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 |
|---|---|---|---|---|---|---|---|
P32121 | Q495A1 | 2 | binding | up-regulates activity | 0.2 | With TIGIT/PVR engagement, cytoplasmic TIGIT was phosphorylated at Tyr-225 and Tyr-231 residues. Phosphorylated Tyr-225 recruits adaptor protein beta arrestin 2|TIGIT/PVR signaling mediates suppression of IFN- gamma production via the NF-kappaB pathway. We identified a new adaptor β-arrestin 2 that associates with phosphorylated TIGIT and mediates recruitment of inositol phosphatase SHIP1 through the ITT-like motif (Fig. 7). Finally, SHIP1 impairs TRAF6 autoubiquitination to abolish NF-kappaB activation, leading to inhibition of IFN- gamma production in NK cells. | SIGNOR-261482 |
P00390 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.405 | NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy | SIGNOR-279871 |
P19086 | P35372 | 2 | binding | up-regulates activity | 0.51 | 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-257106 |
Q9UKX2 | Q02078 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.325 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238703 |
P15692 | Q9ULU4 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported | SIGNOR-262041 |
O14641 | Q06330 | 2 | binding | down-regulates activity | 0.269 | Mechanistically, Dishevelled binds and directly inhibits CSL transcription factors downstream of Notch receptors, reducing their activity. Furthermore, our data suggest that this crosstalk mechanism is conserved between vertebrate and invertebrate homologues. Thus, we identify a dual function for Dishevelled as an inhibitor of Notch signalling and an activator of the Wnt pathway that sharpens the distinction between opposing Wnt and Notch responses, allowing for robust cell-fate decisions. | SIGNOR-243999 |
P04406 | Q13131 | 0 | phosphorylation | up-regulates activity | 0.293 | Under glucose starvation, but not amino acid starvation, cytoplasmic GAPDH is phosphorylated on Ser122 by activated AMPK. This causes GAPDH to redistribute into the nucleus. Inside the nucleus, GAPDH interacts directly with Sirt1, displacing Sirt1's repressor and causing Sirt1 to become activated. | SIGNOR-259857 |
P50750 | P84022 | 1 | phosphorylation | down-regulates activity | 0.622 | Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. | SIGNOR-161589 |
Q9BXW4 | Q9Y4P1 | 0 | cleavage | up-regulates activity | 0.757 | Human atg4 homologues cleave the carboxyl termini of the three human atg8 homologues, microtubule-associated protein light chain 3 (lc3), gabarap, and gate-16. | SIGNOR-125489 |
P49792 | P06493 | 0 | phosphorylation | up-regulates activity | 0.474 | Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment. | SIGNOR-259118 |
Q13257 | P12270 | 2 | binding | up-regulates | 0.309 | Tpr directly binds to mad1 and mad2. / depletion of tpr decreases the levels of mad1 at kinetochores during prometaphase, correlating with the inability of mad1 to activate mad2, which is required for inhibiting apc(cdc20). | SIGNOR-181975 |
Q86U44 | Q9BZX2 | 1 | post transcriptional regulation | up-regulates quantity by stabilization | 0.2 | Furthermore, the m6A modification regulated by METTL3 led to UCK2 increased messenger RNA (mRNA) stability in melanoma cancer. Functional and mechanistic experiments indicated that UCK2 enhanced the metastasis of melanoma cancer cells through the WNT/β-catenin pathway. | SIGNOR-275862 |
P15036 | O15550 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase | SIGNOR-260035 |
P49840 | Q2M1Z3 | 1 | phosphorylation | up-regulates activity | 0.337 | We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation. | SIGNOR-262878 |
Q6P1N0 | P08908 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.371 | Akt kinase-interacting protein 1 (Aki1)/Freud-1/CC2D1A is localized in the cytosol, nucleus, and centrosome. Aki1 plays distinct roles depending on its localization. In the cytosol, it acts as a scaffold protein in the phosphoinositide 3-kinase (PI3K)/3-phosphoinositide-dependent protein kinase 1 (PDK1)/Akt pathway. In the nucleus, it is a transcriptional repressor of the serotonin-1A (5-HT1A) receptor. | SIGNOR-268295 |
O43613 | O43612 | 2 | binding | up-regulates | 0.772 | Identification and initial biological characterization of two orexins as well as their two receptors | SIGNOR-53667 |
Q13148 | O95271 | 2 | binding | up-regulates quantity by stabilization | 0.2 | Upon investigating the functional effect, we find that interaction with Tnks-1/2 inhibits the ubiquitination and proteasomal turnover of TDP-43, leading to its stabilization. We further show that proteasomal turnover of TDP-43 occurs preferentially in the nucleus; our data indicate that Tnks-1/2 stabilizes TDP-43 by promoting cytoplasmic accumulation, which sequesters the protein from nuclear proteasome degradation. | SIGNOR-262115 |
Q16584 | P31749 | 0 | phosphorylation | down-regulates | 0.4 | Negative regulation of mixed lineage kinase 3 by protein kinase b/akt leads to cell survivalthe expression of activated akt1 inhibits mlk3-mediated cell death in a manner dependent on serine 674 phosphorylation. | SIGNOR-252592 |
P42684 | Q14653 | 1 | phosphorylation | up-regulates activity | 0.2 | The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro. IRF3 is phosphorylated by c-Abl and c-Abl-related kinase, Arg, mainly at Y292. | SIGNOR-277441 |
P08559 | P12931 | 0 | phosphorylation | down-regulates activity | 0.348 | Src inactivated PDH through direct phosphorylation of tyrosine-289 of PDH E1α subunit (PDHA1). | SIGNOR-277204 |
P29371 | P50148 | 2 | binding | up-regulates activity | 0.452 | 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-257267 |
Q16654 | P29803 | 1 | phosphorylation | down-regulates | 0.547 | Pyruvate dehydrogenase (pdh) activity (pdha) controls the entry of carbohydrate into the tricarboxylic cycle and is regulated by pdh kinase (pdk), which phosphorylates and inactivates the enzyme, and pdh phosphatase, which dephosphorylates the enzyme to the active form | SIGNOR-121936 |
Q8NE86 | Q13131 | 0 | phosphorylation | up-regulates activity | 0.2 | Cellular ATP levels drop during early mitosis, and the mitochondrial Ca2+ transients boost mitochondrial respiration to restore energy homeostasis. This is achieved through mitosis-specific MCU phosphorylation and activation by the mitochondrial translocation of energy sensor AMP-activated protein kinase (AMPK). |In vitro kinase assays showed that AMPK immunoprecipitated from cells as well as recombinant AMPK phosphorylated MCU at Ser57 | SIGNOR-275547 |
P31749 | Q13131 | 1 | phosphorylation | down-regulates activity | 0.292 | It is proposed that the effect of insulin to antagonize AMP-activated protein kinase activation involves a hierarchical mechanism whereby Ser 485/Ser 491 phosphorylation by protein kinase B reduces subsequent phosphorylation of Thr 172 by LKB1 and the resulting activation of AMP-activated protein kinase. | SIGNOR-252739 |
Q13492 | Q9BSJ6 | 0 | relocalization | down-regulates | 0.2 | The cats interaction domain of calm was mapped to aa 221-335 of calm. This domain is contained in the calm/af10 fusion protein. Cats localizes to the nucleus and shows a preference for nucleoli. Expression of cats was able to markedly increase the nuclear localization of calm and of the leukemogenic fusion protein calm/af10. | SIGNOR-144680 |
P62136 | P08047 | 1 | dephosphorylation | down-regulates activity | 0.266 | Transcription factors Sp1 and Sp3 activate alpha-ENaC2 transcription through a GC-rich element (Sp1-binding site) in the promoter. Sp1 and Sp3 are essential for alpha-ENaC2 transcription in lung epithelial cells and that dephosphorylation of the Sp transcription factors by PP1 suppresses alpha-ENaC2 expression. | SIGNOR-251952 |
P14778 | Q9Y4K3 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.9 | We found that of all TRAFs and E3 ligases examined, TRAF6 preferentially ubiquitinated IL-1R1. | SIGNOR-278576 |
P20823 | Q63ZE4 | 1 | 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 |
P24928 | Q9GZU7 | 0 | dephosphorylation | up-regulates activity | 0.431 | Phosphorylation and dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II (Pol II) represent a critical regulatory checkpoint for transcription. Transcription initiation requires Fcp1/Scp1-mediated dephosphorylation of phospho-CTD. | This combined structure-function analysis discloses the residues in Scp1 involved in CTD binding and its preferential dephosphorylation of P.Ser5 of the CTD heptad repeat. | SIGNOR-248785 |
Q15303 | O14511 | 2 | binding | up-regulates | 0.788 | The neuregulins (also called heregulins and neu differentiation factors) nrg-1 and nrg-2 bind erbb-3 and erbb-4;and nrg-3 and nrg-4 bind erbb-4. | SIGNOR-26211 |
P51151 | O60664 | 1 | null | up-regulates activity | 0.591 | Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector | SIGNOR-253089 |
P19086 | Q96G91 | 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-257328 |
P04637 | Q13464 | 0 | phosphorylation | up-regulates quantity | 0.409 | Besides, ROCK1 phosphorylated p53 at ser15 to up-regulate its protein level. | SIGNOR-280108 |
P54829 | Q12879 | 1 | dephosphorylation | down-regulates activity | 0.432 | STEP inhibition by TC-2153 enhanced Tyr phosphorylation of GluN2A (XREF_FIG, 1 EGTA+TC-2153, n = 5, P < 0.05 compared with 1mM EGTA) without altering phosphorylation of Src (XREF_FIG, 1 EGTA+TC-2153, n = 5, P> 0.05 compared with 1 EGTA).|These findings confirm that not only GluN2B and Fyn but also GluN2A are substrates of STEP. | SIGNOR-277089 |
Q02750 | Q00613 | 1 | phosphorylation | up-regulates activity | 0.287 | This study indicates that mTORC1, MEK1, p38 and DYRK2 induce HSF1 activity to a similar level but phosphorylate HSF1 primarily at S326 as well as S363, a known inhibitory site [71,72], S221, also thought to be an inhibitory site [70], or at S241 and S344, which are two novel phosphorylation sites with unknown function.|While AKT1, mTORC1, MEK1, p38 and DYRK2 can all activate HSF1, the current study indicates that activity of only AKT1 and mTORC1 maintains a strong association with HSF1 activity in tumours (Fig. 4). | SIGNOR-279208 |
O15379 | P25490 | 1 | deacetylation | down-regulates activity | 0.6 | Previous studies have established that YY1 interacts with histone acetyltransferases p300 and CREB-binding protein (CBP) and histone deacetylase 1 (HDAC1), HDAC2, and HDAC3. Here, we present evidence that the activity of YY1 is regulated through acetylation by p300 and PCAF and through deacetylation by HDACs. YY1 was acetylated in two regions: both p300 and PCAF acetylated the central glycine-lysine-rich domain of residues 170 to 200, and PCAF also acetylated YY1 at the C-terminal DNA-binding zinc finger domain. Acetylation of the central region was required for the full transcriptional repressor activity of YY1 and targeted YY1 for active deacetylation by HDACs. | SIGNOR-268837 |
Q969H0 | Q6U7Q0 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | CK1delta and GSK3beta kinases sequentially phosphorylate ZNF322A at serine-396 and then serine-391. Moreover, the doubly phosphorylated ZNF322A protein creates a destruction motif for the ubiquitin ligase FBXW7alpha leading to ZNF322A protein destruction. | SIGNOR-264898 |
P00742 | P02749 | 1 | cleavage | down-regulates activity | 0.386 | In the previous study, we found that factor Xa can produce the nicked form by cleaving Lys 317-Thr 318, using recombinant human domain V (r-Domain V). |The cleavage was completely inhibited by plasmin inhibitor (alpha2PI). The nicked form was demonstrated to show reduced affinity for CL with a dissociation constant of one order of magnitude larger than that of the intact beta2GPI. | SIGNOR-266997 |
P17612 | Q13698 | 1 | phosphorylation | up-regulates activity | 0.346 | To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2. | SIGNOR-263112 |
P10600 | P10600 | 2 | binding | up-regulates | 0.2 | The active form of tgf-b is a dimer stabilized by hydrophobic interactions and usually further strengthened by an intersubunit disulfide bridge | SIGNOR-148611 |
Q12800 | P27361 | 0 | phosphorylation | down-regulates | 0.2 | We previously established that phosphorylation of lsf in early g1 at ser-291 and ser-309 inhibits its transcriptional activity and that dephosphorylation later in g1 is required for its reactivation. At the peak activities of erk and cyclin c/cdk2 in early g1, lsf is efficiently phosphorylated on ser-291 and ser-309. | SIGNOR-184176 |
Q13363 | Q9C0J9 | 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 |
O43791 | Q9UBN7 | 1 | ubiquitination | down-regulates quantity | 0.2 | Cullin3 SPOP ubiquitin E3 ligase promotes the poly-ubiquitination and degradation of HDAC6 | SIGNOR-268862 |
Q14393 | Q14938 | 0 | transcriptional regulation | down-regulates quantity | 0.205 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268888 |
P17676 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.326 | These studies implicate Ser276 of CIEBPP as the major in vim phosphorylation site for CaMKII. | Phosphorylation of serine at position 276 within the leucine zipper of C/EBP beta appeared to confer calcium-regulated transcriptional stimulation of a promoter that contained binding sites for C/EBP beta. | SIGNOR-250617 |
O00506 | Q9H4B6 | 1 | phosphorylation | down-regulates activity | 0.28 | STK25 inhibits the ability of SAV1 to counteract STRIPAK.|Using this antibody, we confirmed that SAV1 WT was indeed phosphorylated by STK25 at T26 in human cells (XREF_FIG). | SIGNOR-278369 |
P12931 | P17655 | 1 | phosphorylation | up-regulates activity | 0.525 | CAPN2 itself was a bone fide substrate of SRC that was primarily phosphorylated at Y625 by SRC and exhibited increased proteolysis activity upon phosphorylation. | SIGNOR-277598 |
O15530 | P05106 | 1 | phosphorylation | down-regulates activity | 0.473 | PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3. | SIGNOR-250266 |
Q92834 | Q96KN7 | 2 | binding | down-regulates activity | 0.714 | The RPGR H98Q and F130C mutants exhibit compromised interaction with RPGRIP1, suggesting that RPGR–RPGRIP1 interaction may be an important determinant of RPGR activity. As RPGRIP1 appears to link RPGR to the cilium, it is possible that RPGR's effect on RAB8A function may occur in distinct subcellular compartments of photoreceptors and that RPGRIP1 and other interacting proteins may modulate targeting of RPGR to such compartments. | SIGNOR-253031 |
P08754 | P18089 | 2 | binding | up-regulates activity | 0.47 | 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-256857 |
P17252 | P19086 | 1 | phosphorylation | up-regulates | 0.442 | Functional role of amino-terminal serine16 and serine27 of g alphaz in receptor and effector coupling. | SIGNOR-48681 |
P00533 | P00367 | 1 | phosphorylation | up-regulates activity | 0.2 | EGFR phosphorylates GDH1 at Y135 and contributes to GDH1 activation.|Mechanistically, GDH1 is activated by EGFR through phosphorylation at tyrosine 135 and, together with RSK2, enhances the cAMP response element-binding protein (CREB) activity via CaMKIV signaling, thereby promoting metastasis. | SIGNOR-279706 |
P08754 | P25103 | 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-257161 |
P22674 | P06493 | 2 | binding | up-regulates activity | 0.335 | CDK2 is the predominant activating complex form of CCNO, but CCNO can bind to CDK1 to form an activating complex in the absence of CDK2. | SIGNOR-275617 |
P46937 | Q15561 | 2 | binding | up-regulates activity | 0.927 | The multifunctional cytokine TGF-β has been identified as a potent inducer of CTGF expression, activating CTGF transcription through the canonical Smad signaling pathway. It is worth noting that TGF-β synergizes with Hippo–Yes-associated protein (YAP) signaling, a key regulator of tumorigenesis, to induce the expression of CTGF by the formation of a YAP-TEAD4-Smad3-p300 complex on the CTGF promoter | SIGNOR-277685 |
Q92915 | Q9NY46 | 2 | binding | down-regulates activity | 0.244 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253445 |
Q9H488 | P46531 | 2 | binding | up-regulates | 0.745 | Notch_ is modified in its epidermal growth factor-like domains by the addition of_ fucose_ to serine or threonine residues. O-fucosylation is mediated by protein o-fucosyltransferase 1 and down-regulation of this enzyme by rna interference or mutation of the ofut1 gene in drosophila or by mutation of the pofut1 gene in mouse prevents notch signaling. | SIGNOR-104627 |
Q5T1C6 | P31749 | 2 | binding | down-regulates | 0.699 | Here, we describe a protein partner for pkbalpha termed ctmp, or carboxyl-terminal modulator protein, that binds specifically to the carboxyl-terminal regulatory domain of pkbalpha at the plasma membrane. Binding of ctmp reduces the activity of pkbalpha by inhibiting phosphorylation on serine 473 and threonine 308. | SIGNOR-111003 |
Q9UPN4 | Q86YT6 | 0 | ubiquitination | down-regulates | 0.43 | We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation. Whereas these proteins are degraded prior to the ciliation process, MIB1 appears to maintain its targets in a latent state through inhibitory ubiquitylation that is reversed during ciliogenesis and in response to cell stress.The precise mechanism by which MIB1 inhibits primary cilium formation through ubiquitylation of ciliogenesis-promoting target proteins such as AZI1 and PCM1 remains to be determined. | SIGNOR-272876 |
P19838 | P07288 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | NF-kappa B activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer. | SIGNOR-253668 |
P46934 | O15399 | 1 | ubiquitination | down-regulates activity | 0.328 | Nedd4 coexpression with GluN2D enhances GluN2D ubiquitination and reduces GluN1/GluN2D NMDA receptor responses.|This suggests that Nedd4 association reduces GluN2D function, mostly likely by promoting GluN2D ubiquitination and internalization. | SIGNOR-278636 |
P54821 | O75444 | 2 | binding | down-regulates activity | 0.353 | Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf. | SIGNOR-221893 |
O43623 | O96013 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | P21 activated kinase 4 (PAK4) directly phosphorylates Slug, resulting in pro malignant Slug stabilization. | SIGNOR-280057 |
Q99835 | Q9NRP7 | 2 | binding | up-regulates | 0.48 | Smo then activates stk36 serine/threonine kinase to stabilize gli family members and to phosphorylate sufu for nuclear accumulation of gli.| sufu binds to the kinesin cos2 to transduce the hh signal downstream of smo | SIGNOR-150540 |
Q9P286 | P15923 | 1 | phosphorylation | up-regulates activity | 0.2 | The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the transcription factor E47 is a direct repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). |In this study, we found that PAK5-mediated E47 phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47 and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation | SIGNOR-275653 |
P56524 | P12830 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.287 | GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells. | SIGNOR-275663 |
P00533 | P0DP23 | 1 | phosphorylation | down-regulates | 0.404 | Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule. | SIGNOR-24778 |
Q99836 | P12931 | 0 | phosphorylation | up-regulates activity | 0.445 | Because MyD88 was phosphorylated at the tyrosine 58 residue in hemi-ITAM by LPS ( xref ), whether Src phosphorylates MyD88 at the tyrosine 58 residue was examined further, and MyD88 was phosphorylated by Src at Y58 ( xref ).|Src activates MyD88 by phosphorylation at Y58 via the Src kinase domain. | SIGNOR-279655 |
Q14980 | P06493 | 0 | phosphorylation | down-regulates | 0.587 | Cdk1-mediated phosphorylation at t2055 negatively regulates numa cortical localization and that this phosphorylation is counteracted by ppp2ca phosphatase activity. | SIGNOR-194825 |
P63279 | P06493 | 0 | phosphorylation | up-regulates activity | 0.512 | Overall, these results suggest that Cdk1 and cyclin B mediates the phosphorylation of Ubc9 at serine 71. | SIGNOR-278174 |
Q9BXM7 | P04637 | 1 | phosphorylation | up-regulates activity | 0.321 | Our studies thus indicated that mitophagy\npositively regulated hepatic CSCs by suppressing p53, which otherwise would be activated by\nPINK1 to suppress the expression of NANOG and hepatic CSCs.|These results indicated that the phosphorylation of p53 at S392 by\nPINK1 likely took place on mitochondria. | SIGNOR-278418 |
Q9NZQ7 | Q92905 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.2 | The results suggested that TNF-α upregulates expression of CSN5, which interacts and deubiquitinates PD-L1 for protein stabilization. | SIGNOR-274977 |
P17252 | P54792 | 2 | binding | up-regulates | 0.2 | Our findings suggest a molecular interaction between pka, hdpr1, and dvl and a possible contribution of this interaction to tumorigenesis. | SIGNOR-199454 |
Q96P68 | O95837 | 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-257417 |
Q9UGP5 | P24941 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.335 | Phosphorylation of DNA polymerase λ is required to maintain its stability. Recently, we identified Pol lambda as an interaction partner of cyclin-dependent kinase 2 (CDK2) that is central to the cell cycle G1/S transition and S-phase progression. Experiments with phosphorylation-defective mutants suggest that phosphorylation of Thr 553 is important for maintaining Pol lambda stability, as it is targeted to the proteasomal degradation pathway through ubiquitination unless this residue is phosphorylated. | SIGNOR-276169 |
P41182 | O75376 | 2 | binding | up-regulates activity | 0.57 | The POZ domains of BCL-6 and several other POZ proteins interact with corepressors N-CoR and SMRT. | SIGNOR-252239 |
P41279 | Q99558 | 1 | phosphorylation | up-regulates activity | 0.559 | In studies of NIK, we found that Thr-559 located within the activation loop of its kinase domain regulates NIK action. Alanine substitution of Thr-559 but not other serine or threonine residues within the activation loop abolishes its activity and its ability to phosphorylate and activate IKKalpha | SIGNOR-249387 |
P18848 | P49588 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269414 |
P07949 | P17612 | 0 | phosphorylation | down-regulates | 0.4 | Furthermore, we find that activation of protein kinase a (pka) by forskolin reduces the recruitment of shp2 to ret and negatively affects ligand-mediated neurite outgrowth. In agreement with this, mutation of ser(696), a known pka phosphorylation site in ret, enhances shp2 binding to the receptor and eliminates the effect of forskolin on ligand-induced outgrowth. | SIGNOR-167349 |
P01189 | P32245 | 2 | binding | up-regulates activity | 0.778 | The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins | SIGNOR-268710 |
Q08493 | P28482 | 0 | phosphorylation | down-regulates | 0.256 | The short-form pde4b2 isoenzyme was activated by erk2 phosphorylation. sub-family selective actions in the ability of erk2 map kinase to phosphorylate and regulate the activity of pde4 cyclic amp-specific phosphodiesterases | SIGNOR-83187 |
P19174 | Q13470 | 2 | binding | up-regulates quantity | 0.34 | GST-protein precipitations from cell lysates confirmed that GST-PLC-gamma1(SH3) associated with endogenously expressed Tnk1. | SIGNOR-273864 |
O43541 | Q15750 | 2 | binding | down-regulates | 0.568 | Smad6 interacts with tak1 and tab1, and smad7 with tab1. The interaction of i-smads with tak1 and/or tab1 implies that several mechanisms exist underlying the repression of the tak1-p38 kinase pathway by i-smads. | SIGNOR-112642 |
P38432 | P24941 | 0 | phosphorylation | up-regulates | 0.381 | In particular, we have recently found that the cdk2/cyclin e complex can phosphorylate coilin in vitro . there is but a single consensus cdk2/cyclin e phosphorylation site in coilin, located at serine 184. when serine 184 was mutated to an alanine (s184a), mimicking a dephosphorylated state, a nucleolar mislocalization similar to that of gfp-coilin(1_248) was observed | SIGNOR-84949 |
A2RUS2 | O75385 | 0 | phosphorylation | up-regulates activity | 0.435 | ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12. | SIGNOR-264731 |
Q9BXF6 | Q15208 | 0 | phosphorylation | up-regulates activity | 0.2 | We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation. | SIGNOR-263035 |
Q08378 | Q9HD26 | 2 | binding | up-regulates activity | 0.48 | Golgin-160 belongs to the golgin family of Golgi-localized proteins, which have been implicated in Golgi structure and function. PIST (also known as GOPC, CAL, and FIG) has been implicated in the trafficking of a subset of plasma membrane proteins, supporting a role of golgin-160 in vesicular trafficking. binding of golgin-160, TC10, and syntaxin-6 to PIST may coordinate membrane trafficking of some plasma membrane proteins in cell types where these proteins are expressed. | SIGNOR-261234 |
P53350 | Q9UNE7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.252 | As indicated in xref , all three Plk1 fragments were ubiquitinated by CHIP, suggesting that CHIP targets multiple sites of Plk1 for ubiquitination.|Mechanistically, CHIP mediated degradation of AR and Plk1 leads to enhanced efficacy of HSP90 inhibitors. | SIGNOR-278532 |
P10276 | Q15596 | 2 | binding | up-regulates | 0.631 | Transcriptional coactivator for steroid receptors and nuclear receptors.nteracts with casp8ap2 and ttll5/stamp. Interacts with esr1, rara and rxra. | SIGNOR-96827 |
P17252 | Q99801 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of wild-type nkx3.1 decreased the apparent binding affinity of the protein for the consensus sequence by 3-fold relative to the nonphosphorylated protein (fig. 3) _ . | SIGNOR-86723 |
P11802 | P43694 | 1 | phosphorylation | up-regulates activity | 0.356 | In addition, we have shown that CDK4 can enhance cardiogenic activity of GATA4 (XREF_FIG).|The physical and functional interactions between GATA4 and Cyclin D2 depend on phosphorylation of Ser 160 of GATA4, which can be mediated in vitro by CDK4. | SIGNOR-279148 |
O75144 | Q9Y6W8 | 2 | binding | up-regulates activity | 0.2 | ICOSL expression is largely restricted to professional antigen-presenting cells (APCs), including B cells [in which ICOSL is regulated by BAFFR and non-canonical NFκB signaling (20)], macrophages, and dendritic cells (DCs) (12, 17, 21, 22), but is also expressed by certain endothelial cells (23) and lung epithelium | SIGNOR-272497 |
P49815 | P49840 | 0 | phosphorylation | up-regulates | 0.362 | Gsk3 inhibits the mtor pathway by phosphorylating tsc2 in a manner dependent on ampk-priming phosphorylation. | SIGNOR-149377 |
Q9Y6M4 | P07948 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane. | SIGNOR-275395 |
P10415 | Q07812 | 2 | binding | down-regulates activity | 0.636 | Bcl-2 has the unique oncogenic role of extending cell survival by inhibiting a variety of apoptotic deaths. Bcl-2 exerts its action through heterodimerization with bax. | SIGNOR-36898 |
Q70Z35 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.406 | 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-260570 |
Q4ZG55 | Q15796 | 2 | binding | down-regulates activity | 0.2 | GREB1 is localized to the nucleus where it binds Smad2/3 in a competitive manner with p300 and inhibits TGFβ signaling, thereby promoting HepG2 HB cell proliferation. Binding of GREB1 to Smad2/3 inhibits transcription | SIGNOR-265884 |
Q9Y271 | P08754 | 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-256883 |
O94782 | P06493 | 0 | phosphorylation | up-regulates activity | 0.371 | In this study, we show that Ser313 phosphorylation in USP1 is required for its interaction with UAF1 and for the stimulation of USP1's activity. We further demonstrated that CDK1 is responsible for Ser313 phosphorylation, and protein phosphatase treatment of USP1 can lead to inactivation of USP1/UAF1. | SIGNOR-276423 |
P35414 | P08754 | 2 | binding | up-regulates activity | 0.435 | 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-256824 |
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