493 | Q8TF76 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation by Cyclin B-Cdk1 allows Haspin to bind Plk1-PBD. Phosphorylation of Haspin at T128 and Plk1 target sites is required for full H3T3ph generation and normal Aurora B localization in mitosis. | SIGNOR-275419 |
Q9UHC7 | P38936 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.313 | Makorin Ring Finger Protein 1 (MKRN1) is a transcriptional co-regulator and an E3 ligase. Here, we show that MKRN1 simultaneously functions as a differentially negative regulator of p53 and p21. In normal conditions, MKRN1 could destabilize both p53 and p21 through ubiquitination and proteasome-dependent degradation. As a result, depletion of MKRN1 induced growth arrest through activation of p53 and p21. | SIGNOR-271845 |
P19419 | O75582 | 0 | phosphorylation | up-regulates | 0.2 | Phosphorylation on ser383 and ser389 of elk-1 by mapk enhances this basal binding but, most importantly, elk-1 exhibits new interactions with p300. | SIGNOR-85514 |
P17612 | Q13224 | 1 | phosphorylation | up-regulates activity | 0.414 | Here we identify serine residue 1166 (Ser1166) in the carboxy-terminal tail of the NMDAR subunit GluN2B to be a direct molecular and functional target of PKA phosphorylation critical to NMDAR-dependent Ca(2+) permeation and Ca(2+) signaling in spines. | SIGNOR-276616 |
P08631 | Q9UHD2 | 1 | phosphorylation | down-regulates activity | 0.2 | The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation. | SIGNOR-276727 |
O60500 | P06241 | 0 | phosphorylation | up-regulates activity | 0.738 | Fyn directly bound Nephrin via its SH3 domain, and Fyn directly phosphorylated Nephrin.|Similar to Fyn deletion, simultaneous deletion of Fyn and Yes reduced Nephrin phosphorylating activity. | SIGNOR-279523 |
P12931 | Q03135 | 1 | phosphorylation | down-regulates activity | 0.764 | Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn | SIGNOR-118007 |
P35354 | P59594 | 0 | transcriptional regulation | up-regulates activity | 0.2 | Spike protein of SARS‐CoV activated COX‐2 expression in a protein concentration‐dependent manner | SIGNOR-262315 |
Q02556 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.353 | We found that Bcr-abl-induced, Shp2 dependent dephosphorylation of Icsbp impaired repression of GAS2 by this transcription factor. | SIGNOR-277173 |
Q05397 | Q00535 | 0 | phosphorylation | up-regulates | 0.305 | Here, we show that fak phosphorylation by cdk5 at s732 is important for microtubule organization, nuclear movement, and neuronal migration. In cultured neurons, s732-phosphorylated fak is enriched along a centrosome-associated microtubule fork that abuts the nucleus. Overexpression of the nonphosphorylatable mutant fak s732a results in disorganization of the microtubule fork and impairment of nuclear movement in vitro, and neuronal positioning defects in vivo. | SIGNOR-86223 |
P05556 | Q9GZZ0 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Consistently, ITGB1 promoter activity was decreased by HOXD1 knockdown in ECs. Furthermore, we identified the putative HOXD1-binding sites in the promoter region of ITGB1. Together, these findings suggest that HOXD1 plays a significant role in EC functions by regulating the expression of ITGB1. | SIGNOR-261648 |
Q9H0M0 | Q13887 | 1 | ubiquitination | up-regulates activity | 0.459 | WWP1 and Smurf2 were adopted to induce ubiquitination of endogenous KLF5 protein in cells.|WWP1 or Smurf2 degrades KLF5 by ubiquitination to repress fracture healing. | SIGNOR-278683 |
P62714 | P31751 | 1 | dephosphorylation | down-regulates | 0.481 | These results confirm that the activity changes observed are achieved by a reversible phosphorylation mechanism, and also argue that pp2a may negatively regulate rac-pk activity in vivo. Dephosphorylation of the activated rac-pk in itro by pp2ac resulted in an 87% reduction of kinase activity | SIGNOR-42123 |
Q16539 | P23769 | 1 | phosphorylation | up-regulates | 0.269 | P38_ increases gata_2 activity at endogenous target genes by inducing gata_2 multi_site phosphorylation. | SIGNOR-205242 |
O43318 | O00743 | 0 | dephosphorylation | down-regulates activity | 0.372 | Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway|From proteomic analysis of TAK1-binding proteins, we identified protein phosphatase 6 (PP6), a type-2A phosphatase, and demonstrated that PP6 associated with and inactivated TAK1 by dephosphorylation of Thr-187. | SIGNOR-248292 |
Q13200 | Q05086 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.277 | 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-265133 |
P68431 | O15054 | 0 | demethylation | down-regulates activity | 0.2 | Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) and Jumonji D3 (JMJD3) as novel histone demethylases that catalyze the removal of di- and trimethyl groups on histone H3 lysine 27, thereby promoting target gene activation. | SIGNOR-260018 |
O43353 | Q5S007 | 0 | phosphorylation | up-regulates activity | 0.376 | Altogether, our results indicate a scenario that LRRK2 physically interacts with Rip2 and promotes phosphorylation of Rip2.|Taken together, our results show that LRRK2 enhances Rip2 activity by promoting the phosphorylation of Rip2 at Ser176. | SIGNOR-278953 |
Q14164 | Q14653 | 1 | phosphorylation | up-regulates activity | 0.741 | Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. | SIGNOR-178379 |
Q71F23 | P53350 | 0 | phosphorylation | down-regulates | 0.741 | S77 and t78 of pbip1 are important for plk1-dependent pbip1 phosphorylation and degradation. Here, we demonstrate that a pbd-binding protein, pbip1, is crucial for recruiting plk1 to the interphase and mitotic kinetochores. Unprecedentedly, plk1 phosphorylated pbip1 at t78. Later in mitosis, plk1 also induced pbip1 degradation in a t78-dependent manner, thereby enabling itself to interact with other components critical for proper kinetochore functions | SIGNOR-150457 |
P05198 | Q13144 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.84 | 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-269123 |
Q9UK17 | P07948 | 0 | 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-276395 |
Q9Y4K3 | P14778 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.9 | We found that of all TRAFs and E3 ligases examined, TRAF6 preferentially ubiquitinated IL-1R1. | SIGNOR-278576 |
P12830 | O14757 | 0 | phosphorylation | down-regulates activity | 0.301 | Phosphorylation of Cdh1 by Chk1 promotes recognition of Cdh1 by SCF betaTRCP1.|These data suggest that Chk1 negatively regulates APC/C Cdh1 activity by both promoting Cdh1 destruction and by destabilizing its association with the APC/C. | SIGNOR-278396 |
Q9NRX4 | O15554 | 1 | dephosphorylation | down-regulates activity | 0.549 | We now show that the mammalian protein histidine phosphatase (PHPT-1) directly binds and inhibits KCa3.1 by dephosphorylating histidine 358 on KCa3.1.|Overexpression of wild-type, but not a phosphatase dead, PHPT-1 inhibited KCa3.1 channel activity. | SIGNOR-277071 |
O60674 | P29350 | 0 | dephosphorylation | down-regulates activity | 0.729 | Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1 | SIGNOR-248466 |
Q9UJD0 | Q96E17 | 1 | relocalization | up-regulates activity | 0.26 | N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle | SIGNOR-264380 |
Q9NRA8 | P45983 | 0 | phosphorylation | up-regulates | 0.322 | Identification of 4e-t phosphorylation sites regulated by jnk. identification of these residues as phosphorylation sites (ser301, ser374, ser513, ser587, ser693, and ser752) was obtained by ms/ms sequencing, these results demonstrate that jnk activity is required to stimulate the assembly of pbs in response to oxidative stress. | SIGNOR-199004 |
Q13562 | O00712 | 0 | transcriptional regulation | up-regulates quantity | 0.282 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268897 |
Q8WZ73 | Q13546 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.468 | We report that CARP-2, a RING domain-containing ubiquitin protein ligase (E3), is a negative regulator of TNF-induced NF-kappaB activation. By virtue of its phospholipid-binding FYVE domain, CARP-2 localized to endocytic vesicles, where it interacted with internalized TNF-receptor complex, resulting in RIP ubiquitination and degradation. | SIGNOR-271482 |
Q14653 | P0C6X7-PRO_0000037311 | 0 | deubiquitination | down-regulates activity | 0.2 | Here we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro’s DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response. | SIGNOR-260249 |
Q13315 | Q9UPU5 | 1 | phosphorylation | up-regulates activity | 0.25 | Taken together, these data suggest that the ATM kinase mediated phosphorylation of USP24 is involved in USP24 stabilization/up regulation following UV irradiation.|Taken together, these data suggest that the ATM kinase-mediated phosphorylation of USP24 is involved in USP24 stabilization/up-regulation following UV irradiation. | SIGNOR-280043 |
P17612 | Q9NPC2 | 1 | phosphorylation | up-regulates | 0.2 | Patch clamp analysis, flow cytometry, and immunocytochemistry studies of hek293 transfected with wt hk2p3.1 and cultured in the presence of pka activators or inhibitors all confirm that activation of pka resulted in an increase in hk2p3.1 current expression (figs. 4_4?6) and demonstrate the dynamic regulatory effect of pka activity on k2p3.1 channel expression. | SIGNOR-172466 |
P07948 | Q9HCP0 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane. | SIGNOR-275396 |
P22681 | P62993 | 0 | relocalization | up-regulates | 0.904 | The underlying mechanism seems to involve recruitment of a grb2 c-cbl complex to grb2-specific docking sites of egfr, and concurrent acceleration of receptor ubiquitylation and desensitization. | SIGNOR-114704 |
P60174 | P12931 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | As shown in xref , Tim was phosphorylated by both Hck and c-Src, and to a lesser extent by Fyn and c-Yes.|In the case of Hck and Fyn, co-expression led to enhanced Tim turnover, while c-Src and c-Yes promoted Tim stability. | SIGNOR-280136 |
P12931 | Q07912 | 1 | phosphorylation | up-regulates activity | 0.385 | We identified two Src phosphorylation sites within the MHR (Y859, Y860). Addition of Src-phosphorylated MHR to the Ack1 KD enhanced enzymatic activity. | SIGNOR-276342 |
Q9BYP7 | Q9H4A3 | 1 | phosphorylation | up-regulates activity | 0.282 | We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro. | SIGNOR-260789 |
Q96S44 | P04637 | 1 | phosphorylation | up-regulates | 0.76 | The intrinsic transcriptional activity of p53 was up-regulated by a transient transfection of prpk to cos-7 cells. Prpk was shown to bind to p53 and to phosphorylate p53 at ser-15. | SIGNOR-157471 |
O15151 | P48729 | 0 | phosphorylation | up-regulates | 0.371 | Previous studies showed that casein kinase 1? (ck1?) Stably associates with mdmx, stimulates mdmx-p53 binding, and cooperates with mdmx to inactivate p53ck1? Binding to the mdmx central domain and phosphorylation of s289 disrupts the intramolecular interaction, allowing the n terminus to bind p53 with increased affinity. After dna damage, the mdmx-ck1? Complex is disrupted by chk2-mediated phosphorylation of mdmx at s367, leading to reduced mdmx-p53 binding. | SIGNOR-199015 |
O43318 | Q9NQC7 | 0 | deubiquitination | up-regulates activity | 0.636 | Mechanistically, CYLD interacts directly with the kinase TAK1 and removes its K63-linked polyubiquitin chain, which blocks downstream activation of the JNK-p38 cascades. | SIGNOR-266437 |
O60260 | P27695 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Based on these results, we conclude that Parkin directly ubiquitinates APE1.|These results indicated that degradation of APE1 by Parkin was limited compared to the transiently expressed APE1, suggesting that a large portion of APE1 is not in contact with the Parkin and PINK1 without induction of stresses such as oxidative stress. | SIGNOR-278531 |
P18031 | O43561 | 1 | dephosphorylation | down-regulates activity | 0.504 | Using a pharmacological inhibitor, we provide evidence that PTP1B activation and LAT dephosphorylation processes were required for irreversible platelet aggregation.|In collagen-stimulated platelets, the signaling complexes recruited by tyrosine-phosphorylated LAT are essential for PLCgamma2 activation | SIGNOR-248403 |
O15084 | P49840 | 0 | phosphorylation | down-regulates activity | 0.2 | We provide evidence for a dual kinase-mediated regulation of the PITK holoenzyme whereby PITK phosphorylation at S1017 is catalyzed by calcium/calmodulin-dependent kinase II-delta (CaMKIIdelta), promoting the subsequent phosphorylation of S1013 by glycogen synthase kinase-3 (GSK3) in vitro.|the phosphorylation of PITK at these specific residues altered PP1 binding and subsequent PITK-directed dephosphorylation of hnRNP K | SIGNOR-264792 |
Q01151 | Q8TEB7 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.352 | In this study, we show that GRAIL can down-modulate the expression of CD83 (previously described as a cell surface marker for mature dendritic cells) on CD4 T cells. GRAIL-mediated down-modulation of CD83 is dependent on an intact GRAIL extracellular protease-associated domain and an enzymatically active cytosolic RING domain, and proceeds via the ubiquitin-dependent 26S proteosome pathway. Ubiquitin modification of lysine residues K168 and K183, but not K192, in the cytoplasmic domain of CD83 was shown to be necessary for GRAIL-mediated degradation of CD83. | SIGNOR-271850 |
Q13568 | P42229 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.287 | The GM-CSF receptor forms a dodecamer structure and recruits JAK2, leading to the activation of STAT5, extracellular signal-regulated kinase (ERK), V-Akt murine thymoma viral oncogene homolog 1 (AKT), and the nuclear translocation of NF-kappaB and IRF5 | SIGNOR-249508 |
P17612 | O95477 | 1 | phosphorylation | up-regulates activity | 0.508 | Ser-1042 and Ser-2054, located in the nucleotide binding domains of ABCA1, are major phosphorylation sites for PKA. ABCA1 phosphorylation may affect ApoA-I-dependent phospholipid efflux by either altering the conformation of the protein to a more active state or by affecting the interaction between ABCA1 and its partner proteins. | SIGNOR-250326 |
Q9H211 | P45983 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.368 | We discovered that human Cdt1, an essential origin licensing protein whose activity must be restricted to G(1) phase, is a substrate of the stress-activated mitogen-activated protein (MAP) kinases p38 and c-Jun N-terminal kinase (JNK). These MAP kinases phosphorylate Cdt1 both during unperturbed G(2) phase and during an acute stress response. Phosphorylation renders Cdt1 resistant to ubiquitin-mediated degradation during S phase and after DNA damage by blocking Cdt1 binding to the Cul4 adaptor, Cdt2. | SIGNOR-276361 |
O14793 | Q9UBK2 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.361 | PGC-1 alpha specifically induces IGF1 and represses myostatin, and expression of PGC-1a 4 in vitro and in vivo induces robust skeletal muscle hypertrophy | SIGNOR-256151 |
P05771 | P43629 | 1 | phosphorylation | down-regulates activity | 0.2 | Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII. | SIGNOR-276079 |
Q9UM73 | P29353 | 1 | phosphorylation | up-regulates | 0.456 | Anaplastic lymphoma kinase (alk), which turned out to be one of these phosphoproteins, was constitutively activated and associated with the ptb domain of shcc in three neuroblastoma cells. In vitro kinase assay revealed that shcc is a potent substrate of the activated alk kinase. The alk gene locus was significantly amplified in both of these cell lines, suggesting that gene amplification leads to constitutive activation of the alk kinase, which results in hyperphosphorylation of shcc. | SIGNOR-91534 |
Q2M2I8 | Q9BXS5 | 1 | phosphorylation | up-regulates | 0.2 | Aak1 is enriched at presynaptic terminals, whereas in nonneuronal cells it colocalizes with clathrin and ap2 in clathrin-coated pits and at the leading edge of migrating cells. Aak1 specifically phosphorylates the mu subunit in vitro, and stage-specific assays for endocytosis show that mu phosphorylation by aak1 results in a decrease in ap2-stimulated transferrin internalization. Together, these results provide strong evidence that aak1 is the endogenous mu 2 kinase and plays a regulatory role in clathrin-mediated endocytosis. | SIGNOR-115589 |
Q9Y2I7 | Q96BR1 | 0 | phosphorylation | up-regulates activity | 0.461 | The Western blot in XREF_FIG demonstrates that SGK3 as well as PKB phosphorylate PIKfyve at position S318, thereby indicating that PIKfyve could be a physiological target of SGK3.|We here identify a novel mechanism involving NMDA receptor triggered, SGK3 dependent stimulation of PIKfyve with subsequent formation of PI (3,5) P 2, which modulates RAB11A facilitated vesicle transport to the plasma membrane, leading to an increased abundance of GluA1 receptor subunits in the plasma membrane. | SIGNOR-279113 |
P06239 | P16284 | 1 | phosphorylation | up-regulates activity | 0.588 | We demonstrated that phosphorylation of PECAM-1 by Src or Csk family kinases was sufficient to trigger its association with SHP-2. Moreover, it was able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine phosphatase expressed in hemopoietic cells. Taken together, these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM-1 and triggering its association with SH2 domain-containing phosphatases under physiological circumstances. | SIGNOR-262742 |
Q12860 | Q9UHC6 | 0 | relocalization | up-regulates activity | 0.477 | These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr. | SIGNOR-269074 |
Q9P2K8 | P05198 | 1 | phosphorylation | down-regulates activity | 0.914 | Translation initiation factor 2α [eukaryotic translation initiation factor 2α (eIF2α)] kinase phosphorylates serine51 (Ser51) of eIF2α and downregulates cellular protein synthesis. | SIGNOR-246157 |
P25054 | P11926 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.268 | APC-dependent regulation of ornithine decarboxylase in human colon tumor cells|Upon induction of APC expression, ODC promoter activity and RNA levels were suppressed | SIGNOR-253670 |
P17252 | Q13393 | 1 | phosphorylation | up-regulates | 0.714 | Serine 2, threonine 147, and serine 561 were identified as phosphorylation sites of pld1 by pkcalpha in the cells. | SIGNOR-69938 |
P24941 | P33981 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.411 | Cdk2 phosphorylates Mps1 at T468, attenuating the function of a degradation signal found in amino acids 420\u2013507 (encoded by exons 12 and 13) and allowing the accumulation of a centrosomal pool of Mps1 that represents no more than 10% of total cellular Mps1 ( xref ). | SIGNOR-279398 |
Q6N021 | Q02750 | 0 | 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 |
P10301 | P29323 | 0 | phosphorylation | down-regulates activity | 0.612 | Tyrosine 66 of R-Ras is phosphorylated by EphB2|. R-Ras, a small intracellular GTPase, regulates the binding of integrins to their ligands outside the cell. |Cells in which EphB2 is activated become poorly adherent to substrates coated with integrin ligands, and a tyrosine residue in the R-Ras effector domain is phosphorylated. | SIGNOR-251125 |
P10275 | Q07912 | 0 | phosphorylation | up-regulates activity | 0.545 | Ack1 interacted with and phosphorylated AR protein at Tyr 267 and Ack1 was shown to be required for optimal AR target gene expression and AR recruitment.|Two intracellular tyrosine kinases, Ack1 (activated cdc42 associated kinase) and Src, phosphorylate and enhance AR activity and promote prostate xenograft tumor growth in castrated animals. | SIGNOR-278194 |
O14795 | Q86UR5 | 0 | relocalization | up-regulates activity | 0.798 | N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle | SIGNOR-264385 |
P69905 | P17509 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | HOXB6 protein represses globin transcript levels in stably transfected K562 cells in a DNA-binding dependent fashion. | SIGNOR-261637 |
Q9Y613 | Q13464 | 0 | phosphorylation | up-regulates | 0.309 | Rock phosphorylates the c-terminal residues ser1131, ser1137, and thr1141 of formin homology domain protein 1 (fhod1). Phosphorylation of fhod1 at the three residues fully disrupts the autoinhibitory interaction, which culminates in formation of stress fibres. | SIGNOR-160548 |
O60674 | Q13651 | 0 | 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 |
Q04206 | Q96JY6 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.347 | Here we report that PDLIM2 negatively regulated NF-kappaB activity, acting as a nuclear ubiquitin E3 ligase targeting the p65 subunit of NF-kappaB. PDLIM2 bound to p65 and promoted p65 polyubiquitination. | SIGNOR-271651 |
P10721 | P42224 | 1 | phosphorylation | up-regulates activity | 0.725 | KIT is responsible for the permanent phosphorylation of all three STAT proteins. STAT1, -3, and -5 were phosphorylated on their activation-specific Tyr701, Tyr704, and Tyr694, respectively, following KIT stimulation. | SIGNOR-251365 |
P15311 | P61586 | 0 | phosphorylation | up-regulates activity | 0.76 | Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies. | SIGNOR-268429 |
P48735 | P36888 | 0 | phosphorylation | down-regulates activity | 0.421 | FLT3 promotes mIDH2 acetylation through Y107 phosphorylation of mIDH2 that enhances ACAT1 recruitment, | SIGNOR-267632 |
P53801 | P12931 | 0 | phosphorylation | up-regulates activity | 0.2 | Src induction leads to phosphorylation at PBF residue Y174. Abrogation of this residue results in PM retention and a markedly reduced ability to bind NIS. | SIGNOR-273810 |
Q14980 | P53350 | 0 | phosphorylation | down-regulates activity | 0.534 | Phosphorylation of NuMA by Plk1 at 1833/34 residue can impact its cortical localization.|These data strongly suggest that Plk1 negatively regulate cortical NuMA localization and that this impact of Plk1 on NuMA is presumably independent of LGN, at least in the anaphase cells. | SIGNOR-279345 |
Q8TCQ1 | P79483 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination. | SIGNOR-271410 |
P35503 | P17252 | 0 | phosphorylation | up-regulates activity | 0.2 | Curcumin and calphostin C suppressed the activity and phosphorylation of recombinant UGT1A3 expressed in Sf9 cells. These results indicate that UGT1A3 undergoes phosphorylation, which is required for its catalytic activity. Calphostin C is a highly specific protein kinase C (PKC) inhibitor, so three predicted PKC phosphorylation sites in UGT1A3 were examined. In conclusion, phosphorylation plays an important role in UGT1A3 activity, and the serine at site 43 in UGT1A3 is most likely a phosphorylation site. | SIGNOR-273823 |
Q05655 | P06241 | 0 | phosphorylation | up-regulates activity | 0.597 | In conclusion, our in vitro data and previous report ( xref ) demonstrate that Fyn phosphorylation of Y311 on PKC\u03b4 activates the apoptotic signaling cascade in DAergic neurons in response to neurotoxic insults. | SIGNOR-279737 |
Q9NX47 | O75460 | 1 | ubiquitination | down-regulates activity | 0.2 | MITOL promotes K63-linked chain ubiquitination of IRE1\u03b1 at lysine 481 (K481), thereby preventing hyper-oligomerization of IRE1\u03b1 and regulated IRE1\u03b1-dependent decay (RIDD). | SIGNOR-278609 |
Q6IQ55 | O00139 | 1 | phosphorylation | down-regulates activity | 0.406 | TTBK2 phosphorylates KIF2A primarily at growing MT ends and counteracts the depolymerization activity of KIF2A | SIGNOR-260926 |
P01574 | O15226 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.358 | Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappaB-repressing factor), a nuclear inhibitor of NF-kappaB | SIGNOR-266227 |
Q15797 | O00238 | 0 | phosphorylation | up-regulates | 0.643 | Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression. | SIGNOR-187190 |
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