IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 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 |
|---|---|---|---|---|---|---|---|
Q6T4R5 | Q7L576 | 2 | binding | up-regulates activity | 0.2 | We show that the WHD of NHS interacts with the Abi family of proteins, HSPC300, Nap1 and Sra1, and is important for the localization of NHS to the leading edge. | SIGNOR-253575 |
P25098 | P32245 | 1 | phosphorylation | down-regulates activity | 0.2 | Mutagenesis studies revealed that Thr312 and Ser329/330 in the C-terminal tail are potential sites for PKA and GRK phosphorylation and may play an essential role in the recruitment of beta-arrestin to the activated receptor. | SIGNOR-247770 |
P43405 | Q8TB45 | 1 | phosphorylation | down-regulates activity | 0.2 | We found that tyrosine (Tyr) 289 phosphorylation of DEPTOR impairs its interaction with mTOR, leading to increased mTOR activation. Using proximity biotinylation assays, we identified SYK (spleen tyrosine kinase) as a kinase involved in DEPTOR Tyr 289 phosphorylation in an ephrin (erythropoietin-producing hepatocellular carcinoma) receptor-dependent manner. | SIGNOR-277572 |
P18858 | P24941 | 0 | phosphorylation | up-regulates activity | 0.457 | We show that three residues (ser51, ser76, and ser91), which are part of cyclin-dependent kinase sites, are phosphorylated in a cell cycle-dependent manner. | SIGNOR-103254 |
Q15672 | P28482 | 0 | phosphorylation | up-regulates | 0.304 | We identified the serine 68 (s68) as a major phosphorylation site of twist1 by mass spectrometry and with specific antibodies. This s68 is phosphorylated by p38, jnk and erk1/2 in vitro, and its phosphorylation levels positively correlate with twist1 protein levels in hek293 and breast cancer cells. | SIGNOR-173401 |
Q71UI9 | Q86Y13 | 0 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271756 |
P15559 | P31749 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.369 | Akt phosphorylates NQO1 on S40 and T128 residues. Here we show that Akt phosphorylates NQO1 at T128 residues and triggers its polyubiquitination and proteasomal degradation, abrogating its antioxidative effects in PD. Akt binds NQO1 in a phosphorylation-dependent manner. Interestingly, Akt, but not PINK1, provokes NQO1 phosphorylation and polyubiquitination with Parkin as an E3 ligase. | SIGNOR-276868 |
P22681 | P29317 | 2 | binding | down-regulates quantity by destabilization | 0.638 | In our present study, we demonstrate that ligand-mediated stimulation causes EphA2 to be internalized and degraded. The mechanism of this response involves ligand-mediated autophosphorylation of EphA2, which promotes an association between EphA2 and the c-Cbl adaptor protein. We also show that c-Cbl promotes stimulation-dependent EphA2 degradation. | SIGNOR-272590 |
Q13547 | P37231 | 0 | relocalization | down-regulates | 0.617 | These data suggest that c/ebp beta activates a single unified pathway of adipogenesis involving its stimulation of ppargamma expression, which then activates c/ebp alpha expression by dislodging hdac1 from the promoter for degradation in the proteasome | SIGNOR-143961 |
P46527 | Q9Y463 | 0 | phosphorylation | up-regulates | 0.355 | Mirk phosphorylates p27 at ser-10, thus stabilizing p27 and blocking its nuclear export and degradation | SIGNOR-235805 |
P29992 | P30556 | 2 | binding | up-regulates activity | 0.512 | The angiotensin II type 1 receptor (AT1 R) is a G q/11-coupled G protein-coupled receptor that is widely expressed in multiple tissues, including vascular smooth muscle cells, brain, and kidney. | SIGNOR-278125 |
Q86V81 | P31749 | 0 | phosphorylation | up-regulates | 0.449 | Nuclear akt directly binds aly and phosphorylates it on the t219 residue. gfp-aly t219d displayed comparable activity to gfp control and wild-type aly, indicating that aly phosphorylation by akt is sufficient to enhance mrna export. | SIGNOR-252518 |
Q12904 | P45983 | 0 | phosphorylation | down-regulates | 0.473 | We further demonstrated that serine-140 residue of aimp1 was phosphorylated by jnk and alanine mutation of serine-140 suppressed lps-induced cell surface altogether, these results suggest that aimp1 is phosphorylated by jnk through tlr-myd88 pathway and lose the regulatory activity for er retention of gp96expression of gp96. | SIGNOR-165763 |
Q8TEW6 | P06241 | 2 | binding | up-regulates | 0.536 | Insulin receptor-phosphorylated irs5/dok4 associates with rasgap, crk, src, and fyn, but not phosphatidylinositol 3-kinase p85, grb2, shp-2, nck, or phospholipase cgamma src homology 2 domains, and activates mapk in cells. | SIGNOR-100999 |
Q9NR96 | Q86XR7 | 2 | binding | up-regulates activity | 0.401 | To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group | SIGNOR-266750 |
Q00653 | Q01201 | 2 | binding | up-regulates activity | 0.762 | The map3k14-activated chuk/ikka homodimer phosphorylates nfkb2/p100 associated with relb, inducing its proteolytic processing to nfkb2/p52 and the formation of nf-kappa-b relb-p52 complexes. The nf-kappa-b heterodimeric relb-p52 complex is a transcriptional activator. | SIGNOR-182835 |
P63096 | P49286 | 2 | binding | up-regulates activity | 0.471 | 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-256707 |
P46531 | Q8IUQ4 | 0 | relocalization | up-regulates | 0.26 | The overexpression of siah1 causes the re-localization of notch from the cell surface to the cytoplasm and to the nucleus, which is indicative of notch activation | SIGNOR-168460 |
P01100 | O15391 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.392 | YY2 activated the p53 promoter. However, in contrast to YY1, which represses the activity of c-Fos, YY2 increased the activity of the c-Fos promoter. | SIGNOR-266212 |
P57059 | Q6UUV7 | 1 | phosphorylation | down-regulates | 0.418 | These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities. | SIGNOR-147703 |
P36897 | P36873 | 0 | dephosphorylation | down-regulates | 0.469 | We found smad7 interacts with growth arrest and dna damage protein, gadd34, a regulatory subunit of the protein phosphatase 1 (pp1) holoenzyme, which subsequently recruits catalytic subunit of pp1 (pp1c) to dephosphorylate t?RI. | SIGNOR-121277 |
Q6VAB6 | P04049 | 2 | binding | up-regulates activity | 0.606 | In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. | SIGNOR-273879 |
P30304 | P11802 | 1 | dephosphorylation | up-regulates activity | 0.705 | Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs. | SIGNOR-267568 |
P14635 | P30307 | 0 | dephosphorylation | up-regulates activity | 0.832 | Cdc25C is an activator of Cdc2 kinase and dephosphorylates and activates the CyclinB-Cdc2 complex shortly before the entry into the mitosis. | SIGNOR-277099 |
Q9UHD2 | Q92630 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.413 | We further found that DYRK2 phosphorylated Ser527 of TBK1, which is essential for the recruitment of NLRP4 and for the E3 ubiquitin ligase DTX4 to degrade TBK1. | SIGNOR-276939 |
O00187 | P0C0L4 | 1 | cleavage | up-regulates activity | 0.798 | MASP-2 cleaves C4 releasing C4a and generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester. C2 binds to C4b and is also cleaved by MASP-2 to form the C3 convertase (C4b2a). | SIGNOR-263431 |
Q12864 | Q99626 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.406 | The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L) | SIGNOR-253963 |
P78352 | Q9NZ94 | 0 | relocalization | up-regulates activity | 0.755 | 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-264189 |
P08754 | Q9UKP6 | 2 | binding | up-regulates activity | 0.265 | 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-257164 |
P10275 | O15393 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.575 | The prostate-specific TMPRSS2 gene, while upregulated by AR activity in luminal cells, is also transcribed in basal populations, confirming that AR acts as an expression modulator. | SIGNOR-253687 |
P16234 | Q05397 | 1 | phosphorylation | up-regulates activity | 0.429 | Focal adhesion kinase (FAK) has a crucial role in integration of signals from integrins and growth factor receptors. In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor Met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate FAK on Tyr194 in the FERM domain (band 4.1 and ezrin/radixin/moesin homology domain). Upon binding to Met or phosphoinositides, FAK may undergo conformational changes, which renders Tyr194 accessible for phosphorylation. Substitution of Tyr194 with Phe significantly suppresses the activation of FAK by Met. | SIGNOR-259400 |
P46531 | Q96J02 | 0 | ubiquitination | down-regulates | 0.644 | Itch binds to the n-terminal portion of the notch intracellular domain via its ww domains and promotes ubiquitination of notch through its hect ubiquitin ligase domain. | SIGNOR-80702 |
P05023 | P28482 | 0 | phosphorylation | down-regulates activity | 0.519 | Parathyroid hormone (PTH) inhibits Na+,K+-ATPase activity through protein kinase C- (PKC) and extracellular signal-regulated kinase- (ERK) dependent pathways and increases serine phosphorylation of the α1-subunit. These results suggest that PTH regulates Na(+),K(+)-ATPase by PKC and ERK-dependent alpha(1)-subunit phosphorylation and that the phosphorylation requires the expression of a serine at the 11 position of the Na(+),K(+)-ATPase alpha(1)-subunit. | SIGNOR-262940 |
Q04206 | O75676 | 0 | phosphorylation | up-regulates | 0.272 | 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) msk 1 and 2 can directly phosphorylate and activate transcription factors such as creb, atf1, the nf-kb isoform p65 and stat 1 and 3. | SIGNOR-151436 |
Q9HCE7 | Q13873 | 1 | ubiquitination | down-regulates | 0.56 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps. | SIGNOR-153402 |
P63000 | P46940 | 2 | binding | down-regulates activity | 0.715 | Although the name implies that it functions as a GTPase-activating protein, IQGAP1 actually stabilizes Cdc42 and Rac1 in the active, GTP-bound form (5, 8, 17). Thus, IQGAP1 acts as an “anti-GTPase-activating protein” for Cdc42 and Rac1, with marked effects on the cytoskeleton. | SIGNOR-261889 |
O14965 | Q6PGQ7 | 2 | binding | up-regulates | 0.729 | Both drosophila and human bora can bind to aurora-a and activate the kinase in vitro. | SIGNOR-148661 |
Q9H0D6 | P50750 | 0 | phosphorylation | up-regulates activity | 0.278 | Among the RNA processing factors phosphorylated by Cdk9 was the 5'-to-3' "torpedo" exoribonuclease Xrn2, required in transcription termination by Pol II, which we validated as a bona fide P-TEFb substrate in vivo and in vitro. Phosphorylation by Cdk9 or phosphomimetic substitution of its target residue, Thr439, enhanced enzymatic activity of Xrn2 on synthetic substrates in vitro. | SIGNOR-277194 |
P30304 | Q9UM11 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.464 | We found that Cdc25 A degradation during mitotic exit and in early G(1) is mediated by the anaphase-promoting complex or cyclosome (APC/C)(Cdh1) ligase, and that a KEN-box motif in the N-terminus of the protein is required for its targeted degradation. | SIGNOR-271388 |
P35558 | O95071 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.308 | Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase |UBR5 ubiquitinates the acetylated PEPCK1 | SIGNOR-267600 |
Q9Y6Q9 | Q16659 | 0 | phosphorylation | up-regulates | 0.481 | Here, we report that erk3 interacted with and phosphorylated steroid receptor coactivator 3 (src-3), an oncogenic protein overexpressed in multiple human cancers at serine 857 (s857) | SIGNOR-196957 |
P04271 | O43248 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.252 | HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells. | SIGNOR-261647 |
Q9H9S0 | Q9HCS4 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.341 | These experiments showed that Tcf3 is associated with chromatin in the Nanog promoter regions and that the DNA-binding activity of Tcf3 was required for repression. | SIGNOR-266081 |
P16333 | Q13153 | 2 | binding | up-regulates activity | 0.709 | Both nck and grb4 proteins could associate with receptor tyrosine kinases and the sh3-binding proteins pak, sos1, and prk2, and they synergized with v-abl and sos to induce gene expression via the transcription factor elk-1. Association of nck with pak1 may serve to link this important regulatory kinase to cell activation by growth factor receptors. | SIGNOR-236512 |
P06239 | P25963 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.586 | Loss of tyrosine kinase p56lck in Jurkat cells abolished NFkappaB activation and partially suppressed and delayed phosphorylation of Tyr-42 of IkappaB upon pervanadate treatment. |Transfection of these cells with wild type Lck but not with mutant Lck F394 followed by H/R induces the tyrosine phosphorylation of inhibitor of nuclear factor kappaB (IkappaBalpha) and transcriptional activation of NFkappaB, and these are inhibited by Lck inhibitors | SIGNOR-249374 |
Q15653 | Q9Y297 | 2 | binding | down-regulates quantity by destabilization | 0.582 | Interaction with beta-TrCP is also necessary for ubiquitination of IkappaBbeta upon stimulation of cells, and deletion of the F-box in beta-TrCP abolishes its ability to ubiquitinate IkappaBbeta. Therefore, these results indicate that beta-TrCP plays a critical role in the activation of NF-kappaB by assembling the ubiquitin ligase complex for both phosphorylated IkappaBalpha and IkappaBbeta.β-TrCP recognizes IκBα phosphorylated at Ser-32 and Ser-36 through its WD40 domain, whereas the F-box motif recruits additional proteins including Skp1 and Cullin to form the Skp1-cullin-F-box (SCF) ubiquitin ligase complex | SIGNOR-272554 |
Q96A56 | Q9H492 | 2 | binding | up-regulates | 0.348 | Tp53inp1-lc3 interaction occurs via a functional lc3-interacting region (lir). | SIGNOR-196670 |
P53350 | Q12778 | 1 | phosphorylation | down-regulates activity | 0.316 | In conclusion, we provide evidence that PLK1-dependent phosphorylation of FOXO1 induces its nuclear exclusion and negatively regulates FOXO1 transcriptional activity in PCa.|We previously demonstrated that PLK1 inhibits the transcriptional activity of FOXO1 by promoting its nuclear exclusion in U2OS cells . | SIGNOR-278269 |
P10147 | Q92794 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We further demonstrate that the histone acetyltransferase, MOZ, can activate the MIP-1a promoter in T-cells and that this activation is largely dependent upon the proximal RUNX site. Moreover, we show that co-expression of MOZ and RUNX1 can activate the MIP-1a promoter. | SIGNOR-251726 |
P28482 | P04150 | 1 | phosphorylation | down-regulates activity | 0.623 | Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple CDK complexes modify serines 224 and 232.|MAPKs and CDKs exert opposite effects on receptor transcriptional enhancement. From our results, we speculate that activators of the MAPK pathway, such as growth factors, insulin, and certain oncoproteins, or inhibitors of CDK function, such as tumor growth factor beta (TGF_), p21, and p27, might attenuate receptor-induced transcrip- tional responses. In contrast, negative regulators of MAPK, such as pKA, as well as activators of CDK, such as the cyclins or CAKs, should potentiate receptor action. | SIGNOR-249428 |
P40763 | O43293 | 0 | phosphorylation | up-regulates activity | 0.401 | ZIPK phosphorylated STAT3 on serine 727 (Ser727) and enhanced STAT3 transcriptional activity. | SIGNOR-279702 |
Q9Y5K6 | P60709 | 2 | binding | up-regulates activity | 0.2 | One such regulator is the adaptor protein CD2AP, which delivers capping proteins to the barbed ends of polymerizing F-actin. Capping growing filaments can promote the formation of actin branches by increasing the G-actin pool available to form branches | SIGNOR-264770 |
Q15555 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.537 | Together, these data indicate that Aurora B and CDK1 phosphorylate EB2 at distinct sites and maintain the hyperphosphorylation of EB2 and its binding affinity to MTs while SAC activity is sustained. | SIGNOR-279591 |
P28482 | P09874 | 1 | phosphorylation | up-regulates | 0.519 | Parp1 phosphorylation by erk1/2 is required for maximal parp-1 activation after dna damage. S372a and t373a mutations impaired parp-1 activation. | SIGNOR-146224 |
Q8TDI8 | Q96QU1 | 2 | binding | up-regulates activity | 0.45 | Although several studies show that the tip links, composed of PCDH15 and CDH23, are required for normal mechanotransduction, it is unclear how they are coupled to the transduction machinery. Likewise, it has been demonstrated that the transmembrane channel-like proteins TMC1 and TMC2 are required for mechanosensitive responses in hair cells, but how they interact with other components of the mechanotransduction complex is not known. Here, we show that TMC1 and TMC2 can interact with PCDH15, thereby establishing a critical connection between the tip link and these putative components of the mechanotransduction channel in hair cells. | SIGNOR-262582 |
P06493 | Q09472 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.404 | In this study, we found that p300 was highly phosphorylated and its level was decreased during mitosis and tumorigenesis. In vitro and in vivo experiments aimed showed that cyclin-dependent kinase 1 (CDK1) and ERK1/2 phosphorylated p300 on Ser1038 and Ser2039. Mutations of Ser1038 and Ser2039 increased p300 protein stability and levels. | SIGNOR-276457 |
P42345 | Q13541 | 1 | phosphorylation | down-regulates activity | 0.926 | Specifically as part of mTORC1, mTOR directly phosphorylates the ribo- somal protein S6 kinases (S6K1 and S6K2) and the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BP1 and 4E-BP2), both of which control specific steps in the initiation of cap-dependent translation | SIGNOR-167184 |
P46020 | P46020 | 2 | phosphorylation | up-regulates activity | 0.2 | Phk is activated in vitro by autophosphorylation. Ser1018 and at least three of the other six serine residues (Ser972, -985, and -1007) can be phosphorylated in vitro by Phk itself (autophosphorylation) | SIGNOR-250282 |
Q9NQU5 | P48431 | 1 | phosphorylation | up-regulates quantity | 0.2 | PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas.|The absence of PAK5 abolishes self-renewal ability of LUSC cells by decreasing the expression and phosphorylation of SOX2 in vitro and in vivo. | SIGNOR-280060 |
O75581 | Q93098 | 2 | binding | up-regulates | 0.617 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-132027 |
P49771 | P36888 | 2 | binding | up-regulates | 0.885 | Flt3 ligand (fl) is an early-acting potent co-stimulatory cytokine that regulates proliferation and differentiation of a number of blood cell lineages. Its receptor flt3/flk2 belongs to class iii receptor tyrosine kinases that also include the receptors for colony-stimulating factor 1 | SIGNOR-65564 |
P38398 | Q86YC2 | 2 | binding | up-regulates activity | 0.851 | The BRCA1-PALB2 interaction is required for homologous recombination repair.Here, we report that PALB2, the partner and localizer of BRCA2, binds directly to BRCA1, and serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex. | SIGNOR-244487 |
P23443 | Q15633 | 1 | phosphorylation | up-regulates activity | 0.322 | We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. | SIGNOR-274068 |
P19784 | P55957 | 1 | phosphorylation | up-regulates activity | 0.286 | Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. | These results suggest that residues S61, S64, and to a much lesser extent T58 are sites of phosphorylation of Bid. | SIGNOR-250978 |
Q8N5C8 | O43318 | 2 | binding | up-regulates activity | 0.833 | We have identified a new binding partner of the tgfbeta (transforming growth factor-beta)-activated protein kinase (tak1), termed tab.two distinct tak1 complexes are present in cells. One comprises tak1 complexed with tab1 and tab2, and the other tak1 complexed with tab1 and tab3 (tak1-binding protein-3). Both complexes are activated in response to tumour necrosis factor-alpha or interleukin-1. | SIGNOR-120325 |
P28482 | P19793 | 1 | phosphorylation | down-regulates activity | 0.534 | In colon cancer cells, the Ras/mitogen‐activated protein kinase (MAPK) pathway phosphorylates RXRalpha, which impairs its function as a heterodimeric partner for PPARgamma|A point‐mutated RXRalpha T82A/S260A, which mimics the unphosphorylated form of RXRalpha, can form a heterodimer with PPARgamma and thereby activate target gene expression by binding to the PPRE | SIGNOR-262958 |
P23396 | O14920 | 0 | phosphorylation | up-regulates activity | 0.332 | IKKbeta overexpression activated NF-kappaB measured by luciferase assays , and also induced the nuclear translocation of wild-type, but not S209A, RPS3 (XREF_FIG).|Therefore, RPS3 S209 phosphorylation by IKK\u03b2 is apparently required for RPS3 in directing NF-\u03baB to a specific subset of target genes. | SIGNOR-278360 |
Q05655 | Q13263 | 1 | phosphorylation | down-regulates | 0.2 | This work demonstrates that tif1beta is phosphorylated on ser473, the alteration of which is dynamically associated with cell cycle progression and functionally linked to transcriptional regulation. Phosphorylation of tif1beta/ser473 is mediated by the pkcdelta pathway and is closely linked to cell proliferation. Phosphorylation of tif1beta/ser473 coincides with the induction of cell cycle gene cyclin a2 at the s-phase. Promoter of cyclin a2 gene is occupied by tif1beta and such occupancy is inversely correlated with ser473 phosphorylation. Non-phosphorylated tif1beta/ser473 allowed greater tif1beta association with the regulatory regions and the consequent repression of these genes. | SIGNOR-179250 |
O00254 | P08754 | 2 | binding | up-regulates activity | 0.2 | 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-257146 |
Q9Y397 | P01111 | 1 | palmitoylation | up-regulates activity | 0.404 | Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein. | SIGNOR-261355 |
Q9UKV5 | Q8IWA4 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.309 | Gp78 induces ubiquitylation and proteasomal degradation of Mfn1 and Mfn2. | SIGNOR-272886 |
Q04724 | O95475 | 2 | binding | up-regulates activity | 0.396 | Biochemical and mutational analysis shows that the Six domain of both SIX3 and SIX6 strongly interact with the QD domain of TLE1 and AES. TLE1 over-expression induces an enlargement of the eye field and reinforcesSIX3/SIX6 capability of initiating retina formation | SIGNOR-234592 |
P50148 | P35367 | 2 | binding | up-regulates activity | 0.428 | 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-257376 |
Q15349 | P42345 | 0 | phosphorylation | up-regulates activity | 0.392 | Subsequently, mTOR phosphorylates and activates the 70-kDa ribosomal protein S6 kinase (p70S6K), which results in increased translation either directly or indirectly by activating initiation and elongation factors, eIF-2, eIF-4E (through 4E-BP) and eEF-2 (Bodine et al. xref | SIGNOR-279232 |
P13051 | O15297 | 0 | dephosphorylation | down-regulates activity | 0.377 | PPM1D dephosphorylation of UNG2 is correlated with reduced UNG2 activity on uracil-containing templates.|This result suggests that PPM1D specifically inhibits UNG2 and not other uracil DNA glycosylases. | SIGNOR-277156 |
P67775 | 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-248634 |
P45983 | P08047 | 1 | phosphorylation | up-regulates | 0.705 | In addition, for mutation of the jnk-1 phosphorylated residues of sp1, namely, sp1(t278/739a) and sp1(t278/739d), the effect of ga on sp1 stability was reversed. | SIGNOR-184194 |
P78368 | P84022 | 1 | phosphorylation | down-regulates | 0.337 | Cki?2 Directly phosphorylates smad3 at ser418, leading to the increased ubiquitination and proteasomal degradation of activated smad3 following tgf-? Treatment. | SIGNOR-181069 |
P61073 | P63096 | 2 | binding | up-regulates activity | 0.561 | Using this model, we have reported that CXCL12 activates Gi1, Gi2, or Gi3 heterotrimeric G proteins in a concentration-dependent manner | SIGNOR-278102 |
O94761 | Q8IWV7 | 2 | binding | up-regulates | 0.492 | The isolated recql4, assayed as a complex with ubr1 and ubr2, exhibited dna-stimulated atpase activity but was inactive as either dna helicase or dna translocase / the discovery, in the present work, that these ub ligases, ubr1 and ubr2, interact with the putative helicase recql4 (fig. 2), and that recql4 is a long-lived, non-ubiquitylated protein in hela cells | SIGNOR-128169 |
P05771 | O60346 | 0 | dephosphorylation | down-regulates quantity | 0.341 | Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle | SIGNOR-237047 |
Q06187 | P42768 | 1 | phosphorylation | up-regulates activity | 0.743 | These results demonstrate that WASP, under this experimental condition, can be tyrosine-phosphorylated by the kinase activity of Btk and that the direct interaction between WASP and the SH3 domain of Btk is required for this phosphorylation to occur. | SIGNOR-273958 |
P06493 | P49450 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.68 | Here, we report that the phosphorylation of CENP-A Ser68 primes the ubiquitin-proteasome-mediated proteolysis of CENP-A during mitotic phase in human cultured cells.the mitotic CENP-A degradation specifically depends on Cdk1 activity. | SIGNOR-277576 |
P56178 | P01106 | 1 | transcriptional regulation | up-regulates quantity | 0.274 | Here we demonstrate by luciferase assay that the MYC promoter is specifically activated by overexpression of DLX5 and that two DLX5 binding sites in the MYC promoter are important for transcriptional activation of MYC. We also show that DLX5 binds to the MYC promoter both in vitro and in vivo and that transfection of a DLX5 expression plasmid promotes the expression of MYC in a dose-dependent manner in mammalian cells | SIGNOR-241914 |
P62140 | Q96A00 | 2 | binding | down-regulates activity | 0.505 | We conclude that ILK may activate smooth-muscle contraction both directly, via phosphorylation of myosin, and indirectly, via phosphorylation and activation of CPI-17 and PHI-1, leading to inhibition of MLCP.|CPI-17 and PHI-1 thiophosphorylated by ILK at Thr(38) or Thr(57) respectively inhibited myosin light-chain phosphatase (MLCP) activity bound to myosin | SIGNOR-265742 |
O15055 | Q9Y2K2 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In the current study, we found that SIK3 promotes phosphorylation of PER2 and regulates the abundance of the protein by accelerating its degradation. | SIGNOR-279570 |
P08754 | Q9H1C0 | 2 | binding | up-regulates activity | 0.419 | 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-256861 |
Q13546 | Q13233 | 1 | phosphorylation | up-regulates activity | 0.455 | These findings strongly suggest that rip phosphorylates mekk1 at ser-957 and ser-994. | SIGNOR-108257 |
O00429 | P48454 | 0 | dephosphorylation | up-regulates activity | 0.262 | When mitochondrial depolarization is associated with sustained cytosolic Ca(2+) rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis. | SIGNOR-248506 |
Q96SN8 | Q38SD2 | 0 | phosphorylation | up-regulates activity | 0.505 | Interestingly, LRRK1 in turn phosphorylates CDK5RAP2(Cep215), a human homologue of Drosophila Centrosomin (Cnn), in its gamma-tubulin-binding motif, thus promoting the interaction of CDK5RAP2 with gamma-tubulin. LRRK1 phosphorylation of CDK5RAP2 Ser 140 is necessary for CDK5RAP2-dependent microtubule nucleation. | SIGNOR-275468 |
P53350 | P24941 | 0 | phosphorylation | up-regulates activity | 0.375 | Thus, CycA2-CDK2 can stimulate phosphorylation of PLK1 T210 in vitro and the interactions required for CycA2-mediated PLK1 T210 phosphorylation are detected in the cytoplasm, but not in the nucleus.|We find that Cyclin A2-CDK2 can activate the mitotic kinase PLK1 through phosphorylation of Bora, and that only cytoplasmic Cyclin A2 interacts with Bora and PLK1. | SIGNOR-280212 |
Q14469 | Q9UL68 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | ChIP–seq experiments showed that 80% of Myt1l targets, including the transcription factor Hes1, were co-bound by the repressive Sin3b–HDAC1 complex early during reprogramming | SIGNOR-266775 |
P19086 | O95622 | 2 | binding | down-regulates activity | 0.52 | Activated a z inhibits the activity of type I and type V adenylyl cyclases. | SIGNOR-278045 |
Q05655 | Q9UQL6 | 1 | phosphorylation | down-regulates activity | 0.352 | In this report, we show that VEGF stimulates PKD-dependent phosphorylation of HDAC5 at Ser259/498residues in ECs, which leads to HDAC5 nuclear exclusion and myocyte enhancer factor-2 (MEF2) transcriptional activation. | SIGNOR-260875 |
P17252 | Q96KS0 | 1 | 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 |
P16220 | Q15796 | 2 | binding | up-regulates | 0.325 | We demonstrate that human smad2 and smad4, two essential smad proteins involved in mediating tgf-beta transcriptional responses in endothelial and other cell types, can functionally interact with the transcriptional coactivator creb binding protein (cbp). This interaction is specific in that it requires ligand (tgf-beta) activation and is mediated by the transcriptional activation domains of the smad proteins. | SIGNOR-59462 |
Q8WZ42 | P17252 | 0 | phosphorylation | up-regulates activity | 0.271 | In summary, titin is a PKC substrate with PKCalpha phosphorylating predominately the full-length titin molecule.|Mechanical experiments with skinned LV myocardium revealed that PKCalpha significantly increases titin based passive tension, an effect that is reversed by PP1. | SIGNOR-278382 |
P0DMV8 | Q9HC29 | 2 | 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 |
P61244 | Q14582 | 2 | binding | up-regulates activity | 0.482 | the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences. | SIGNOR-240224 |
Q12899 | Q96FI4 | 1 | ubiquitination | down-regulates quantity | 0.247 | Mule and TRIM26 ubiquitylate NEIL1 in vitro within C-terminal lysine residues.|Similar to these previous results, we again demonstrate that a knockdown of Mule or TRIM26 causes an elevation in the protein stability of NEIL1 in comparison to non-targeting siRNA, unirradiated control (Figure and ; compare lanes 1 and 2). | SIGNOR-278647 |
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