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 |
|---|---|---|---|---|---|---|---|
P23409 | Q14814 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.573 | Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis. | SIGNOR-238715 |
P29992 | P35348 | 0 | binding | up-regulates activity | 0.573 | 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-278121 |
Q02224 | Q9BW19 | 0 | binding | up-regulates activity | 0.573 | We found that KIFC1 could directly bind to CENPE in SKOV3 cells (Figure 4C, 4D). | SIGNOR-266116 |
P45985 | Q12852 | 0 | phosphorylation | up-regulates activity | 0.572 | As expected, DLK significantly increased MKK4 phosphorylation on Ser257 / Thr261, and myrAKT1 enhanced MKK4 phosphorylation on Ser78 (XREF_FIG).|While MKK4 activated by DLK had strong activity in phosphorylating JNK3, MKK4 expressed with DLK and AKT1 together exhibited little activity, even though the two samples had similar levels of Ser257 / Thr261 phosphorylation (XREF_FIG). | SIGNOR-279629 |
P29353 | P17706 | 0 | dephosphorylation | down-regulates activity | 0.572 | However, TC45 inhibited the EGF-induced association of p52Shc with Grb2, which was attributed to the ability of the PTP to recognize specifically p52Shc phosphorylated on Y239. These results indicate that TC45 recognizes not only selected substrates in a cellular context but also specific sites within substrates and thus may regulate discrete signaling events. | SIGNOR-248397 |
Q15436 | Q9Y6Y8 | 0 | binding | up-regulates activity | 0.572 | The results showed that the N-terminal region of p125 is important for the interaction with Sec23p. We confirmed the interaction between the two proteins by a yeast two-hybrid assay. Overexpression of p125, like that of mammalian Sec23p, caused disorganization of the endoplasmic reticulum-Golgi intermediate compartment and Golgi apparatus, suggesting its role in the early secretory pathway. | SIGNOR-265307 |
P22681 | Q15303 | 0 | binding | up-regulates | 0.572 | Erbb4 might not be able to directly recruit cbl, and therefore downregulation of this receptor is slow. | SIGNOR-147841 |
Q92945 | Q16539 | 0 | phosphorylation | down-regulates activity | 0.572 | KSRP, an important factor for AU-rich element (ARE)-directed mRNA decay, undergoes p38-dependent phosphorylation during muscle differentiation. KSRP phosphorylated by p38 displays compromised binding to ARE-containing transcripts and fails to promote their rapid decay, although it retains the ability to interact with the mRNA degradation machinery | SIGNOR-235856 |
P03372 | P04626 | 0 | phosphorylation | up-regulates | 0.572 | The results presented here show for the first time that er redistribution to the cytoplasm and its interaction with her2 are important downstream effects of her2 overexpression, that erk1/2 is important for er cytoplasmic localization, and that subcellular localization of er may play a mechanistic role in determining the responsiveness of breast cancer cells to tamoxifen. | SIGNOR-124962 |
P23443 | O60346 | 0 | dephosphorylation | down-regulates activity | 0.572 | Here we report the identification of ribosomal protein S6 kinase 1 (S6K1) as a novel substrate of PHLPP. | SIGNOR-237454 |
Q02241 | O43663 | 0 | binding | up-regulates activity | 0.572 | These data indicate that PRC1 binds to KIF4, MKLP1 and CENP-E during late mitosis; however, it apparently does not interact simultaneously with more than one of these motor proteins. | SIGNOR-265989 |
Q04759 | O15530 | 0 | phosphorylation | up-regulates | 0.572 | We demonstrate that 3-phosphoinositide-dependent kinase 1 (pdk1) has an essential role in this pathway by regulating the activation of pkc and through signal-dependent recruiting of both pkc and card11 to lipid rafts. | SIGNOR-134869 |
P06396 | P12931 | 0 | phosphorylation | up-regulates | 0.572 | Identification of tyr438 as the major in vitro c-src phosphorylation site in human gelsolin recently | SIGNOR-67014 |
P42701 | P29459 | 0 | binding | up-regulates | 0.572 | Like il-12, il-23 binds to the il-12r subunit il-12rbeta1. | SIGNOR-87677 |
Q9Y3M2 | P31749 | 0 | phosphorylation | up-regulates activity | 0.572 | These observations argue that Chibby is a bona fide Akt substrate and that Akt kinase phosphorylates Chibby at the serine 20 residue. | SIGNOR-279002 |
P43146 | P06241 | 0 | phosphorylation | up-regulates activity | 0.572 | Fyn tyrosine kinase, but not Src, regulates the phosphorylation of DCC in N1E-115 neuroblastoma cells.Both DCC phosphorylation and Netrin-1-induced axon outgrowth are impaired in Fyn(-/-) CN and spinal cord explants. We propose that DCC is regulated by tyrosine phosphorylation and that Fyn is essential for the response of axons to Netrin-1. these results show that DCC is phosphorylated by Fyn, but not Src, in N1E-115 cells, and that tyrosines 1261 and 1418 are the major phosphorylation sites of Fyn in vivo. | SIGNOR-268176 |
Q14674 | P06493 | 0 | phosphorylation | down-regulates | 0.572 | Both cdc2/cyclinb1 and mapk (erk2) efficiently phosphorylate separase at its major inhibitory site in vitro | SIGNOR-113126 |
O43524 | O15111 | 0 | phosphorylation | down-regulates | 0.572 | Ikappab kinase promotes tumorigenesis through inhibition of forkhead foxo3a. The tnf treatment of ht-29 cells increased ikk-dependent foxo3 ser644 phosphorylation. | SIGNOR-124203 |
P60953 | Q6XZF7 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.572 | 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-260547 |
P04070 | P38435 | 0 | carboxylation | up-regulates activity | 0.572 | Gamma-carboxylation is essential in the activation and proper functioning of multiple VK-dependent proteins (VKDP), the most well-known of which are involved in blood clotting, including coagulation factors (FII, FVII, FIX and FX) and natural anti-clotting agents (protein C, protein S (ProS; OMIM*176880) and protein Z | SIGNOR-265925 |
O96017 | O15297 | 0 | dephosphorylation | up-regulates activity | 0.572 | an in vitro phosphatase assay revealed that Wip1 (WT), but not Wip1 (D314A), dephosphorylates Thr68 on phosphorylated Chk2 in vitro, resulting in the inhibition of Chk2 kinase activity toward glutathione S-transferase-Cdc25C. | SIGNOR-248318 |
O75581 | O96014 | 0 | binding | up-regulates activity | 0.572 | 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-131637 |
Q9NS23 | Q96BY2 | 0 | binding | up-regulates activity | 0.572 | Modulator of apoptosis 1 (MOAP-1) is a BH3-like protein that plays key roles in cell death or apoptosis. It is an integral partner to the tumor suppressor protein, Ras association domain family 1A (RASSF1A), and functions to activate the Bcl-2 family pro-apoptotic protein Bax. | SIGNOR-272914 |
P09651 | Q92973 | 0 | relocalization | up-regulates activity | 0.572 | TNPO1 only mediates the nuclear import of a subset of proteins.|Among TNPO1 cargos, the most extensively characterized is the RNA binding protein heterogeneous nuclear ribonucleoprotein 1 (hnRNPA1) (27), which functions in several processes including mRNA biogenesis and promotion of transcription factor activity (28–30). NPC protein NUP153 is also a target for TNPO1-mediated nuclear import | SIGNOR-262099 |
P04637 | O15391 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.572 | 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-266213 |
P19634 | Q16539 | 0 | phosphorylation | up-regulates | 0.571 | Trophic factor withdrawal: p38 mitogen-activated protein kinase activates nhe1, which induces intracellular alkalinization. activated p38 mapk directly phosphorylated the c terminus of nhe1 within a 40-amino-acid region. Analysis by mass spectroscopy identified four phosphorylation sites on nhe1, thr 717, ser 722, ser 725, and ser 728. | SIGNOR-111043 |
P38405 | P21728 | 0 | binding | up-regulates activity | 0.571 | 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-256939 |
Q16659 | O60729 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.571 | Reciprocally, we found that the phosphatases Cdc14A and Cdc14B (Cdc is cell-division cycle) bind to ERK3 and reverse its C-terminal phosphorylation in mitosis. Importantly, alanine substitution of the four C-terminal phosphorylation sites markedly decreased the half-life of ERK3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.|In vitro phosphorylation of a series of ERK3-deletion mutants by mitotic cell extracts revealed that phosphorylation is confined to the unique C-terminal extension of the protein. Using MS analysis, we identified four novel phosphorylation sites, Ser684, Ser688, Thr698 and Ser705, located at the extreme C-terminus of ERK3. | SIGNOR-248336 |
Q15831 | Q13315 | 0 | phosphorylation | up-regulates | 0.571 | We demonstrate that both dna-pk and atm efficiently phosphorylate lkb1 at thr-366 in vitro and provide evidence that atm mediates this phosphorylation in vivo. | SIGNOR-92873 |
P61586 | O94989 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.571 | 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-260540 |
P45984 | Q13387 | 0 | binding | up-regulates | 0.571 | These experiments demonstrated that 10 different jnk isoforms bound to both jip proteins. | SIGNOR-70866 |
Q02962 | Q6ZW49 | 0 | binding | up-regulates activity | 0.571 | PTIP promotes assembly of the ALR complex and H3K4 methylation at a PAX2-binding DNA element. Without PTIP, Pax2 binds to this element but does not assemble the ALR complex | SIGNOR-251711 |
P03372 | Q12837 | 0 | binding | up-regulates activity | 0.571 | the POU domain of Brn-3a and Brn-3b was shown to interact with the DNA-binding domain of the ER. Brn-3-ER interactions also affect transcriptional activity of an ERE-containing promoter, such that in estradiol-stimulated cells, Brn-3b strongly activated the promoter via the ERE, while Brn-3a had a mild inhibitory effect. | SIGNOR-241208 |
O75197 | Q9GZT5 | 0 | binding | up-regulates | 0.571 | 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-131619 |
Q96BA8 | Q14703 | 0 | cleavage | up-regulates | 0.571 | Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes | SIGNOR-143785 |
P31947 | Q14258 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.571 | Here we show that Efp is a RING-finger-dependent ubiquitin ligase (E3) that targets proteolysis of 14-3-3 sigma, a negative cell cycle regulator that causes G2 arrest. | SIGNOR-271548 |
Q04206 | Q13547 | 0 | binding | down-regulates | 0.571 | Phosphorylation at thr505 by the chk1 inhibits rela transactivation and results in its increased association with hdac1. | SIGNOR-151425 |
Q14451 | P07949 | 0 | binding | up-regulates | 0.571 | Grb7 and grb10, likely relay signals emanating from ret to other, as yet, unidentified targets within the cell | SIGNOR-41765 |
Q15078 | P07384 | 0 | cleavage | up-regulates activity | 0.571 | Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain | SIGNOR-251583 |
P26358 | Q16576 | 0 | binding | down-regulates activity | 0.571 | AMPK inhibited DNMT1 through phosphorylation of Ser730 in DNMT1 and Ser314 in RBBP7|association with RBBP7 could inhibit DNMT1 | SIGNOR-264785 |
P04637 | P19525 | 0 | phosphorylation | up-regulates | 0.571 | The double-stranded rna activated protein kinase pkr physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro. | SIGNOR-68033 |
P67775 | Q9NRL3 | 0 | binding | up-regulates activity | 0.571 | The striatin family proteins interact with the structural (A) and catalytic (C) subunits of the protein phosphatase, PP2A, and are also termed the B‴ family of PP2A subunits (4). Within heterotrimeric PP2A complexes, striatins function as one of many regulatory B subunits thought to be responsible for substrate selection and localization of PP2A isoforms | SIGNOR-261697 |
P04234 | P06239 | 0 | phosphorylation | up-regulates activity | 0.571 | Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. | SIGNOR-259929 |
P54274 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.571 | Telomeric protein pin2/trf1 as an important atm target in response to double strand dna breaks. activated atm directly phosphorylated pin2/trf1 preferentially on the conserved ser(219)-gln site in vitro and in vivo. | SIGNOR-108419 |
P30542 | P00813 | 0 | binding | up-regulates activity | 0.571 | The results show that human ADA, apart from reducing the adenosine concentration and thus preventing A(1)R desensitization, binds to A(1)R behaving as an allosteric effector that markedly enhances agonist affinity and increases receptor functionality. | SIGNOR-269105 |
P48058 | P17252 | 0 | phosphorylation | up-regulates | 0.57 | Receptor internalization, altered;intracellular localization | SIGNOR-97554 |
P00519 | P06400 | 0 | binding | down-regulates | 0.57 | A domain in the c-terminus of rb, outside of the a/b pocket, binds to the atp-binding lobe of the c-abl tyrosine kinase, resulting in kinase inhibition. | SIGNOR-37139 |
Q8IWI9 | P61244 | 0 | binding | up-regulates activity | 0.57 | 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-240261 |
P84022 | Q9UNE7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.57 | These results suggest that Smad3 could be easily ubiquitinated and degraded by CHIP when Hsp90 activity was inhibited.To demonstrate the role of Hsp70 and Hsp90 on the regulation of Smad3 by CHIP, we over-expressed Hsp70 and Hsp90 in mammalian cells. | SIGNOR-278785 |
P62136 | Q8IWU2 | 0 | phosphorylation | down-regulates activity | 0.57 | Kpi-2 kinase domain phosphorylated protein phosphatase-1 (pp1c) at thr(320), which attenuated pp1c activity. | SIGNOR-94631 |
P41182 | O75376 | 0 | binding | up-regulates activity | 0.57 | The POZ domains of BCL-6 and several other POZ proteins interact with corepressors N-CoR and SMRT. | SIGNOR-252239 |
P11940 | O00571 | 0 | binding | up-regulates activity | 0.57 | In the present study, we indentified the SG marker PABP1 [poly(A)-binding protein 1] as another direct interaction partner of DDX3. Interestingly, down-regulation of DDX3 interfered with SG assembly, led to nuclear accumulation of PABP1 and reduced cell viability following stress. Conversely, supplementation with a shRNA (short hairpin RNA)-resistant DDX3 restored SG formation, the translocation of PABP1 into SGs and cell survival. | SIGNOR-269201 |
P35222 | P31751 | 0 | phosphorylation | up-regulates | 0.57 | Phosphorylation of beta-catenin by akt promotes beta-catenin transcriptional activitywe have demonstrated that akt phosphorylates beta-catenin at ser552 in vitro and in vivo. | SIGNOR-152958 |
P78314 | P29350 | 0 | dephosphorylation | down-regulates | 0.57 | Shp-1 dephosphorylates 3bp2 and potentially downregulates 3bp2-mediated t cell antigen receptor signaling | SIGNOR-146508 |
O43426 | P29323 | 0 | phosphorylation | down-regulates | 0.57 | Ephb2 causes tyrosine phosphorylation in the proline-rich domain of synaptojanin 1, and inhibits both the interaction with endophilin and the 5'-phosphatase activity of synaptojanin 1 | SIGNOR-135274 |
O43318 | O43541 | 0 | binding | down-regulates activity | 0.57 | Smad6 interacts with tak1 and tab1, and smad7 with tab1. The interaction of i-smads with tak1 and/or tab1 implies that several mechanisms exist underlying the repression of the tak1-p38 kinase pathway by i-smads. | SIGNOR-235571 |
O15534 | Q9Y297 | 0 | ubiquitination | down-regulates | 0.57 | We have found that per1 interacts with both _-trcp1 and _-trcp2 in a manner that depends on casein kinase 1 activity, and depletion of both _-trcp1 and _-trcp2 by rnai leads to dramatic stabilization of per1 | SIGNOR-137755 |
Q92630 | Q00987 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.57 | Under normal conditions, nuclear and not cytoplasmic DYRK2 is ubiquitinated by MDM2, resulting in its constitutive degradation.|Upon exposure to genotoxic stress, ATM phosphorylates DYRK2 at Thr-33 and Ser-369, which enables DYRK2 to escape from degradation by dissociation from MDM2 and to induce the kinase activity toward p53 at Ser-46 in the nucleus. | SIGNOR-275579 |
P08754 | P08908 | 0 | binding | up-regulates activity | 0.57 | 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-256836 |
O95405 | P37173 | 0 | binding | up-regulates activity | 0.57 | Sara functions to recruit smad2 to the tgfbeta receptor by controlling the subcellular localization of smad2 and by interacting with the tgfbeta receptor complex | SIGNOR-245093 |
Q06418 | Q14393 | 0 | 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 |
O75122 | P06493 | 0 | phosphorylation | up-regulates activity | 0.569 | Overall, these results support the idea that phosphorylation of CLASP2 on S1234 by Cdk1, but not phosphorylation of the CLASP2 C terminal by Plk1, is required to maintain mitotic spindle bipolarity.|We propose that Cdk1 and Plk1 mediate a CLASP2 phospho-switch that is necessary to stabilize KT-MT attachments in human cells. | SIGNOR-278233 |
Q92597 | O00141 | 0 | phosphorylation | up-regulates | 0.569 | Transient expression of active (sgk1-s422d) and inactive (sgk1-k127a) sgk1 mutants confirmed that activating sgk1 stimulates ndrg1-thr(346/356/366) phosphorylation. dexamethasone (0.2 mum) acutely activated sgk1 and the peak of this response (2-3 h) coincided with the induction of g (na), and both responses were pi3k-dependent. While these data suggest that sgk1 might mediate the rise in g (na), transient expression of the inactive sgk1-k127a mutant did not affect the hormonal induction of g (na) but did suppress the activation of sgk1. | SIGNOR-180821 |
P29353 | Q05655 | 0 | phosphorylation | up-regulates | 0.569 | Pkc delta phosphorylates p52shca at ser29 to regulate erk activation in response to h2o2. | SIGNOR-149398 |
P60484 | O60307 | 0 | binding | up-regulates | 0.569 | Pten binds to and is phosphorylated by mast kinases./ Pdz domain-mediated binding to pten facilitates its phosphorylation by mast kinases / pdz domain binding increases pten protein stability. | SIGNOR-138077 |
P78347 | Q13976 | 0 | phosphorylation | up-regulates | 0.569 | G-kinase phosphorylated tfii-i in vitro and in vivo on ser(371) and ser(743) outside of the interaction domain. G-kinase strongly enhanced tfii-i transactivation of a serum-response element-containing promoter in cos7 cells | SIGNOR-89849 |
O14920 | Q99759 | 0 | phosphorylation | up-regulates activity | 0.569 | Genetic analysis showed that MEKK3, which is thought to activate IKK2 through phosphorylation (Yang et al., 2001), is necessary for TNF-alpha-induced NF-kappaB activation.|Our results also suggest that IKK2 is phosphorylated on S177 and S181 on its activation loop by MEKK3. | SIGNOR-279468 |
P20807 | P20810 | 0 | binding | down-regulates activity | 0.569 | In addition to Ca2+, calpastatin has a key role in the regulation of calpain. Calpastatin, a heat-stable protein ranging from ~70 to ~140 kDa of apparent molecular weight depending on the cell type, is considered a specific endogenous inhibitor of calpains|The calpastatin molecule contains four inhibitory units [75–77]. Each of these units binds to one calpain molecule [75–77]. Therefore, the ratio calpain/calpastatin plays a key role in the regulation of calpain activity [78–80]. The inhibitory effect of calpastatin requires Ca2+-dependent high-affinity binding to three sites of calpain | SIGNOR-251603 |
Q8N8S7 | Q9UQB8 | 0 | binding | up-regulates activity | 0.569 | We conclude that the interaction of Cdc42 with the partial CRIB motif of IRSp53 relieves an intramolecular, autoinhibitory interaction with the N terminus, allowing the recruitment of Mena to the IRSp53 SH3 domain. This IRSp53:Mena complex initiates actin filament assembly into filopodia. | SIGNOR-268423 |
O60674 | P08887 | 0 | phosphorylation | up-regulates activity | 0.569 | On binding of IL-6 to its receptor IL-6R, JAK2 is phosphorylated, then STAT3 is phosphorylated by JAK2 | SIGNOR-254405 |
Q9UQQ2 | P06239 | 0 | phosphorylation | up-regulates | 0.569 | In vitro tyrosine phosphorylation of lnk by lck and zap-70. Tyrosine 297 would appear to be an attractive target for phosphorylation within the c-terminal domain. Our studies suggest that although lnk may participate in tcr signaling, its functions are in no way limiting during t cell development or activation. | SIGNOR-48850 |
P11717 | Q9Y5X3 | 0 | binding | down-regulates quantity | 0.569 | Here, we discovered that the binding between SNX-BARs and CI-MPR or IGF1R is mediated by the phox-homology (PX) domain of SNX5 or SNX6 and a bipartite motif, termed SNX-BAR-binding motif (SBM), in the cargoes. our studies establish that SNX-BARs function as a direct cargo-selecting module for a large set of transmembrane proteins transiting the endosome, in addition to their roles in phospholipid recognition and biogenesis of tubular structures. | SIGNOR-269442 |
Q9UHW9 | Q9UEW8 | 0 | phosphorylation | down-regulates activity | 0.569 | We observed that in vitro activated STE20/SPS1-related proline/alanine-rich kinase (SPAK) complexed to its regulatory MO25 subunit phosphorylated KCC3 at Ser-96 and that in Xenopus laevis oocytes Ser-96 of human KCC3 is phosphorylated in isotonic conditions and becomes dephosphorylated during incubation in hypotonicity, leading to a dramatic increase in KCC3 function. | SIGNOR-276597 |
Q9NYJ8 | O15105 | 0 | binding | up-regulates | 0.569 | The formation of smad7-tab2 and smad7-tab3 complexes resulted in the suppression of tnf signaling | SIGNOR-153917 |
P12931 | P41240 | 0 | phosphorylation | down-regulates | 0.569 | The catalytic activity of the src family of tyrosine kinases is suppressed by phosphorylation on a tyrosine residue located near the c terminus (tyr 527 in c-src), which is catalyzed by c-terminal src kinase (csk). | SIGNOR-179417 |
P11802 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.569 | C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation | SIGNOR-102734 |
P50542 | Q13608 | 0 | binding | up-regulates activity | 0.569 | Pex1, Pex6, and Pex26 are involved in Pex5 export from peroxisomes., we found that Pex1 and Pex6 bind to Pex5 (Fig. (Fig.6). Therefore, it is conceivable that Pex1 and Pex6 pull out Pex5 from peroxisome membranes in an ATP-dependent manner. | SIGNOR-253619 |
P20336 | Q92696 | 0 | lipidation | up-regulates activity | 0.569 | Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional | SIGNOR-265574 |
P07737 | P61586 | 0 | null | up-regulates activity | 0.569 | We find that the small GTPase Rho regulates R-cadherin adherens junction formation via Dia1 (also known as p140mDia) and profilin-1-mediated signaling pathway. The role played by Rho in regulating R-cadherin is underscored by the fact that constitutively active RhoA(Q63L) induces R-cadherin junction formation in MDA-MB-231 cells.|Data presented thus far demonstrated that Rho, Dia1, and profilin-1 were required for R-cadherin junction formation in N480 cells. | SIGNOR-253109 |
Q08499 | P17612 | 0 | phosphorylation | up-regulates | 0.569 | Phosphorylation and activation of a camp-specific phosphodiesterase by the camp-dependent protein kinase. | SIGNOR-42515 |
O00429 | Q5S007 | 0 | phosphorylation | up-regulates activity | 0.568 | LRRK2 G2019S directly bound to and phosphorylated Drp1 at Threonine595, whereas P110 treatment abolished this phosphorylation.Threonine595 phosphorylation of Drp1 by LRRK2 G2019S is required for Drp1-mediated mitochondrial fragmentation and excessive autophagy | SIGNOR-276495 |
Q15750 | O43541 | 0 | binding | down-regulates | 0.568 | Smad6 interacts with tak1 and tab1, and smad7 with tab1. The interaction of i-smads with tak1 and/or tab1 implies that several mechanisms exist underlying the repression of the tak1-p38 kinase pathway by i-smads. | SIGNOR-112642 |
Q01196 | Q03164 | 0 | binding | up-regulates quantity by stabilization | 0.568 | Similar to CBFβ, we show that MLL binds to AML1 abrogating its proteasome-dependent degradation.Furthermore, we demonstrate that MLL binds to a region of AML1 (that is conserved in AML2 and AML3) and increases AML1 (AML2 and AML3) protein levels | SIGNOR-255707 |
P50281 | P35625 | 0 | binding | down-regulates activity | 0.568 | FAP cilia regulated the expression of TIMP3, a secreted metalloproteinase inhibitor, that inhibited MMP14 to block adipogenesis. | SIGNOR-255908 |
Q96BA8 | O43462 | 0 | cleavage | up-regulates | 0.568 | Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes | SIGNOR-143820 |
P61586 | Q14CB8 | 0 | gtpase-activating protein | down-regulates activity | 0.568 | 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-260471 |
P17302 | P05129 | 0 | phosphorylation | down-regulates activity | 0.568 | Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication. | SIGNOR-249050 |
O43663 | O95239 | 0 | binding | up-regulates activity | 0.568 | These results suggest that KIF4 and its binding partner PRC1 play essential roles in the organization of central spindles and midzone formation. KIF4 deficiency leads to mislocalization of PRC1, MKLP1, CENP-E and chromosomal passenger proteins | SIGNOR-265988 |
Q9H2X6 | Q9Y6I7 | 0 | ubiquitination | down-regulates | 0.568 | Ubiquitination and degradation of homeodomain-interacting protein kinase 2 by wd40 repeat/socs box protein wsb-1 | SIGNOR-160032 |
P46934 | Q9NV92 | 0 | relocalization | down-regulates activity | 0.568 | Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2. | SIGNOR-260995 |
P78527 | P50876 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.568 | We show that RNF144A induces ubiquitination of DNA-PKcs in vitro and in vivo and promotes its degradation. | SIGNOR-272213 |
P45985 | Q9Y6R4 | 0 | phosphorylation | up-regulates activity | 0.568 | When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro. | SIGNOR-62369 |
P10070 | P48729 | 0 | phosphorylation | down-regulates | 0.568 | Gli2 can also be phosphorylated directly by ck-1 at the non-optimal sites | SIGNOR-146112 |
P35222 | Q9ULB5 | 0 | binding | up-regulates activity | 0.568 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265869 |
P29474 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.568 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251631 |
P50148 | P28335 | 0 | binding | up-regulates activity | 0.568 | 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-257221 |
P49755 | Q9Y3A6 | 0 | binding | up-regulates activity | 0.568 | P28 forms hetero-oligomeric complexes with p23. p23 is a major determinant for efficient targeting of p28 to the ERGIC | SIGNOR-261298 |
Q12879 | P12931 | 0 | phosphorylation | up-regulates activity | 0.567 | To gain further insight into the roles of Src and Fyn in the phosphorylation and regulation of the NMDA receptor, we have characterized the tyrosine phosphorylation of NR2A and NR2B by exogenous Src and FynIn the case of NR2A, three potential tyrosine phosphorylation sites have been proposed: Tyr1105, Tyr1267 and Tyr1387 (Zheng et al. 1998; Bi et al. 2000), all of which are similarly located in the C-terminal, cytoplasmic domain. | SIGNOR-247167 |
P33151 | P12931 | 0 | phosphorylation | down-regulates activity | 0.567 | cadherins also act to prevent epithelial cell motilityCadherin-cytoskeletal interactions occur through a number of adaptor proteins that interact with the C-terminal portion of the cadherin cytoplasmic tail, including the _-, _-, and _-catenin (6, 10). Additionally, VE-cadherin stability at the plasma membrane may be regulated by the binding of p120-catenin to the juxtamembrane region of the cytoplasmic tailWe show here that tyrosine phosphorylation of the adherens junction protein VE-cadherin at two critical tyrosines, Tyr-658 and Tyr-731, via tyrosine kinase activation or phosphatase inactivation was sufficient to prevent the binding of p120- and beta-catenin, respectively, to the cytoplasmic tail of VE-cadherinVE-cadherin becomes phosphorylated on Tyr-658 and/or Tyr-731 in response to Src kinase activity. | SIGNOR-246462 |
O43521 | P31749 | 0 | phosphorylation | down-regulates activity | 0.567 | Recombinant Akt could directly phosphorylate a GST-Bim(EL) fusion protein and identified the Akt phosphorylation site in the Bim(EL) domain as Ser(87). Further, we demonstrated that cytokine stimulation promotes Bim(EL) binding to 14-3-3 proteins. Finally, we show that mutation of Ser(87) dramatically increases the apoptotic potency of Bim(EL). | SIGNOR-252487 |
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