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 |
|---|---|---|---|---|---|---|---|
Q9NS28 | Q13976 | 0 | phosphorylation | up-regulates activity | 0.332 | Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. S216 phosphorylation might activate PP1 leading to dephosphorylation of both 14-3-3 binding sites, S49 and S218, and detachment of 14-3-3. Removal of 14-3-3 activates RGS18 to turn off Gq signaling thus contributing to platelet inhibition. | SIGNOR-273785 |
P78527 | P22415 | 1 | phosphorylation | up-regulates | 0.293 | Feeding induces the recruitment of dna-pk to usf-1 and its phosphorylation, which then allows recruitment of p/caf, resulting in usf-1 acetylation and fas promoter activation. | SIGNOR-184849 |
P31391 | Q03113 | 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-256959 |
P49715 | P28482 | 0 | phosphorylation | down-regulates | 0.352 | Ccaat/enhancer-binding protein alpha (c/ebpalpha) is one of the key transcription factors that mediate lineage specification and differentiation of multipotent myeloid progenitors into mature granulocytes.Here we report that inducers of monocyte differentiation inhibit the alternate cell fate choice, that of granulopoiesis, through inhibition of c/ebpalpha. This inhibition is mediated by extracellular signal-regulated kinases 1 and/or 2 (erk1/2), which interact with c/ebpalpha through an fxfp docking site and phosphorylate serine 21. | SIGNOR-120566 |
P17542 | P31749 | 0 | phosphorylation | down-regulates | 0.374 | Akt phosphorylates tal1 oncoprotein and inhibits its repressor activity. / our results show that akt specifically phosphorylates thr90 of the tal1 protein within its transactivation domain in vitro and in vivo. | SIGNOR-252479 |
P53350 | Q9NWD9 | 1 | phosphorylation | up-regulates activity | 0.2 | In addition, the inhibition of PLK1 activity by BI2536 treatment sharply reduced BEX4 protein, which was localized at the centrosomes in the HeLa cells or the GFP-BEX4 stable cell lines.|PLK1 directly phosphorylates BEX4 at T107 and contributes to BEX4-induced aneuploidy. | SIGNOR-279550 |
P06239 | Q9BWW4 | 1 | phosphorylation | up-regulates activity | 0.2 | The Src tyrosine kinase inhibitor PP2 blocked the nuclear translocation of Ssdp1. Western blot analysis showed that co-expression of Ssdp1 and Lck in 293T cells induces Ssdp1 phosphorylation. Mutation of the Ssdp1 N terminal tyrosine residues 23 and 25 markedly reduced both the phosphorylation and the nuclear localization of Ssdp1. Lck enhanced the transcriptional activity of Ssdp1 in the context of known components of a LIM-homeodomain (LIM-HD)/cofactor complex. | SIGNOR-273648 |
O14733 | O15264 | 1 | phosphorylation | up-regulates activity | 0.436 | 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-273954 |
P23458 | Q9UHF4 | 2 | binding | up-regulates | 0.486 | Each r1-type chain (il-10r1, il-20r1, il-22r1, ifn-_r1 and ifn-_r1) is associated with jak1 tyrosine kinase and mediates recruitment of a variety of signaling molecules after being phosphorylated on its intracellular domain. | SIGNOR-124486 |
Q6EBC2 | Q8NI17 | 2 | binding | up-regulates | 0.648 | Here we identify a four-helix bundle cytokine we have called interleukin 31 (il-31), which is preferentially produced by t helper type 2 cells. Il-31 signals through a receptor composed of il-31 receptor a and oncostatin m receptor. | SIGNOR-125313 |
Q99835 | P06241 | 1 | phosphorylation | up-regulates | 0.425 | Instead, shh rapidly and locally stimulated phosphorylation of the src family kinase (sfk) members src and fyn in a smo-dependent fashion. | SIGNOR-199156 |
O75807 | P36873 | 2 | binding | up-regulates activity | 0.698 | Dephosphorylation of eIF2α is central to ISR signal termination to restore protein synthesis and normal cell functioning 15. It is mediated by protein phosphatase 1 (PP1) complex that recruits a PP1 catalytic subunit (PP1c) and one of the two regulatory subunits. In mammals, phosphatase activity is regulated by either PPP1R15A (also known as growth arrest and DNA damage‐inducible protein, GADD34), which is induced as part of the ISR. the GADD34–PP1 complex acts as an important negative feedback loop to restore protein synthesis once the ER stress has been resolved, and as such aids in cell survival | SIGNOR-260174 |
P29590 | Q9H2X6 | 0 | phosphorylation | up-regulates | 0.438 | In response to dna damage, hipk2 phosphorylates pml at serines 8 and 38. he n-terminal phosphorylation sites contribute to the dna damage-induced pml sumoylation and are required for the ability of pml to cooperate with hipk2 for the induction of cell death. | SIGNOR-182428 |
Q14141 | Q8IYM1 | 2 | binding | down-regulates | 0.2 | Sept12 interacts with sept6 and this interaction alters the filament structure of sept6 in hela cells. | SIGNOR-159537 |
P12931 | P41743 | 1 | phosphorylation | up-regulates | 0.533 | Nerve growth factor stimulates multisite tyrosine phosphorylation and activation of the atypical protein kinase c's via a src kinase pathway. tyrosine 256, 271, and 325 were identified as major sites phosphorylated by src in the catalytic domain. | SIGNOR-111920 |
Q16539 | Q14814 | 1 | phosphorylation | up-regulates activity | 0.612 | Targeting of ash2l to specific genes is mediated by the transcriptional regulator mef2d. Furthermore, this interaction is modulated during differentiation through activation of the p38 mapk signaling pathway via phosphorylation of mef2d. | SIGNOR-159331 |
Q15468 | P06493 | 0 | phosphorylation | down-regulates activity | 0.32 | Importantly, we show that CDK1 and CyclinB phosphorylates the N-terminal domain of STIL, but not the region encompassing the CC or STAN motifs. | SIGNOR-279145 |
Q06330 | Q9UQF2 | 2 | binding | down-regulates | 0.2 | Here, we show that jip1 suppresses notch1 activity. Jip1 was found to physically associate with either intracellular domain of notch1 or rbp-jk and interfere with the interaction between them. | SIGNOR-165713 |
Q13153 | Q99426 | 1 | phosphorylation | up-regulates | 0.448 | P21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor b. Pak1 directly phosphorylated tcob in vitro and in vivo on serines 65 and 128 and colocalized with tcob on newly polymerized microtubules and on centrosomes. Pak1 phosphorylation is necessary for normal tcob function | SIGNOR-135464 |
Q09161 | Q02556 | 2 | binding | up-regulates activity | 0.2 | we found that tyrosine phosphorylated ICSBP activates CYBB and NCF2 transcription, during late myeloid differentiation, by interacting with PU.1, IRF1 and CBP. | SIGNOR-222939 |
Q92997 | Q14332 | 2 | binding | up-regulates activity | 0.641 | 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-258962 |
Q13131 | Q53ET0 | 1 | phosphorylation | down-regulates | 0.544 | Collectively, these findings suggest ampk suppresses glucose production through two transcriptional effects:reduced expression of creb targets via crtc inactivation and reduced expression of foxo target genes via class iia hdac inactivation | SIGNOR-176426 |
P18825 | P19086 | 2 | binding | up-regulates activity | 0.437 | 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-257094 |
Q13153 | Q99523 | 1 | phosphorylation | down-regulates activity | 0.2 | PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction. | SIGNOR-273718 |
P59595 | P53539 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well | SIGNOR-260728 |
Q9Y5U4 | Q12770 | 2 | binding | down-regulates activity | 0.717 | insig-2, a second protein of the endoplasmic reticulum that blocks the processing of sterol regulatory element-binding proteins (SREBPs) by binding to SCAP (SREBP cleavage-activating protein) in a sterol-regulated fashion, thus preventing it from escorting SREBPs to the Golgi. | SIGNOR-256209 |
Q8IXW5 | P24928 | 1 | dephosphorylation | up-regulates activity | 0.738 | In addition, we show that RPAP2 is a CTD Ser5 phosphatase. Taken together, our results indicate that during transcription of snRNA genes, Ser7 phosphorylation facilitates recruitment of RPAP2, which in turn both recruits Integrator and dephosphorylates Ser5.|The Pol II CTD is first phosphorylated on Ser5 and then on Ser7 by CDK7. RPAP2 associates with the Pol II CTD after Ser7 phosphorylation and tethers a subcomplex of Integrator to snRNA genes. RPAP2 dephosphorylates Ser5P of the CTD, facilitating transcription and the subsequent recruitment of the Int11 catalytic subunit of Integrator | SIGNOR-248748 |
Q6UB99 | Q16620 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Ankrd11 knockdown decreases the levels of bdnf and Trkb mRNAs. Next, we examine whether ANKRD11 accesses the Trkb promoter in cortical neurons. We performed the chromatin immunoprecipitation assay (ChIP) using an ANKRD11 antibody followed by PCR to amplify the Trkb promoter region. We found that ANKRD11 binds to the Trkb promoter (Fig. 6E). As expected, the level of ANKRD11 binding was decreased in the Ankrd11 knockdown condition. | SIGNOR-266731 |
Q13263 | P43357 | 2 | binding | up-regulates activity | 0.435 | In this study, we demonstrated that the tripartite motif-containing protein 28 (TRIM28) binds directly to and promotes FBP1 for ubiquitination and degradation. MAGE-A3 and MAGE-C2, which are known to be overexpressed in HCC, can enhance TRIM28-dependent degradation of FBP1 by forming ubiquitin ligase complexes with TRIM28. | SIGNOR-267592 |
Q9UKA4 | P49841 | 2 | binding | down-regulates activity | 0.372 | A-kinase anchoring protein 220 (AKAP220) is a multivalent anchoring protein that can sequester a variety of signal transduction enzymes. These include protein kinase A (PKA) and glycogen synthase kinase 3beta (GSK3beta). Using a combination of molecular and cellular approaches we show that GSK3beta phosphorylation of Thr-1132 on AKAP220 initiates recruitment of this kinase into the enzyme scaffold. We also find that AKAP220 anchors GSK3beta and its substrate beta-catenin in membrane ruffles. | SIGNOR-264817 |
P57073 | Q01167 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.288 | We showed for the first time that Aurora-A interacts directly with SOX8 and phosphorylates the protein at Ser327 to further regulate the SOX8/FOXK1 axis, which modulates cell senescence and glycolysis, ultimately leading to cisplatin resistance.. Our results showed that SOX8 targets FOXK1, thereby regulating its transcription, which has significant impacts on senescence, glycolysis and chemoresistance in ovarian cancer. | SIGNOR-273613 |
Q12913 | P00533 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.49 | We report the identification of PTPRK and PTPRJ (density-enhanced phosphatase-1 [DEP-1]) as EGFR-targeting phosphatases. DEP-1 is a tumor suppressor that dephosphorylates and thereby stabilizes EGFR by hampering its ability to associate with the CBL-GRB2 ubiquitin ligase complex|By employing commercially available antibodies, which are supposed to recognize specific tyrosine phosphorylation sites of EGFR, we found that depletion of endogenous DEP-1 nonselectively increased receptor phosphorylation, affecting all three sites we analyzed (tyrosines 1045, 1068, and 1173 | SIGNOR-248697 |
Q07889 | P62993 | 0 | relocalization | up-regulates activity | 0.912 | Interaction domains of sos1/grb2 are finely tuned for cooperative control of embryonic stem cell fate. | SIGNOR-235773 |
Q13562 | Q02779 | 2 | binding | up-regulates activity | 0.333 | we identified two proteins that interact with ND, huntingtin-associated protein 1 (HAP1) and mixed-lineage kinase 2 (MLK2). Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2 | SIGNOR-234599 |
P42773 | P11802 | 2 | binding | down-regulates | 0.871 | The first group, including p16ink4a, p15ink4b,p18ink4cand p19ink4d, is specific for the g1 cdks,cdk4and cdk6, inhibiting the kinase activity of cyclin d/cdk4-cdk6 complexes on prb. | SIGNOR-44598 |
O14640 | Q14332 | 2 | 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 |
P45984 | P30307 | 1 | phosphorylation | down-regulates | 0.376 | Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset. | SIGNOR-164093 |
Q6T4R5 | Q8WUW1 | 2 | binding | up-regulates activity | 0.2 | We show that the WHD of NHS interacts with the Abi family of proteins, HSPC300, Nap1 and Sra1, and is important for the localization of NHS to the leading edge. | SIGNOR-253574 |
Q2M385 | O96017 | 0 | phosphorylation | up-regulates activity | 0.2 | Chk2 phosphorylates Mps1-T288 after DNA damage.|In the present study, we show that Chk2 stabilizes Mps1 protein and phosphorylates Aurora B-B-serine 331 to prevent mitotic exit in vertebrate cells when the majority of kinetochores are unattached. | SIGNOR-279160 |
P00519 | P55211 | 1 | phosphorylation | up-regulates | 0.513 | C-abl phosphorylates casp9 on tyr-153 in vitro and in vivo in response to dna damage.The Present results demonstrate that c-abl binds directly to casp9. | SIGNOR-133260 |
P63279 | P58012 | 1 | sumoylation | up-regulates | 0.698 | Foxl2 is sumoylated by ubc9, and this ubc9-mediated sumoylation is essential to the transcriptional activity of foxl2 on the star promoter. / the sumoylation site was identified at lysine 25 of foxl2 | SIGNOR-187901 |
Q9GZQ6 | P09471 | 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-256987 |
P29372 | P67775 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Here we report that MID1 catalyzes the in vitro ubiquitination of the catalytic subunit of PP2A (PP2Ac) in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced.The high molecular weight smear pattern was not as obvious, suggesting that domains within the C-terminal half of MID1 may contribute to the polyubiquitination of PP2Ac. | SIGNOR-271930 |
P06493 | Q9NXR1 | 1 | phosphorylation | up-regulates activity | 0.654 | We found that Nudel and NudE were also phosphorylated in M phase (Fig. (Fig.22 and and3).3). First, Nudel and NudE were specifically phosphorylated in M phase. Moreover, both proteins were phosphorylated by Cdc2 and Erk2 in vitro.Due to conservation of the S/TP motifs, NudE may also be phosphorylated at similar sites by these kinases, though it contains an additional potential Cdk site at S282 (SPNR). | SIGNOR-274077 |
Q13043 | Q14653 | 1 | phosphorylation | up-regulates activity | 0.2 | Beyond that, another investigation demonstrated that MST1 directly phosphorylated IRF3 at T75 and T253, which disrupted the dimerization of IRF3 and restrained RLRs and cGAS-mediated innate antiviral response. | SIGNOR-280145 |
P28328 | P28288 | 1 | ubiquitination | up-regulates activity | 0.401 | PEX5 and PMP70 are ubiquitinated by PEX2 during amino acid starvation. | SIGNOR-278708 |
P00519 | O60504 | 1 | phosphorylation | up-regulates activity | 0.412 | Abl kinase interacts with and phosphorylates vinexin. | SIGNOR-280172 |
P78527 | Q9Y6K9 | 1 | phosphorylation | down-regulates activity | 0.296 | Here, we show that DNA-dependent protein kinase (DNA-PK), an enzyme involved in DNA double-strand break (DSB) repair, triggers the phosphorylation of NEMO by genotoxic stress, thereby enabling shuttling of NEMO through the nucleus with subsequent NF-κB activation. We identified serine 43 of NEMO as a DNA-PK phosphorylation site and point mutation of this serine to alanine led to a complete block of NF-κB activation by ionizing radiation (IR). | SIGNOR-277508 |
P28482 | Q14674 | 1 | phosphorylation | down-regulates | 0.277 | Both cdc2/cyclinb1 and mapk (erk2) efficiently phosphorylate separase at its major inhibitory site in vitro | SIGNOR-113130 |
P28223 | P19086 | 2 | binding | up-regulates activity | 0.312 | 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-257021 |
P34947 | P08235 | 1 | phosphorylation | down-regulates | 0.26 | We report that GRK5 phosphorylates and inhibits the cardiac MR whereas GRK2 phosphorylates and desensitizes GPER. | SIGNOR-278478 |
Q9H244 | P08754 | 2 | binding | up-regulates activity | 0.404 | 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-256855 |
P16519 | P01178 | 1 | cleavage | down-regulates quantity | 0.265 | Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension. | SIGNOR-270328 |
Q9H4B6 | Q13188 | 2 | binding | up-regulates | 0.834 | Mst is activated by binding of salvador (sav1, sav in drosophila), which is, in turn, also phosphorylated by mst. | SIGNOR-169829 |
P62714 | Q01105 | 2 | binding | down-regulates | 0.282 | Here we report that both the amino terminal fragment (i(2ntf);aa 1-175) and the carboxy terminal fragment (i(2ctf);aa 176-277) of i(2)(pp2a) inhibit pp2a by binding to its catalytic subunit pp2ac | SIGNOR-175722 |
P23528 | Q9HCK4 | 0 | post transcriptional regulation | up-regulates quantity by expression | 0.257 | Slit2 causes the miRNA miR-182 to release cofilin1 mRNA, potentiating cofilin1 local translation and resulting in growth cone collapse. The use of morpholinos or RNAi to knockdown robo2 and robo3 in X. laevis RGCs, would be useful to further confirm that Robo2 and Robo3 are the receptors involved in Slit2-dependent cofilin1 translation. | SIGNOR-268378 |
Q8IUQ4 | Q9H2X6 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.514 | Here we demonstrate that HIPK2 is an unstable protein that colocalizes and interacts with the E3 ubiquitin ligase Siah-1 in unstressed cells. Siah-1 knockdown increases HIPK2 stability and steady-state levels, whereas Siah-1 expression facilitates HIPK2 polyubiquitination, degradation and thereby inactivation. | SIGNOR-276166 |
P57678 | P35637 | 0 | relocalization | up-regulates activity | 0.2 | Here, we report that FUS associates with the SMN complex, mediated by U1 snRNP and by direct interactions between FUS and SMN.|The FUS IP and pulldown revealed that FUS also associates with components of the SMN complex, including SMN and Gemins 4 and 6 |Remarkably, the number of SMN-stained nuclear bodies was dramatically reduced in the FUS knockdown cells | SIGNOR-262105 |
Q13253 | O00238 | 2 | binding | down-regulates activity | 0.599 | Noggin binds the domain that is re-quired for bmp-7 to interact with bmp type i and type ii receptors.Noggin Inhibits bmp by blocking the molecular interfaces of the binding epitopes for both type i and type ii receptors (pmid 12478285) | SIGNOR-192802 |
P46527 | Q00534 | 0 | phosphorylation | up-regulates | 0.855 | Phosphorylation on ser-10 is the major site of phosphorylation in resting cells, takes place at the g(0)-g1 phase and leads to protein stability.p27(kip1) was phosphorylated by v-cyclin-cdk6 predominantly on ser10, which enhances its cytoplasmic localization. | SIGNOR-140401 |
Q16539 | Q16512 | 0 | phosphorylation | up-regulates | 0.378 | At the same time, rho signals to c-jun n-terminal kinase (jnk) and p38 through rock and protein kinase n (pkn), leading to the transcriptional regulation of jun | SIGNOR-152765 |
Q8TCG1 | Q9UNE7 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | CHIP is the ubiquitin E3 ligase mediating celastrol-triggered CIP2A degradation. | SIGNOR-272877 |
Q96GX5 | O43768 | 1 | phosphorylation | up-regulates activity | 0.732 | We identified cyclic adenosine monophosphateregulated phosphoprotein 19 (Arpp19) and -Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry. | SIGNOR-243690 |
P06213 | P29122 | 0 | cleavage | up-regulates activity | 0.2 | Here we demonstrate that the two IR isoforms are similarly cleaved by furin, but when this furin-dependent maturation is inefficient, IR proforms move to the cell surface where the proprotein convertase PACE4 selectively supports IRB maturation. | SIGNOR-260366 |
P06850 | P03372 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.34 | Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.|Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro. | SIGNOR-268721 |
P37231 | P60484 | 1 | null | down-regulates activity | 0.456 | The PAX8-PPARγ rearrangement leads to strong induction of the PPARγ protein and the consequent abrogation of the normal PPARγ function. PPARγ overexpression abolishes the PTEN-inhibitory effect on immunoactive AKT, which in turn induces the PI3K signaling pathway. | SIGNOR-251997 |
Q96SN8 | O60566 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.27 | These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter | SIGNOR-260312 |
Q15746 | Q13464 | 2 | binding | up-regulates | 0.315 | Rock proteins are known to regulate mlc-phosphorylation, and apoptotic cells exhibit a gradual increase in levels of phosphorylated mlc concomitant with rock i cleavage. | SIGNOR-106552 |
Q9Y243 | Q05513 | 0 | phosphorylation | up-regulates activity | 0.546 | Full activation of the PKB enzyme requires phosphorylation of a threonine in the activation | SIGNOR-249153 |
P04637 | P49915 | 2 | transcriptional regulation | down-regulates quantity by repression | 0.378 | Herein, we identified GMP synthetase (GMPS), a key enzyme of de novo purine biosynthesis, as an important p53 repression target using a large-scale proteomics approach. This p53-mediated repression of GMPS could be validated by immunoblotting in Sk-Hep1, HepG2, and HuH6 cells. | SIGNOR-267342 |
Q06187 | O60674 | 0 | phosphorylation | up-regulates activity | 0.447 | Jak2 and Lyn coimmunoprecipitated with Btk and phosphorylated Btk on tyrosine (XREF_FIG C). | SIGNOR-279196 |
P46527 | O15355 | 0 | dephosphorylation | up-regulates activity | 0.2 | By using genomic phosphatase screening, we identified a PPM family phosphatase, PPM1G, which could reduce p27 phosphorylation at T198.|Functionally, ectopic expression of PPM1G enhanced p27 protein stability and delayed cell cycle progression from G1 to S phase. | SIGNOR-277112 |
Q13322 | P27986 | 2 | binding | up-regulates activity | 0.402 | Grb10 transduces signal from FLT3 by direct interaction with p85 and Ba/F3-FLT3-ITD cells expressing Grb10 exhibits higher STAT5 activation | SIGNOR-255945 |
Q9H6E5 | P48729 | 0 | phosphorylation | up-regulates activity | 0.267 | We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα. | SIGNOR-273619 |
P06241 | P84243 | 1 | phosphorylation | down-regulates activity | 0.2 | Here we provide evidence that fyn kinase, a member of the src kinase family, is involved in the uvb-induced phosphorylation of histone h3 at serine 10 | SIGNOR-130274 |
Q13153 | O14965 | 1 | phosphorylation | up-regulates | 0.417 | The upstream pak1 kinase can phosphorylate aurora a at t288, autophosphorylation appears to be the essential mode of activation. Our experiments suggest that phosphorylation of t288 is important for regulation of the aurora2 kinase both for its activity and its stability | SIGNOR-205110 |
P01178-PRO_0000020495 | P19021 | 0 | cleavage | up-regulates activity | 0.2 | Nevertheless, overall the results of this study show that peptide sequence recognition is an important aspect of the interactions of the prohormone substrates prooxytocin (3d) and procalcitonin (7e) with PAM, which is mirrored in the potency of analogous peptidomimetic glycolate inhibitors of the enzyme. | SIGNOR-268551 |
P23470 | Q05397 | 1 | dephosphorylation | up-regulates activity | 0.243 | 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-254719 |
O75469 | Q15466 | 2 | binding | down-regulates | 0.56 | Our results suggest that shp is a negative regulator of pxr transcriptional activity. This conclusion derives from_ in vitro, cell culture, and_ in vivo_ experiments. | SIGNOR-101924 |
P17612 | O43823 | 2 | binding | up-regulates activity | 0.295 | To determine whether AKAP95 and p105 were present in a complex in mammalian cells, FLAG-tagged AKAP95 wascoexpressed with Myc-tagged p105 in human embryonic kidney (HEK) 293 cells. Immunoprecipitation of either protein pulled down a complex containing AKAP95, p105, and PKA-Ca (Fig. 6D).|The identification of a PKA phosphorylation site in the C-terminal region of p105 suggests that p105 is a candidate substrate for AKAP95-targeted PKA. | SIGNOR-260302 |
P28482 | P27708 | 1 | phosphorylation | up-regulates | 0.382 | Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol | SIGNOR-137171 |
P00533 | O14944 | 2 | binding | up-regulates | 0.892 | Chemical cross-linking experiments showed that [125i]epiregulin directly bound to each of egfr and erbb-4 but not to erbb-2 and erbb-3. remarkably, three members of the epidermal growth factor (egf) family (ereg, areg, and epgn) showed increased expression that was associated with elevated epidermal activation of the egf receptor (egfr) and stat3, a downstream effector of egfr signaling. | SIGNOR-54351 |
O14842 | P50148 | 2 | binding | up-regulates activity | 0.573 | 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-257272 |
Q13562 | P54257 | 2 | binding | up-regulates activity | 0.328 | We identified two proteins that interact with ND, huntingtin-associated protein 1 (HAP1) and mixed-lineage kinase 2 (MLK2). Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2 | SIGNOR-234602 |
P31749 | Q96S44 | 1 | phosphorylation | up-regulates | 0.297 | Here we show that such an activation of prpk is mediated by another kinase, akt/pkb, which phosphorylates prpk at ser250. | SIGNOR-252503 |
Q14457 | O95229 | 2 | binding | up-regulates activity | 0.435 | We show that Beclin-1 interacts directly with Zwint-1-a component of the KMN (KNL-1/Mis12/Ndc80) complex-which is essential for kinetochore-microtubule interactions. This suggests that Beclin-1 acts downstream of the KMN complex to influence the recruitment of outer kinetochore proteins and promotes accurate kinetochore anchoring to the spindle during mitosis. | SIGNOR-265027 |
P29033 | P50570 | 2 | binding | down-regulates | 0.328 | This study identifies dynamin 2 (dyn2) as a cx26 interactor in yeast and mammalian cells / we demonstrate that dyn2 regulates cx26 endocytosis and ubiquitination | SIGNOR-205372 |
Q8TBB1 | O95477 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.242 | We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo. | SIGNOR-272902 |
Q9UNW8 | P50148 | 2 | binding | up-regulates activity | 0.422 | 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-257341 |
P49841 | P24723 | 0 | phosphorylation | down-regulates | 0.2 | Gsk3 is different from most kinases in that it is constitutively partially active and the most common regulatory mechanism is inhibition by phosphorylation of ser21 in gsk3_ or ser9 in gsk3_. This inhibitory phosphorylation can be mediated by several kinases, such as akt/protein kinase b (pkb), protein kinase c (pkc) and protein kinase a (pka). | SIGNOR-188585 |
P01213 | Q9H1B7 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.263 | EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity.These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function. | SIGNOR-267156 |
P62993 | A8K4G0 | 2 | binding | up-regulates activity | 0.462 | The CD300b receptor is a non-classical activating receptor able to deliver signals by associating with the transmembrane adaptor protein DAP-12 and the intracellular mediator Grb-2. | SIGNOR-264833 |
P08151 | Q96J02 | 0 | ubiquitination | down-regulates | 0.578 | The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. we demonstrate that the hedgehog transcription factor gli1 is targeted by numb for itch-dependent ubiquitination, which suppresses hedgehog signals, thus arresting growth and promoting cell differentiation | SIGNOR-150847 |
Q76N32 | P53350 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.44 | We show that the intercentrosomal linker protein Cep68 is degraded in prometaphase through the SCF(βTrCP) (Skp1-Cul1-F-box protein) ubiquitin ligase complex. Cep68 degradation is initiated by PLK1 phosphorylation of Cep68 on Ser 332, allowing recognition by βTrCP. | SIGNOR-275621 |
P49137 | Q07352 | 1 | phosphorylation | down-regulates | 0.62 | Mk2-mediated inhibition of brf1 requires phosphorylation at s54, s92, and s203. Phosphorylation of brf1 by mk2 does not appear to alter its ability to interact with ares or to associate with mrna decay enzymes. Thus, mk2 inhibits brf1-dependent amd through direct phosphorylation. | SIGNOR-161274 |
P45983 | O43521 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.759 | Ser69 can also be phosphorylated by JNK and p38MAPK at least in vitro. Phosphorylation of BimEL on Ser69 promotes its ubiquitination. | SIGNOR-250132 |
Q9Y2H1 | P14373 | 0 | ubiquitination | up-regulates activity | 0.2 | TRIM27 catalyzes non-degradative K6- and K11-linked ubiquitination of the serine/threonine kinase 38-like (STK38L) kinase. In turn, STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination of ULK1 | SIGNOR-270347 |
P30530 | P00533 | 2 | phosphorylation | up-regulates activity | 0.43 | AXL trans-actives EGFR in a ligand independent manner and induces phosphorylation of EGFR on tyrosine 1173.|In our models AXL seems to induce a re-wiring of the EGFR signaling towards the PLCgamma-PKC axis by receptor phosphorylation at tyrosine 1173. | SIGNOR-279141 |
P12931 | Q9NRY4 | 1 | phosphorylation | up-regulates | 0.772 | Phosphorylation of y1105, but not the minor site, was modulated in vivo to a greater extent by overexpression of c-src than by the egf receptor and was efficiently catalyzed by c-src in vitro. Mutation of y1105 from tyr to phe resulted in complete loss of p-tyr-dependent complex formation, indicating that p-y1105 was the sole p-tyr residue mediating binding to p120 | SIGNOR-61670 |
P46019 | P22694 | 0 | phosphorylation | down-regulates activity | 0.325 | Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme. | SIGNOR-267412 |
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