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 |
|---|---|---|---|---|---|---|---|
P35222 | O43474 | 2 | binding | up-regulates activity | 0.686 | The interaction of Beta-catenin with Tcf is important for Beta-catenin s's function in iPSCs induction. In addition, Beta-catenin interacts with Oct4, Sox2, and Klf4, respectively. In the reprogramming process, Beta-catenin further enhances expression of pluripotency-related genes. | SIGNOR-242100 |
P19838 | P41279 | 2 | binding | down-regulates | 0.688 | Tpl-2 is stoichiometrically complexed with the nf-kb inhibitory protein, nf-kb1 p105, and the ubiquitin-binding protein abin-2, both of which are required to maintain tpl-2 protein stability. Binding to p105 also prevents tpl-2 from phosphorylating mek | SIGNOR-196747 |
Q8IYT8 | Q9Y478 | 1 | phosphorylation | down-regulates | 0.329 | Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity | SIGNOR-173092 |
Q70Z35 | P63000 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.609 | 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-260571 |
Q04912 | P35222 | 1 | phosphorylation | up-regulates activity | 0.327 | Ron and beta-catenin associate and Ron kinase activity leads to tyrosine phosphorylation of beta-catenin.|We also show that tyrosine residues 654 and 670 of beta-catenin are important in mediating Ron induced beta-catenin transcriptional activation and cell growth. | SIGNOR-279376 |
P20823 | Q9Y463 | 0 | phosphorylation | up-regulates | 0.502 | Mirk phosphorylates hnf1 at amino acid 249mkk3 enhanced mirk kinase activity and the transcriptional activation of hnf1alpha by mirk | SIGNOR-86728 |
Q13651 | P23458 | 2 | binding | up-regulates activity | 0.809 | Specifically, il-10 effects the activation of jak1 (associated with the il-10 receptor alpha Chain) and tyk2 (associated with the il-10 receptor beta Chain) and induces the activation of stat1, stat3, and, in some cells, stat5. | SIGNOR-68010 |
P20336 | P53611 | 0 | lipidation | up-regulates activity | 0.656 | 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-265575 |
O43193 | P63096 | 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-256737 |
P48436 | P49716 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.272 | Sox9 directly binds to the promoter regions of c/ebpbeta and c/ebpdelta to suppress their promoter activity, preventing adipocyte differentiation | SIGNOR-184283 |
Q06330 | Q9UM47 | 2 | binding | up-regulates | 0.857 | Both notch 1 and notch 3 ics displace the co-repressor smrt from the dna-binding protein rbp-j kappa on the hes promoter. The latter observation suggests that both notch 3 ic and notch 1 ic can access rbp-j kappa in vivo, and that the difference in activation capacity instead stems from structural differences in the two ics when positioned on rbp-j kappa. | SIGNOR-86128 |
Q9Y2H1 | P21333 | 1 | phosphorylation | up-regulates activity | 0.2 | Activated Ndr2 Promotes FLNa Release From LFA-1.|Taken together the data depicted in Figures xref and xref indicate that Ndr2 phosphorylates FLNa at S2152 both in vitro and in vivo . | SIGNOR-278501 |
O43474 | Q7Z6Z7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.34 | K48 linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression.|Instead, we identified the transcription factor KLF4 as a novel Mule substrate that is ubiquitinated by this E3 ligase and thus undergoes proteasomal degradation in T cells.|Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase. | SIGNOR-278749 |
O75385 | Q86WV6 | 1 | phosphorylation | down-regulates activity | 0.2 | Collectively, our data indicates that cGAS is essential for the activation of AMPK and ULK1 suppression of STING (XREF_FIG) and that cGAMPs are responsible for triggering the dephosphorylation of AMPK T172 and activation of ULK1 which phosphorylates STING on S366 to impede its activity (XREF_FIG).|Collectively, our data indicates that cGAS is essential for the activation of AMPK/ULK1 suppression of STING ( xref ) and that cGAMPs are responsible for triggering the dephosphorylation of AMPK T172 and activation of ULK1 which phosphorylates STING on S366 to impede its activity ( xref ). | SIGNOR-279316 |
Q9UJP4 | Q5UEC6 | 2 | binding | up-regulates activity | 0.2 | Indeed, KLHL21 localizes to FA structures preferentially at the leading edge, and in complex with Cul3, ubiquitylates EB1 within its microtubule-interacting CH-domain. Cells lacking CRL3(KLHL21) activity or expressing a non-ubiquitylatable EB1 mutant protein are unable to migrate and exhibit strong defects in FA dynamics, lamellipodia formation and cortical plasticity. Our study thus reveals an important mechanism to regulate cortical dynamics during cell migration that involves ubiquitylation of EB1 at focal adhesions. | SIGNOR-272407 |
Q8N752 | P10070 | 1 | phosphorylation | up-regulates | 0.333 | Gli2 is phosphorylated by gsk3 and ck1 for the fbxw11 (betatrcp2)-mediated degradation ci is phosphorylated by pka at multiple sites priming phosphorylation by both gsk3 and cki, leading to partial proteolysis. The pka, gsk3, and cki sites are conserved in gli2 and gli3, vertebrate homologs of ci that are similarly processed | SIGNOR-179972 |
Q09472 | P52292 | 1 | acetylation | up-regulates | 0.357 | Ampk triggered the acetylation of importin alpha1 on lys(22), a process dependent on the acetylase activity of p300 | SIGNOR-128625 |
O75122 | P49841 | 0 | phosphorylation | down-regulates activity | 0.515 | GSK-3beta directly phosphorylates CLASP2 at Ser533 and Ser537 within the region responsible for the IQGAP1 binding. Phosphorylation of CLASP2 results in the dissociation of CLASP2 from IQGAP1, EB1 and microtubules.| CLASPs were originally identified as CLIP-170-interacting proteins and later found to be required for microtubule stabilisation at the cortical regions of epithelial cells | SIGNOR-264826 |
P20226 | P52657 | 2 | binding | up-regulates activity | 0.9 | The general transcription factor IIA (TFIIA) binds to the TATA binding protein (TBP) and mediates transcriptional activation by distinct classes of activators. |Our results show that different activators utilize the general factor TFIIA in unique ways and that TFIIA contributes transcription activation functions in addition to the facilitation of TBP-DNA binding. | SIGNOR-262591 |
Q13535 | P16104 | 1 | phosphorylation | up-regulates activity | 0.2 | ATR and ATM also phosphorylate histone H2AX at Ser 139 (gammaH2AX) in response to DNA double-strand breaks (DSBs), which spreads along the DNA up to 200-400 kb and helps in the recruitment of proteins involved in DNA damage repair and checkpoint activation . | SIGNOR-279356 |
P35222 | Q86UP0 | 2 | binding | up-regulates activity | 0.551 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265862 |
Q15717 | O15111 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.323 | Furthermore, mutational analysis indicates that IKKα-dependent phosphorylation at Ser-304 is crucial to the binding of HuR to β-TrCP1. Mechanistically, this HuR degradation pathway differs from that reported for heat shock and hypoxia, which underlies the complexity in the regulation of HuR turnover under different stress stimuli. | SIGNOR-276422 |
Q9Y6I3 | P06493 | 0 | phosphorylation | down-regulates activity | 0.323 | Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin. | SIGNOR-262723 |
P09471 | O00398 | 2 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257005 |
P17676 | P36956 | 1 | transcriptional regulation | up-regulates quantity | 0.41 | These results show that GSK3β is involved in regulating phosphorylation and activation of C/EBPβ and that this transcription factor is required to transactivate srebf1a expression, leading to the early steps of adipogenesis | SIGNOR-251645 |
Q7Z6Z7 | O95140 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.42 | AMBRA1 regulates mitophagy at two critical steps. Upon mitophagy stimulation, AMBRA1 mediates the HUWE1 E3 ubiquitin ligase translocation from cytosol to mitochondria (light blue). AMBRA1 acts as a cofactor for HUWE1 E3 ubiquitin ligase activity, favouring its binding to its substrate MFN2 (and maybe other OMM substrates) and targeting it to the proteasome | SIGNOR-272978 |
Q13882 | Q9UGK3 | 1 | phosphorylation | up-regulates activity | 0.724 | Our previous studies revealed that STAP-2 binds to signal transducer and activator of transcription 3 (STAT3) and STAT5, and regulates the signaling pathways downstream of them. In the present study, we identified tyrosine-250 (Tyr250) in STAP-2 as a major site of phosphorylation by Brk, using a series of STAP-2 YF mutants and anti-phospho-STAP-2 Tyr250 antibody. Furthermore, overexpression of the STAP-2 Y250F mutant protein affected Brk-mediated STAT3 activation. | SIGNOR-247067 |
P60953 | Q8WZ64 | 0 | gtpase-activating protein | down-regulates activity | 0.495 | 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-260455 |
P19086 | P28221 | 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-257116 |
P51582 | P30679 | 2 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257214 |
Q9NZV8 | Q6PIL6 | 0 | relocalization | up-regulates activity | 0.773 | KChIP4 increased the current amplitude of Kv4.2, decelerated the inactivation, and accelerated the recovery from inactivation of Kv4.2. KChIP.is known to promote the translocation of Kv4.2 from the endoplasmic reticulum or Golgi to the cell surface | SIGNOR-269004 |
O15287 | Q13813 | 1 | null | up-regulates quantity by stabilization | 0.367 | In FA cells, deficiencies in FA proteins lead to decreased stability of alphaRIISp |These results demonstrate that one of the FA proteins, FANCG, contains a motif that interacts directly with the SH3 domain of alphaIISp. We propose that this binding of FANCG to alphaIISp may be important for the stability of alphaIISp in cells and the role alphaIISp plays in the DNA repair process.| | SIGNOR-263275 |
Q92569 | P04637 | 2 | binding | up-regulates activity | 0.296 | N this study, we aimed to explore the interaction of p55PIK with p53 and the role of p55PIK in regulating p53-dependent apoptosis in cancer cells. We found that p55PIK directly binds to the DBD domain of p53 via N24 domain. Moreover, the upregulation of p55PIK expression increases transcriptional levels of p53-dependent apoptosis-related genes including GADD45α, S100A9, MDM2 and AIP1. Furthermore, synthetic N24 translocated to nucleus can significantly inhibit cancer cell growth. | SIGNOR-261492 |
P63092 | Q9UKP6 | 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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256779 |
Q00536 | P10644 | 1 | phosphorylation | up-regulates activity | 0.272 | PCTK1 regulates spindle orientation in a kinase-dependent manner. Phosphoproteomic analysis together with an RNA interference screen revealed that PCTK1 regulates spindle orientation through phosphorylation of Ser83 on KAP0, a regulatory subunit of protein kinase A (PKA) | SIGNOR-273018 |
Q8IU57 | P29597 | 2 | binding | up-regulates | 0.559 | Despite signaling through distinct receptor complexes, type i ifns and ifn-_s activate similar signaling events and biological activities, consistent with their common ability to mediate an antiviral state in cells (fig. 6). In both cases, receptor engagement leads via the activation of the jak kinases jak1 and tyk2 | SIGNOR-124483 |
Q8IW41 | Q12778 | 1 | phosphorylation | up-regulates activity | 0.422 | The kinase MK5 phosphorylates and activates Foxo1 at serine 215, and this modification is required for Foxo1 to induce Rag transcription. | SIGNOR-280037 |
O75899 | P17612 | 0 | phosphorylation | down-regulates activity | 0.2 | Here we show that the functional coupling of GABA(B)R1/GABA(B)R2 receptors to inwardly rectifying K(+) channels rapidly desensitizes. This effect is alleviated after direct phosphorylation of a single serine residue (Ser892) in the cytoplasmic tail of GABA(B)R2 by cyclic AMP (cAMP)-dependent protein kinase (PKA). | SIGNOR-263150 |
P53779 | Q9UPT6 | 2 | phosphorylation | up-regulates | 0.745 | Phosphoamino acid analysis confirmed that jnk caused thr phosphorylation of jip3 (fig. _(fig.3c).3c). This phosphorylation on thr was markedly decreased when thr266, thr276, and thr287 were replaced with ala. These data indicate that jnk phosphorylated jip3 on thr266, thr276, and thr287 in vitro. | SIGNOR-134533 |
P06493 | P31948 | 1 | phosphorylation | down-regulates activity | 0.264 | Inactivation and phosphorylation mimicking of potential phosphorylation sites in mSTI1 altered the nuclear translocation. Mimicking of phosphorylation at the mSTI1 CKII phosphorylation site (S189E) promoted nuclear localization of mSTI1-EGFP. Mimicking phosphorylation at the cdc2 kinase phosphorylation site (T198E) promoted cytoplasmic localization of mSTI1-EGFP at the G1/S-phase transition,whereas removal of this site (T198A) promoted the nuclear localization of mSTI1-EGFP under the same conditions. | SIGNOR-262729 |
P42345 | Q9P2Y5 | 1 | phosphorylation | up-regulates activity | 0.408 | MTOR phosphorylates UVRAG at serine 550 and serine 571 | SIGNOR-276919 |
P06239 | Q6ISU1 | 2 | binding | up-regulates activity | 0.333 | However, non-canonical mechanisms of p38alfa activation have been also described. One is apparently specific to antigen receptor stimulated t-lymphocytes. This involves phosphorylation of p38alfa on tyr323 by the tcr-proximal tyrosine kinase zap70 and p56lck. | SIGNOR-166658 |
P50148 | P29274 | 2 | binding | up-regulates activity | 0.3 | 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-257364 |
Q00610 | O14976 | 0 | phosphorylation | up-regulates activity | 0.857 | Clathrin heavy chain (CHC) was phosphorylated at T606 by its association partner cyclin G-associated kinase (GAK). This phosphorylation was required for proper cell proliferation and tumor growth of cells implanted into nude mice. | SIGNOR-275448 |
P63092 | P55085 | 2 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256752 |
Q9BXM7 | P49411 | 1 | phosphorylation | down-regulates activity | 0.2 | PINK1 interacts with the autophagy effector TUFm and phosphorylates TUFm at Ser222. These results indicated that p222-hTUFm sequestered more monomer Atg5 and reduced the conjugated Atg5-Atg12 complex to subdue mitophagy. | SIGNOR-266382 |
P00533 | Q8TDY4 | 1 | phosphorylation | up-regulates activity | 0.2 | How ACAP4 regulates membrane dynamics and curvature in response to EGF stimulation is unknown. Here, we show that phosphorylation of the N-terminal region of ACAP4, named the Bin, Amphiphysin, and RSV161/167 (BAR) domain, at Tyr34 is necessary for EGF-elicited membrane remodeling. |EGF stimulation of cells causes phosphorylation of ACAP4 at Tyr34, which subsequently promotes ACAP4 homodimer curvature. | SIGNOR-272234 |
O43915 | P35968 | 2 | binding | up-regulates | 0.2 | Vegf-d is a ligand for both vegf receptors (vegfrs) vegfr-2 (flk1) and vegfr-3 (flt4) and can activate these receptors. | SIGNOR-55163 |
P21918 | P38405 | 2 | binding | up-regulates activity | 0.509 | 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-256914 |
Q8N431 | P01111 | 2 | binding | up-regulates | 0.2 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-161511 |
Q9C0J9 | Q13363 | 2 | binding | up-regulates | 0.266 | We identify the ctip and ctbp corepressors as novel components of the human rbp-jkappa/sharp-corepressor complex and show that ctip binds directly to the sharp repression domain. Functionally, ctip and ctbp augment sharp-mediated repression. | SIGNOR-141613 |
P98177 | Q13131 | 0 | phosphorylation | up-regulates | 0.371 | The energy sensor amp-activated protein kinase (ampk) has been shown to directly phosphorylate foxo factors at six regulatory sites that are distinct from the akt phosphorylation sites, resulting in foxo activation | SIGNOR-157947 |
Q03113 | P32245 | 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-257440 |
P10275 | Q9UNE7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.478 | Via this mechanism, CHIP ubiquitinates and degrades glucocorticoid receptor (GR), androgen receptor (AR), estrogen receptor (ER), ErbB2, and alpha-synuclein, only when bound to Hsp . | SIGNOR-278782 |
Q15572 | O60729 | 0 | dephosphorylation | up-regulates activity | 0.2 | Consistent with prior studies showing that the phosphatase hCdc14B regulates progression through mitosis by counteracting mitotic phosphorylation by Cdk1/cyclin B [ ], hCdc14B dephosphorylates TAFI110, thus promoting its reactivation as cells exit mitosis.|Here we show that hCdc14B, the phosphatase that regulates Cdk1/cyclin B activity and progression through mitosis, promotes reactivation of rDNA transcription by dephosphorylating TAFI110. | SIGNOR-277135 |
P15056 | P15056 | 2 | phosphorylation | down-regulates activity | 0.2 | We previously identified that BRAFWT can autophosphorylate its P-loop (Ser-465/Ser-467) to inactivate itself in the absence of native substrate MEK | SIGNOR-277498 |
P31749 | P55072 | 1 | phosphorylation | up-regulates | 0.509 | Site-directed mutagenesis identified ser-351, ser-745, and ser-747 as akt phosphorylation sites on vcp. however, our study also suggests that other known biological activities of vcp, such as those related to intracellular trafficking, ubiquitin-mediated proteolysis, and activation of transcription (28), might be regulated by akt through the activation of vcp. I | SIGNOR-252491 |
Q5S007 | P31749 | 1 | phosphorylation | up-regulates | 0.379 | Expression of wild-type LRRK2 promoted neuronal survival against apoptosis through activation of the downstream effector, Akt by phosphorylation of Ser473. Phosphorylated Akt in turn inhibited FOXO 1 signaling | SIGNOR-252598 |
P38405 | P13945 | 2 | binding | up-regulates activity | 0.448 | 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-256896 |
P37802 | P60709 | 2 | binding | down-regulates activity | 0.412 | Taken together, our data propose a novel, oncogene-tumor suppressor interplay, where oncogenic PFTK1 confers HCC cell motility through inactivating the actin-binding motile suppressing function of TAGLN2 via phosphorylation. | SIGNOR-265104 |
O14730 | Q9BYX4 | 1 | phosphorylation | down-regulates activity | 0.468 | RIOK3 mediates phosphorylation of MDA5 Ser-828|RIOK3-mediated phosphorylation of MDA5 interferes with its assembly and attenuates the innate immune response | SIGNOR-264576 |
Q68DV7 | P04637 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.451 | Moreover, RNF43 polyubiquitinates p53 which further leads to its destabilization resulting in a decrease in induction of the p53 apoptotic pathway, a hitherto unknown process targeted by NP for p53 stabilization and accumulation. | SIGNOR-278714 |
P42229 | Q06187 | 0 | phosphorylation | up-regulates activity | 0.467 | Ectopically expressed BTK kinase domain was capable of tyrosine-phosphorylating STAT5A both in vitro and in vivo. BTK-mediated tyrosine phosphorylation of ectopically expressed wild type (but not Tyr(694) mutant) STAT5A enhanced its DNA binding activity. | SIGNOR-250603 |
Q15672 | P0C2W1 | 2 | binding | down-regulates quantity by destabilization | 0.26 | One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by the core EMT-inducing transcription factors (EMT-TFs), such as Zeb1/2, Snai1/2 and Twist1. Here, we find that EMT-TFs can be dynamically degraded by an atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 (SPFFbxo45) through the ubiquitin proteasome system (UPS). The key step is recognition of EMT-TFs by Fbxo45 through its SPRY domain for Zeb2, or F-box domain for the other three EMT-TFs Snai1, Snai2 and Twist1, respectively. | SIGNOR-272183 |
P35637 | Q9Y566 | 1 | post transcriptional regulation | up-regulates quantity | 0.2 | These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.|As seen in Figure 7 (top panel), both PSD-95 Q1-Q2 and Shank1a GQ probes pulled down endogenous FUS, whereas their M2 mutants did not, indicating that the GQ structure is sufficient for recognition. | SIGNOR-262104 |
P05771-2 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.446 | Inhibition of PP2A increased phosphorylation at Ser660 that determines calcium sensitivity and activity of PKCbetaII isoform | SIGNOR-248621 |
Q14289 | Q86X29 | 1 | phosphorylation | up-regulates activity | 0.2 | Pyk2 enhances LSR and tricellulin localization to tTJs.|Pyk2-dependent phosphorylation of LSR enhances localization of LSR and tricellulin at tricellular tight junctions. | SIGNOR-280101 |
Q13546 | Q14790 | 2 | binding | up-regulates activity | 0.909 | Tradd and rip1 associate with fadd and caspase-8, forming a cytoplasmic complex | SIGNOR-104255 |
P23458 | Q8IU57 | 2 | binding | up-regulates | 0.78 | 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-124480 |
O94844 | O76074 | 2 | binding | down-regulates quantity by destabilization | 0.2 | RhoBTB1 augmented the cGMP response to nitric oxide by restraining the activity of phosphodiesterase 5 (PDE5) by acting as a substrate adaptor delivering PDE5 to the Cullin-3 E3 Ring ubiquitin ligase complex for ubiquitination inhibiting PDE5. | SIGNOR-272312 |
P24928 | P50750 | 0 | phosphorylation | up-regulates | 0.777 | Cyclin-dependent kinase 9 (cdk9) promotes elongation by rna polymerase ii (rnapii), mrna processing, and co-transcriptional histone modification. Cdk9 phosphorylates multiple targets, including the conserved rnapii elongation factor spt5 and rnapii itself | SIGNOR-203528 |
P42338 | P27986 | 2 | binding | up-regulates activity | 0.851 | Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival | SIGNOR-242640 |
Q01105-2 | P19784 | 0 | phosphorylation | down-regulates | 0.259 | Ckii-mediated phosphorylation at ser9 hinders nuclear import of set | SIGNOR-200802 |
Q7Z434 | Q96J02 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.646 | These data collectively indicate that AIP4 is the E3 ligase for MAVS.|We generated single substitutions (K362A, K371A or K420A) and combined point substitutions of MAVS and tested their degradation. K371A or K420A MAVS showed partial resistance to PCBP2-induced degradation (data not shown), whereas MAVS with the combined substitutions K371A and K420A (KK-AA) completely withstood the degradation | SIGNOR-260362 |
Q8N752 | Q5T0W9 | 2 | binding | up-regulates quantity | 0.2 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273754 |
O14828 | P00533 | 0 | phosphorylation | up-regulates activity | 0.399 | In our efforts to identify cellular tyrosine kinases that phosphorylate SCAMPs, we are quite intrigued by the observation that among a number of kinases, only the EGFR exhibits activity toward SCAMPs. EGF catalyzes the progressive phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that phosphorylation of SCAMPs, either directly or indirectly, may be functionally linked to the internalization/down-regulation of the EGFR. we have observed that there are two tyrosines conserved in SCAMP1 and SCAMP3, which are not found in SCAMP2. Of these two tyrosines (Tyr37 and Tyr73 in SCAMP1; Tyr 41 and Tyr83 in SCAMP3), we consider Tyr37/41 to be a more likely site for tyrosine phosphorylation | SIGNOR-262858 |
P63000 | Q5VT97 | 0 | gtpase-activating protein | down-regulates activity | 0.402 | 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-260522 |
P06493 | P11387 | 1 | phosphorylation | up-regulates activity | 0.349 | In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells. | SIGNOR-276157 |
Q9UKA9 | P31943 | 2 | binding | up-regulates activity | 0.389 | Splicing of the c-src N1 exon in neuronal cells depends in part on an intronic cluster of RNA regulatory elements called the downstream control sequence (DCS). |nPTB binds more stably to the DCS RNA than PTB does but is a weaker repressor of splicing in vitro. nPTB also greatly enhances the binding of two other proteins, hnRNP H and KSRP, to the DCS RNA. | SIGNOR-261269 |
P00519 | P19484 | 1 | phosphorylation | down-regulates activity | 0.2 | Our data show that c-Abl promotes TFEB tyrosine phosphorylation and that its inhibition induces TFEB activity.|c-Abl Inhibition Activates TFEB and Promotes Cellular Clearance in a Lysosomal Disorder Summary The transcription factor EB ( TFEB ) has emerged as a master regulator of lysosomal biogenesis , exocytosis , and autophagy , promoting the clearance of substrates stored in cells . | SIGNOR-279583 |
Q8N6F7 | P43405 | 0 | phosphorylation | up-regulates activity | 0.356 | Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. Y148 (in black) was already phosphorylated before the addition of kinases. We demonstrate that Grb2 facilitates HGAL and Syk binding following BCR stimulation but does not affect the HGAL-mediated increase in Syk kinase activity. Previous studies showed that Grb2 inhibits BCR signaling by decreasing the activation of Syk by Lyn.11 Thus, while HGAL and Grb2 oppositely affect Syk kinase activity, this is not due to direct Grb2 effects on HGAL-mediated Syk kinase activation. | SIGNOR-273570 |
O43613 | P08754 | 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-256876 |
Q6ZWH5 | P04637 | 1 | phosphorylation | up-regulates activity | 0.256 | Here, we describe a function for NEK10 in the regulation of p53 transcriptional activity through tyrosine phosphorylation. NEK10 loss increases cellular proliferation by modulating the p53-dependent transcriptional output. NEK10 directly phosphorylates p53 on Y327, revealing NEK10's unexpected substrate specificity. A p53 mutant at this site (Y327F) acts as a hypomorph, causing an attenuated p53-mediated transcriptional response. | SIGNOR-273881 |
P30279 | P49841 | 0 | phosphorylation | down-regulates | 0.454 | Glycogen synthase kinase-3beta and p38 phosphorylate cyclin d2 on thr280 to trigger its ubiquitin/proteasome-dependent degradation in hematopoietic cells | SIGNOR-154668 |
Q13627 | P35568 | 1 | phosphorylation | up-regulates quantity | 0.2 | DYRK1A interacts with IRS-1 and phosphorylates IRS-1 at Ser-312 and Ser-616.|We found that DYRK1A overexpression up-regulated IRS-1 expression by slowing the turnover of IRS-1 protein. | SIGNOR-279521 |
P27986 | P35968 | 2 | binding | up-regulates activity | 0.505 | null | SIGNOR-261917 |
Q13188 | P00519 | 2 | phosphorylation | down-regulates | 0.2 | Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3 | SIGNOR-181056 |
P78527 | P09629 | 2 | binding | up-regulates activity | 0.333 | Ku70 and Ku80 associated with HOXB7 in vivo. Ku70/Ku80 heterodimer formation is a prerequisite for HOXB7 binding. interaction between Ku70/80 and HOXB7 may affect the catalytic activity of DNA-PK. HOXB7 stimulates DNA-PK activity | SIGNOR-226063 |
P07947 | P27635 | 2 | binding | down-regulates | 0.388 | Several c-yes kinase activity assays indicated that the qm protein reduced c-yes kinase activity by 70% | SIGNOR-90805 |
O75030 | P31749 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.44 | We found that AKT phosphorylates MITF at S510. Phosphorylated MITF S510 enhances its affinity to TP53 and promotes CDKN1A expression. Phosphorylation of MITF by AKT induces its degradation | SIGNOR-277281 |
Q8WZA2 | P61224 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.811 | Epac1 (cAMP-GEFI) and Epac2 (cAMP-GEFII) are closely related guanine nucleotide exchange factors (GEFs) for the small GTPase Rap1, which are directly regulated by cAMP. Here we show that both GEFs efficiently activate Rap2 as well. | SIGNOR-263955 |
Q13243 | P31751 | 0 | phosphorylation | up-regulates activity | 0.362 | Here we show that Akt2 kinase phosphorylated SRp40 in vivo and in vitro. Mutation of Ser86 on SRp40 blocked in vitro phosphorylation. | SIGNOR-262633 |
Q92499 | Q9NR30 | 2 | binding | up-regulates activity | 0.32 | We demonstrated here that DDX1-DDX21-DHX36 represents a dsRNA sensor that uses the adaptor molecule TRIF to activate the NF-κB pathway and type I IFN responses in dendritic cells. Our study suggests that the DDX1-DDX21-DHX36 complex represents this missing poly I:C sensor, which uses DDX1 to bind poly I:C and uses DDX21 and DXH36 to bind TRIF. Poly I:C is a synthetic form of RNA that mimics double-stranded viral RNA. | SIGNOR-260191 |
P00533 | P24752 | 1 | phosphorylation | up-regulates activity | 0.2 | We found that purified EGFR and FGFR1 directly phosphorylate and activate ACAT1 ( xref ).|We found that purified EGFR and FGFR1 directly phosphorylate and activate ACAT1 (XREF_FIG). | SIGNOR-279996 |
Q9GZM8 | O14965 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.603 | Here, we show that Aurora-A phosphorylates NDEL1 at Ser251 at the beginning of mitotic entry. Interestingly, NDEL1 phosphorylated by Aurora-A was rapidly downregulated thereafter by ubiquitination-mediated protein degradation. | SIGNOR-263159 |
P27361 | Q16690 | 0 | dephosphorylation | down-regulates | 0.76 | Extracellular regulated kinases (erk) 1 and erk2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase vhr. A novel role in down-regulating the erk pathway | SIGNOR-67358 |
P31749 | Q13309 | 1 | phosphorylation | down-regulates activity | 0.515 | We further show that Akt1 phosphorylates Skp2 at Ser72, which is required to disrupt the interaction between Cdh1 and Skp2. | SIGNOR-278274 |
Q8IWT3 | Q96AC1 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | M-phase-specific CDK1–cyclin B1 complex directly binds KIND1 and KIND2 and phosphorylates a conserved proline-directed CDK1 consensus motif in the flexible and intrinsically disordered loop of the F1 domain. This then results in the recruitment of the CUL9–FBXL10 complex, modification with K48-linked polyubiquitin chains and proteasomal degradation of KIND1 and KIND2. | SIGNOR-276717 |
P46531 | Q13761 | 2 | binding | down-regulates | 0.689 | To investigate the possible mechanism of the down-regulation of hes-1 by runx3, we performed western blot and reporter assay and found that runx3 suppressed intracellular domain of notch1 (icn1)-mediated transactivation of notch signaling while it did not alter the expression of icn1 and recombination signal binding protein-j kappa (rbp-j) in smmc7721 cells. | SIGNOR-188338 |
Q05655 | Q15717 | 1 | phosphorylation | up-regulates | 0.637 | Tandem phosphorylation of serines 221 and 318 by protein kinase cdelta coordinates mrna binding and nucleocytoplasmic shuttling of hurstabilization of mrna by the ubiquitous rna binding protein human antigen r (hur), a member of the embryonic lethal abnormal vision (elav) protein family, requires canonical binding to au-rich element (are)-bearing target mrna and export of nuclear hur-mrna complexes to the cytoplasm. In human mesangial cells (hmc) both processes are induced by angiotensin ii (angii) via protein kinase cdelta (pkcdelta)-triggered serine phosphorylation of hur. | SIGNOR-163524 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.