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 |
|---|---|---|---|---|---|---|---|
P45985 | Q99759 | 2 | binding | up-regulates activity | 0.604 | These data indicate that mkk3 is preferentially activated by mekk3, whereas mkk4 is activated both by mekk2 and mekk3. | SIGNOR-48628 |
P35318 | P17676 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.245 | These findings suggest that NF-IL6 and AP-2 sites in the promoter region are the functional elements in the transcriptional regulation of human AM gene in vascular endothelial cells. | SIGNOR-254047 |
P04275 | Q76LX8 | 0 | cleavage | down-regulates activity | 0.599 | Proteolytic degradation of VWF by ADAMTS-13 downregulates the proinflammatory potential of VWF. | SIGNOR-251966 |
O75717 | Q9HAW4 | 2 | binding | up-regulates activity | 0.392 | And-1 is phosphorylated at T826 by ATR following replication stress, and this phosphorylation is required for And-1 to accumulate at the damage sites, where And-1 promotes the interaction between Claspin and Chk1, thereby stimulating efficient Chk1 activation by ATR. Significantly, And-1 binds directly to ssDNA and facilitates the association of Claspin with ssDNA. | SIGNOR-262665 |
P12272 | Q03431 | 2 | binding | up-regulates activity | 0.761 | Prostate-specific antigen was found to specifically cleave PTHrP 1-141 in a time- and dose-dependent manner.|The preferred PSA cleavage site of PTHrP 1-141 was determined to be at the carboxyl-terminus of phenylalanine 23, consistent with chymotryptic-like enzymatic activity of PSA. Cleavage of PTHrP by PSA completely abolished the ability of PTHrP to stimulate cAMP production. | SIGNOR-270549 |
Q13683 | P15172 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.286 | Only myogenin and MyoD were able to efficiently trans-activate the alpha7 promoter-CAT construct (Fig. 7). Myogenin trans-activated the promoter by _2-fold whereas MyoD was able to trans-activate by nearly 4-fold, indicating that both of these factors may play a role in alpha7 gene expression during muscle development. | SIGNOR-241518 |
Q7Z6Z7 | Q07820 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.502 | Mule was identified as Mcl-1 ubiquitin ligase E3 to promote Mcl-1 degradation via the proteasomal pathway [46]. We found that knockdown of Mule (Fig. 4C) but not β-TRCP or FBXW7 (data not shown) prevented Mcl-1 downregulation caused by PKCη depletion. | SIGNOR-261909 |
Q92905 | Q13485 | 1 | ubiquitination | down-regulates | 0.433 | We report a novel mechanism of smad4 degradation. Jab1 interacts directly with smad4 and induces its ubiquitylation for degradation | SIGNOR-114697 |
P29317 | O15197 | 2 | binding | down-regulates activity | 0.422 | EphB6 is frequently silenced in invasive and metastatic cancers; however, its role in cancer progression is poorly understood. Here we show that EphB6 interacts with EphA2 and suppresses EphA2-mediated promotion of anoikis resistance in MCF7 breast cancer cells. | SIGNOR-273853 |
Q99835 | P12931 | 1 | phosphorylation | up-regulates | 0.436 | Instead, shh rapidly and locally stimulated phosphorylation of the src family kinase (sfk) members src and fyn in a smo-dependent fashion. | SIGNOR-178610 |
P13631 | P28702 | 2 | binding | up-regulates | 0.714 | Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins. | SIGNOR-16662 |
P35222 | Q9NQB0 | 2 | binding | up-regulates activity | 0.9 | Hypophosphorylation of β-catenin and translocation into the nucleus leads to binding with members of the lymphoid-enhancer-binding factor/T-cell-specific transcription factor (LEF/TCF) family and activation of WNT target genesAs a member of LEF/TCF family, transcription factor 7 like 2 (Tcf7l2, formerly called Tcf4) is an important transcription factor triggering the downstream responsive genes of WNT signaling | SIGNOR-85757 |
P11802 | P28749 | 1 | phosphorylation | up-regulates activity | 0.807 | Here we assessed the effects of alanine substitution at the individual or combined Cdk4(6)-specific sites in p130, compared with homologous sites in p107 (Thr(369)/Ser(650)/Ser(964)). In U-2-OS cells, the triple p107(DeltaCdk4)* mutant strongly inhibited E2F-4 activity and imposed a G(1) arrest resistant to cyclin D1 coexpression. | SIGNOR-250764 |
P22392 | Q9UII4 | 0 | ubiquitination | up-regulates quantity by stabilization | 0.307 | HERC5 is required for ubiquitination of Nm23B. In summary, Nm23B ubiquitination is mediated by HERC5. Stable Nm23B protein in presence of HERC5 as well as proteasome-independent ubiquitination suggest that ubiquitination of Nm23B serves a different purpose than marking it for degradation. | SIGNOR-271778 |
Q13464 | P53671 | 1 | phosphorylation | up-regulates | 0.632 | Specific activation of lim kinase 2 via phosphorylation of threonine 505 by rock, a rho-dependent protein kinase | SIGNOR-82755 |
Q6PIY7 | P17612 | 0 | phosphorylation | down-regulates activity | 0.2 | We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition. | SIGNOR-259402 |
Q12933 | Q15628 | 2 | binding | up-regulates activity | 0.87 | The high affinity of the tradd-traf2 interaction is required for efficient suppression of apoptosis upon stimulation of the tumor necrosis factor receptor1 (tnfr1), tnf-receptor-associated death domain (tradd) provides a scaffold for the assembly of complex i at the plasma membrane by binding receptor interacting protein 1 (rip1), tnfreceptor- associated factor 2 ,traf2 these results provide evidence that tradd can serve as an adaptor protein and recruit traf1, traf2, or both to tnfrsf1a. The demonstration that tradd interacts with traf2 and fadd, and can recruit both to tnfrsf1a, suggested that traf2 and fadd may be involved in tnfrsf1a tradd-mediated signaling. That these interactions define two distinct signaling pathways emanating from tradd (figure 9) is supported by the ability of traf2 and fadd to activate nf-kb and induce apoptosis, respectively. | SIGNOR-179446 |
P52732 | P06493 | 0 | phosphorylation | up-regulates activity | 0.638 | Nek6 phosphorylated Eg5 at several sites in vitro and one of these sites, Ser1033, is phosphorylated in vivo during mitosis. Whereas CDK1 phosphorylates nearly all Eg5 at Thr926 during mitosis, Nek6 phosphorylates approximately 3% of Eg5, primarily at the spindle poles. | SIGNOR-273887 |
P16333 | P07766 | 0 | relocalization | up-regulates activity | 0.372 | We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3ϵ and results in recruitment of the adaptor protein Nck. | SIGNOR-259934 |
P29350 | P14784 | 1 | dephosphorylation | down-regulates | 0.532 | We have found that il-2 induces association of shp-1 with the il-2 receptor complex, and that once shp-1 is recruited to the activated receptor it is able to decrease tyrosine phosphorylation of il-2rbeta and the associated tyrosine kinases jak1 and jak3. | SIGNOR-55989 |
P17655 | P12931 | 0 | phosphorylation | up-regulates activity | 0.525 | CAPN2 itself was a bone fide substrate of SRC that was primarily phosphorylated at Y625 by SRC and exhibited increased proteolysis activity upon phosphorylation. | SIGNOR-277598 |
P23588 | Q15418 | 0 | phosphorylation | up-regulates | 0.529 | S6k1/s6k2 specifically phosphorylate ser422 in vitro. Substitution of ser422 with ala results in a loss of activity in an in vivo translation assay, indicating that phosphorylation of this site plays an important role in eif4b function. | SIGNOR-123993 |
Q99828 | P60763 | 2 | binding | up-regulates activity | 0.348 | We here report that CIB, a protein that binds to the alpha(IIb)beta(3) fibrinogen receptor, interacts exclusively with activated (V12) Rac3 but not Rac1 or Rac2. Binding of V12Rac3 to CIB was mediated by the C-terminal end of Rac3 and by Rac3 membrane localization | SIGNOR-269060 |
P17096 | P24941 | 0 | phosphorylation | down-regulates | 0.264 | Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation. | SIGNOR-158612 |
O43614 | P09471 | 2 | 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-257008 |
P12931 | P05106 | 1 | phosphorylation | down-regulates activity | 0.661 | The phosphorylation level of beta(3) integrin was modulated using a temperature-sensitive v-Src kinase. Increased beta(3) phosphorylation abolished alpha(v)beta(3)- but not alpha(5)beta(1)-mediated adhesion to fibronectin. Thus, phosphorylation of the cytoplasmic domain of beta(3) is a negative regulator of alpha(v)beta(3)-fibronectin binding strength. | SIGNOR-247207 |
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 |
P27361 | P23396 | 1 | phosphorylation | up-regulates | 0.351 | Erk phosphorylates threonine 42 residue of ribosomal protein s3. | SIGNOR-137175 |
Q06609 | O14757 | 0 | phosphorylation | up-regulates | 0.843 | We demonstrate that chk1 interacts with rad51, and that rad51 is phosphorylated on thr 309 in a chk1-dependent manner | SIGNOR-133375 |
Q7KZI7 | Q05513 | 0 | phosphorylation | down-regulates | 0.266 | Hpar-1b is phosphorylated by apkc on threonine 595 importantly, phosphorylation of hpar-1b on t595 negatively regulates the kinase activity and plasma membrane localization of hpar-1b in vivo. | SIGNOR-124217 |
Q01094 | Q13535 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.377 | These results thus suggest that this serine 31 residue is indeed an atm/atr phosphorylation site and in fact is the major site for atm/atr-mediated phosphorylation within e2f1. Thus, it is possible that the atm/atr-mediated phosphorylation inhibits the binding and function of skp2 and thus prevents the normal degradation of e2f1 | SIGNOR-109420 |
P14784 | P60568 | 2 | binding | up-regulates | 0.869 | Il-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits il-2r alpha, il-2r beta, and gamma(c). | SIGNOR-144540 |
O14641 | P31431 | 2 | binding | up-regulates | 0.257 | Like other wnt co receptors, syndecan 4 directly interacts with dvl during pcp. | SIGNOR-199635 |
Q14203 | P30622 | 2 | binding | up-regulates activity | 0.782 | MT-unbound CLIP-170 can adopt a folded conformation through an intramolecular interaction of its terminal domains. Binding to MTs correlates with the unfolding of CLIP-170, which allows the interaction of the COOH-terminal domain with its binding partners, such as dynactin, resulting in their recruitment to the MT tip. The NH2 terminus of p150Glued binds directly to the COOH terminus of CLIP-170 through its second metal-binding motif. | SIGNOR-252164 |
P12931 | P35968 | 1 | phosphorylation | up-regulates activity | 0.614 | In contrast, our analysis showed that over-expression of c-Src significantly enhances the ability of VEGFR-2 to stimulate proliferation of PAE cells and over-expression of dominant negative Src (Src kinase-dead) inhibits the VEGFR-2 driven proliferation of PAE cells (XREF_FIG).|Taken together, the data demonstrate that Src kinases upon activation by VEGFR-2 phosphorylate Y1173 of VEGFR-2 (XREF_FIG). | SIGNOR-279120 |
Q9Y2H0 | P78352 | 2 | binding | up-regulates activity | 0.803 | SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area. | SIGNOR-264212 |
P25098 | O76070 | 1 | phosphorylation | down-regulates activity | 0.2 | GRK-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and PLD2. Mutation of Ser124 dramatically inhibits γ-synuclein phosphorylation by GRK2 | SIGNOR-251204 |
Q14344 | Q92888 | 2 | binding | up-regulates activity | 0.608 | It turned out that RGS domain of p115RhoGEF is specific for Gα12 and Gα13, and does not bind Gαi, Gαs and Gαq (Kozasa et al., 1998). The binding of Gα13 but not Gα12 stimulated GEF activity for Rho | SIGNOR-256521 |
P15692 | P40763 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.786 | Stat3 directly regulated the promoter of the VEGF gene. Blockade of activated Stat3 by ectopic expression of dominant-negative Stat3 significantly inhibited VEGF expression, and the growth and metastasis of human pancreatic cancer cells. | SIGNOR-259456 |
P68431 | O75582 | 0 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun. | SIGNOR-138483 |
Q9NZJ5 | P00441 | 2 | binding | up-regulates activity | 0.274 | SOD1mut-induced ER stress |we first examined whether SOD1mut induces ER stress in NSC34 motor neurons, as assessed by band-shift analyses of the ER transmembrane kinase receptors IRE1 and PERK. Adenovirus (Ad)-mediated expression of ALS-linked SOD1mut (SOD1G93A) was detectable within 48 h of infection (Supplemental Fig. S1A). SOD1mut (SOD1A4V, SOD1G85R, and SOD1G93A) but not wild-type SOD1 (SOD1wt) activated IRE1 and PERK | SIGNOR-262787 |
P19174 | Q9Y2X7 | 2 | binding | up-regulates | 0.557 | Git1 interaction with plcgamma is required for plcgamma activation based on inhibition of tyrosine phosphorylation | SIGNOR-118454 |
Q92544 | Q9UI12 | 2 | binding | up-regulates activity | 0.271 | Here, we demonstrate that TM9SF4 represents a novel V-ATPase-associated protein involved in V-ATPase activation. We have observed in HCT116 and SW480 colon cancer cell lines that TM9SF4 interacts with the ATP6V1H subunit of the V-ATPase V1 sector. Suppression of TM9SF4 with small interfering RNAs strongly reduces assembly of V-ATPase V0/V1 sectors, thus reversing tumor pH gradient with a decrease of cytosolic pH, alkalization of intracellular vesicles and a reduction of extracellular acidity. | SIGNOR-266885 |
Q96G21 | O00566 | 2 | binding | up-regulates activity | 0.818 | Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome. In eukaryotes, ribosome assembly is a highly complex process that involves more than 200 assembly factors that ensure the folding, modification and processing of the different rRNA species as well as the timely association of ribosomal proteins. One of these factors, Mpp10 associates with Imp3 and Imp4 to form a complex that is essential for the normal production of the 18S rRNA. | SIGNOR-261174 |
P17252 | O43526 | 1 | phosphorylation | up-regulates activity | 0.324 | Phosphorylation of KCNQ2 channels was increased by muscarinic stimulation; this was prevented either by coexpression with AKAP(DeltaA) or pretreatment with PKC inhibitors that compete with diacylglycerol. These inhibitors also reduced muscarinic inhibition of M-current. | These results suggest that Ser534 and 541 are key sites for PKC phosphorylation, although we have not ruled out the possibility that other PKC sites are involved in this process. | SIGNOR-249209 |
P16220 | Q9UBK2 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.554 | CREB was found to induce expression of the gluconeogenic programme through the nuclear receptor coactivator PGC-1, which is shown here to be a direct target for CREB regulation in vivo | SIGNOR-256150 |
Q14344 | P21554 | 2 | binding | up-regulates activity | 0.25 | 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-257346 |
P25490 | Q9HAU4 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.364 | In addition, Smurf2 decreased the protein half-life and transcriptional activity of YY1.|Wild type Smurf2, but not the E3 ubiquitin ligase defective mutant, increased the poly-ubiquitination of YY1. | SIGNOR-278544 |
P23470 | P12931 | 1 | dephosphorylation | down-regulates activity | 0.307 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254725 |
P03230 | P63279 | 2 | binding | up-regulates activity | 0.2 | One mechanism by which LMP1 regulates cellular activation is through the induction of protein posttranslational modifications. We have now identified a specific target of LMP1-induced sumoylation, interferon regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces the sumoylation of IRF7, limiting its transcriptional activity and modulating the activation of innate immune responses. We recently documented that LMP1 induces a third major protein modification by physically interacting with the SUMO-conjugating enzyme Ubc9 through CTAR3 and inducing the sumoylation of cellular proteins in latently infected cells. we identified that IRF7 is sumoylated at lysine 452. | SIGNOR-266838 |
Q16512 | P61586 | 2 | binding | up-regulates activity | 0.852 | PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome. | SIGNOR-275465 |
O15379 | Q8N163 | 2 | 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 |
Q5VUA4 | Q92769 | 2 | binding | up-regulates activity | 0.329 | A central domain of TZF is required for repression of AR-mediated transactivation. The results revealed that HDAC2 was coimmunoprecipitated with TZF (Fig. 6A), These results indicate that AR, TZF and HDAC2 form a ternary complex during the repression of AR-mediated transactivation. | SIGNOR-261188 |
P10275 | Q9H3R0 | 2 | binding | up-regulates activity | 0.2 | JMJD2C was found to be co-localized with AR and LSD1 in the epithelium of prostate carcinoma and normal prostate cells. For the detailed mechanism, JMJD2C, AR and LSD1 assembled on the chromatin to remove the methyl groups from mono-, di- and trimethylated H3K9. Importantly, JMJD2C specifically removed the demethylation of the trimethyl H3K9 marks and modulated the transcriptional activity of AR. Moreover, JMJD2C cooperated with LSD1 and activated AR-mediated gene expression via decreasing H3K9me3 at the promoter of AR targeting genes KLK2 and PSA. | SIGNOR-263879 |
P02786 | Q9P0V3 | 2 | binding | down-regulates | 0.353 | Here, we report that ttp (sh3bp4), a sh3-containing protein, specifically regulates the internalization of the transferrin receptor (tfr). / overexpression of ttp specifically inhibits tfr internalization | SIGNOR-142840 |
P67775 | O43318 | 1 | dephosphorylation | down-regulates | 0.329 | Our results demonstrate that pp6 specifically down-regulates tak1 through dephosphorylation of thr-187 in the activation loop, which is likely important for suppressing inflammatory responses via tak1 signaling pathways. | SIGNOR-150369 |
P49959 | P53350 | 0 | phosphorylation | down-regulates activity | 0.2 | Plk1 phosphorylates Mre11 at S649.Mre11 phosphorylation at S649/S688 inhibits its binding to dsDNA and antagonizes the ATM signaling. | SIGNOR-265943 |
O43464 | Q00535 | 0 | phosphorylation | up-regulates | 0.456 | Here we report that cyclin-dependent kinase-5 (cdk5), a kinase implicated in the pathogenesis of several neurodegenerative diseases, is responsible for phosphorylating htra2 at s400.We have shown previously that phosphomimetic mutants of htra2 at s400 result in increased proteolytic activity and contribute to enhanced resistance to mitochondrial stress | SIGNOR-174598 |
Q9Y2K7 | Q04206 | 1 | demethylation | down-regulates | 0.459 | Fbxl11 and nsd1 have opposite effects on nf-kb; both bind to p65 subunit after activation of nf-kb. / nsd1 activates nf-kb and reverses the inhibitory effect of fbxl11 / these data confirm that fbxl11 and nsd1 constitute an enzyme pair that methylates and demethylates p65 on k218 and 221 in response to cytokine stimulation. | SIGNOR-163384 |
P15172 | Q14469 | 0 | transcriptional regulation | down-regulates activity | 0.294 | Notch signaling up-regulated HES1 mRNA expression within 1 h and subsequently reduced expression of MyoD mRNA | SIGNOR-243181 |
P07384 | P25116 | 1 | cleavage | up-regulates activity | 0.376 | PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus | SIGNOR-263559 |
P01584 | Q04206 | 0 | transcriptional regulation | down-regulates activity | 0.555 | Early Inhibition of IL-1 beta Expression by IFN-gamma Is Mediated by Impaired Binding of NF-kappa B to the IL-1 beta Promoter but Is Independent of Nitric Oxide|We report that IFN-γ suppressed bacterial RNA and LPS induced IL-1β transcription in primary murine macrophages | SIGNOR-251736 |
P16403 | Q8IYW5 | 0 | polyubiquitination | down-regulates | 0.2 | ITCH biochemically antagonized RNF168 and RNF8 in polyubiquitination of histone H1.2 ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. Both RNF168 and RNF8 elicited higher Ubn levels of K46R-H1.2 compared to WT-H1.2, suggesting that Ubn of H1.2 by both E3 ligases occurs at a site apart from K46. | SIGNOR-272927 |
P04626 | Q8NEM2 | 1 | phosphorylation | up-regulates activity | 0.2 | Blocking HER2 activation using trastuzumab effectively abolished EGF-induced nuclear localization of SHCBP1 in gastric cancer cells [7].|In addition, nuclear translocation of SHCBP1 is a downstream consequence of HER2 activation, which is dependent on phosphorylation of SHCBP1 at the Ser273 site. | SIGNOR-280009 |
Q02535 | P24941 | 0 | phosphorylation | down-regulates | 0.342 | We now show that an analogous cell-cycle-regulated phosphorylation of id3 alters the specificity of id3 for abrogating both e-box-dependent bhlh homo- or heterodimer complex formation in vitro and e-box-dependent reporter gene function in vivo._ | SIGNOR-53306 |
P54821 | Q9ULX9 | 2 | binding | down-regulates activity | 0.354 | Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf. | SIGNOR-221890 |
O60890 | P63000 | 1 | gtpase-activating protein | up-regulates activity | 0.591 | OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro | SIGNOR-268399 |
Q9Y575 | P20333 | 2 | binding | down-regulates quantity by destabilization | 0.397 | While the ankyrin repeats of ASB3 interact with the C-terminal 37 amino acids of TNF-R2, the SOCS box of ASB3 is responsible for recruiting the E3 ubiquitin ligase adaptors Elongins-B/C, leading to TNF-R2 ubiquitination on multiple lysine residues within its C-terminal region. Downregulation of ASB3 expression by a small interfering RNA inhibited TNF-R2 degradation and potentiated TNF-R2-mediated cytotoxicity. The data presented here implicate ASB3 as a negative regulator of TNF-R2-mediated cellular responses to TNF-alpha by direct targeting of TNF-R2 for ubiquitination and proteasome-mediated degradation | SIGNOR-271546 |
Q06418 | Q14393 | 2 | binding | up-regulates | 0.57 | We report the identification of ligands for tyro 3 (alternatively called sky, rse, brt, or tif) and axl (alternatively, ark or ufo), members of a previously orphan family of receptor-like tyrosine kinases. These ligands correspond to protein s, a protease regulator that is a potent anticoagulant, and gas6, a protein related to protein s but lacking any known function. | SIGNOR-34414 |
P27361 | Q16665 | 1 | phosphorylation | up-regulates | 0.695 | We show that at least two different nuclear protein kinases, one of them identified as p42/p44 mapk, can modify hif-1_. Analysis of in vitro phosphorylated hif-1_ by mass spectroscopy revealed residues ser-641 and ser-643 as possible mapk phosphorylation sites these data suggest that phosphorylation of ser-641/643 by mapk promotes the nuclear accumulation and transcriptional activity of hif-1_ | SIGNOR-178731 |
Q7L9L4 | Q9NRM7 | 2 | binding | up-regulates | 0.876 | Lats1/2 are activated by association with the highly homologous scaffold proteins mps one binder kinase activator-like 1a (mobkl1a) and 1b (mobkl1b), which are collectively referred to as mob1. | SIGNOR-169798 |
P07288 | P19838 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | NF-kappa B activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer. | SIGNOR-253668 |
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 |
Q16671 | O00238 | 2 | binding | up-regulates | 0.43 | See table2 | SIGNOR-121596 |
P42336 | P27986 | 2 | phosphorylation | up-regulates activity | 0.936 | We find that p110 alpha phosphorylates p85 alpha Ser608 in vivo with significant stoichiometry. However, p110 beta is far less efficient at phosphorylating p85 alpha Ser608, identifying a potential difference in the mechanisms by which these two isoforms are regulated. The p85 alpha Ser608 phosphorylation was increased by treatment with insulin, platelet-derived growth factor, and the phosphatase inhibitor okadaic acid. The functional effects of this phosphorylation are highlighted by mutation of Ser608, which results in reduced lipid kinase activity and reduced association of the p110 alpha catalytic subunit with p85 alpha. | SIGNOR-276004 |
P84243 | Q7LBC6 | 0 | demethylation | down-regulates activity | 0.2 | We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation. | SIGNOR-266636 |
P35568 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.646 | Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101). | SIGNOR-249267 |
P12931 | P60953 | 1 | phosphorylation | up-regulates | 0.695 | Epidermal growth factor-dependent regulation of cdc42 is mediated by the src tyrosine kinaseegf signaling through src appears to have dual regulatory effects on cdc42: 1). it leads to the activation of cdc42 as mediated by the vav2 guanine nucleotide exchange factor, and 2). it results in the phosphorylation of cdc42, which stimulates the binding of rhogdi, perhaps to direct the movement of cdc42 to a specific cellular site to trigger a signaling response, because cdc42-rhogdi interactions are essential for cdc42-induced cellular transformation. | SIGNOR-118206 |
P49840 | P52630 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.263 | GSK3α/β are critical kinases to regulate STAT2 protein stability mediated by FBXW7.The 4-point mutant (STAT2-4A) of STAT2 at S381A/T385A/E389A/S393A inhibited GSK3α/β-mediated STAT2 phosphorylation. | SIGNOR-276761 |
Q9BVS4 | P53350 | 0 | phosphorylation | up-regulates activity | 0.429 | Here, we report that the atypical protein kinase Rio2 is a novel substrate of Plk1 and can be phosphorylated by Plk1 at Ser-335, Ser-380, and Ser-548. Overexpression of Rio2 causes a prolonged mitotic exit whereas knockdown of Rio2 accelerates mitotic progression, suggesting that Rio2 is required for the proper mitotic progression. F urthermore, time-lapse imaging data show that overexpression of Rio2 but not Rio2 S3A results in a slowed metaphase-anaphase transition. Collectively, these findings strongly indicate that the Plk1-mediated phosphorylation of Rio2 regulates metaphase-anaphase transition during mitotic progression. | SIGNOR-262937 |
Q7Z6J0 | P45985 | 2 | binding | up-regulates | 0.31 | We confirmed that posh binds activated rac1 and find that it also binds all mlk family members tested and interacts with mkk4/7 as well as jnk1 and jnk2. | SIGNOR-96952 |
O14965 | P14635 | 1 | phosphorylation | up-regulates activity | 0.576 | A second wave of Cyclin B1-CDK1 phosphorylation by AurA occurs in late prophase.|Simultaneously, AurA activates and targets the Cyclin B1-CDK1 complex at centrosomes [ xref ]. | SIGNOR-280186 |
Q99574 | Q86TM6 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | In this study, we demonstrate that two ER-associated E3 ligases, Hrd1 and gp78, are involved in the ubiquitination and degradation of mutant neuroserpin. | SIGNOR-272757 |
P61586 | Q9H3F6 | 2 | binding | down-regulates quantity | 0.269 | BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex. | SIGNOR-264237 |
Q13009 | P63000 | 2 | binding | up-regulates | 0.75 | Lpa-induced rac activation requires tiam1 | SIGNOR-94691 |
Q9Y6K9 | P12931 | 0 | phosphorylation | down-regulates activity | 0.416 | Either IKKγ/NEMO WT or the Y374F mutant was coexpressed with each member of the Src family protein tyrosine kinases (SF-PTKs) in HEK 293T cells. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation. | SIGNOR-276370 |
Q9Y297 | P19838 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.589 | Here we demonstrate that following IkappaB kinase (IkappaK)-mediated phosphorylation, the C-terminal domain of p105 (residues 918-934) serves as a recognition motif for the SCF(beta)(-TrCP) ubiquitin ligase.In vitro, SCF(beta)(-TrCP) specifically conjugates and promotes processing of phosphorylated p105. | SIGNOR-272570 |
P27348 | P07196 | 2 | binding | down-regulates activity | 0.299 | 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-252399 |
P12931 | Q68CZ2 | 1 | phosphorylation | up-regulates | 0.408 | Tyrosines in the sh2 domain contribute to the biological activity of tensin-3, and phosphorylation of these tyrosines can regulate ligand binding. tensin-3 is a src substrate | SIGNOR-187843 |
Q9Y5I2 | Q9Y5G7 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265716 |
P19793 | P10828 | 2 | binding | up-regulates | 0.721 | Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr | SIGNOR-81449 |
Q14524 | Q13131 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | AMPK was found to phosphorylate Nav1.5 at threonine (T) 101, which then regulates the interaction between Nav1.5 and the autophagic adaptor protein, microtubule-associated protein 1 light chain 3 (LC3), by exposing the LC3-interacting region adjacent to T101 in Nav1.5. | SIGNOR-277432 |
Q9UJD0 | O95153 | 2 | binding | down-regulates activity | 0.2 | SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins. | SIGNOR-264373 |
P0CG48 | O60260 | 2 | binding | up-regulates activity | 0.2 | Mechanism of phospho-ubiquitin-induced PARKIN activation|PhosphoUb binding leads to straightening of a helix in the RING1 domain, and the resulting conformational changes release the Ubl domain from the PARKIN core; this activates PARKIN|Our results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity. These findings demonstrate that phosphorylated ubiquitin is a parkin activator. | SIGNOR-249692 |
Q15118 | P11362 | 0 | phosphorylation | up-regulates | 0.347 | Mitochondrial pdhk1 is tyrosine phosphorylated and activated by fgfr1 in cancer cells further mass spectrometric analysis identified three tyrosine residues of pdhk1, including y136, y243 and y244, that are phosphorylated by fgfr1 | SIGNOR-193454 |
P38398 | Q99728 | 2 | binding | up-regulates | 0.795 | Brac1 dimerizes with brca1?associated Ring domain protein 1 (bard1) to yield a functional e3 ligase. | SIGNOR-162499 |
Q9UJU2 | P49674 | 0 | phosphorylation | down-regulates | 0.268 | Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays. | SIGNOR-134497 |
P00734 | P25116 | 1 | cleavage | up-regulates | 0.887 | The par1 receptor subtype is activated when the n terminus is proteolytically cleaved by the serine protease thrombin, resulting in an irreversible activation of the receptor. Thrombin activates platelets by binding and cleaving protease-activated receptors 1 and 4 (par1 and par4). | SIGNOR-199007 |
P49917 | P78527 | 0 | phosphorylation | down-regulates | 0.808 | Using tandem mass spectrometry, we identified a dna-pk phosphorylation site at thr-650 in human lig4 and a potential second phosphorylation site at ser-668 or ser-672. Phosphorylation of lig4 per se was not required for lig4 dna end joining activity. Substitution of these amino acids with alanine, individually or in combination, led to changes in lig4 protein stability of mouse lig4. The phosphomimetic mutation s650d returned lig4 stability to that of the wild-type protein. Furthermore dna-pk was found to negatively regulate lig4 protein stability. | SIGNOR-125877 |
P55210 | P49810 | 1 | cleavage | up-regulates activity | 0.318 | In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329. | SIGNOR-261751 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.