IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q99873 | P35637 | 1 | methylation | down-regulates activity | 0.485 | PRMT1 catalyzes the arginine methylation of Fused in Sarcoma (FUS), an RNA-binding protein that interacts with RALY. We demonstrate that RALY down-regulation decreases protein arginine N-methyltransferase 1 levels, thus reducing FUS methylation. It is known that mutations in the FUS nuclear localization signal (NLS) retain the protein to the cytosol, promote aggregate formation, and are associated with amyotrophic lateral sclerosis. | SIGNOR-262274 |
P17252 | O60341 | 1 | phosphorylation | up-regulates activity | 0.352 | Together, these data indicate that LPS-induced LSD1 phosphorylation by PKC\u03b1 is required for its interaction with p65 in the nucleus.|We have previously reported that LSD1 is phosphorylated by PKCalpha on serine 112 site, and knockin mice bearing phosphorylation defective Lsd1 SA/SA alleles show altered circadian rhythms and impaired phase resetting (Nam et al., 2014). | SIGNOR-279425 |
P01178-PRO_0000020496 | Q92824 | 0 | cleavage | up-regulates quantity | 0.2 | Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension. | SIGNOR-270336 |
P12830 | Q68DV7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.267 | To identify the E-cadherin ubiquitination site, we individually mutated three lysines in its cytoplasmic domain, including K816A, K855A, and K871A, of which E-cad K816A failed to restore E-cadherin ubiquitination (Additional file xref : Figure S3D), indicating that RNF43 ubiquitinated E-cadherin at the cytoplasmic lysine 816.|Together , these results suggest that RNF43 potentially downregulates E-cadherin in lung adenocarcinoma in the context of c-Src activation . | SIGNOR-278598 |
P45983 | P19419 | 1 | phosphorylation | up-regulates activity | 0.512 | However, both of these stimuli strongly activate two other mapks, jnk1 and jnk2, and stimulate elk-1 transcriptional activity and phosphorylation jnk phosphorylation sites include ser383 and ser389, the major residues whose phosphorylation is responsible for enhancement of elk-1 trascriptional activity. | SIGNOR-236432 |
P28482 | Q15418 | 1 | phosphorylation | up-regulates activity | 0.759 | Several lines of evidence indicate that the mapkap-k1 isoforms are also activated by mapks in vivo via the ras-dependent protein kinase cascade that is triggered by growth factors or tumor-promoting phorbol esters, such as phorbol 12-myristate 13-acetate (pma). here we identify six sites in mapkap-k1a that become phosphorylated in transfected cos-1 cells. The inactive form of mapkap-k1a in unstimulated cells is partially phosphorylated at ser222 and ser733. Stimulation with phorbol 12-myristate 13-acetate induces the phosphorylation of thr360, ser364, thr574, and ser381 and increases the phosphorylation of ser222 and ser733. | SIGNOR-219308 |
P05129 | P30086 | 1 | phosphorylation | up-regulates activity | 0.381 | Here we report that one mechanism involves dissociation of Raf kinase inhibitory protein (RKIP) from Raf-1. Classic and atypical but not novel PKC isoforms phosphorylate RKIP at serine 153 (Ser-153). RKIP Ser-153 phosphorylation by PKC either in vitro or in response to 12-O-tetradecanoylphorbol-13-acetate or epidermal growth factor causes release of RKIP from Raf-1, whereas mutant RKIP (S153V or S153E) remains bound. I | SIGNOR-249190 |
Q07820 | P28482 | 0 | phosphorylation | up-regulates | 0.527 | We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage. | SIGNOR-92593 |
P17677 | P40763 | 0 | 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 |
P29474 | P24723 | 0 | phosphorylation | down-regulates activity | 0.2 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251634 |
O43294 | Q14289 | 0 | phosphorylation | up-regulates activity | 0.71 | Hic-5 is a CAKbeta-binding protein localized at focal adhesions. Here we show that overexpression of CAKbeta or Fyn, but not FAK, enhanced the tyrosine phosphorylation of coexpressed Hic-5 in COS-7 cells. The Y60F mutant of Hic-5 was not phosphorylated, and Hic-5 phosphorylated on tyrosine 60 was bound specifically to the SH2 domain of Csk. Specific phosphorylation of Hic-5 by CAKbeta and Fyn may activate a signaling pathway mediated by Hic-5. | SIGNOR-262876 |
Q969V5 | O75385 | 1 | ubiquitination | down-regulates quantity | 0.347 | MUL1 promotes ubiquitination of ULK1.|Overexpression of MUL1 and treatment with selenite promotes ULK1 degradation through the proteasome pathway. | SIGNOR-278759 |
P37802 | O94921 | 0 | phosphorylation | down-regulates activity | 0.315 | This newly identified oncogene–tumor suppressor cascade, where oncogenic PFTK1 inactivates a tumor suppressor gene TAGLN2 via phosphorylation|. Our data therefore underline much importance for S83 and S163 residues on TAGLN2 in its actin-binding capacity. | SIGNOR-265103 |
P37231 | P36406 | 0 | ubiquitination | up-regulates quantity by stabilization | 0.2 | In this study, we showed that TRIM23 mediates atypical polyubiquitin conjugation including M1- and K27 linked ubiquitin chains to PPARgamma and that ubiquitination of PPARgamma by TRIM23 causes reduced recognition of PPARgamma by 26S proteasome. | SIGNOR-278577 |
P35637 | Q92973 | 0 | relocalization | up-regulates activity | 0.642 | The C-terminal nuclear localization sequence of FUsed in Sarcoma (FUS-NLS) is critical for its nuclear import mediated by transportin (Trn1). | SIGNOR-262101 |
Q13469 | P48454 | 0 | dephosphorylation | up-regulates activity | 0.408 | NFAT1 is phosphorylated on fourteen conserved phosphoserine residues in its regulatory domain, thirteen of which are dephosphorylated upon stimulation. Dephosphorylation of all thirteen residues is required to mask a nuclear export signal (NES), cause full exposure of a nuclear localization signal (NLS), and promote transcriptional activity | SIGNOR-248512 |
P62714 | P32519 | 1 | dephosphorylation | down-regulates activity | 0.2 | Elf-1 enhances the expression of CD3zeta, whereas it suppresses the expression of FcRgamma gene and lupus T cells have decreased amounts of DNA-binding 98 kDa form of Elf-1. We show that the aberrantly increased PP2A in lupus T cells dephosphorylates Elf-1 at Thr-231. Dephosphorylation results in limited expression and binding of the 98 kDa Elf-1 form to the CD3zeta and FcRgamma promoters. Suppression of the expression of the PP2A leads to increased expression of CD3zeta and decreased expression of FcRgamma genes and correction of the early signaling response | SIGNOR-248591 |
P06241 | P84243 | 1 | phosphorylation | down-regulates activity | 0.2 | Here we provide evidence that fyn kinase, a member of the src kinase family, is involved in the uvb-induced phosphorylation of histone h3 at serine 10 | SIGNOR-130274 |
P68400 | Q14493 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.328 | Phosphorylation of Thr61 is necessary for subsequent phosphorylation of Thr60 by CK2 in vitro. Inhibitors of CK2 also prevent degradation of SLBP at the end of S phase. Thus, phosphorylation of Thr61 by cyclin A/Cdk1 primes phosphorylation of Thr60 by CK2 and is responsible for initiating SLBP degradation. | SIGNOR-265260 |
P45983 | P30305 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.284 | Recently, we showed that Cdc25B is degraded rapidly by non-genotoxic stimuli that activate stress-responsive MAPKs, such as Jun N-terminal kinase (JNK) and p38 (Uchida et al., 2009). Our results suggested that these kinases phosphorylate specific Ser residues in the N-terminal region (S101 and S103) to induce Cdc25B degradation.Here, we report that Cdc25B was ubiquitylated by SCF(βTrCP) E3 ligase upon phosphorylation at two Ser residues in the βTrCP-binding-motif-like sequence D(94)AGLCMDSPSP(104). | SIGNOR-276352 |
P10275 | P55089 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | When cells were treated with DHT alone, AR was upregulated and translocated into the nuclei, which might repress UCN1 expression via a potential androgen-responsive element found in human CRF family promoter|These data suggest that DHT differentially influences UCN1 levels under normal and inflammatory conditions in human umbilical vein endothelial cells, which involves AR-dependent and -independent mechanisms respectively. | SIGNOR-253688 |
P04637 | Q9H0A0 | 0 | acetylation | up-regulates quantity by stabilization | 0.337 | NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity. | SIGNOR-272406 |
Q9BV47 | P04637 | 1 | dephosphorylation | down-regulates activity | 0.366 | Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma|Inhibiting DUSP26 expression in the IMR-32 neuroblastoma cell line enhanced doxorubicin-induced p53 phosphorylation at Ser20 and Ser37, p21, Puma, Bax expression as well as apoptosis | SIGNOR-248765 |
O14733 | Q12852 | 0 | phosphorylation | up-regulates activity | 0.556 | Collectively, these data suggest the hypothesis that ApoE activates DLK by increasing its levels | SIGNOR-279630 |
O14490 | Q9Y566 | 1 | relocalization | up-regulates activity | 0.857 | 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-264586 |
Q9Y566 | Q15398 | 0 | relocalization | up-regulates activity | 0.448 | 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-264598 |
Q96PU5 | Q99250 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.317 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253459 |
P54132 | O96017 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.526 | We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3β- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates.Phosphorylation on BLM Thr171 and Ser175 depends on prior phosphorylation at Thr182 by Chk1/Chk2. Thr182 phosphorylation not only controls BLM ubiquitylation and degradation during mitosis but is also a determinant for its localization on the ultrafine bridges. | SIGNOR-276908 |
P19105 | Q13177 | 0 | phosphorylation | up-regulates activity | 0.495 | In this study we report that gamma-PAK, which is activated by the GTP-binding proteins Cdc42 and Rac, catalyses phosphorylation of intact non-muscle myosin II and isolated recombinant RLC. Phosphopeptide maps and phosphoamino acid analysis revealed that gamma-PAK phosphorylates Ser-19 but does not phosphorylate Thr-18.Taken together, these data suggest that myosin II activation by the p21-activated family of kinases may be physiologically important in regulating cytoskeletal organization. | SIGNOR-263020 |
P04406 | Q86Y07 | 0 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation. | SIGNOR-277840 |
P27361 | Q07820 | 1 | phosphorylation | up-regulates | 0.436 | We then showed that erk could phosphorylate mcl-1 at two consensus residues, thr 92 and 163, which is required for the association of mcl-1 and pin1, resulting in stabilization of mcl-1. | SIGNOR-179812 |
P99999 | Q9Y243 | 0 | phosphorylation | down-regulates activity | 0.265 | Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain. | SIGNOR-277235 |
P18031 | O15344 | 0 | ubiquitination | down-regulates quantity | 0.2 | Proteasome inhibitor treatment diminished the decrease of PTP1B (Figure 5F) caused by TRIM18 overexpression.|TRIM18 Interacts With PTP1B and Promotes PTP1B Ubiquitination. | SIGNOR-278703 |
P27361 | Q8N122 | 1 | phosphorylation | up-regulates activity | 0.469 | We found three proline-directed residues within raptor, ser(8), ser(696), and ser(863), which are directly phosphorylated by erk1/2. Expression of phosphorylation-deficient alleles of raptor revealed that phosphorylation of these sites by erk1/2 normally promotes mtorc1 activity and signaling to downstream substrates, such as 4e-bp1. | SIGNOR-169530 |
P51692 | Q13882 | 0 | phosphorylation | up-regulates | 0.429 | Phosphospecific antibodies, mutational analysis, and in vitro kinase assays demonstrated that brk specifically mediated stat5b phosphorylation at the activating tyrosine, y699. | SIGNOR-159066 |
P17252 | O60716 | 1 | phosphorylation | down-regulates activity | 0.251 | PKC\u03b1 phosphorylation of p120 at S879 is a critical phospho-switch mediating disassociation of p120 from VE-cadherin that results in AJ disassembly.|We surmised that PKCalpha may function to disrupt AJs by signaling dissociation of p120 from VE-cadherin. | SIGNOR-278261 |
Q8TB45 | P35790 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | These data suggests that CKI overexpression may overcome a requirement for phosphorylation at the major mTOR sites in DEPTOR for formation of the degron and are consistent with our finding that CKI can phosphorylate S286 and S287 in DEPTOR in vitro in the absence of mTOR. | SIGNOR-279605 |
Q8WVD3 | Q9NQB0 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.325 | Here, we show that NARF induces the ubiquitylation of TCF/LEF in vitro and in vivo, and functions as an E3 ubiquitin-ligase that specifically cooperates with the E2 conjugating enzyme E2-25K. We found that NLK augmented NARF binding and ubiquitylation of TCF/LEF, and this required NLK kinase activity. The ubiquitylated TCF/LEF was subsequently degraded by the proteasome. | SIGNOR-271593 |
P12931 | Q99961 | 1 | phosphorylation | down-regulates | 0.639 | Further, we identified an interaction between fak's second pro-rich motif and endophilin a2's sh3 domain. This interaction served as an autophosphorylation-dependent scaffold to allow src phosphorylation of endophilin a2 at tyr315. Tyr315 phosphorylation inhibited endophilin/dynamin interactions, and blockade of tyr315 phosphorylation promoted endocytosis of mt1-mmp. Together, these results suggest a regulatory mechanism of cell invasion whereby fak promotes cell-surface presentation of mt1-mmp by inhibiting endophilin a2-dependent endocytosis. | SIGNOR-139150 |
Q13698 | P17612 | 0 | phosphorylation | up-regulates activity | 0.346 | To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2. | SIGNOR-263112 |
Q06413 | Q9UPW0 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.317 | Foxj3 transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity. | SIGNOR-261606 |
P45983 | O43524 | 1 | phosphorylation | up-regulates activity | 0.65 | As JNK1 phosphorylates FOXO3 at S574, 12 allowing formation of the proapoptotic species, we tested whether FOXO3 acetylation is required for the JNK1-FOXO3 interaction. | SIGNOR-280030 |
P15311 | P12931 | 0 | phosphorylation | up-regulates | 0.648 | Src phosphorylates ezrin at tyrosine 477 and induces a phosphospecific association between ezrin and a kelch-repeat protein family member | SIGNOR-132907 |
O95198 | Q9HA47 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.346 | We demonstrated that the ubiquitin E3 ligase KLHL2 interacted with UCK1 and mediated its polyubiquitination at the K81 residue and degradation. We showed that deubiquitinase USP28 antagonized KLHL2-mediated polyubiquitylation of UCK1. | SIGNOR-275962 |
O75525 | Q8IUQ4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.473 | We found that SIAH1 bound to an octapeptide sequence in T-STAR targeting it for proteasome-dependent degradation. | SIGNOR-272671 |
Q99717 | Q13485 | 1 | phosphorylation | up-regulates | 0.675 | Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common smad (co-smad; smad4 in mammals) and shuttle into the nucleus. | SIGNOR-168737 |
P12931 | Q04760 | 1 | phosphorylation | up-regulates activity | 0.2 | We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D). | SIGNOR-276189 |
Q96KS0 | P17252 | 0 | phosphorylation | down-regulates | 0.364 | Thus, recombinant phd1 was examined for in vitro phosphorylation using protein kinase a, protein kinase calpha, casein kinase i and ii and erk2. The protein was most strongly phosphorylated by protein kinase calpha, and the phosphorylation sites were found to be ser-132, ser-226 and ser-234.Mutation Of ser-132 or ser-234 to asp or glu diminished the enzymatic activity to 25-60%, while mutation of ser-226 scarcely influenced the activity. | SIGNOR-180203 |
O95835 | Q9H093 | 0 | phosphorylation | down-regulates | 0.307 | Phosphorylation at ser-464 by nuak1 and nuak2 leads to decreased protein level and is required to regulate cellular senescence and cellular ploidy | SIGNOR-161796 |
P20807 | P49840 | 1 | cleavage | up-regulates activity | 0.2 | Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase | SIGNOR-251606 |
Q04206 | P49841 | 0 | phosphorylation | up-regulates | 0.357 | Rela is phosphorylated at: ser276 by the catalytic subunit of protein kinase a (pkac), msk1 and msk2; at ser311 by the atypical pkczeta; at ser468 by ikkbeta, ikkepsilon and glycogen-synthase kinase-3beta (gsk3beta); at ser529 by ck2; and at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1)) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k) . | SIGNOR-151422 |
P10636 | P06241 | 0 | phosphorylation | down-regulates | 0.535 | In this study we determined that human tau tyr18 was phosphorylated by the src family tyrosine kinase fyn. | SIGNOR-123099 |
P00519 | P46108 | 1 | phosphorylation | down-regulates activity | 0.76 | Negative regulation of crk by abl is essential for the antitumorigenic effects of ephrinb2,similar pathways may operate for crkl | SIGNOR-175135 |
P55075 | P40425 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.251 | Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription | SIGNOR-265778 |
P60484 | P51149 | 1 | dephosphorylation | up-regulates activity | 0.373 | PTEN dephosphorylates Rab7 on two conserved residues S72 and Y183, which are necessary for GDP dissociation inhibitor (GDI)-dependent recruitment of Rab7 on to late endosomes and subsequent maturation. | SIGNOR-276960 |
O14757 | Q7Z6Z7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.298 | Taken together, these results are consistent with our hypothesis that HUWE1 directly poly-ubiquitinates and targets Chk1 to the proteasome. | SIGNOR-278568 |
Q00613 | Q04759 | 0 | phosphorylation | up-regulates | 0.349 | At the same time, ea causes pkc?-Mediated phosphorylation and activation of the transcription factor heat shock factor 1, an inducer of glucose dependence. | SIGNOR-200576 |
P13861 | O43164 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.328 | Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits | SIGNOR-271856 |
P07900 | P16591 | 1 | phosphorylation | down-regulates activity | 0.3 | Hsp90 and tyrosine616 are required for Fer tyrosine kinase activity.Taken together, our findings underscore the importance of Hsp90 and the residue, tyrosine616, which resides in the Hsp90 recognition loop, in maintaining Fer tyrosine kinase activity. | SIGNOR-277818 |
P17252 | O14986 | 1 | phosphorylation | down-regulates | 0.2 | Collaboration of ampk and pkc to induce phosphorylation of ser413 on pip5k1b resulting in decreased kinase activity and reduced ptdins(4,5)p2 synthesis in response to oxidative stress and energy restriction. we demonstrate that pkc can directly phosphorylate ser413 in vitro | SIGNOR-194820 |
P17612 | P36956 | 1 | phosphorylation | down-regulates | 0.2 | Sterol regulatory element-binding protein 1 is negatively modulated by pka phosphorylation. ser338 of srebp-1a and ser314 of srebp-1c are pka phosphorylation sites. | SIGNOR-143392 |
Q8NHY2 | P17676 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We show expression of c/EBPβ in microglia is regulated post-translationally by the ubiquitin ligase COP1 (also called RFWD2). In the absence of COP1, c/EBPβ accumulates rapidly and drives a potent pro-inflammatory and neurodegeneration-related gene program, evidenced by increased neurotoxicity in microglia-neuronal co-cultures. | SIGNOR-261924 |
O60381 | Q15759 | 0 | phosphorylation | up-regulates | 0.428 | A mutation of the p38 map kinase phosphorylation site at aa 401 [(s-a)401hbp1] also triggered hbp1 protein instability. While protein stability was compromised by mutation, the specific activities of (s-a)401hbp1 and of wild-type hbp1 appeared comparable for transcriptional repression. | SIGNOR-119134 |
Q13153 | P35222 | 1 | phosphorylation | up-regulates | 0.557 | Pak1 directly phosphorylates _-catenin proteins at ser675 site and this leads to more stable and transcriptional active _-catenin | SIGNOR-175944 |
P53350 | P11413 | 1 | phosphorylation | up-regulates activity | 0.346 | We find that Plk1 interacts with and directly phosphorylates glucose-6-phosphate dehydrogenase (G6PD). By activating G6PD through promoting the formation of its active dimer, Plk1 increases PPP flux and directs glucose to the synthesis of macromolecules.|the kinase domain of Plk1 phosphorylates T406, T466 of G6PD | SIGNOR-267581 |
P23458 | Q9Y5X2 | 1 | phosphorylation | up-regulates activity | 0.341 | IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKβ to the JAK1 complex. | SIGNOR-273647 |
Q8IW93 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.636 | 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-260543 |
Q9NYD6 | P55268 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The specificity of binding of these two proteins to the Lamin B2 origin is confirmed by both band-shift and in vitro footprinting assays. In addition, the ability of HOXC10 and HOXC13 to increase the activity of a promoter containing the 74 bp sequence, as assayed by CAT-assay experiments, demonstrates a direct interaction of these homeoproteins with the origin sequence in mammalian cells. | SIGNOR-261645 |
P98177 | P31749 | 0 | phosphorylation | down-regulates | 0.763 | Foxo4 transcription factor, also referred to afx, contains three putative phosphorylation motif sites for protein kinase b (pkb), thr32, ser197, and ser262, and it is proposed that phosphorylated foxo4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression | SIGNOR-252486 |
O14757 | A0AVK6 | 1 | phosphorylation | down-regulates activity | 0.315 | Chk1 inhibits the transcriptional repressor function of E2F7 and E2F8 to promote cell cycle progression and prevent apoptosis.|Here, we demonstrate that Chk1 phosphorylates both E2F7 and E2F8 in response to DNA damage. | SIGNOR-279693 |
Q9UKX7 | P27361 | 0 | phosphorylation | down-regulates activity | 0.2 | Erk phosphorylates nup50 at ser221 and ser315 phosphorylation of nup50 reduces affinity for importin-beta | SIGNOR-187378 |
P04629 | P35222 | 1 | phosphorylation | up-regulates activity | 0.415 | EGFR and TRKA effect on WNT3a mediated Topflash induction was abolished by U0126 or expression of dominant negative LRP6-5A mutant (XREF_FIG), demonstrating that both EGFR and TRKA signal via ERK and LRP6 pathway to upregulate WNT and beta-catenin signaling.|FGFR2, FGFR3, EGFR and TRKA Phosphorylate \u03b2-catenin at Tyr142. | SIGNOR-279240 |
P41743 | P12931 | 0 | phosphorylation | up-regulates | 0.533 | Nerve growth factor stimulates multisite tyrosine phosphorylation and activation of the atypical protein kinase c's via a src kinase pathway. tyrosine 256, 271, and 325 were identified as major sites phosphorylated by src in the catalytic domain. | SIGNOR-111920 |
Q8NG06 | O95786 | 1 | ubiquitination | up-regulates activity | 0.2 | Specifically, the ubiquitin E3 ligase TRIM25 ubiquitinates K172 in the CARD2 of RIG-I, which is essential for the efficient interaction of RIG-I with MAVS and thereby for antiviral signal transduction | SIGNOR-264582 |
P0C0S8 | P46736 | 0 | deubiquitination | down-regulates | 0.2 | Brcc36 regulates the abundance of lys(63)-linked ubiquitin chains at chromatin and that one of its substrates is diubiquitinated histone h2a | SIGNOR-167142 |
P49137 | P35900 | 1 | phosphorylation | up-regulates activity | 0.2 | P38 phosphorylates the type II keratin, K8 at Ser73, whereas MK2 phosphorylates the binding partners K18 at Ser52 and K20 at Ser13. | SIGNOR-263071 |
P12931 | Q14258 | 1 | phosphorylation | up-regulates activity | 0.271 | Here, we demonstrated that TRIM25 interacted with c-Src and underwent tyrosine phosphorylation by c-Src kinase upon viral infection and the phosphorylation is required for the complete activation of RIG-I signaling. Analysis using a c-Src inhibitor and TRIM25 mutant, in which tyrosine 278 is substituted by phenylalanine (Y278F), suggested that the phosphorylation positively regulates K63-linked polyubiquitination of RIG-I and subsequent antiviral signaling. | SIGNOR-277405 |
P08253 | P10915 | 1 | cleavage | down-regulates quantity by destabilization | 0.339 | Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix. | SIGNOR-256333 |
Q13546 | Q5VWQ8 | 1 | phosphorylation | up-regulates activity | 0.426 | We further show that RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation as demonstrated by both overexpression and small interfering RNA knockdown of RIP1 in EC. | SIGNOR-259976 |
O00533 | P16157 | 1 | relocalization | up-regulates quantity | 0.532 | Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains. | SIGNOR-266724 |
P08246 | P12259 | 1 | cleavage | up-regulates activity | 0.366 | Human neutrophil elastase activates human factor V but inactivates thrombin-activated human factor V|NH2-terminal sequence analysis of F.V treated with HNE indicated cleavage at Ile819 and Ile1484 under conditions during which the procofactor expressed enhanced cofactor activity in the prothrombinase complex. | SIGNOR-263637 |
P78371 | Q15418 | 0 | phosphorylation | up-regulates | 0.249 | Furthermore, both the s260a and s260d mutants showed a decreased folding capacity as compared to cells expressing the wild-type cct_ subunit ( fig.?_5e), suggesting that a cyclic phosphorylation of the s260 site by s6k1 is likely to be important for chaperonin function and that mutation of this site interferes with this process. | SIGNOR-172986 |
Q99426 | Q13153 | 0 | phosphorylation | up-regulates | 0.448 | P21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor b. Pak1 directly phosphorylated tcob in vitro and in vivo on serines 65 and 128 and colocalized with tcob on newly polymerized microtubules and on centrosomes. Pak1 phosphorylation is necessary for normal tcob function | SIGNOR-135464 |
Q12778 | Q13131 | 0 | phosphorylation | up-regulates | 0.446 | The energy sensor amp-activated protein kinase (ampk) has been shown to directly phosphorylate foxo factors at six regulatory sites that are distinct from the akt. | SIGNOR-157941 |
Q9HAW4 | Q9BTU6 | 0 | phosphorylation | down-regulates | 0.2 | These results indicate that plx1 phosphorylates claspin on s934, which is relatively close to the plx1-docking site at t906. Human claspin also contains a serine at position 984 in a homologous sequence | SIGNOR-159937 |
O15534 | Q16649 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.346 | E4BP4, a basic leucine zipper transcription factor, contains a DNA-binding domain closely related to DBP, HLF, and TEF, which are PAR proteins. Here, we show that the phase of e4bp4 mRNA rhythm is opposite to that of the dbp, hlf, and tef rhythms in the suprachiasmatic nucleus (SCN), the mammalian circadian center, and the liver. The protein levels of E4BP4 and DBP also fluctuate in almost the opposite phase. All PAR proteins activate, whereas E4BP4 suppresses the mPer1 promoter through the same sequence | SIGNOR-268056 |
Q9H8V3 | P53350 | 0 | phosphorylation | up-regulates activity | 0.75 | Phosphorylation of Ect2 by Plk1 during anaphase might alleviate this intramolecular inhibition by dissociating the Ect2 amino from the carboxyl terminus.|Together with the presence of a prominent microtubule array at the midzone, these data suggest that Plk1 is not essential for the formation of the central spindle at anaphase.The specific failure of Ect2 to localize to the midzone raised the interesting possibility that Plk1 might trigger the initiation of cytokinesis by promoting the interaction of Ect2 with centralspindlin and, thereby, Ect2 activation and recruitment to the central spindle. | SIGNOR-279553 |
P06899 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265381 |
P00519 | Q9Y6N7 | 1 | phosphorylation | down-regulates | 0.606 | Abl functions to antagonize robo signaling both abl and ena can directly bind to robo's cytoplasmic domain. | SIGNOR-78993 |
P12830 | P48730 | 0 | phosphorylation | down-regulates activity | 0.27 | Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846 | SIGNOR-274046 |
P43403 | Q12959 | 0 | phosphorylation | up-regulates activity | 0.53 | Immunoblot analysis showed that phosphorylation of the activating ZAP70 kinase domain residue Tyr 493 was decreased in the DLG1 KD cells. Similarly, the Tyr 319 residue of ZAP70 and Tyr 83 residue of TCR- ζ also showed reduced phosphorylation. | SIGNOR-274142 |
O43283 | O14733 | 1 | phosphorylation | up-regulates | 0.584 | Lzk directly phosphorylated and activated mkk7. | SIGNOR-112349 |
O76064 | Q9H0D6 | 1 | ubiquitination | up-regulates activity | 0.2 | Mechanistically, RNF8 interacts with XRN2, which is crucial for transcription termination and R-loop resolution. We report that RNF8 ubiquitylates XRN2 to facilitate its recruitment to R-loop-prone genomic loci and that RNF8 deficiency in BRCA1-mutant breast cancer cells decreases XRN2 occupancy at R-loop-prone sites, thereby promoting R-loop accumulation, transcription-replication collisions, excessive genomic instability, and cancer cell death. | SIGNOR-277195 |
P37840 | P43405 | 0 | phosphorylation | down-regulates | 0.532 | Here, we show that alpha-synuclein (alpha-syn) is an outstanding substrate for the protein tyrosine kinase p72syk (syk), which phosphorylates three tyrosyl residues in its c-terminal domain (y-125, y-133, and y-136), here, we show that _-syn is an outstanding substrate for syk and that once it is tyrosine phosphorylated, it loses the ability to form oligomers. | SIGNOR-113065 |
O00712 | P41221 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268883 |
P17252 | O14939 | 1 | phosphorylation | up-regulates | 0.692 | The phosphorylation sites in phospholipase d2 (pld2) induced by activation of protein kinase calpha (pkcalpha) in cos 7 cells were analyzed by mass spectrometry. Ser134, 146, and 243, and thr72, 99/100, and 252 were identified. These sites were mutated to ala and the double mutation of ser243 and thr252 eliminated the phosphorylation. / the s243/t252a mutant showed a partial decrease in pld2 activity | SIGNOR-138355 |
Q01995 | P17481 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively | SIGNOR-261642 |
Q96BA8 | O43462 | 0 | cleavage | up-regulates | 0.568 | Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes | SIGNOR-143820 |
O60674 | P17252 | 0 | phosphorylation | up-regulates activity | 0.26 | These results suggest that PKC activates JAK2 and thereby STAT3 by directly phosphorylating T174 and S518. | SIGNOR-277262 |
O15111 | P03372 | 1 | phosphorylation | up-regulates activity | 0.47 | These results demonstrated an estrogen-mediated increase in the phosphorylation of ER\u03b1 at serine residue 118 by IKK\u03b1 ( Figure 5 H, bottom).|Wt IKKalpha, but not the IKKalpha kinase mutant, increased both estrogen dependent and -independent ERalpha activation. | SIGNOR-279696 |
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