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 |
|---|---|---|---|---|---|---|---|
Q14653 | P03209 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | EBV Rta selectively down-regulates the expression of IRF3 and IRF7, the main regulators of the Type I IFNs. | SIGNOR-266644 |
Q8IX90 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.455 | Aurora B directly phosphorylated Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3 impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers), disrupting mitotic progression. We propose that Aurora B phosphorylation antagonizes the interaction between the Ska complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments. | SIGNOR-262661 |
P63092 | P27986 | 2 | binding | up-regulates | 0.294 | Notably, the fzd7 receptor complex was associated with g_?(s) and pi(3)k and these components were required for wnt7a to activate the akt/mtor growth pathway in myotubes. These data led us to hypothesize that g_?s Mediates the activation of pi3kinase following wnt7a binding to fzd7. | SIGNOR-191561 |
P28482 | O43524 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.717 | Here, we show that erk downregulates forkhead box o 3a (foxo3a) by directly interacting with and phosphorylating foxo3a at ser 294, ser 344 and ser 425, which consequently promotes cell proliferation and tumorigenesisMDM2 is required for ERk-mediated FOXO3a degradation. | SIGNOR-160415 |
Q6TDP4 | Q13002 | 2 | binding | down-regulates quantity by destabilization | 0.496 | Here, we report that actinfilin is able to bind to GluR6, a kainate-type glutamate receptor subunit, and target GluR6 for degradation. Like many members of its protein family, actinfilin acts as a substrate adaptor, binding Cullin 3 (Cul3) and linking GluR6 to the E3 ubiquitin-ligase complex. Together our data demonstrate that actinfilin acts as a scaffold, linking GluR6 to the Cul3 ubiquitin ligase to provide a novel mechanism for kainate receptor degradation. | SIGNOR-271612 |
P08754 | Q9NS75 | 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-256746 |
P14618 | P29350 | 0 | dephosphorylation | down-regulates activity | 0.2 | SHP-1 dephosphorylates PKM2 at Y105 to inhibit nuclear function of PKM2 and determines the efficacy of targeted drugs.|SHP-1 directly dephosphorylated PKM2 at Y105 and further decreased the proliferative activity of PKM2; similar effects were found in sorafenib-treated hepatocellular carcinoma cells.|SHP-1 dephosphorylates p-PKM2Y105 and further affects the nucleus-related cell proliferation. | SIGNOR-276997 |
Q8WV28 | P23470 | 0 | dephosphorylation | up-regulates activity | 0.2 | 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-254692 |
Q04206 | P56524 | 2 | binding | up-regulates | 0.316 | P65 and histone deacetylases 4 cooperate to inhibit the ability of mef2 factors to induce the klf2 promoter | SIGNOR-138368 |
P40424 | P12830 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.267 | We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4. | SIGNOR-267241 |
P15056 | P23760 | 1 | phosphorylation | up-regulates activity | 0.308 | BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development.|We found that BRAF clearly induced phosphorylation of PAX3 at Ser205 in both cell types (XREF_FIG). | SIGNOR-278435 |
P17252 | P10721 | 1 | phosphorylation | down-regulates | 0.531 | Phosphorylation of kit/scfr by pkc-_ in vitro: identification of ser-741 and ser-746 as the major phosphorylation sites for pkc / pkc, which acts in an scf-stimulated feedback loop, that negatively controls kit/scfr kinase activity | SIGNOR-28605 |
Q99608 | Q9UBK2 | 2 | binding | up-regulates quantity by stabilization | 0.326 | Necdin binds and stabilizes PGC-1α|Necdin strongly stabilizes PGC-1α by inhibiting its ubiquitin-dependent degradation. Forced expression of necdin enhances mitochondrial function in primary cortical neurons and human SH-SY5Y neuroblastoma cells to prevent mitochondrial respiratory chain inhibitor-induced degeneration. | SIGNOR-253390 |
P55283 | O60610 | 0 | null | up-regulates activity | 0.2 | Taken together, data obtained from MCF10A cells were consistent with the idea that Rho signaling to Dia1 and profilin-1 was essential for R-cadherin adherens junction formation. | SIGNOR-253110 |
P01106 | P48729 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.282 | Together, our findings provide evidence for CK1α-mediated destruction of c-Myc and identify c-Myc S252 as a crucial CK1α phosphorylation site for c-Myc degradation. | SIGNOR-276387 |
P0C0S8 | Q8IYW5 | 2 | binding | up-regulates | 0.2 | Rnf168 is recruited to sites of dna damage by binding to ubiquitylated histone h2a. | SIGNOR-183890 |
Q12851 | Q12933 | 2 | binding | up-regulates | 0.535 | Both full-lenght gck and the gck-ctd can form complexes in vivo with traf2. | SIGNOR-59685 |
P63000 | O43295 | 0 | gtpase-activating protein | down-regulates activity | 0.566 | 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-260518 |
Q8TEU7 | P01111 | 1 | guanine nucleotide exchange factor | up-regulates | 0.331 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-183799 |
P06493 | P06400 | 1 | phosphorylation | down-regulates | 0.688 | The retinoblastoma gene product (prb) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. The active form of prb is underphosphorylated. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has allowed the identification of five sites. S249, t252, t373, s807 and s811 are phosphorylated in vivo, and in each case these sites correspond closely to the consensus sequence for phosphorylation by p34cdc2. | SIGNOR-21564 |
Q02078 | Q09472 | 2 | binding | up-regulates | 0.861 | Once released from associated repressors, MEF2 is bound by the p300 coactivator, which possesses histone acetyltransferase activity. Thus, the net result of CaMK signaling to MEF2 complexes is increased histone acetylation (Ac), which relaxes chromatin and stimulates MEF2 target gene transcription. | SIGNOR-232165 |
P09769 | Q04760 | 1 | phosphorylation | up-regulates activity | 0.2 | We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D). | SIGNOR-276188 |
P49815 | Q15418 | 0 | phosphorylation | down-regulates | 0.768 | The mitogen-activated protein kinase (mapk)-activated kinase, p90 ribosomal s6 kinase (rsk) 1, was found to interact with and phosphorylate tuberin at a regulatory site, ser-1798, located at the evolutionarily conserved c terminus of tuberin. Rsk1 phosphorylation of ser-1798 inhibits the tumor suppressor function of the tuberin/hamartin complex, resulting in increased mtor signaling to s6k1 | SIGNOR-128634 |
Q8TDX7 | Q9HC35 | 1 | phosphorylation | up-regulates activity | 0.274 | The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stability and interfered with chromosome congression. In addition, constitutive activation of NEK6 or NEK7 reduced the association of EML4 with interphase microtubules. Together, these data support a model in which NEK6- and NEK7-dependent phosphorylation promotes the dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression. | SIGNOR-273884 |
Q13153 | P15259 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | The ability of Pak1 to phosphorylate wild-type PGAM2 was increased after exposure of the cells to etoposide (XREF_FIG).|Bar, 20 \u00b5m. (E) Primary mouse embryonic fibroblasts at early passages were treated with 20 \u00b5M etoposide in the presence of 20 \u00b5M MG132, and cell lysates were immunoblotted with antibodies against Pak1 and phospho-Ser118 in phosphoglycerate mutase as indicated. (F) Pak1 kinase phosphorylates PGAM2 at Ser118 in vitro. | SIGNOR-280237 |
Q8IYT8 | O75143 | 2 | phosphorylation | up-regulates | 0.75 | Ulks directly phosphorylates atg13. | SIGNOR-184126 |
P17612 | P10644 | 2 | binding | down-regulates activity | 0.886 | Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets | SIGNOR-258751 |
Q16539 | Q9HBH9 | 1 | phosphorylation | up-regulates | 0.415 | Erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity | SIGNOR-48349 |
Q9H082 | Q676U5 | 2 | binding | up-regulates | 0.751 | Olgi-resident small gtpase rab33b interacts with atg16l and modulates autophagosome formation. | SIGNOR-178542 |
Q96RR4 | P49841 | 0 | phosphorylation | down-regulates | 0.272 | Cdk5 and gsk3 phosphorylate ser-129, ser-133, and ser-137. Mutation of ser-129, ser-133, and ser-137 increases autonomous activity with little change in ca2 /cam-dependent activity. | SIGNOR-198134 |
Q16637 | Q86YT6 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.324 | The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein | SIGNOR-253112 |
P28482 | P29590 | 1 | phosphorylation | up-regulates | 0.359 | We report here that as(2)o(3) treatment induces phosphorylation of the pml protein through a mitogen-activated protein (map) kinase pathway. Increased pml phosphorylation is associated with increased sumoylation of pml and increased pml-mediated apoptosis. | SIGNOR-124248 |
O14503 | Q6R6M4 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.2 | Upon DNA damage, DEC1 is rapidly induced in an ATM/ATR-dependent manner. DEC1 induction results from protein stabilization via a mechanism that requires the USP17 ubiquitin protease. USP17 binds and deubiquitylates DEC1, markedly extending its half-life. | SIGNOR-276852 |
P31749 | P78362 | 1 | phosphorylation | up-regulates | 0.465 | Here we show that srpk2, a protein kinase specific for the serine/arginine (sr) family of splicing factors, triggers cell cycle progression in neurons and induces apoptosis through regulation of nuclear cyclin d1. Akt phosphorylates srpk2 on thr-492 and promotes its nuclear translocation leading to cyclin d1 up-regulation, cell cycle reentry, and neuronal apoptosis. | SIGNOR-186760 |
P43657 | P19086 | 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-257120 |
Q9GZU7 | Q15672 | 1 | dephosphorylation | down-regulates activity | 0.2 | These results indicate that SCP1 is the phosphatase that counter-regulates the MAPK-mediated phosphorylation of S68-Twist1. | SIGNOR-245962 |
P43405 | P78314 | 1 | phosphorylation | up-regulates activity | 0.552 | By using the transient expression system in COS-7 cells, we have demonstrated that 3BP2 was predominantly phosphorylated on Tyr174, Tyr183, and Tyr446 when it was coexpressed with Syk. | SIGNOR-246596 |
Q9P289 | Q9Y4P1 | 1 | phosphorylation | up-regulates activity | 0.2 | ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. | SIGNOR-275833 |
P19419 | P17252 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.442 | The luciferase reporter assay results revealed that the presence of both MZF-1 and Elk-1 significantly contributed to the upregulation of PKCα gene transcription activity. | SIGNOR-256336 |
P49683 | P63096 | 2 | binding | up-regulates activity | 0.278 | 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-256694 |
Q9BQQ3 | P06493 | 0 | phosphorylation | down-regulates activity | 0.715 | Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. Phosphorylation of Ser-277 is also dramatically increased during mitosis, however this is mediated by Cdk1 and not by ERK. These results argue against Ser-277 phosphorylation alone causing the dissolution of GRASP65 oligomers and cisternal unstacking, although it may make a significant contribution to these events. | SIGNOR-262840 |
P52948 | P06493 | 0 | phosphorylation | down-regulates activity | 0.397 | We show that npc disassembly is a phosphorylation-driven process, dependent on cdk1 activity and supported by members of the nima-related kinase (nek) family. mitotic hyperphosphorylation of nup98 is accomplished by multiple kinases, including cdk1 and neks. | SIGNOR-172217 |
P48729 | Q6ZRV2 | 2 | binding | up-regulates quantity | 0.387 | 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-273747 |
P18084 | O96013 | 0 | phosphorylation | up-regulates | 0.451 | Pak4 specifically phosphorylated the integrin beta5 subunit at ser-759 and ser-762 within the beta5-sers-motif. Point mutation of these two serine residues abolished the pak4-induced cell migration, indicating a functional role for these phosphorylations in migration. | SIGNOR-165702 |
P49841 | Q9UK32 | 0 | phosphorylation | down-regulates activity | 0.2 | Moreover, RSK4 stabilized Beta-catenin in the presence of GSK-3Beta WT but not RSK4 stabilizes Beta-catenin through phosphorylation of GSK-3Beta (Ser9) in ESCC cells|GSK-3Beta S9A in ESCC cells, which was similar to overexpression of GSK3Beta S9D| | SIGNOR-275801 |
Q9Y261 | O15111 | 0 | phosphorylation | down-regulates | 0.2 | Here, we show that ikk_, an important downstream kinase of tnf_, interacts with and phosphorylates foxa2 at s107/s111, thereby suppressing foxa2 transactivation activity and leading to decreased numb expression | SIGNOR-195316 |
P67809 | P51608 | 2 | binding | up-regulates activity | 0.506 | In this study, we show that MeCP2 interacts with the RNA-binding protein Y box-binding protein 1 and regulates splicing of reporter minigenes. Importantly, we found aberrant alternative splicing patterns in a mouse model of RTT. Thus, we uncovered a previously uncharacterized function of MeCP2 that involves regulation of splicing, in addition to its role as a transcriptional repressor. | SIGNOR-277700 |
P53350 | P11309 | 0 | phosphorylation | down-regulates activity | 0.294 | This data strongly indicates that Pim1 phosphorylates PLK1 at threonine 210, a site previously reported to be phosphorylated by aurora A kinase during mitosis. | SIGNOR-279749 |
Q92934 | Q9Y243 | 0 | phosphorylation | down-regulates | 0.542 | Ser-136 is the major phosphoacceptor site for akt;akt can weakly phosphorilate ser-155. | SIGNOR-81122 |
O15169 | Q9H2K2 | 0 | ADP-ribosylation | down-regulates quantity by destabilization | 0.705 | Together, these findings are consistent with the hypothesis that TNKS promotes the ubiquitination and degradation of axin, which may be mediated, at least in part, through the direct PARsylation of axin. | SIGNOR-263378 |
Q8NE35 | O76050 | 0 | ubiquitination | up-regulates activity | 0.47 | If Neurl1 interacts and modulates the activity of CPEB3 and increases the translation of GluA1 and GluA2 mRNAs, this effect would be blocked if we abolished the interaction between CPEB3 and Neurl1.|Neurl1 Interacts with and Ubiquitinates a Translational Regulator of GluA1 and GluA2 : the Cytoplasmic Polyadenylation Element Binding Protein 3. | SIGNOR-278588 |
Q8IXI2 | Q9BXM7 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.775 | PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. in Miro1, Ser156 (homologous to Ser182 in Drosophila) and Thr298, 299 (homologous to Ser324, 325 in Drosophila, Figure 6C). | SIGNOR-272728 |
O95837 | Q13639 | 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-257416 |
Q9UBY5 | P30679 | 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-257406 |
P12931 | Q14118 | 1 | phosphorylation | down-regulates | 0.55 | Tyrosine 892 is now thought to be the principal site for recognition by the c-src tyrosine kinase;. We show that upon tyrosine phosphorylation, beta-dystroglycan undergoes a profound change in its sub-cellular localization (e.g., from the plasma membrane to an internal membrane compartment). One possibility is that the net negative charge at position 892 causes the redistribution of beta-dystroglycan to this intracellular vesicular location | SIGNOR-101655 |
P19484 | P08236 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.249 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276553 |
O75385 | O75143 | 1 | phosphorylation | up-regulates | 0.917 | Ulks directly phosphorylate atg13 | SIGNOR-183957 |
O43526 | P17252 | 0 | phosphorylation | up-regulates activity | 0.324 | Phosphorylation of KCNQ2 channels was increased by muscarinic stimulation; this was prevented either by coexpression with AKAP(DeltaA) or pretreatment with PKC inhibitors that compete with diacylglycerol. These inhibitors also reduced muscarinic inhibition of M-current. | These results suggest that Ser534 and 541 are key sites for PKC phosphorylation, although we have not ruled out the possibility that other PKC sites are involved in this process. | SIGNOR-249209 |
P06493 | Q9HCH0 | 1 | phosphorylation | down-regulates activity | 0.2 | Inhibiting Cdk1 with purvalanol A in nocodazole arrested cells increased fluorescent intensity of Cep169 at centrosomes relative to the value at the cytosol (2.36 +/- 0.12), while control cells indicated 1.13 +/- 0.03.|Taken together, these results suggest that the Cdk1-dependent phosphorylation of Cep169 mediates the dissociation from centrosomes during mitosis. | SIGNOR-279144 |
P00441 | Q15046 | 2 | binding | down-regulates quantity by destabilization | 0.2 | In the presence of mutant SOD1, mitoKARS displays a high propensity to misfold and aggregate prior to its import into mitochondria, becoming a target for proteasome degradation. | SIGNOR-262800 |
P19793 | P35222 | 2 | binding | down-regulates | 0.419 | Rxr agonists still inactivated endogenous beta-catenin via rxr alpha. | SIGNOR-101293 |
P68400 | O95786 | 1 | phosphorylation | down-regulates | 0.2 | Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of rig-i are phosphorylated by casein kinase ii (ck2) in the resting state of the cell and dephosphorylated when cells are infected by rna virus. Mutation at aa position 770 or 854 to 855 of rig-i renders it constitutively active | SIGNOR-169404 |
P42574 | O43903 | 1 | cleavage | up-regulates | 0.451 | We now demonstrate that gas2 is a substrate of caspase-3 but not of caspase-6. Proteolytic processing both in vitro and in vivo is dependent on aspartic residue 279. | SIGNOR-72347 |
P17535 | P28482 | 0 | phosphorylation | up-regulates | 0.529 | Menin binds the jun family transcription factor jund and inhibits its transcriptional activity. The menin-jund interaction blocks jun n-terminal kinase (jnk)-mediated jund phosphorylation and suppresses jund-induced transcription. We found a role for phosphorylation of the ser100 residue of jund;jund phosphorylation were prevented by inhibitors of calcium, calmodulin, or erk1/2 kinase. | SIGNOR-196030 |
Q12913 | P17948 | 1 | dephosphorylation | down-regulates | 0.362 | Vegf acts by binding to two high affinity receptor tyrosine kinases: vegf receptor (vegfr)* 1 also called flt-1, and vegfr-2, also called flk-1/kdr a dominant-negative mutant of high cell densityenhanced ptp 1 (dep-1)//cd148 as well as reduction of its expression by rna interference partially restore vegfr-2 phosphorylation and map kinase activation. | SIGNOR-101272 |
P08588 | P38405 | 2 | binding | up-regulates activity | 0.392 | 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-256901 |
Q15910 | Q9P275 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.2 | We observed a MELK-mediated increase of EZH2 S220 phosphorylation along with a concomitant loss of EZH2 K222 ubiquitination, suggesting a phosphorylation-dependent regulation of EZH2 ubiquitination. Furthermore, we identify USP36 as the deubiquitinating enzyme that deubiquitinates EZH2 at K222. | SIGNOR-277481 |
P49674 | Q5T0W9 | 2 | binding | up-regulates quantity | 0.256 | 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-273762 |
O75636 | O00187 | 2 | binding | up-regulates activity | 0.517 | In the lectin pathway, mannose-binding lectin (MBL) and ficolins bind to pathogens and activate MBL-associated serine protease-2 (MASP-2) | SIGNOR-263412 |
P09917 | P27361 | 0 | phosphorylation | up-regulates activity | 0.328 | Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells. | SIGNOR-264440 |
P11233 | P98177 | 1 | phosphorylation | up-regulates activity | 0.2 | We conclude that Ral-mediated phosphorylation of threonines 447 and 451 is required for proper activity of AFX-WT. | SIGNOR-249665 |
P12931 | P63000 | 1 | phosphorylation | up-regulates activity | 0.615 | In addition, Rac1 is phosphorylated at Y64 by FAK and Src kinases ( xref ); Y64 phosphorylation targets Rac1 to focal adhesions. | SIGNOR-280132 |
P28482 | Q01860 | 1 | phosphorylation | down-regulates | 0.38 | We demonstrate that oct4a interacts with erk1/2 by using both in vitro gst pulldown and in vivo co-immunoprecipitation assays. Ms analysis identified phosphorylation of oct4a at ser-111. / serine 111 phosphorylation regulates oct4a protein subcellular distribution and degradation. | SIGNOR-192097 |
Q9BXL7 | O95999 | 2 | binding | up-regulates | 0.845 | Card11 cooperates with bcl10 in a card domain-dependent manner.;These results implicate card11 in factor- specific activation of nf-kappab | SIGNOR-93869 |
Q00975 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.317 | Here, we report a direct modulation of ca(v)2.2 channel inactivation properties by 14-3-3, a family of signaling proteins involved in a wide range of biological processes.Wild-type gst fusion proteins containing the putative 14-3-3-binding motif (aa 2076__?2140) werein vitro phosphorylated at s2126 by either camkii or pka, as detected by thesequence- and phosphorylation-specific antibody, anti-ps2126 (middle panel). Phosphorylation of s2126 significantly increases its binding to recombinant 14-3-3? | SIGNOR-149684 |
Q38SD2 | P63000 | 1 | phosphorylation | up-regulates activity | 0.292 | In vitro kinase assays confirmed that recombinant Lrrk1 phosphorylated RAC1-GST protein, and immunoprecipitation showed that the interaction of Lrrk1 with RAC1 occurred within 10 min after RANKL treatment.|Lrrk1 phosphorylates and activates RAC1 and Cdc42 small GTPase proteins in osteoclasts. | SIGNOR-279626 |
P68400 | Q9HA82 | 1 | phosphorylation | up-regulates activity | 0.2 | Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue. | SIGNOR-273984 |
P17612 | O14558 | 1 | phosphorylation | down-regulates | 0.2 | Hosphorylation of hsp20 at ser16 is not only associated with cyclic nucleotide-dependent vasorelaxation but also inhibits agonist-induced contractile responses. | SIGNOR-66493 |
P02545 | P55212 | 0 | cleavage | down-regulates | 0.662 | Lamin a breakdown is largely mediated by caspase-6 during the execution phase of apoptosis. | SIGNOR-83611 |
Q13315 | Q16665 | 1 | phosphorylation | up-regulates | 0.432 | Here we show that hypoxia results in ataxia telangiectasia mutated (atm)-dependent phosphorylation of hypoxia-inducible factor 1-alpha (hif-1_) on serine(696) and mediates downregulation of mtorc1 signaling. phosphorylation of hif-1_ by atm is required for its stability | SIGNOR-169999 |
P63096 | P33032 | 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-257070 |
Q13546 | Q9NWF9 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.503 | Triad3A promotes proteolytic degradation of adapter proteins. Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins. | SIGNOR-271608 |
Q99835 | P19087 | 2 | binding | up-regulates | 0.262 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling. | SIGNOR-148534 |
Q96LR5 | Q6ZMZ0 | 2 | binding | up-regulates activity | 0.506 | We demonstrated that both UbcH7 and UbcH8 bind to full-length NKLAM. We demonstrated decreased protein expression and enhanced ubiquitination of URKL-1 in the presence of NKLAM. These data indicate that NKLAM is a RING finger protein that binds Ubcs and | SIGNOR-271592 |
Q9UBS0 | Q05195 | 1 | phosphorylation | down-regulates | 0.2 | In this study, we showed that mad1 is a substrate of p90 ribosomal kinase (rsk) and p70 s6 kinase (s6k). Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway | SIGNOR-178594 |
P54762 | P54762 | 2 | phosphorylation | up-regulates activity | 0.2 | Co-immunoprecipitation was used to confirm the interaction of Grb7 with the cytoplasmic domain of EphB1 as well as the full-length receptor in intact cells. This interaction is mediated by the SH2 domain of Grb7 and requires tyrosine autophosphorylation of EphB1. We also found that EphB1 could phosphorylate Grb7 and mutation of either Tyr-928 or Tyr-594 to Phe decreased this activity. | SIGNOR-251123 |
O43516 | Q5T1M5 | 2 | binding | up-regulates activity | 0.2 | However, we did detect WAFL binding to bothWIP and actin by immunoprecipitation (Fig. 4). In conclusion, we propose a model whereby WAFL associates toendocytic vesicles by its coiled-coil domain and is involved in actin-based movement of early endosomes via WIP and binding to actin. | SIGNOR-260596 |
Q13233 | Q6UUV9 | 1 | phosphorylation | up-regulates | 0.321 | We report on the activation oftorc1through mekk1-mediated phosphorylation. | SIGNOR-180816 |
Q96EP1 | Q96GM5 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.307 | Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination. | SIGNOR-271459 |
P05556 | Q9UN72 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-265667 |
Q96BI3 | Q9NZ42 | 2 | binding | up-regulates | 0.962 | Furthermore, overexpression of aph-1 facilitates pen-2-mediated ps1 proteolysis, resulting in a significant increase in ps1 fragments. Our data reveal a direct role of pen-2 in proteolytic cleavage of ps1 and a regulatory function of aph-1, in coordination with pen-2, in the biogenesis of the ps1 complex. | SIGNOR-97104 |
Q5VST9 | Q8WZ42 | 0 | relocalization | up-regulates quantity | 0.58 | Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins. | SIGNOR-266728 |
Q00987 | P61254 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.498 | In addition, Mdm2 ubiquitylates L26, leading to its proteasome-mediated degradation.|We now report that Mdm2 regulates p53 levels also by targeting ribosomal protein L26. | SIGNOR-278828 |
Q08828 | O14775 | 2 | binding | down-regulates activity | 0.456 | The D2-class dopamine receptors (D2, D3, and D4) couple to the Gi/o family of G proteins and thus induce inhibition of AC | SIGNOR-264996 |
P28482 | Q14005 | 1 | phosphorylation | up-regulates | 0.265 | The precursor form of the cytokine il-16 (proil-16) was shown to be phosphorylated on ser144 . the phosphorylation of proil-16 is dependent on activation of the kinases erk1/2. Il-16 is secreted by mitogen-activated t cells, and the biochemical link between proil-16 and erk1/2, revealed by studies with pap-1, prompted analysis of the role of map kinases in this response. | SIGNOR-121852 |
P06493 | Q93008 | 1 | phosphorylation | up-regulates activity | 0.279 | Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis. | SIGNOR-275608 |
P50281 | P35625 | 2 | 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 |
Q9BYT3 | P28482 | 1 | phosphorylation | up-regulates activity | 0.273 | In vitro kinase assay results indicated that STK33 can phosphorylate ERK2.|STK33 phosphorylated ERK2 and increased the activity of ERK2 and promote the tumorigenesis of colorectal cancer HCT15 cells. | SIGNOR-279351 |
P45983 | Q9NRA8 | 1 | phosphorylation | up-regulates | 0.322 | Identification of 4e-t phosphorylation sites regulated by jnk. identification of these residues as phosphorylation sites (ser301, ser374, ser513, ser587, ser693, and ser752) was obtained by ms/ms sequencing, these results demonstrate that jnk activity is required to stimulate the assembly of pbs in response to oxidative stress. | SIGNOR-199004 |
P50148 | P21728 | 2 | binding | up-regulates activity | 0.495 | 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-257335 |
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