IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q9UP38 | P56706 | 0 | binding | up-regulates | 0.67 | Wnt7b can bind to fzd1 and -10 on the cell surface and cooperatively activate canonical wnt signaling. | SIGNOR-137931 |
O75197 | Q13467 | 0 | binding | up-regulates activity | 0.67 | Here we report that Wnt receptor Frizzled (Frz) and theco-receptors LRP5 and LRP6 (LRP5/6) directly interact with each other and this interaction is regulated by the LRP6 ectodomain. | SIGNOR-258969 |
P00734 | P38435 | 0 | carboxylation | up-regulates activity | 0.669 | We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. | SIGNOR-263676 |
P50391 | P10082 | 0 | binding | up-regulates | 0.669 | Human y4 bound human pp family members in i-pyy membrane binding assays with a distinctive rank order (table 1): pp > pyy > npy > npy free acid. | SIGNOR-29767 |
O15169 | O14641 | 0 | binding | up-regulates activity | 0.669 | Dishevelled (dvl) transduces the wnt signal by interacting with the cytoplasmic axin complex. | SIGNOR-155221 |
O15198 | Q9HCE7 | 0 | ubiquitination | down-regulates | 0.669 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps | SIGNOR-195669 |
Q9UBU9 | Q16629 | 0 | binding | up-regulates | 0.669 | 9g8 and srp20 also enhance the tap rna-binding activity | SIGNOR-161338 |
P19634 | P28482 | 0 | phosphorylation | up-regulates | 0.669 | We have demonstrated that the map kinases extracellular signal-regulated kinases 1 and 2 (erk1/2) are implicated in growth factor activation of nhe1. / our results suggest that amino acids ser770 and ser771 mediate erk-dependent activation of the na+/h+ exchanger in vivo. | SIGNOR-151925 |
P22736 | P28482 | 0 | phosphorylation | up-regulates activity | 0.669 | NGFI-B is an inducible orphan nuclear receptor that initiates apoptosis. Growth factors such as EGF activate the MAP kinase ERK, whose activity may determine if a cell survives or undergoes apoptosis. EGF stimulation of cells leads to phosphorylation of threonine in NGFI-B. Thr-142 of NGFI-B is comprised in a consensus MAP kinase site and was identified as a preferred substrate for ERK2 (but not ERK1) in vitro. | SIGNOR-249430 |
Q9NSE2 | P42229 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.669 | The STAT5 target gene CIS, a member of the suppressor of cytokine signaling (SOCS) protein family, was highly induced by Flt3-ITD | SIGNOR-261544 |
Q86X95 | Q06330 | 0 | binding | up-regulates | 0.669 | In the mechanism of cbf1-mediated repression, cbf1 binds to a unique corepressor cir. Targeting of cir to cbf1 is an important component of repression. Cir binds to histone deacetylase and to sap30 and serves as a linker between cbf1 and the histone deacetylase complex. | SIGNOR-62932 |
Q99638 | O14757 | 0 | phosphorylation | up-regulates activity | 0.669 | Chk1 inhibition with small interfering RNA (siRNA) reduces Rad9A stabilization and accumulation.|In the case of DNA damage, an activated Chk1 phosphorylates Rad9A or other proteins (TLK1) as a feedback mechanism to prevent Rad9A (poly) ubiquitination and degradation. | SIGNOR-279503 |
P60953 | Q86VW2 | 0 | guanine nucleotide exchange factor | up-regulates | 0.669 | Exogenous expression of geft promotes myogenesis of c2c12 cells via activation of rhoa, rac1, and cdc42 and their downstream effector proteins, while a dominant negative mutant of geft inhibits this process. | SIGNOR-235391 |
P48443 | P10276 | 0 | binding | up-regulates | 0.669 | Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins | SIGNOR-16466 |
P43146 | O95185 | 0 | binding | down-regulates activity | 0.669 | In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. | SIGNOR-268165 |
Q15796 | P35813 | 0 | dephosphorylation | down-regulates | 0.668 | Ppm1a dephosphorylates and promotes nuclear export of tgfbeta-activated smad2/3; these results suggest that phospho-smad2 is a direct substrate of mg2+-dependent ppm1a. in conclusion, ppm1a is a bona fide phosphatase that directly dephosphorylates the critical sxs motif of r-smads. | SIGNOR-146919 |
P42338 | P01111 | 0 | binding | up-regulates | 0.668 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k | SIGNOR-175225 |
Q9Y294 | Q86UE8 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.668 | We found that only S192A in hASF1a and S198A in hASF1b significantly affected phosphorylation by hTLK2 | Consistent | SIGNOR-260787 |
P35968 | P29350 | 0 | dephosphorylation | down-regulates activity | 0.668 | Src homology 2 (SH2) domain containing protein tyrosine phosphatase-1 (SHP-1) dephosphorylates VEGF Receptor-2 and attenuates endothelial DNA synthesis, but not migration|Knockdown of SHP-1 by siRNA or inhibition of c-Src by an inhibitor, results in augmented DNA synthesis perhaps due to increased phosphorylation of at least three tyrosine residues of KDR 996, 1059 and 1175 | SIGNOR-248474 |
P62330 | O43150 | 0 | gtpase-activating protein | up-regulates activity | 0.668 | Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Pap protein exhibits Arf GAP activity in vitro. | SIGNOR-269706 |
O15111 | P31749 | 0 | phosphorylation | up-regulates | 0.668 | Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta | SIGNOR-187006 |
P61586 | P12931 | 0 | phosphorylation | down-regulates activity | 0.668 | When these RhoA mutants were coexpressed with Bcr-Abl, phosphorylation levels of Y34F and Y66F RhoA mutants dramatically decreased to 32% and 17%, respectively. As expected, when Y34 and Y66 were both mutated to phenylalanine, phosphorylation was completely abolished. Together, these observations indicate that Y34 and Y66 are the two predominant phosphorylation sites, and that the Src kinase and Bcr-Abl are the two candidate kinases that may phosphorylate these sites.|In contrast to active RhoA, RhoAQ63L(Y34,66E) had a dramatic decrease in RBD binding. This binding fraction was even lower than that of WT RhoA, suggesting phosphorylation at these sites could have a negative effect on RhoA activity | SIGNOR-271701 |
P04637 | P68400 | 0 | phosphorylation | up-regulates activity | 0.668 | Furthermore, we demonstrate that anisomycin- and tumor necrosis factor-alpha-induced phosphorylation of p53 at Ser-392, which is important for the transcriptional activity of this growth suppressor protein, requires p38 MAP kinase and CK2 activities. | SIGNOR-250967 |
P46937 | P62136 | 0 | dephosphorylation | up-regulates activity | 0.668 | In the present study, we demonstrate that PP1A (catalytic subunit of protein phosphatase-1) interacts with and dephosphorylates YAP2 in vitro and in vivo, and PP1A-mediated dephosphorylation induces the nuclear accumulation and transcriptional activation of YAP2.|PP1A dephosphorylates endogenous YAP2 at serine 127. | SIGNOR-276999 |
P41145 | P01213 | 0 | binding | up-regulates activity | 0.668 | We recently cloned a human kappa opioid receptor and stably expressed it in Chinese hamster ovary (CHO) cells. In this study, the effects of activation of the human kappa receptor by agonists on [35S]GTPgammaS binding to CHO cell membranes were examined.. The rank order of potencies of opioid ligands tested in stimulating [35S]GTPgammaS binding was dynorphin A 1-17 > (+/-)-ethylketocyclazocine > beta-funaltrexamine, (-)-U50,488H, tifluadom > nalorphine > pentazocine, nalbuphine > buprenorphine. | SIGNOR-258411 |
Q13424 | P53778 | 0 | phosphorylation | up-regulates | 0.668 | Sapk3 phosphorylates alpha1-syntrophin at serine residues 193 and 201 in vitro and phosphorylation is dependent on binding to the pdz domain of alpha1-syntrophin. The finding that sapk3 co-localizes with _1-syntrophin in skeletal muscle, that it binds to the pdz domain of _1-syntrophin, and that phosphorylation of _1-syntrophin depends on this interaction identifies a novel mechanism for targeting a protein kinase to its substrates. | SIGNOR-67061 |
P61586 | A1A4S6 | 0 | gtpase-activating protein | down-regulates activity | 0.668 | 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-260465 |
P47712 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.668 | These results provide the first direct evidence that p38 kinase is responsible for cpla2 phosphorylation in sfllrn-stimulated platelets and is involved in the early phosphorylation of cpla2 in thrombin-stimulated platelets | SIGNOR-44673 |
Q99558 | Q13114 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.668 | TRAF2 and TRAF3 mediate NIK ubiquitination by forming a complex with the E3 ligase cIAP (cIAP1 or cIAP2).|We demonstrated further that TRAF3 mediates the degradation of NIK and thereby serves as a pivotal negative regulator of noncanonical NF-kappaB signaling. | SIGNOR-278673 |
P37231 | P28702 | 0 | binding | up-regulates | 0.668 | Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology | SIGNOR-105454 |
P14923 | P12931 | 0 | phosphorylation | up-regulates activity | 0.668 | Tyrosine phosphorylation of plakoglobin causes contrary effects on its association with desmosomes and adherens junction components and modulates beta-catenin-mediated transcriptionFor instance, Src, which mainly phosphorylates Tyr86 in beta-catenin, modifies Tyr643 in plakoglobin, decreasing the interaction with E-cadherin and alpha-catenin and increasing the interaction with the alpha-catenin-equivalent protein in desmosomes, desmoplakin. | SIGNOR-247310 |
O14508 | P42229 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.668 | We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling | SIGNOR-261547 |
P17676 | P27361 | 0 | phosphorylation | up-regulates | 0.668 | Thr235 phosphorylation occurs in nuclei of differentiated macrophages, but not in monocytes. | SIGNOR-184917 |
P17676 | P35638 | 0 | transcriptional regulation | down-regulates quantity | 0.668 | We find that expression of CHOP, a nuclear protein that dimerizes avidly with C/EBP isoforms alpha and beta and directs the resulting heterodimer away from classic C/EBP-binding sites, markedly inhibits this differentiation process. | SIGNOR-255914 |
O60353 | Q9H1J7 | 0 | binding | up-regulates | 0.668 | Human wnt5a, wnt5b and wnt11 are non-canonical wnt ligands transducing pcp signals through fzd3 or fzd6 receptors. | SIGNOR-141443 |
P61586 | Q9NR80 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.667 | 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-260531 |
P46531 | P09958 | 0 | binding | up-regulates | 0.667 | The proteolytic activity of furin responsible for processing full length notch-1 (p300) plays a critical role in notch signaling. | SIGNOR-196914 |
Q9ULB1 | Q02410 | 0 | binding | up-regulates activity | 0.667 | Mint1 and Mint2 Interact with the Cytoplasmic Domain of Neurexin I. The interaction of Mint1 with neurexins is mediated by its PDZ domains and allows the formation of mixed CASK-Mint complexes. Both CASK and Mint1 can bind directly to neurexins and to each other. Therefore, the assembly of various multimeric complexes could proceed as CASK could be indirectly recruited to neurexin-bound Mint1 and vice versa. | SIGNOR-264038 |
O14640 | Q14332 | 0 | binding | up-regulates activity | 0.667 | Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling. | SIGNOR-258956 |
P41143 | P01213 | 0 | chemical activation | up-regulates activity | 0.667 | Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors. | SIGNOR-258415 |
P52907 | Q6JBY9 | 0 | binding | up-regulates | 0.667 | An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B). Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ. | SIGNOR-263088 |
Q9GZM8 | P62258 | 0 | binding | up-regulates activity | 0.667 | 14-3-3epsilon is involved in the proper localization of NUDEL and LIS1 in axons. 14-3-3ε binds to NUDEL phosphorylated by cyclin-dependent kinase (cdk5) and maintains NUDEL phosphorylation. Deficiency of 14-3-3ε causes mislocalization of the NUDEL/LIS1 complex from axons, suggesting that 14-3-3ε regulates the axonal targeting of the NUDEL/LIS1 complex by sustaining NUDEL phosphorylation | SIGNOR-252160 |
P06400 | Q00987 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.667 | In this study, we found that Mdm2, a ubiquitin ligase for p53, promoted ubiquitin-dependent degradation of pRB | SIGNOR-278530 |
O75581 | Q14332 | 0 | binding | up-regulates activity | 0.667 | Here we show that both Fz and Dvl functions are critical for Wnt-induced Lrp6 phosphorylation through Fz-Lrp6 interaction. | SIGNOR-258965 |
P14317 | P43405 | 0 | phosphorylation | up-regulates | 0.667 | Here, we show that bcr-associated tyrosine kinases lyn and syk synergistically phosphorylate hs1, and that tyr-378 and tyr-397 of hs1 are the critical residues for its bcr-induced phosphorylation. once the two tyrosine residues are both phosphorylated, processive phosphorylation of hs1 by lyn and the other src family kinases would take place, producing hyperphosphorylated form of hs1. Finally, it is this hyperphosphorylated form of hs1 that translocates to the nucleus and activates b cell apoptosis. | SIGNOR-47342 |
P29353 | P12931 | 0 | phosphorylation | up-regulates activity | 0.666 | Here, we report the identification of two major and novel Shc tyrosine phosphorylation sites, Y239 and Y240. Y239/240 are co-ordinately phosphorylated by the src protein-tyrosine kinase in vitro, and in response to epidermal growth factor stimulation or in v-src-transformed cells in vivo. phosphorylation of y317 has been implicated in grb2 binding and activation of the ras pathway. | SIGNOR-44870 |
Q07666 | P28482 | 0 | phosphorylation | up-regulates | 0.666 | In support of this assumption, purified gst_sam68 protein was phosphorylated by recombinant erk2we found that sam68 mutated in ser 58, thr 71 and thr 84 showed the same extent of impairment in induced exon inclusion as did sam68 mutated in all s/tp sites | SIGNOR-96414 |
Q9NRL3 | Q9P2B4 | 0 | binding | up-regulates activity | 0.666 | Although CTTNBP2 and CTTNBP2NL are different in terms of tissue and subcellular distribution, our data indicate that, similar to CTTNBP2NL, CTTNBP2 associates with members of the striatin family, namely striatin and zinedin. Moreover, CTTNBP2 is critical for the distribution of striatin and zinedin in dendritic spines. The role of CTTNBP2 in the regulation of the synaptic distribution of striatin and zinedin suggests that CTTNBP2 regulates synaptic signaling through PP2A. | SIGNOR-261701 |
P60484 | Q6P0Q8 | 0 | phosphorylation | up-regulates | 0.666 | We further demonstrate that binding of pten to specific pdz domains diminishes its degradation rate and facilitates its phosphorylation by mast kinases. Our results suggest a regulatory role of pdz domain binding on pten function by controlling its stability and phosphorylation status. | SIGNOR-138051 |
Q9NPB9 | O00585 | 0 | binding | up-regulates activity | 0.666 | In the present study, however, we demonstrate for the first time the concentration-dependent recruitment of β-arrestins to the atypical chemokine receptor CCX-CKR upon stimulation with CCL19, CCL21, or CCL25 using three different methodologies in various transfected cell lines. | SIGNOR-268417 |
Q9NVI1 | O94782 | 0 | deubiquitination | down-regulates activity | 0.666 | Phosphorylation of FANCI may also turn the ubiquitinated ID complex into a poor substrate for deubiquitination by the USP1–UAF1 complex, resulting in increased levels of monoubiquitinated FANCD2. | SIGNOR-263272 |
P07948 | P08575 | 0 | dephosphorylation | down-regulates activity | 0.666 | CD45 negatively regulates lyn activity by dephosphorylating both positive and negative regulatory tyrosine residues in immature B cells.| Phosphoamino acid analysis confirmed that Lyn is tyrosine phosphorylated with little serine or threonine phosphorylation. In CD45-negative cells, two bands at 8.2 and 4.1 kDa were phosphorylated in the absence of B cell Ag receptor (BCR) ligation. The 8.2-kDa band corresponded to a fragment containing the positive regulatory site (Tyr397), as assessed by its size and its phosphorylation in an in vitro kinase assay. The 4.1-kDa band was phosphorylated by COOH-terminal Src kinase, suggesting that it contains the COOH-terminal negative regulatory site (Tyr508) | SIGNOR-248354 |
Q9NR28 | Q96CA5 | 0 | binding | down-regulates | 0.666 | These results suggest that ml-iap might regulate apoptosis by sequestering smac and preventing it from antagonizing xiap-mediated caspases, rather than by direct caspases. | SIGNOR-129869 |
P63000 | P15882 | 0 | gtpase-activating protein | down-regulates activity | 0.666 | 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-260499 |
Q96FE5 | Q9NQC3 | 0 | binding | up-regulates | 0.666 | Nogo-a, myelin-associated glycoprotein (mag), and oligodendrocyte myelin glycoprotein (omgp)...signal through a common receptor complex in neurons, which includes the ligand binding nogo-66 receptor (ngr), and two signal-transducing binding partners, p75 and lingo-1, | SIGNOR-133752 |
P27361 | P51452 | 0 | dephosphorylation | down-regulates activity | 0.665 | The activation of the mapk activity requires the dual phosphorylation of the ser/thr and tyr residues in the txy kinase activation motif (1113), and deactivation occurs through the action of either ser/thr protein phosphatase (14), protein-tyrosine phosphatase (ptp) (14, 15), or dual specificity phosphatases | SIGNOR-103035 |
P01574 | Q14653 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.665 | Similarly, exogenous expression of wild-type Pin1 suppressed TLR3-mediated, IRF3-dependent activation of the IFN-beta promoter and reduced IFN-beta secretion in culture supernatants | SIGNOR-252257 |
P53350 | O14965 | 0 | phosphorylation | up-regulates | 0.665 | We find that aurora a (aurka) can directly phosphorylate plk1 on thr 210;activation of plk1 requires phosphorylation of a conserved threonine residue (thr 210). | SIGNOR-179422 |
Q16539 | Q13115 | 0 | dephosphorylation | down-regulates | 0.665 | This result suggests that dusp4 represses gluconeogenesis through dephosphorylation of p38 | SIGNOR-147958 |
P38398 | P11802 | 0 | phosphorylation | down-regulates | 0.665 | In particular, we have identified ser 632 of brca1 as a cyclin d1/cdk4 phosphorylation site in vitro. Using chromatin immunoprecipitation assays, we observed that the inhibition of cyclin d1/cdk4 activity resulted in increased brca1 dna binding at particular promoters in vivo. | SIGNOR-153450 |
P13569 | Q99942 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.665 | JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation. | SIGNOR-271494 |
Q8NFJ6 | Q9HC23 | 0 | binding | up-regulates | 0.665 | We have cloned two closely related receptors for pk1 and pk2. These receptors, named prokineticin receptor 1 and 2 (pkr1 and pkr2) | SIGNOR-87919 |
P63000 | P10911 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.665 | 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-260557 |
P60484 | Q8NEB9 | 0 | binding | up-regulates | 0.665 | Direct positive regulation of pten by the p85 subunit of phosphatidylinositol 3-kinase.Thus p85 regulates both p110-pi3k and pten-phosphatase enzymes through direct interaction | SIGNOR-164075 |
Q99743 | P35398 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.665 | Direct Regulation of the NPAS2 Promoter by RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding. | SIGNOR-267980 |
Q03060 | Q5TD97 | 0 | binding | up-regulates activity | 0.665 | ACT (for activator of CREM in testis), a LIM-only protein which specifically associates with CREM. ACT is expressed coordinately with CREM in a tissue- and developmentally regulated manner. It strongly stimulates CREM transcriptional activity in yeast and mammalian cells and contains an intrinsic activation function. | SIGNOR-222111 |
Q04771 | P27037 | 0 | binding | up-regulates | 0.664 | The major bmp7 type i receptor observed was alk2, | SIGNOR-60234 |
P08151 | Q9Y297 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.664 | Here we show that Gli is rapidly destroyed by the proteasome and that mouse basal cell carcinoma induction correlates with Gli protein accumulation. We identify two independent destruction signals in Gli1, D(N) and D(C), and show that removal of these signals stabilizes Gli1 protein and rapidly accelerates tumor formation in transgenic animals.Levels of _TrCP appeared to be limiting for Gli1 degradation, as increasing the levels of _TrCP protein significantly decreased steady-state levels of Gli1 protein | SIGNOR-235631 |
Q9UP38 | O00744 | 0 | binding | up-regulates | 0.664 | Inhibition of adipogenesis by wnt10b is likely mediated by wnt receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 6 | SIGNOR-89134 |
Q00526 | P38936 | 0 | binding | down-regulates | 0.664 | P21cip1 is a cyclin-dependent kinase (cdk) inhibitor that is transcriptionally activated by p53 in response to dna damage. We have explored the interaction of p21 with the currently known cdks. p21 effectively inhibits cdk2, cdk3, cdk4, and cdk6 kinases. | SIGNOR-29954 |
Q9NP70 | Q8IXL6 | 0 | phosphorylation | up-regulates activity | 0.664 | Disruption of Fam20C completely eliminated AMBN phosphorylation, suggesting that Fam20C is the kinase that phosphorylates enamel matrix proteins in vivo (XREF_FIG). | SIGNOR-280010 |
Q9NPB9 | Q99731 | 0 | binding | up-regulates activity | 0.664 | In the present study, however, we demonstrate for the first time the concentration-dependent recruitment of β-arrestins to the atypical chemokine receptor CCX-CKR upon stimulation with CCL19, CCL21, or CCL25 using three different methodologies in various transfected cell lines. | SIGNOR-268416 |
O95390 | P19883 | 0 | binding | down-regulates activity | 0.664 | Follistatin (FST) is a member of the tissue growth factor β family and is a secreted glycoprotein that antagonizes many members of the family, including activin A, growth differentiation factor 11, and myostatin. |FST315-ΔHBS-Fc induced improvements in muscle repair after injury/atrophy by modulating the early inflammatory phase allowing for increased macrophage density, and Pax7-positive cells leading to an accelerated restoration of myofibers and muscle function. | SIGNOR-251716 |
Q9NPB9 | O15444 | 0 | binding | up-regulates activity | 0.664 | In the present study, however, we demonstrate for the first time the concentration-dependent recruitment of β-arrestins to the atypical chemokine receptor CCX-CKR upon stimulation with CCL19, CCL21, or CCL25 using three different methodologies in various transfected cell lines. | SIGNOR-268418 |
P10827 | P19793 | 0 | binding | up-regulates | 0.663 | 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-81446 |
Q96SN8 | Q9P209 | 0 | relocalization | up-regulates activity | 0.663 | By bringing CDK5RAP2 to the centrosome, the centriolar satellite proteins CEP72 and SPAG5 are required for the centrosomal localization of the other three MCPH proteins despite not interacting with them biochemically. | SIGNOR-271720 |
P10415 | Q9BXH1 | 0 | binding | down-regulates activity | 0.663 | Only bimbh3 and bbc3 had comparable strong affinitiesfor all the prosurvival proteins. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1. | SIGNOR-133808 |
O15519 | Q13490 | 0 | ubiquitination | down-regulates quantity | 0.663 | Moreover, API-1 increased c-FLIP ubiquitination and decreased c-FLIP stability.|Thus, we conclude that API-1 reduces c-FLIP levels by facilitating its degradation through the ubiquitin and proteasome dependent pathway. | SIGNOR-278687 |
P63092 | P16473 | 0 | binding | up-regulates activity | 0.663 | The primary signal transduction pathway for TSH receptor is activation of adenylate cyclase via a Gαs G protein-coupled receptor. | SIGNOR-267136 |
P30305 | P53350 | 0 | phosphorylation | up-regulates activity | 0.663 | These data indicated that PLK1 phosphorylates CDC25B and that pre-phosphorylation of CDC25B by CDK1/CyclinB enhances its substrate properties for PLK1 in vitro | SIGNOR-267560 |
P04637 | Q14694 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.662 | Since USP10 is known as a deubiquitinating protease of p53 (Yuan et al., 2010), inhibition of USP10 by spautin-1 may promote the degradation of p53. | SIGNOR-260297 |
P02545 | P55212 | 0 | cleavage | down-regulates | 0.662 | Lamin a breakdown is largely mediated by caspase-6 during the execution phase of apoptosis. | SIGNOR-83611 |
O00329 | P01112 | 0 | binding | up-regulates | 0.662 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. it was also described that ras interacts with pi3k in a direct manner. lysine residue 227 is essential for the interaction of ras with pi3k | SIGNOR-175192 |
Q9P296 | P01031 | 0 | binding | up-regulates | 0.662 | Here we report that the orphan receptor c5l2/gpr77, which shares 35% amino acid identity with cd88, binds c5a with high affinity. | SIGNOR-113558 |
P23771 | P42226 | 0 | null | up-regulates | 0.662 | GATA-3 plays a central role in regulating Th1 and Th2 cell differentiation. Upon interleukin (IL)-4 binding to its receptor, GATA-3 is induced through the action of Stat6 | SIGNOR-254299 |
O15105 | Q9Y5K5 | 0 | binding | up-regulates | 0.662 | Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases. | SIGNOR-138879 |
P62714 | Q9UIC8 | 0 | methylation | up-regulates activity | 0.661 | Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1) | SIGNOR-265751 |
P43146 | Q6ZN44 | 0 | binding | down-regulates activity | 0.661 | In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. | SIGNOR-268164 |
Q02078 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.661 | We show that mef2a, but not mef2b or mef2d, is a substrate for p38. Threonines 312 and 319 are the key regulatory phosphorylation sites by p38 in mef2a. Phosphorylation at these sites enhances transcriptional activity of mef2a | SIGNOR-62780 |
P05106 | P12931 | 0 | phosphorylation | down-regulates activity | 0.661 | The phosphorylation level of beta(3) integrin was modulated using a temperature-sensitive v-Src kinase. Increased beta(3) phosphorylation abolished alpha(v)beta(3)- but not alpha(5)beta(1)-mediated adhesion to fibronectin. Thus, phosphorylation of the cytoplasmic domain of beta(3) is a negative regulator of alpha(v)beta(3)-fibronectin binding strength. | SIGNOR-247207 |
P32121 | Q99835 | 0 | binding | up-regulates | 0.661 | Grk2-mediated phosphorylation of vertebrate smo allows smo to bind to beta-arrestins 1 or 2 | SIGNOR-132759 |
Q96S42 | P13385 | 0 | binding | up-regulates activity | 0.661 | Nodal effects are dependent upon interactions with Cripto, a small cysteine-rich extracellular protein that is attached to the plasma membrane through a glycosyl phosphatidyl inositol linkage. Cripto interacts with Nodal and ALK4, independently, and promotes the formation of a stable high affinity complex with activin type II receptors. | SIGNOR-251937 |
O95166 | Q8IZQ1 | 0 | binding | down-regulates quantity by destabilization | 0.661 | Here, we show that ALFY binds selectively to LC3C and the GABARAPs through a LIR in its WD40 domain. Binding of ALFY to GABARAP is indispensable for its recruitment to LC3B-positive structures and, thus, for the clearance of certain p62 structures by autophagy. | SIGNOR-266796 |
Q02750 | Q13233 | 0 | phosphorylation | up-regulates activity | 0.661 | Phosphorylation at ser-218 and ser-222 by map kinase kinase kinases (raf or mekk1) positively regulates mek1 kinase activity. | SIGNOR-235587 |
P31749 | Q15173 | 0 | dephosphorylation | down-regulates | 0.661 | Activation of pp2a is the intermediate step between the abeta-ceramide cascade and the subsequent inactivation of akt. | SIGNOR-252615 |
O15264 | P52564 | 0 | phosphorylation | up-regulates activity | 0.661 | p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation. | SIGNOR-273952 |
Q13542 | P42345 | 0 | phosphorylation | down-regulates | 0.661 | Here, we show that cancer cells acquire resistance to astori by downregulating eukaryotic translation initiation factor (eif4e)-binding proteins (4e-bps-eif4ebp1, eif4ebp2). | SIGNOR-122014 |
P29992 | P35368 | 0 | binding | up-regulates activity | 0.661 | In this report, we demonstrate that in transfected cos-7 cells Gal4 and Ga16, like Gaq and Ga11, can activate PIPLC j3l and that all three al-ARs, alA, alB and alC, can activate endogenous PI-PLC by coupling to Gaq or Ga11. | SIGNOR-278122 |
Q8IVT5 | Q7Z569 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.661 | Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15. | SIGNOR-272028 |
P08238 | O95433 | 0 | binding | up-regulates activity | 0.661 | The N-terminal region of Aha1 interacts with the central domain of Hsp90 and stimulates Hsp90 ATPase activity | SIGNOR-252212 |
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