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 |
|---|---|---|---|---|---|---|---|
P19086 | Q9NQS5 | 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-257099 |
P61764 | Q99767 | 2 | binding | up-regulates activity | 0.701 | Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1. | SIGNOR-264037 |
O15516 | Q15466 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.388 | CLOCK knockdown activated MTP promoter and reduced small heterodimer partner (SHP, NROB2). CLOCK upregulated SHP by binding to its E box. | SIGNOR-253698 |
Q9H0D6 | P50613 | 0 | phosphorylation | up-regulates activity | 0.247 | CDKs and Xrn2 phosphorylation promote transcription termination. | Cdk7 phosphorylated Xrn2-Thr439 but was less efficient than Cdk9. | | SIGNOR-259851 |
P48357 | P40763 | 2 | binding | up-regulates activity | 0.759 | LRb signaling is initiated by leptin binding to the extracellular domain of the LRb dimer, leading to Jak2 transphosphorylation and activation. Activated Jak2 mediates the tyrosine phosphorylation of Tyr985 and Tyr1138of LRb. These phosphotyrosine residues immediately function as binding sites (double-ended lines) for SHP-2 and STAT3, both of which quickly become tyrosine-phosphorylated by Jak2. | SIGNOR-263495 |
Q06945 | Q9UPY3 | 1 | transcriptional regulation | up-regulates quantity | 0.395 | .... showed that Sox4 positively regulates Dicer expression by binding to its promoter sequences and enhancing its activity. We found that knockdown of Dicer enhances the matrigel invasion of melanoma cells by at least twofold. In addition, we revealed that overexpression of exogenous Dicer reverts the enhanced melanoma cell invasion upon Sox4 knockdown | SIGNOR-258987 |
O14842 | Q03113 | 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-257338 |
P08575 | Q05655 | 1 | dephosphorylation | down-regulates activity | 0.297 | Taken together, these data indicate that CD45 inhibits PMA dependent PKCdelta activation by impeding PMA dependent PKCdelta tyrosine phosphorylation.|reduction in CD45 expression caused the duration of peak PMA-induced MEK and extracellular signal-regulated kinase (ERK) 1/2 activity to increase from 5 min to 30 min while leading to a 4-fold increase in PMA-dependent PKCdelta activation. | SIGNOR-277028 |
Q9Y6Y8 | Q15437 | 2 | binding | up-regulates activity | 0.347 | The results showed that the N-terminal region of p125 is important for the interaction with Sec23p. We confirmed the interaction between the two proteins by a yeast two-hybrid assay. Overexpression of p125, like that of mammalian Sec23p, caused disorganization of the endoplasmic reticulum-Golgi intermediate compartment and Golgi apparatus, suggesting its role in the early secretory pathway. | SIGNOR-265306 |
Q9Y5I1 | P05556 | 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-265670 |
P55211 | Q9Y2G2 | 2 | binding | down-regulates | 0.425 | Tucan is a recently identified card-containing protein that can complex with caspase-9 and prevent cytochrome c-induced caspase activation. | SIGNOR-146663 |
Q63ZE4 | P20823 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Luciferase reporter gene constructs containing the OAT5 (SLC22A10) and OAT7 (SLC22A9) promoter regions were transactivated by HNF-1 in HepG2 cells. | SIGNOR-268983 |
Q13188 | P25098 | 0 | phosphorylation | up-regulates activity | 0.2 | Taken together, these studies support a role for GRK2 phosphorylation of Mst2 residues Ser-18 and Ser-316 in EGF-promoted centrosome separation.|Thus GRK2 appears to mediate EGF promoted cleavage and activation of Mst2. | SIGNOR-278206 |
Q13185 | Q16695 | 2 | binding | up-regulates activity | 0.2 | A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing. | SIGNOR-264495 |
Q05193 | Q13627 | 0 | phosphorylation | down-regulates | 0.416 | Mnb/dyrk1a was shown to phosphorylate dynamin 1 and alter its interactions with several sh3 domain-containing endocytic accessory proteins.Phosphorylation At s795 and s857 was confirmed in full-length dynamin 1, and s857 was subsequently determined to be the major mnb/dyrk1a phosphorylation site in vitro. Phosphorylation at s857 was demonstrated to be the basis for altering the binding of dynamin 1 to amphiphysin 1 and grb 2 by site-directed mutants mimicking phosphorylation. | SIGNOR-127440 |
Q9NRC8 | Q13131 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here, the authors show that energy stress induces an AMPK-dependent phosphorylation of Sirt7, which promotes its ubiquitin-independent degradation by REGγ, resulting in the down-regulation of rRNA transcription and cell survival.|These results strongly suggest that the phosphorylation status of SirT7 at T153 plays a crucial role in determining its subcellular distribution, degradation and binding to REGγ. | SIGNOR-275864 |
Q9BXS6 | P06493 | 0 | phosphorylation | down-regulates | 0.431 | We report here that cdk1 phosphorylates nusap at threonine 300 and 338 in early mitosis. Phosphorylation of nusap inhibits its microtubule-binding activity in vitro and in vivo. | SIGNOR-177549 |
Q9ULT6 | Q14332 | 1 | ubiquitination | down-regulates | 0.292 | Znrf3 is associated with the wnt receptor complex, and inhibits wntby promoting the turnover of frizzled and lrp6. | SIGNOR-197417 |
P0DOX6 | Q99856 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels.| Figure 3 shows that both anti-Bright and anti-TFII-I precipitated the bf150 Bright binding site from the B-cell line but not from a T-cell line that contains but does not express the V1 gene. | SIGNOR-268532 |
Q04771 | Q16671 | 2 | binding | up-regulates | 0.553 | See table2 | SIGNOR-121593 |
P63096 | P14416 | 2 | binding | up-regulates activity | 0.483 | 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-256701 |
Q92823 | Q01484 | 1 | relocalization | up-regulates quantity | 0.737 | Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains. | SIGNOR-266719 |
P01111 | Q8N9B8 | 2 | binding | up-regulates | 0.385 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-183829 |
P48736 | Q9Y4H2 | 2 | binding | up-regulates | 0.558 | There was a high level of irs-2 expression and insulin-stimulated tyrosyl phosphorylation as early as embryonic day 15 with robust pi3k binding and activation | SIGNOR-103174 |
O95185 | O95631 | 2 | binding | up-regulates | 0.832 | We provide evidence that netrin-1 triggers the formation of a receptor complex of dcc and unc5 proteins and simultaneously derepresses the interaction between their cytoplasmic domains, thereby converting dcc-mediated attraction to unc5/dcc-mediated repulsion. | SIGNOR-69047 |
Q3KRB8 | P60953 | 1 | gtpase-activating protein | down-regulates activity | 0.49 | 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-260468 |
P15927 | P54727 | 2 | binding | up-regulates activity | 0.523 | GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo | SIGNOR-275699 |
Q09472 | Q15059 | 2 | binding | up-regulates activity | 0.317 | Brd3 interacts with both IRF3 and p300, increases p300-mediated acetylation of IRF3, and enhances the association of IRF3 with p300 upon virus infection.|Brd3 enhances p300-mediated acetylation of IRF3 | SIGNOR-262044 |
P11831 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.2 | Protein kinase C delta blocks immediate-early gene expression in senescent cells by inactivating serum response factor.|The phosphorylation of T160 of SRF by PKC delta in vitro and in vivo led to loss of SRF DNA binding activity. | SIGNOR-279347 |
Q07869 | P19793 | 2 | binding | up-regulates | 0.597 | Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology | SIGNOR-105345 |
Q99102 | P42224 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.393 | Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level. | SIGNOR-254099 |
Q96PU5 | Q99250 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.317 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253459 |
Q15306 | Q13568 | 1 | null | down-regulates activity | 0.456 | IL-4-induced c-Myc activity controls a subset of M2-associated genes. IL-4 also induces the M2-polarizing JMJD3-IRF4 axis to inhibit IRF5-mediated M1 polarization. | SIGNOR-249560 |
O75874 | Q13309 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | During the cell cycle S phase, Cyclin A-CDK2 phosphorylates IDH1 on its Threonine 157 residue (Threonine 197 in IDH2) to facilitate its recognition and ubiquitination by Skp2 E3 ubiquitin, followed by degradation through 26S proteasome | SIGNOR-267625 |
P31749 | Q96B36 | 1 | phosphorylation | down-regulates activity | 0.782 | Treatment of these cells with 4-hydroxytamoxifen stimulated the phosphorylation of wt PRAS40 but not the mutant PRAS40 in which Thr-246 was mutated. These results demonstrate that activation of Akt alone is sufficient to induce phosphorylation of PRAS40 | SIGNOR-252544 |
Q99836 | Q9H2U1 | 2 | binding | up-regulates activity | 0.524 | We further showed that both DHX9 and DHX36 are localized within the cytosol and are directly bound to the Toll-interleukin receptor domain of MyD88 via their helicase-associated domain 2 and DUF domains. This study demonstrates that DHX9/DHX36 represent the MyD88-dependent DNA sensors in the cytosol of pDCs and suggests a much broader role for DHX helicases in viral sensing. | SIGNOR-260956 |
Q01094 | P27361 | 0 | phosphorylation | up-regulates | 0.292 | Erk also undergoes rapid translocation into the nucleus, where it phosphorylates and activates a variety of transcription factor targets, including sp1, e2f, elk-1, and ap1 | SIGNOR-121991 |
P53667 | Q8WYL5 | 0 | dephosphorylation | down-regulates activity | 0.597 | In addition to its cofilin\u2013phosphatase activity, SSH1 can also dephosphorylate LIMK1 and LIMK2, although LIMK1 is a better substrate than LIMK2 [63] .|SSH1 suppresses the kinase activity of LIMK1 toward cofilin by dephosphorylation at Thr 508 in the kinase catalytic domain and other autophosphorylated residues [63]. | SIGNOR-277096 |
Q15052 | Q04759 | 0 | phosphorylation | up-regulates activity | 0.2 | Recently, we have reported that the active form of Rac 1 GTPase binds to the glycogen phosphorylase muscle isoform (PYGM) and modulates its enzymatic activity leading to T cell proliferation.|More specifically, αPIX, a known guanine nucleotide exchange factor for the small GTPases of the Rho family, preferentially Rac 1, mediates PYGM activation in Kit 225 T cells stimulated with IL-2. Using directed mutagenesis, phosphorylation of αPIX Rho-GEF serines 225 and 488 is required for activation of the Rac 1/PYGM pathway. | SIGNOR-272168 |
O95863 | Q92626 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | TGF-β1 induced Snai1 binding to the PXDN promoter (as assessed by chromatin immunoprecipitation-PCR) and significantly repressed luciferase reporter gene expression, as did Snai1 overexpression. | SIGNOR-265249 |
P49841 | P60953 | 2 | binding | down-regulates | 0.377 | Phospho-gsk3b-specific antibodies also revolved that lkb1 regulates gsk3b phosphorylation at a known inhibitory site, serine-9. This localized phosphorylation is cdc42 and pkc-zeta-dependent. | SIGNOR-119885 |
Q9BTL3 | O43148 | 2 | binding | up-regulates activity | 0.2 | Maturation and translation of mRNA in eukaryotes requires the addition of the 7-methylguanosine cap. In vertebrates, the cap methyltransferase, RNA guanine-7 methyltransferase (RNMT), has an activating subunit, RNMT-Activating Miniprotein (RAM). Here we report the first crystal structure of the human RNMT in complex with the activation domain of RAM. | SIGNOR-268344 |
Q08117 | Q96F45 | 2 | binding | down-regulates activity | 0.2 | these results show that Grg5 can specifically interact with the C-terminus of Nolz1. these data suggest that Nolz1 functions as a repressor molecule, and that Grg5 interactions with Nolz1 serve to modulate Nolz1 repressor function. Mechanistically, Grg5 is known to modulate Grg co-repressor activity, raising the possibility that classical Grg proteins mediate Nolz1-dependent transcriptional repression. GalNolz1ΔC22 showed increased repressor activity compared with GalNolz1, consistent with the ability of Grg5 to modulate Nolz1 repressor function. | SIGNOR-261192 |
P01275 | P43220 | 2 | binding | up-regulates | 0.782 | In the present study we stably expressed the rat b-cell glp-i receptor in cho cells and studied binding characteristics and receptor activation utilizing the naturally occurring receptor agonist glp-i(7-36)-amide (glp-i), the proglucagon-derived glp-i-related peptide oxyntomodulin, the glp-i receptor agonist exendin-4, and the specific antagonist exendin | SIGNOR-34855 |
Q15418 | P32004 | 1 | phosphorylation | up-regulates activity | 0.506 | Western blot analysis demonstrated that the L1 kinase activity from PC12 cells that phosphorylated this site was co-eluted with the S6 kinase, p90(rsk). Moreover, S6 kinase activity and p90(rsk) immunoreactivity co-immunoprecipitate with L1 from brain, and metabolic labeling studies have demonstrated that Ser1152 is phosphorylated in vivo in the developing rat brain. | These data demonstrate that the membrane-proximal 15 amino acids of the cytoplasmic domain of L1 are important for neurite outgrowth on L1, and the interactions it mediates may be regulated by phosphorylation of Ser1152. | SIGNOR-248948 |
P35368 | P50148 | 2 | binding | up-regulates activity | 0.614 | 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-257079 |
Q13535 | Q86YC2 | 1 | phosphorylation | up-regulates activity | 0.307 | ATR promotes PALB2 accumulation at DNA damage sites.|In the context of PALB2 regulation, the phosphorylation of PALB2 by ATR plays a positive role in PALB2 recruitment. | SIGNOR-279588 |
P21359 | P01116 | 2 | binding | down-regulates activity | 0.721 | Sprouty-related, EVH1 domain-containing (SPRED) proteins negatively regulate RAS/mitogen-activated protein kinase (MAPK) signaling following growth factor stimulation. This inhibition of RAS is thought to occur primarily through SPRED1 binding and recruitment of neurofibromin, a RasGAP, to the plasma membrane. Here, we report the structure of neurofibromin (GTPase-activating protein [GAP]-related domain) complexed with SPRED1 (EVH1 domain) and KRAS. The structure provides insight into how the membrane targeting of neurofibromin by SPRED1 allows simultaneous interaction with activated KRAS. | SIGNOR-273661 |
Q9NZ94 | P78352 | 1 | relocalization | up-regulates activity | 0.755 | Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions. | SIGNOR-264189 |
P23409 | P17661 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.242 | Desmin, the muscle specific intermediate filament (IF) protein, is expressed at low levels in myoblasts and at the onset of differentiation its expression increases several fold. In an effort to explore the mechanism involved in the tissue-specific and developmentally regulated expression of desmin, we have isolated the mouse desmin gene.Co-transfection of myoD, myogenin, MRF4 and Myf5, with the desmin-CAT construct into 10T-1/2 cells demonstrated that all these factors could transactivate desmin gene expression | SIGNOR-241497 |
P20382 | Q969V1 | 2 | binding | up-regulates | 0.613 | Upon several purification steps, followed by mass spectrometric analysis and peptide sequencing, the ligand was identified as melanin concentrating hormone (mch), revealing that the orphan slc-1 is the mch receptor. | SIGNOR-70520 |
Q13547 | Q01543 | 1 | deacetylation | up-regulates | 0.2 | Hdac1 interacts with fli1 and mediates its deacetylation / our previous studies have shown that pcaf-dependent acetylation of fli1 at lysine 380 decreases its protein stability / p300 promotes the interaction of fli1 with hdac1 and increases the dna binding ability of fli1 through deacetylation of lysine 380 | SIGNOR-202689 |
Q9NUX5 | P27694 | 2 | binding | down-regulates activity | 0.294 | The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA | SIGNOR-263325 |
Q9BXM7 | O95202 | 1 | phosphorylation | up-regulates activity | 0.358 | Here we demonstrate that PINK1 directly interacts with and phosphorylates LETM1 at Thr192 in vitro.|Phosphorylated LETM1 or the phospho-mimetic LETM1-T192E increase calcium release in artificial liposomes and facilitates calcium transport in intact mitochondria. | SIGNOR-262540 |
P13945 | P63092 | 2 | binding | up-regulates activity | 0.621 | 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-256753 |
P30411 | O95837 | 2 | binding | up-regulates activity | 0.387 | 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-257199 |
Q15554 | P31943 | 0 | post transcriptional regulation | down-regulates quantity | 0.334 | During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels. | SIGNOR-266807 |
P46663 | 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-257237 |
Q13627 | Q12879 | 1 | phosphorylation | up-regulates quantity | 0.397 | DYRK1A enhances the surface expression of GluN1 and GluN2A receptors.|Mechanistically, the DYRK1A-dependent phosphorylation of GluN2A at Ser 1048 hinders the internalization of GluN1/GluN2A, causing an increase of surface GluN1/GluN2A in heterologous systems, as well as in primary cortical neurons. | SIGNOR-279327 |
Q13586 | P06493 | 0 | phosphorylation | down-regulates | 0.345 | Stim1 is phosphorylated during mitosis. Removal of ten mpm-2 recognition sites by truncation at amino acid 482 abolished mpm-2 recognition of mitotic stim1, and significantly rescued stim1 rearrangement and soce response in mitosis. We identified ser 486 and ser 668 as mitosis-specific phosphorylation sites, and stim1 containing mutations of these sites to alanine also significantly rescued mitotic soce. | SIGNOR-189017 |
P26038 | P61586 | 0 | phosphorylation | up-regulates activity | 0.61 | Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies. | SIGNOR-268431 |
Q13158 | Q9H422 | 0 | phosphorylation | down-regulates activity | 0.436 | FIST/HIPK3 causes FADD phosphorylation, thereby promoting FIST/HIPK3-FADD-Fas interaction.  Phosphorylation occurs on Ser194 close to the COOH terminus of human FADD| Fas ligand-induced activation of Jun NH(2)-terminal kinase is impaired by overexpressed active FIST/HIPK3 | SIGNOR-251272 |
Q13489 | Q13490 | 2 | binding | up-regulates activity | 0.496 | Ligand-stimulated aggregation of receptor complexes causes recruitment of multiple traf2 trimers, which in turn leads to cIAP1 or cIAP2 dimerization. | SIGNOR-199088 |
P42345 | Q15349 | 1 | phosphorylation | up-regulates activity | 0.392 | Subsequently, mTOR phosphorylates and activates the 70-kDa ribosomal protein S6 kinase (p70S6K), which results in increased translation either directly or indirectly by activating initiation and elongation factors, eIF-2, eIF-4E (through 4E-BP) and eEF-2 (Bodine et al. xref | SIGNOR-279232 |
Q12857 | P15173 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog, | SIGNOR-263983 |
P84243 | Q15326 | 2 | binding | up-regulates activity | 0.2 | We found that full-length BS69 specifically interacted with H3K36me3 in native nucleosome co-immunoprecipitation (co-IP) experiments. We propose that BS69 specifically associates with H3K36me3-enriched chromatin through the PWWP domain, which facilitates the recruitment of MYND-bound transcription and chromatin remodeling factors including EZH2, HDAC1, Brg1 and E2F6 to target gene loci, thereby repressing target gene transcription. | SIGNOR-263897 |
P49841 | Q9UQB3 | 1 | phosphorylation | down-regulates quantity | 0.347 | Therefore, our data which supports that partial inhibition of GSK-3beta increases delta-catenin expression, raises an interesting possibility that delta-catenin may be an important downstream target of GSK-3beta signaling that participates in modulating neuronal morphology.|We demonstrate that GSK-3beta forms a stable complex with delta-catenin and phosphorylates delta-catenin in neurons, an event that mediates ubiquitination and subsequent proteasome degradation of delta-catenin. | SIGNOR-279719 |
P19793 | P49841 | 0 | phosphorylation | up-regulates activity | 0.275 | GSK3β-induced RXRα phosphorylation decreased for RXRα-S49A, RXRα-S66A and RXRα-S78A in HEK293 cells compared with RXRα WT by western blot analysis. | SIGNOR-277371 |
Q9C0J9 | Q9Y618 | 2 | binding | up-regulates | 0.2 | The spen protein, sharp (smrt/hdac1-associated repressor protein), was identified as a component of transcriptional repression complexes in both nuclear receptor and notch/rbp-jkappa signaling pathways. | SIGNOR-104489 |
Q5T447 | P04049 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | By western blot, we observed robust degradation of endogenous native CRAF in untransformed HEK293 cells treated with control siRNA 24 hr after the addition of AUY922, but this was substantially reduced in cells in which HECTD3 was knocked down, confirming that endogenous CRAF is a bona fide degradation target of HECTD3 | SIGNOR-272328 |
Q9BR76 | Q6UB99 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons. | SIGNOR-266737 |
O14950 | Q13153 | 0 | phosphorylation | up-regulates activity | 0.484 | It has been shown that PAK1 phosphorylates and activates MLC2, leading to cell motility [ xref ]. | SIGNOR-280053 |
O00755 | O75197 | 2 | binding | up-regulates activity | 0.59 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131900 |
Q6P5Z2 | Q8N392 | 1 | phosphorylation | up-regulates activity | 0.2 | We present strong evidence that PKN3-ARHGAP18 interaction is increased upon ARHGAP18 phosphorylation and that the phosphorylation of ARHGAP18 by PKN3 enhances its GAP domain activity and contributes to negative regulation of active RhoA.|These results support our data from phosphoproteomic screen and suggest that ARHGAP18 can be phosphorylated by PKN3 on Thr154, Ser156 and Thr158. | SIGNOR-264572 |
Q9H0M0 | P04637 | 1 | ubiquitination | up-regulates activity | 0.319 | Unlike other E3 ligases, WWP1 increases p53 stability; inhibition of WWP1 expression or expression of a ligase-mutant form results in decreased p53 expression.|WWP1 associates with p53 and induces p53 ubiquitylation. | SIGNOR-278649 |
P58012 | O95835 | 0 | phosphorylation | up-regulates activity | 0.452 | LATS1 phosphorylates forkhead L2 and regulates its transcriptional activity.|Last, we demonstrated that coexpression with LATS1 enhances FOXL2 's activity as a repressor of the StAR promoter, and this results from the kinase activity of LATS1. | SIGNOR-279624 |
O60741 | Q13127 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Levels of NRSF and its physical binding to the Hcn1 gene were augmented after SE, resulting in repression of HCN1 expression and HCN1-mediated currents (I(h) ), and reduced I(h) -dependent resonance in hippocampal CA1 pyramidal cell dendrites. | SIGNOR-268970 |
P10636 | P20807 | 0 | cleavage | down-regulates activity | 0.324 | Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains | SIGNOR-251605 |
O43318 | Q9NYJ8 | 2 | binding | up-regulates activity | 0.936 | Our results indicate that two distinct TAK1 complexes are present in cells. One comprises TAK1 complexed with TAB1 and TAB2, and the other TAK1 complexed with TAB1 and TAB3. Both complexes are activated in response to tumour necrosis factor-alpha or interleukin-1 in human epithelial KB cells or bacterial lipopolysaccharide in RAW264.7 macrophages | SIGNOR-120268 |
O95989 | P31751 | 2 | binding | up-regulates | 0.2 | Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation | SIGNOR-81759 |
Q13153 | P29320 | 0 | phosphorylation | up-regulates activity | 0.277 | Etk kinase directly phosphorylates and activates PAK1 in response to estrogen.|We demonstrated that estrogen-activated Etk directly phosphorylated PAK1 on Tyr153. | SIGNOR-278398 |
P24941 | P04150 | 1 | phosphorylation | up-regulates activity | 0.291 | Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple CDK complexes modify serines 224 and 232.|MAPKs and CDKs exert opposite effects on receptor transcriptional enhancement. From our results, we speculate that activators of the MAPK pathway, such as growth factors, insulin, and certain oncoproteins, or inhibitors of CDK function, such as tumor growth factor beta (TGF_), p21, and p27, might attenuate receptor-induced transcrip- tional responses. In contrast, negative regulators of MAPK, such as pKA, as well as activators of CDK, such as the cyclins or CAKs, should potentiate receptor action. | SIGNOR-249427 |
P49768 | Q9Y4K3 | 0 | ubiquitination | up-regulates quantity by stabilization | 0.559 | We have also observed that ubiquitination of PS1 by TRAF6 increases the stability of PS1 holoprotein, and TRAF6-deficiency coincides with reduced endogenous PS1 and PS2 levels. | SIGNOR-278601 |
Q05655 | P05230 | 1 | phosphorylation | up-regulates quantity | 0.2 | Translocated FGF1 can be phosphorylated by PKC\u03b4 on serine 130. | SIGNOR-278451 |
P43250 | Q01726 | 1 | phosphorylation | down-regulates activity | 0.313 | Overexpression of GRK6 Inhibits Agonist-Induced cAMP Production in HBL Human Melanoma Cells, without Affecting MC1R Gene Expression | SIGNOR-252389 |
Q9BXW9 | P68400 | 0 | phosphorylation | down-regulates activity | 0.2 | Here, we report a cluster of phosphosites on FANCD2 whose phosphorylation by CK2 inhibits both FANCD2 recruitment to ICLs and its monoubiquitination in vitro and in vivo. We have found that phosphorylated FANCD2 possesses reduced DNA binding activity, explaining the previous observations. | SIGNOR-276730 |
Q7L7X3 | Q13315 | 0 | phosphorylation | up-regulates | 0.42 | The dna damage kinase ataxia telangiectasia mutated (atm) phosphorylates taos in vitro;radiation induces phosphorylation of tao on a consensus site for phosphorylation by the atmprotein kinase in cells. | SIGNOR-154171 |
Q96EP1 | Q14807 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.399 | Chfr ubiquitinates Kif22 and promotes its degradation. | SIGNOR-271469 |
Q8NCQ5 | Q9UJA2 | 2 | binding | down-regulates quantity by destabilization | 0.333 | Fbxo15 Targets CLS1 Protein for Ubiquitination and Degradation to Disrupt Mitochondrial Function. S. aureus infection induces expression of a kinase, PINK1, that phosphorylates an indispensable protein CLS1, which in turn triggers CLS1 ubiquitination and degradation by the F box protein (SCFFbxo15). | SIGNOR-272170 |
Q6P1J9 | P35222 | 2 | binding | up-regulates | 0.695 | Parafibromin/hyrax activates wnt/wg target gene transcription by direct association with beta-catenin/armadillo | SIGNOR-146282 |
Q9Y6H6 | P51787 | 2 | binding | up-regulates activity | 0.66 | Sexual dimorphism and oestrogen regulation of KCNE3 expression modulates the functional properties of KCNQ1 K⁺ channels|The KCNQ1 potassium channel associates with various KCNE ancillary subunits that drastically affect channel gating and pharmacology. Co-assembly with KCNE3 produces a current with nearly instantaneous activation | SIGNOR-275923 |
P55291 | Q4KMG0 | 2 | binding | up-regulates activity | 0.499 | Cdo binds promyogenic cadherins form complexes with n- and m-cadherin. | SIGNOR-99250 |
P01189 | P16220 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.37 | Transcriptional activation of the proopiomelanocortin gene by cyclic AMP-responsive element binding protein|Further, expression of a dominant inhibitory mutant of CREB reduced cAMP stimulated transcription of the full length POMC promoter and the PTRE. | SIGNOR-268620 |
P28482 | P30041 | 1 | phosphorylation | up-regulates | 0.693 | These results show that the mapks can mediate phosphorylation of prdx6 at thr-177 with a consequent marked increase in its aipla(2) activity. | SIGNOR-183379 |
Q9UEE5 | P04637 | 1 | phosphorylation | up-regulates | 0.286 | Genetic and biochemical studies have shown that ser20 phosphorylation in the transactivation domain of p53 mediates p300-catalyzed dna-dependent p53 acetylation and b-cell tumor suppression. a cell-free ser20 phosphorylation site assay was used to identify a broad range of calcium calmodulin kinase superfamily members, including chk2, chk1, dapk-1, dapk-3, drak-1, and ampk, as ser20 kinases. | SIGNOR-153532 |
Q9NPB6 | Q05513 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.841 | APKC associates and phosphorylates Par6 on S345. aPKC expression stabilizes Par6 protein levels. We show that the aPKC, PKCι, interacts with TGF-β receptors through Par6 and that these proteins localize to the leading edge of migrating cells. Furthermore, Par6 phosphorylation on serine 345 by TGF-β receptors is enhanced in the presence of aPKC. aPKC kinase activity, as well as an association with Par6, were found to be important for Par6 phosphorylation. | SIGNOR-276433 |
P31749 | P15056 | 1 | phosphorylation | down-regulates activity | 0.458 | Akt phosphorylates both S364 and S428. Akt downregulates B-Raf activity in vivo | SIGNOR-251472 |
P24928 | Q14004 | 0 | phosphorylation | up-regulates activity | 0.541 | Together, these studies demonstrate the important, yet largely redundant, role for CDK12 and CDK13 for the regulation of POLII CTD phosphorylation at multiple residues, as well as the global role for both of these kinases in regulating POLII occupancy across the genome.|CDK12 and CDK13 are thus evolutionarily related and structurally similar kinases, and biochemical assays have demonstrated that both have POLII C-terminal domain (CTD) kinase activity and the ability to phosphorylate the Ser2 residue of the repetitive CTD heptad sequence | SIGNOR-273054 |
P50458 | P01215 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.266 | In Cos cells, LH-2 activated the a-subunit promoter approximately twofold | SIGNOR-266055 |
P17252 | Q96PY5 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCα associates with and phosphorylates FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the release of formin autoinhibition. | SIGNOR-273796 |
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