IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q16236 | Q9NP59 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.257 | NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. SLC40A1 is a target gene of NFE2L2, with a putative ARE identified approximately -7 kb upstream of the SLC40A1 core promoter. | SIGNOR-279863 |
Q99626 | Q9HAW8 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.257 | Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter. | SIGNOR-253968 |
Q9Y243 | Q01860 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.257 | Here we show that in ECCs, Akt phosphorylated the master pluripotency factor Oct4 at threonine 235, and that the levels of phosphorylated Oct4 in ECCs correlated with resistance to apoptosis and tumorigenic potential. Phosphorylation of Oct4 increased its stability and facilitated its nuclear localization and its interaction with Sox2, which promoted the transcription of the core stemness genes POU5F1 and NANOG. | SIGNOR-242107 |
P49841 | Q8NHW3 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.257 | We also demonstrate that gsk-3 triggers mafa sequential phosphorylation on residues s61, t57, t53, and s49 /we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity./ Taken together, these results suggest that, in contrast to what can be expected from ubiquitination/degradation, gsk-3-mediated mafa phosphorylation increases its transactivating ability, thereby controlling its biological activity. | SIGNOR-159462 |
P06241 | P54646 | 1 | phosphorylation | down-regulates activity | 0.257 | Here we identified that Fyn phosphorylates the α subunit of AMPK on Y436 and inhibits AMPK enzymatic activity without altering the assembly state of the AMPK heterotrimeric complex. | SIGNOR-277279 |
Q9HCE7 | O95947 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.257 | Smad6 mediates Tbx6 ubiquitination and proteasomal degradation. Tbx6 forms a ternary complex with Smad6 and Smurf1. Here, we report that Tbx6 interacts directly with Smad6, an inhibitory Smad that antagonizes the BMP signal. This interaction is mediated through the Mad homology 2 (MH2) domain of Smad6 and residues 90-180 of Tbx6. We demonstrate that Smad6 facilitates the degradation of Tbx6 protein through recruitment of Smurf1, a ubiquitin E3 ligase. | SIGNOR-272784 |
Q9NWF9 | Q9NR97 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.257 | E3 ligase RNF216 (ring finger protein 216) targets TLR8 for ubiquitination and degradation. | SIGNOR-272257 |
P10646 | P98155 | 1 | binding | up-regulates | 0.257 | Binding studies revealed that full-length tfpi, but not the truncated tfpi molecule, is recognized by the very low density lipoprotein receptor (vldl receptor) indicating that this receptor is a novel high affinity endothelial cell receptor for tfpi | SIGNOR-106353 |
Q8IYT4 | Q9UJT1 | 1 | binding | down-regulates quantity by destabilization | 0.257 | Here we show that KATNAL2 is critical for numerous aspects of this developmental process, including the initiation of the axoneme from the basal body, suppression of the spermatid centriole duplication cycle, sperm nuclear sculpting via the manchette, the attachment of the acrosome to the nucleus and the tethering of elongated spermatids to Sertoli cells via the tubulobulbar complex and ultimately sperm release via spermiation. KATNAL2 does not sever microtubules composed of α- and β-tubulin but does interact with δ- and ε-tubulin | SIGNOR-267175 |
P31749 | Q92900 | 1 | phosphorylation | up-regulates activity | 0.257 | AKT-Mediated UPF1 Phosphorylation at T151 Promotes UPF1 Helicase Activity | SIGNOR-277597 |
Q15714 | P23582 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.257 | TSC-22 significantly enhanced CNP promoter activity in GH3 cells. | SIGNOR-266226 |
Q12857 | O75093 | 1 | transcriptional regulation | up-regulates quantity | 0.257 | 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-268892 |
P17948 | P63096 | 1 | phosphorylation | up-regulates activity | 0.257 | RTKs directly phosphorylate Gαi on Y154, 155, and Y320. | SIGNOR-277230 |
O15379 | P12830 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.257 | GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells. | SIGNOR-275662 |
P06493 | O94992 | 1 | phosphorylation | down-regulates activity | 0.257 | Given that Cdk1 phosphorylation promotes Clp1 nucleoplasmic accumulation upon genotoxic stress and Cdk1 phosphorylation inhibits Clp1 activity, Clp1 may be only primed by its nucleolar release but not actually active under these circumstances.|In addition, Cdk1 directly phosphorylates Clp1 on TP sites primarily in early mitosis and inhibits Clp1 catalytic activity. | SIGNOR-279508 |
Q9Y3I1 | Q96SW2 | 1 | binding | down-regulates quantity by destabilization | 0.257 | We have shown that CRBN is also targeted for degradation by SCFFbxo7 ubiquitin ligase. | SIGNOR-272311 |
Q9HCK4 | P23528 | 1 | post transcriptional regulation | up-regulates quantity by expression | 0.257 | Slit2 causes the miRNA miR-182 to release cofilin1 mRNA, potentiating cofilin1 local translation and resulting in growth cone collapse. The use of morpholinos or RNAi to knockdown robo2 and robo3 in X. laevis RGCs, would be useful to further confirm that Robo2 and Robo3 are the receptors involved in Slit2-dependent cofilin1 translation. | SIGNOR-268378 |
Q9HCU9 | O60341 | 1 | binding | up-regulates activity | 0.257 | Our results have showed that BRMS1 together with LSD1 are required for inhibition of breast cancer cell migration and invasion. Collectively, these findings demonstrate that BRMS1 executes transcriptional suppression of breast cancer metastasis by associating with the LSD1 and thus can be targeted for breast cancer therapy. | SIGNOR-266409 |
Q13443 | P21802 | 1 | cleavage | down-regulates quantity by destabilization | 0.257 | Truncated FGFR2 was observed in cells transfected with wild-type ADAM9, but not in those with inactive mutant ADAM9 (Figure 5E). In line with this, cells transfected with wild-type ADAM9 showed reduced pErK1/2 in response to FGF2 as compared to controls or cells expressing mutant ADAM9.|Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9, hence protecting FGFR2 from ADAM9-mediated ectodomain shedding on the cell surface. | SIGNOR-260300 |
Q9H4E7 | P62834 | 1 | binding | up-regulates activity | 0.257 | Mechanistic studies revealed that SLAT interacts, through its PH domain, with a key component of inside-out signaling, namely the active form of the small GTPase Rap1 (which has two isoforms, Rap1A and Rap1B). This interaction has been further shown to facilitate the interdependent recruitment of Rap1 and SLAT to the T cell immunological synapse upon TCR engagement. Furthermore, a SLAT mutant lacking its PH domain drastically inhibited LFA-1 activation and CD4(+) T cell adhesion. | SIGNOR-253365 |
P16157 | O00631 | 1 | binding | down-regulates activity | 0.257 | These results suggest that sAnk1 interacts with SLN both directly and in complex with SERCA1 and reduces SLN's inhibitory effect on SERCA1 activity. | SIGNOR-265930 |
P24468 | P10589 | 1 | binding | up-regulates | 0.257 | Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site. | SIGNOR-79443 |
Q9UQM7 | Q7Z6G8 | 1 | phosphorylation | down-regulates activity | 0.257 | CaMKII-mediated displacement of AIDA-1 out of the postsynaptic density core. The present study indicates that CaMKII activation is necessary for the NMDA-induced movement of AIDA-1 out of the PSD core. | SIGNOR-264231 |
P54646 | O14920 | 1 | phosphorylation | up-regulates | 0.257 | These results demonstrate that the ikk is a direct substrate of ampk_2 and that its phosphorylation on ser177 and ser181no initiates the activation of the ampk_2 in endothelial cells which in turn phosphorylates and activates the _-subunit of the ikk. The latter also induces a higher rate of ikk auto-inactivation and thus attenuates the activation of nf_b and the expression of inflammatory genes | SIGNOR-174405 |
P51817 | P98161 | 1 | phosphorylation | up-regulates | 0.257 | The possibility of functional interactions between pkd1-encoded polycystin-1 and prkx was suggested by the renal co-distribution of prkx and polycystin-1 and the binding and phosphorylation of the c-terminal of polycystin-1 by prkx at s4166 in vitro. Taken together these results suggest that prkx can reverse the abnormalities in epithelial adhesion, migration and morphogenesis associated with pkd1 inhibition and cyst formation in adpkd. | SIGNOR-158852 |
P18848 | Q9HA77 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.257 | 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-269417 |
O75385 | P19367 | 1 | phosphorylation | up-regulates activity | 0.257 | Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown). | SIGNOR-274033 |
P23443 | Q9UD71 | 1 | phosphorylation | up-regulates activity | 0.257 | D1R-PKA appears intact and elevated DARPP-32(pT34) in Rheb(S16H) mice is reduced by S6K1 inhibition (Figure 3).|S6K1 directly phosphorylates DARPP-32. | SIGNOR-279654 |
Q14680 | Q12778 | 1 | phosphorylation | down-regulates quantity | 0.257 | Direct phosphorylation of FOXO1 and FOXO3 by MELK.|Our findings revealed that siRNA mediated MELK knockdown increased protein levels of FOXO1 and FOXO3, which might increase p21 transcriptional level in a p53 independent manner. | SIGNOR-279543 |
P31431 | O14641 | 1 | binding | up-regulates | 0.257 | Like other wnt co receptors, syndecan 4 directly interacts with dvl during pcp. | SIGNOR-199635 |
Q13535 | Q9BW19 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.257 | ATM and ATR kinases phosphorylate KIFC1-S26 during DNA-damage conditions.KIFC1 was stabilized upon phosphorylation and thus promoted centrosome clustering, CIN, and tumor recurrence both in vivo and in vitro. | SIGNOR-277296 |
O15294 | Q01813 | 1 | glycosylation | down-regulates activity | 0.257 | Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267583 |
Q13888 | P03372 | 1 | phosphorylation | up-regulates activity | 0.257 | TFIIH Phosphorylates Human Estrogen Receptor α at Serine 118 | We report here that Cdk7 overexpression stimulates transcription activation by ERα by stimulating phosphorylation of S118 in a ligand-dependent manner. | SIGNOR-260817 |
P06493 | Q13286 | 1 | phosphorylation | down-regulates activity | 0.257 | (D) Phosphorylation of Cln3 by Cdk1 is independent of Ssa1 T36.|Thereby, both Cdk1 and Pho85can promote Cln3 degradation, though under distinct circumstances. | SIGNOR-279013 |
Q13976 | Q03393 | 1 | phosphorylation | up-regulates | 0.257 | Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps. Addition of cgmp stimulated phosphotransferase activity 2-fold. Extracts from transfected cos-1 cells overexpressing cgkii stimulated ser(19) phosphorylation more than 100-fold.In assays with purified enzymes, wild-type but not ptps-s19a was a specific substrate for the cgmp-dependent protein kinase (cgk) type i and ii. Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps | SIGNOR-71680 |
Q05655 | P53671 | 1 | phosphorylation | down-regulates | 0.256 | Activation of pkc by phorbol ester treatment of endothelial cells stimulated limk2 phosphorylation at ser-283 and inhibited nuclear import of limk2 | SIGNOR-137927 |
Q9UKN1 | P05412 | 1 | binding | up-regulates activity | 0.256 | MUC12 promoted the recruitment of c-Jun on the promoter of TGF-β1, leading to its transcription. | SIGNOR-265474 |
P11362 | P56945 | 1 | phosphorylation | up-regulates | 0.256 | Five tyrosine phosphorylation sites were identified in p130cas on tyr-128, tyr-249, tyr-306, tyr-327, and tyr-410. These tyrosine residues are all located in the substrate domain of p130cas that mediates binding to the sh2 domain of the adaptor molecule crk. Fgf-1-transduced fibroblasts demonstrated a > 10-fold increase in migration, an observation correlated with increased tyrosine phosphorylation of p125fak and p130cas. | SIGNOR-82760 |
Q13131 | O15503 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.256 | Here we report that AMPK interacts with and mediates phosphorylation of Insig. Thr222 phosphorylation following AMPK activation is required for protein stabilization of Insig-1, inhibition of cleavage and processing of SREBP-1, and lipogenic gene expression in response to metformin or A769662. AMPKα1 subunit associates with Insig-1 in a dose-dependent manner. | SIGNOR-277430 |
P28482 | Q08493 | 1 | phosphorylation | down-regulates | 0.256 | The short-form pde4b2 isoenzyme was activated by erk2 phosphorylation. sub-family selective actions in the ability of erk2 map kinase to phosphorylate and regulate the activity of pde4 cyclic amp-specific phosphodiesterases | SIGNOR-83187 |
Q9UQM7 | P07101 | 1 | phosphorylation | up-regulates | 0.256 | This increase in ser19 phosphorylation was associated with enhanced th activity and was due, in part, to glutamate-receptor-mediated calcium influx and possibly calcium/calmodulin-dependent protein kinase ii (camkii) activation. | SIGNOR-20912 |
P15918 | P42345 | 1 | relocalization | up-regulates | 0.256 | Rag gtpases, together with a multi-protein complex called ragulator, mediate amino acid-mediated mtor recruitment to the lysosome surface where mtor becomes activated. | SIGNOR-198242 |
P60484 | Q13285 | 1 | dephosphorylation | down-regulates activity | 0.256 | The fact that SF-1 and PIP3 is robustly dephosphorylated by PTEN, yet SF-1 and PIP2 is resistant to phosphorylation by p110 PI3-kinases, suggests that nuclear proteins like SF-1 can help decouple PTEN signaling in the nucleus from p110 signaling.|We also showed that PTEN can dephosphorylate the SF-1 and PIP3 product of the IPMK reaction, and that PTEN inhibits SF-1 transcriptional activity. | SIGNOR-277117 |
Q16566 | P53667 | 1 | phosphorylation | up-regulates activity | 0.256 | An active form of CaMKIV but not CaMKI enhanced Thr 508 phosphorylation of LIMK1 and increased the kinase activity of LIMK1.|Taken together, our results suggest that LIMK1 mediated cofilin phosphorylation is critical for ionomycin induced neurite outgrowth and that CaMKIV mediates ionomycin induced LIMK1 activation. | SIGNOR-280201 |
P35637 | O00571 | 1 | relocalization | down-regulates activity | 0.256 | We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. | We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons | SIGNOR-262811 |
O75925 | Q13642 | 1 | sumoylation | down-regulates | 0.256 | Pias1 (the protein inhibitor of activated stat1) interacts with kyot2 directly and attenuates kyot2-mediated transcriptional repression. We demonstrate that kyot2 is modified by sumoylation at two lysine residues, k144 and k171. Sumoylation of the transfected kyot2 is enhanced by pias1 | SIGNOR-154801 |
Q05655 | P17405 | 1 | phosphorylation | up-regulates | 0.256 | Activation of acid sphingomyelinase by protein kinase cdelta-mediated phosphorylation. Phosphorylation of ser(508) proved to be an indispensable step for asmase activation and membrane translocation in response to pma | SIGNOR-153276 |
P0DMV8 | Q9HC29 | 1 | binding | up-regulates quantity by stabilization | 0.256 | The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease. | SIGNOR-252416 |
Q9H2G2 | P04637 | 1 | phosphorylation | up-regulates activity | 0.256 | The Ste20 like kinase SLK promotes p53 transactivation and apoptosis.|Thus SLK induces p53 phosphorylation and transactivation, which enhances apoptosis after in vitro ischemia-reperfusion injury. | SIGNOR-279285 |
P60484 | Q14653 | 1 | dephosphorylation | up-regulates activity | 0.256 | PTEN can dephosphorylate IRF-3 S97 residue and facilitate its nuclear import for the IFN signaling pathway (7).|PTEN expression directly increases activated IRF-3 nuclear import and subsequent interferon (IFN) synthesis. | SIGNOR-277025 |
Q92630 | P05412 | 1 | phosphorylation | down-regulates | 0.256 | Degradation of c-jun/c-myc is a critical process for the g(1)/s transition, which is initiated upon phosphorylation by glycogen synthase kinase 3 ? (gsk3?). However, a specific kinase or kinases responsible for priming phosphorylation events that precede this gsk3? Modification has not been definitively identified. Here, we found that the dual-specificity tyrosine phosphorylation-regulated kinase dyrk2 functions as a priming kinase of c-jun and c-myc.The finding that kinase-active dyrk2 phosphorylated gst_c-jun210_310-wt by detection with an anti_phospho_c-jun(ser243) antibody demonstrated that dyrk2 is a ser243 kinase in vitro | SIGNOR-195771 |
Q13153 | Q96IF1 | 1 | phosphorylation | up-regulates activity | 0.256 | The Rac effector PAK1 was also transiently activated upon cell-cell adhesion and directly phosphorylated Ajuba (Thr172). | SIGNOR-278449 |
O15530 | P36507 | 1 | phosphorylation | up-regulates | 0.256 | The identified pdk1 phosphorylation sites in mek1 and mek2 are ser222 and ser226, respectively, and are known to be essential for full activation. | SIGNOR-125176 |
Q5T0W9 | P49674 | 1 | binding | up-regulates quantity | 0.256 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273762 |
P17612 | P11831 | 1 | phosphorylation | up-regulates | 0.256 | Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. | Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha. | SIGNOR-188177 |
O95071 | P48431 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.256 | We identified UBR5 as a major ubiquitin E3 ligase that induces SOX2 degradation through ubiquitinating SOX2 at lysine 115. | SIGNOR-277446 |
Q13315 | P20823 | 1 | phosphorylation | up-regulates | 0.256 | Serine 249 phosphorylation by atm protein kinase regulates hepatocyte nuclear factor-1_ transactivation | SIGNOR-205087 |
Q92626 | P53420 | 1 | catalytic activity | up-regulates quantity by stabilization | 0.256 | Peroxidasin (PXDN), an ECM protein with peroxidase activity, is integral to basement membrane consolidation through catalysis of sulfilimine bonds in collagen IV. PXDN has been shown to form dityrosine crosslinks and also catalyses sulfilimine bonds, in the presence of hypohalous acids, to connect collagen IV protomers, which are an integral component of the basement membrane | SIGNOR-265250 |
P17252 | P08581 | 1 | phosphorylation | down-regulates | 0.256 | These data show that phosphorylation of ser985 is a key mechanism for the negative regulation of hgf/sf receptor. | SIGNOR-37718 |
Q6ZWH5 | P04637 | 1 | phosphorylation | up-regulates activity | 0.256 | Here, we describe a function for NEK10 in the regulation of p53 transcriptional activity through tyrosine phosphorylation. NEK10 loss increases cellular proliferation by modulating the p53-dependent transcriptional output. NEK10 directly phosphorylates p53 on Y327, revealing NEK10's unexpected substrate specificity. A p53 mutant at this site (Y327F) acts as a hypomorph, causing an attenuated p53-mediated transcriptional response. | SIGNOR-273881 |
P45984 | P16949 | 1 | phosphorylation | down-regulates | 0.256 | Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. Here we show that in response to hyperosmotic stress, jnk phosphorylates a key cytoplasmic microtubule regulatory protein, stathmin (stmn), on conserved ser-25 and ser-38 residues. In in vitro biochemical studies, we identified stmn ser-38 as the critical residue required for efficient phosphorylation by jnk and identified a novel kinase interaction domain in stmn required for recognition by jnk. We revealed that jnk was required for microtubule stabilization in response to hyperosmotic stress. | SIGNOR-166698 |
P61328 | P35499 | 1 | binding | down-regulates activity | 0.255 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253432 |
P06493 | O43148 | 1 | phosphorylation | up-regulates activity | 0.255 | We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. | SIGNOR-265501 |
Q86UW7 | P63027 | 1 | binding | up-regulates activity | 0.255 | CAPS interactions with N-terminal regions of the SNARE motif of VAMP2 were also detected, which suggests that CAPS might recruit VAMP2 into syntaxin-1/SNAP-25 heterodimers for RQaQbc-SNARE complex assembly. | SIGNOR-264341 |
P30550 | P04054 | 1 | binding | up-regulates | 0.255 | Grpr stimulation activates phospholipase a2 (pla2) and cyclooxygenase 2 (cox2), which leads to prostaglandin e2 (pge2) production and ep receptor stimulation. | SIGNOR-152756 |
P32239 | P09471 | 1 | binding | up-regulates activity | 0.255 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257238 |
P57682 | O95600 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.255 | Here we report that Klf8 is repressed by Klf3 in vivo and is up-regulated by Klf1. Transcript analysis indicates that Klf8 has two promoters, both containing multiple CACCC elements. Transactivation assays and chromatin immunoprecipitation experiments indicate that Klf3 represses Klf8 directly and that Klf1 activates Klf8 directly. | SIGNOR-266049 |
P68400 | Q9UHH9 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.255 | CK2 physiologically phosphorylates IP6K2 at amino acid residues S347 and S356 contained within a PEST sequence, a consensus site for ubiquitination. HCT116 cells depleted of IP6K2 are resistant to cell death elicited by CK2 inhibitors. CK2 phosphorylation at the degradation motif of IP6K2 enhances its ubiquitination and subsequent degradation. | SIGNOR-273625 |
Q15139 | Q13936 | 1 | phosphorylation | up-regulates | 0.255 | Both the expression of a dominant-negative mutant of pkd and the mutation of serine 1884 but not serine 1930, putative targets of pkd, strongly reduced l-type calcium currents and single channel activity without affecting the channel's expression at the plasma membrane. Our results suggest that serine 1884 is essential for the regulation of hcav1.2 by pkd. | SIGNOR-177481 |
O14965 | Q05397 | 1 | phosphorylation | up-regulates activity | 0.255 | A schematic of regulation between these three kinases is shown in XREF_FIG, suggesting that Src was the upstream kinase regulating both FAK and AURA, whereas FAK might be downstream of AURA (as AURA phosphorylation of FAK yielded more incorporation of [32 P] gammaATP compared to FAK phosphorylation of AURA).|The effect of AURA on cell migration is augmented in the presence of Src and, in return, AURA also activates FAK. | SIGNOR-280188 |
P31749 | Q96KG9 | 1 | phosphorylation | up-regulates activity | 0.255 | In previous work, we demonstrated that TEIF (transcriptional element-interacting factor) distributes in the centrosomes and regulates centrosome status under both physiologic and pathologic conditions.|A consensus motif for Akt phosphorylation (RHRVLT) proved to be involved in centrosomal TEIF localization, and the 469-threonine of this motif may be phosphorylated by Akt both in vitro and in vivo. Elimination of this phosphorylated site on TEIF caused reduced centrosome distribution and centrosome splitting or amplification. | SIGNOR-265496 |
Q16566 | Q9UNW9 | 1 | phosphorylation | up-regulates quantity | 0.255 | CaMKIV Phosphorylates Nova-2 and Regulates Its Nuclear Localization. CaMKIV Phosphorylates Nova-2 and Regulates Its Nuclear Localization. Conversely, Nova-2 with single or double mutations to alanine (2A and 1A2A) was predominantly nuclear, like the WT (Figures 5H and and5I).5I). In contrast, glutamate mutations at site 3 had no effect on Nova-2 localization (Figures 5H and and5I)5I) or on Nova-2 binding to RNA (Figure S5E). These results showed that active CaMKIV reduces Nova-2 nuclear localization by phosphorylating sites 1 and 2 (S25, T27). | SIGNOR-273521 |
Q00535 | P35611 | 1 | phosphorylation | up-regulates activity | 0.255 | We found that Cdk5 directly phosphorylated the actin-binding protein adducin-1 (ADD1) at T724 in vitro and in intact cells. | SIGNOR-277487 |
Q9H3K2 | P99999 | 1 | relocalization | down-regulates quantity | 0.255 | MICS1 was clearly coprecipitated with cytochrome c-3FLAG and the amount was DSP concentration-dependent (Figure 6A). Together with the finding that overexpression of exogenous MICS1 delayed the apoptotic release of cytochrome c in normal-serum level medium (Figure 4A), these results suggest that MICS1 helps to retain cytochrome c in the inner membrane, apart from the morphological changes. | SIGNOR-260294 |
P33176 | Q9UBS5 | 1 | relocalization | up-regulates activity | 0.255 | GABABR1 co-immunoprecipitated with Marlin-1 and kinesin-I, providing evidence for the existence of a complex between these proteins. Kinesin-I modulates GABAB receptor transport. | SIGNOR-260990 |
P29074 | P40763 | 1 | dephosphorylation | down-regulates activity | 0.255 | In terms of molecular mechanisms, we revealed that PTPN4 dephosphorylates pSTAT3 at the Tyr705 residue with a direct interaction, which might provide novel targets for the therapy of CRC.|Loss of PTPN4 Activates STAT3 to Promote the Tumor Growth in Rectal Cancer. | SIGNOR-277057 |
P31751 | Q01860 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.255 | Here we show that in ECCs, Akt phosphorylated the master pluripotency factor Oct4 at threonine 235, and that the levels of phosphorylated Oct4 in ECCs correlated with resistance to apoptosis and tumorigenic potential. Phosphorylation of Oct4 increased its stability and facilitated its nuclear localization and its interaction with Sox2, which promoted the transcription of the core stemness genes POU5F1 and NANOG. | SIGNOR-242097 |
Q8WUI4 | Q6DJT9 | 1 | deacetylation | down-regulates | 0.255 | Plag1 and plagl2 are also regulated by acetylation. They are acetylated and activated by p300 and deacetylated and repressed by hdac7. | SIGNOR-140950 |
P30519 | P69905 | 1 | null | down-regulates activity | 0.254 | Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular hemoprotein, hemoglobin, and heme | SIGNOR-251814 |
O14965 | Q13526 | 1 | phosphorylation | down-regulates activity | 0.254 | Here, we found that aurora a can interact with and phosphorylate pin1 at ser16, which suppresses the g2/m function of pin1 by disrupting its binding ability and mitotic entry. | SIGNOR-202487 |
Q16512 | P18669 | 1 | phosphorylation | down-regulates | 0.254 | Activated pak1 inhibits glycolysis by association of its catalytic domain with pgam-b and subsequent phosphorylation of the enzyme on serine residues 23 and 118, thereby abolishing pgam activity. | SIGNOR-91602 |
P29376 | P48736 | 1 | binding | up-regulates | 0.254 | Although c-cbl is found to be phosphorylated by ltk and therefore is a second candidate linking ltk with the pi3-kinase pathway along with irs-1, we found that the p85 subunit of pi3 kinase directly binds to tyrosine 753 of ltk, which is located within a yxxm motif, a consensus binding amino acid sequence for the sh2 domain of p85 | SIGNOR-49622 |
P24941 | Q06830 | 1 | phosphorylation | down-regulates | 0.254 | Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.Prx i was also phosphorylated, with an efficiency similar to that observed with cdc2, when incubated in vitro with cdk2, cdk4, or cdk6 that had been immunoprecipitated from hela cell lysates with specific antibodies (data not shown). | SIGNOR-87101 |
P06493 | P60891 | 1 | phosphorylation | up-regulates activity | 0.254 | CDK1 contributes to upregulation of PRPS1 activity by phosphorylating PRPS1 at S103|In conclusion, compared with upregulation of PRPS1 expression levels, increased PRPS1 activity, which is marked by S103 phosphorylation | SIGNOR-265728 |
P49840 | P12036 | 1 | phosphorylation | down-regulates activity | 0.254 | Our results demonstrate that whereas GSK-3 alpha, GSK-3 beta, and cdk-5 will all phosphorylate NF-H, they generate different antibody reactivity profiles. | SIGNOR-279783 |
Q8N752 | O75581 | 1 | phosphorylation | up-regulates | 0.254 | Ck1 also phosphorylates lrp6 at the second ser residue in the pppspxs motif ck1_ in the lrp5/e-cadherin/p120-catenin complex temporally coincides with p120-catenin phosphorylation in ser268. moreover, and considering the close similarity between the catalytic domains of ck1_ and ck1_, it is possible that ck1_ is indeed responsible for the phosphorylation at ser1420 and ser1430 in lrp5/6 that negatively affects wnt signaling by still not defined mechanisms | SIGNOR-173853 |
Q13618 | P46821 | 1 | ubiquitination | down-regulates quantity | 0.254 | Gigaxonin is the substrate-specific adaptor for a new Cul3-E3-ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and tubulin cofactor B. | SIGNOR-268946 |
Q96GD4 | Q3KR16 | 1 | phosphorylation | up-regulates | 0.254 | In this study we report that aurora b-mediated phosphorylation of myogef at thr-544 creates a docking site for plk1, leading to the localization and activation of myogef at the central spindle. | SIGNOR-204534 |
Q96GD4 | Q9NP77 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.254 | Here we report that Aurora B kinase directly interacts with and phosphorylates Ssu72, a new cohesin-binding phosphatase, at Ser 19 in vitro and in vivo. The Aurora B-mediated phosphorylation of Ssu72 causes the structural modification of Ssu72 protein, downregulates phosphatase activity and triggers the ubiquitin-dependent degradation of Ssu72. | SIGNOR-275529 |
Q8N163 | O15379 | 1 | binding | down-regulates activity | 0.254 | Besides SIRT1, CCAR2 inhibits the activity of the histone-modifying enzymes SUV39H1 and HDAC3 [9, 10], thus playing an important role in chromatin structure regulation. | SIGNOR-267665 |
P07947 | P11802 | 1 | phosphorylation | down-regulates | 0.254 | We purified tyrosine 17 kinases from hela cells and found that the src family non-receptor tyrosine kinase c-yes contributes a large fraction of the tyrosine 17 kinase activity in hela lysatesthis site is equivalent to tyrosine 15 of cyclin dependent kinase 1, which undergoes inhibitory phosphorylation by wee1 and myt1 | SIGNOR-178624 |
Q9H6Z9 | O43521-1 | 1 | hydroxylation | up-regulates quantity by stabilization | 0.254 | EglN3 hydroxylase stabilizes BIM-EL linking VHL type 2C mutations to pheochromocytoma pathogenesis and chemotherapy resistance|EglN3 Hydroxylates BIM-EL at the Proline67/70 Residues | SIGNOR-262003 |
Q9H2X6 | P46527 | 1 | phosphorylation | up-regulates | 0.254 | Homeodomain-interacting protein kinase-2 stabilizes p27(kip1) by its phosphorylation at serine 10 and contributes to cell motility | SIGNOR-174617 |
P31946 | P07196 | 1 | binding | down-regulates activity | 0.254 | These results suggest the important role of 14-3-3 in the dynamic regulation of NF-L assembly, and in the capacity to prevent the formation of NF-L aggregates. all seven isoforms specifically interacted with NF-L, but not NF-M or NF-H. specific interaction of 14-3-3 proteins with phosphorylated NF-L subunits also indicated the role of 14-3-3 and NF-L phosphorylation in the disassembly of neurofilaments. What is more, binding of 14-3-3 to phosphorylated NF-L subunits may prevent the dephosphorylation of these subunits by phosphatases, maintaining the hyperphosphorylation state of the subunits, which facilitates the disassembly of neurofilaments. | SIGNOR-252396 |
P17612 | Q8IWU9 | 1 | phosphorylation | up-regulates | 0.254 | We also demonstrate that phosphorylation of serine 19, a protein kinase a consensus site located in this n-terminal domain, results in increased tph2 stability and consequent increases in enzyme output in cell culture systems | SIGNOR-178018 |
P06241 | P04629 | 1 | phosphorylation | up-regulates activity | 0.254 | Here, we demonstrate that Fyn can directly phosphorylate the intracellular domain of TrkA and that its kinase activity towards Trk is increased by GPCR stimulation ( Fig. 4 ). | SIGNOR-279410 |
P53350 | Q13485 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.254 | We observed that PLK1 could significantly promote the ubiquitination and degradation of Smad4 wild type, Smad4 S171A, Smad4 S187A, Smad4 S191A, respectively, but PLK1-induced the ubiquitination and degradation of Smad4 T197A were obviously inhibited (Fig. 1M). | SIGNOR-277591 |
P28335 | P19086 | 1 | binding | up-regulates activity | 0.253 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257129 |
P35414 | O95837 | 1 | binding | up-regulates activity | 0.253 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256960 |
P53350 | P67809 | 1 | phosphorylation | up-regulates quantity | 0.253 | Here we identify that PLK1 inhibition can induce apoptosis and DNA damage of GSCs, we have also delineat the possible underlying molecular mechanisms: PLK1 interacts with YBX1 and directly phosphorylates serine 174 and serine 176 of YBX1.|Inhibition of PLK1 reduces the phosphorylation level of YBX1, and decreased phosphorylation of YBX1 prevents its nuclear translocation, thereby inducing apoptosis and DNA damage of GSCs. | SIGNOR-279255 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.