IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 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 |
|---|---|---|---|---|---|---|---|
P45983 | O43602 | 1 | phosphorylation | up-regulates activity | 0.286 | DCX phosphorylation by JNK1 is required for glioma suppression. | SIGNOR-279217 |
Q6PHR2 | Q96CF2 | 1 | phosphorylation | down-regulates activity | 0.286 | CHMP4C was phosphorylated by recombinant ULK3 in these experiments, whereas CHMP4A and CHMP4B were not (Figure 7\u2014figure supplement 1A). | SIGNOR-279771 |
Q15418 | Q96QZ7 | 1 | phosphorylation | up-regulates activity | 0.286 | We report herein that p90RSK associates with MAGI1 in ECs and executes 2 independently regulated PTMs of MAGI1: S741 phosphorylation and K931 deSUMOylation. MAGI1-S741 phosphorylation is vital for Rap1 activation. | SIGNOR-273837 |
Q07912 | P40763 | 1 | phosphorylation | up-regulates activity | 0.286 | Since STAT1 and STAT3 are structurally related [3], we also assessed if ACK1 could induce the phosphorylation of STAT3 at residue Y705 (p-STAT3).|Our work demonstrates that catalytically active ACK1 can promote the activation of STAT1 and STAT3.|Here we demonstrate that catalytically active ACK1 induces the tyrosine phosphorylation of STAT1 and STAT3. | SIGNOR-279312 |
P00519 | Q92769 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.285 | C-Abl stabilizes HDAC2 levels by tyrosine phosphorylation repressing neuronal gene expression in Alzheimer's disease. | SIGNOR-260928 |
P49841 | Q9BZS1 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.285 | Our previous study showed, by mass spectrometry analysis, that GSK-3β phosphorylates Foxp3 at Ser270 and Ser275 | SIGNOR-277245 |
P68400 | Q8TEA8 | 1 | phosphorylation | up-regulates activity | 0.285 | Here we show that DUE-B is de-phosphorylated in M phase and phosphorylated in G1/S phase. Phosphorylated DUE-B forms homodimers, whereas de-phosphorylated DUE-B interacts with the Mcm2–7 complex and aminoacyl-tRNA synthetases. We find that CKII can prime DUE-B for Cdc7 phosphorylation. Confirming the importance of DUE-B phosphorylation in replication initiation, a C-terminal Ser/Thr to Ala mutant blocks Cdc45 and RPA loading on sperm chromatin and inhibits DNA replication. DUE-B C-terminal phosphorylation sites (serine 179, 181, 182, 194, 196, 197, 204, 205, and threonine 187) were mutated to unphosphorylatable alanine (DUE-B(S/T)-A) or phosphomimic aspartic acid (DUE-B(S/T)-D). | SIGNOR-273970 |
Q13131 | P41235 | 1 | phosphorylation | down-regulates activity | 0.285 | Here we demonstrate that ampk directly phosphorylates hnf4 and represses its transcriptional activity. Ampk-mediated phosphorylation of hnf4 on serine 304 had a 2-fold effect | SIGNOR-101101 |
Q16566 | P09429 | 1 | phosphorylation | up-regulates activity | 0.285 | Collectively, our results demonstrate that CaMKIV promotes the nucleocytoplasmic shuttling of HMGB1 and suggest that the process may be mediated through CaMKIV-dependent serine phosphorylation of HMGB1. | SIGNOR-278510 |
P17655 | P49841 | 1 | cleavage | up-regulates activity | 0.285 | Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase | SIGNOR-251613 |
P49841 | O15379 | 1 | phosphorylation | up-regulates activity | 0.285 | Given that pharmacological inhibition of GSK3beta inhibits HDAC3 neurotoxicity, we explored the possibility that HDAC3 was directly phosphorylated by GSK3beta.|HDAC3 is directly phosphorylated by GSK3\u03b2, suggesting that the neuronal death-promoting action of GSK3\u03b2 could be mediated through HDAC3 phosphorylation. | SIGNOR-278400 |
Q9UFD9 | Q9UJD0 | 1 | binding | down-regulates activity | 0.285 | SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins. | SIGNOR-264370 |
P23469 | P06213 | 1 | dephosphorylation | down-regulates activity | 0.285 | In this study, we showed that receptor-type PTPepsilon (PTP epsilonM) dephosphorylated IR in rat primary hepatocytes and tyrosines 972, 1158, 1162 and 1163| These results suggest that PTPepsilonM is a negative regulator of IR signaling and involved in insulin-induced glucose metabolism mainly through direct dephosphorylation and inactivation of IR in hepatocytes and liver. | SIGNOR-248444 |
P05129 | P04004 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.285 | Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin. | SIGNOR-248964 |
Q05655 | Q99986 | 1 | phosphorylation | down-regulates activity | 0.285 | PKC\u03b4 phosphorylates VRK1 on Ser-355 in vitro.|PKCdelta negatively regulates VRK1 kinase activity in vitro. | SIGNOR-278219 |
Q8TE12 | O14529 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.285 | Lmx1a drives Cux2 expression in the cortical hem through activation of a conserved intronic enhancer. Lmx1a knockdown abolishes activation of the Cux2 enhancer in the cortical hem | SIGNOR-263961 |
Q13131 | Q6UUV9 | 1 | phosphorylation | down-regulates | 0.285 | Here we show that both ampk and calcineurin modulate longevity exclusively through post-translational modification of crtc-1, the sole c. elegans crtc. We demonstrate that crtc-1 is a direct ampk target. | SIGNOR-172136 |
O43189 | P31260 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.285 | These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression. | SIGNOR-260071 |
O15550 | P31271 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.285 | Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters. | SIGNOR-260022 |
Q96PX9 | P60953 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.285 | 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-260565 |
Q02156 | P78352 | 1 | phosphorylation | up-regulates quantity | 0.285 | PKCepsilon directly phosphorylated PSD-95 and JNK1 in vitro Inhibiting PKCepsilon, JNK, or calcium/calmodulin dependent kinase II activity prevented the effects of PKCepsilon activators on PSD-95 phosphorylation.|These results indicate that PKCepsilon promotes synaptogenesis by activating PSD-95 phosphorylation directly through JNK1 and calcium/calmodulin dependent kinase II and also by inducing expression of PSD-95 and synaptophysin. | SIGNOR-280087 |
P0C2W1 | P37275 | 1 | binding | down-regulates quantity by destabilization | 0.285 | One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by the core EMT-inducing transcription factors (EMT-TFs), such as Zeb1/2, Snai1/2 and Twist1. Here, we find that EMT-TFs can be dynamically degraded by an atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 (SPFFbxo45) through the ubiquitin proteasome system (UPS). The key step is recognition of EMT-TFs by Fbxo45 through its SPRY domain for Zeb2, or F-box domain for the other three EMT-TFs Snai1, Snai2 and Twist1, respectively. | SIGNOR-272179 |
Q9Y4K3 | O43474 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.285 | We further found that inhibition of polo-like kinase 1 could downregulate the expression of KLF4 and that PLK1 directly phosphorylated KLF4 at Ser234. Notably, phosphorylation of KLF4 by PLK1 caused the recruitment and binding of the E3 ligase TRAF6, which resulted in KLF4 K32 K63-linked ubiquitination and stabilization. | SIGNOR-277464 |
Q9UKA9 | P12931 | 1 | post transcriptional regulation | down-regulates quantity by repression | 0.285 | Splicing of the c-src N1 exon in neuronal cells depends in part on an intronic cluster of RNA regulatory elements called the downstream control sequence (DCS). |nPTB binds more stably to the DCS RNA than PTB does but is a weaker repressor of splicing in vitro. nPTB also greatly enhances the binding of two other proteins, hnRNP H and KSRP, to the DCS RNA. | SIGNOR-261267 |
Q6ISU1 | P43403 | 1 | binding | up-regulates activity | 0.285 | Stimulation of the T-cell antigen receptor (TCR) leads to tyrosine phosphorylation of a number of cellular proteins, including phospholipase C (PLC) gamma 1 and the TCR zeta chain. We describe here a 70-kDa tyrosine phosphoprotein (ZAP-70) that associates with zeta within 15 sec following TCR stimulation. The phosphorylation of ZAP-70 and its association with zeta is independent of the other TCR chains | SIGNOR-134325 |
Q09472 | P17861-2 | 1 | acetylation | up-regulates quantity by stabilization | 0.285 | P300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity.. The mRNA encoding the active spliced form of XBP1 (XBP1s) is generated from the unspliced form by IRE1 (inositol-requiring enzyme 1) during the UPR. | SIGNOR-260429 |
P12931 | O60331 | 1 | phosphorylation | up-regulates | 0.285 | Phosphorylation by src of the tyrosine adjacent to s650 (y649 in human pipki gamma) was shown to enhance pipki gamma targeting to focal adhesions. We find that y649 phosphorylation does not stimulate directly pipki gamma binding to talin, but may do so indirectly by inhibiting s650 phosphorylation. | SIGNOR-134459 |
P48730 | Q9Y6Q9 | 1 | phosphorylation | up-regulates | 0.284 | In this study, we show that both eralpha and aib1 are substrates for ck1delta in vitro, and identify a novel aib1 phosphorylation site (s601) targeted by ck1delta, significant for the co-activator function of aib1. | SIGNOR-184946 |
P17252 | P08670 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.284 | We reported that stoichiometric phosphorylation by either cAMP-dependent protein kinase or protein kinase C induces disassembly of vimentin filaments. In the present work, we attempted to identify the sites of vimentin phosphorylated by each protein kinase. Sequential analysis of the purified phosphopeptides, together with the known primary sequence, revealed that Ser-8, Ser-9, Ser-20, Ser-25, Ser-33, and Ser-41 were specifically phosphorylated by protein kinase C, whereas Ser-46 was phosphorylated preferentially by cAMP-dependent protein kinase. Both kinases reacted with Ser-6, Ser-24, Ser-38, Ser-50, and Ser-65. | SIGNOR-248880 |
O75592 | O75385 | 1 | ubiquitination | down-regulates quantity | 0.284 | Cell-based results demonstrate that the human PHR protein PAM restricts ULK1 protein levels (Fig.\u00a05h, i), and is sufficient to ubiquitinate ULK1 in a proteasome-dependent manner (Fig.\u00a05j).|Human PAM ubiquitinates ULK1 and regulates ULK1 levels. | SIGNOR-278765 |
Q12857 | Q13562 | 1 | transcriptional regulation | up-regulates quantity | 0.284 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268890 |
P45983 | P30305 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.284 | Recently, we showed that Cdc25B is degraded rapidly by non-genotoxic stimuli that activate stress-responsive MAPKs, such as Jun N-terminal kinase (JNK) and p38 (Uchida et al., 2009). Our results suggested that these kinases phosphorylate specific Ser residues in the N-terminal region (S101 and S103) to induce Cdc25B degradation.Here, we report that Cdc25B was ubiquitylated by SCF(βTrCP) E3 ligase upon phosphorylation at two Ser residues in the βTrCP-binding-motif-like sequence D(94)AGLCMDSPSP(104). | SIGNOR-276352 |
Q8N4C8 | Q12809 | 1 | binding | up-regulates | 0.284 | Herg, a human homologue of the ether-a-go-go gene of the fruitfly drosophila melanogaster, encodes aproteinthat produces the rapidly activating cardiac delayed rectifier (i[kr]). / our results show that mink physically associates with herg and that the interaction leads to increased ikr current density. | SIGNOR-49869 |
P98170 | Q16665 | 1 | ubiquitination | up-regulates activity | 0.284 | HIF1alpha is ubiquitinated by XIAP.|Lys 63 -linked ubiquitination of HIF1alpha by XIAP is dependent on the activity of E2 ubiquitin conjugating enzyme Ubc13.|We find that XIAP and Ubc13 dependent Lys 63 -linked polyubiquitination promotes HIF1alpha nuclear retention leading to an increase in the expression of HIF1 responsive genes.|The data indicate that XIAP promotes the formation of the non-degradative Lys63-linked ubiquitin chains onto hypoxia inducible factor1\u03b1, but does not affect the formation of Lys48-linked chains. | SIGNOR-278740 |
Q9NQS5 | P63096 | 1 | binding | up-regulates activity | 0.284 | 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-256704 |
P00519 | Q70E73 | 1 | phosphorylation | up-regulates activity | 0.284 | Here we show that phosphorylation of Lpd by c-Abl increases its interaction with Ena/VASP proteins. This analysis revealed that, in vitro, four Lpd peptides harboring tyrosines (Y426, Y456, Y513, Y1226) are highly phosphorylated, and eight additional peptides are phosphorylated to a lesser extent (Figure 1C). | SIGNOR-262606 |
P78536 | P07359 | 1 | cleavage | down-regulates activity | 0.284 | GPIbα is shed by metalloproteases such as ADAM17, a process that releases a soluble GPIbα fragment termed glycocalicin. ADAM17 cleaves within the GPIbα-based peptide (LRGV465LK) through a mechanism that is only partially understood [42]. GPIbα shedding has been shown to be constitutive but it can be increased by activation of protein kinases C (PKC) or inhibition of calmodulin [42, 43]. Shedding leads to decreased receptor density | SIGNOR-261861 |
Q01543 | Q9UPS8 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.284 | In healthy individual, RUNX1/FLI1 complex negatively regulates ANKRD26 gene expression in MKs. | SIGNOR-266070 |
Q05397 | P46937 | 1 | phosphorylation | up-regulates activity | 0.284 | Then, FAK phosphorylates and activates YAP, leading to the activation and nuclear translocation of YAP/TAZ transcription factor, which is known to be involved in such cellular mechanoresponses [ xref , xref ]. | SIGNOR-280099 |
Q8IXJ9 | P19793 | 1 | binding | up-regulates activity | 0.284 | In this study, we demonstrate that mammalian ASXL1 interacts with the AF-2 AD core of RAR (and RXR) through a novel, promiscuous NR box (LVMQLL) and enhances transcriptional activity of the receptors in certain cells. | SIGNOR-255911 |
P00519 | P32119 | 1 | phosphorylation | down-regulates activity | 0.284 | Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation. | SIGNOR-276280 |
P12931 | P25490 | 1 | phosphorylation | down-regulates activity | 0.284 | YY1 phosphorylation is mediated by Src family kinases. | SIGNOR-276940 |
P17676 | P28845 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.284 | In conclusion, C/EBPalpha and C/EBPbeta control basal transcription, and TNF-alpha upregulates 11beta-HSD1, most likely by p38 MAPK-mediated increased binding of C/EBPbeta to the human HSD11B1 promoter. | SIGNOR-268972 |
P11802 | Q02078 | 1 | binding | down-regulates | 0.284 | In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms. | SIGNOR-176515 |
P21728 | P63096 | 1 | binding | up-regulates activity | 0.284 | 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-257068 |
Q92630 | P43686 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.284 | Through a kinome-wide screen, we have identified dual-specificity tyrosine-regulated kinase 2 (DYRK2) as the primary kinase that phosphorylates Rpt3-Thr25, leading to enhanced substrate translocation and degradation. | SIGNOR-275845 |
P49841 | P19544 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.284 | Glycogen synthase kinase 3β promoted phosphorylation of cugWT1 at S64, resulting in ubiquitination and degradation of the cugWT1 associated with the F-box-/- WD repeat-containing protein 8. | SIGNOR-277540 |
P46934 | Q9HC16 | 1 | ubiquitination | up-regulates activity | 0.284 | APOBEC3G ubiquitination by Nedd4-1 favors its packaging into HIV-1 particles|This could be explained in at least two ways : first, endogenous Nedd4 is naturally expressed at a level largely sufficient to target APOBEC3G into the VLP or virions. | SIGNOR-278635 |
P17612 | Q14500 | 1 | phosphorylation | down-regulates activity | 0.283 | Phosphorylation of the Kir2.2 C terminus by protein kinase A inhibited the association with SAP97.‚ | SIGNOR-249998 |
P54762 | Q8WXD9 | 1 | phosphorylation | up-regulates activity | 0.283 | EphB1 phosphorylates Caskin1 on tyrosine 296 and 336. Tyrosine phosphorylated Caskin1 then likely promotes reorganization of the actin cytoskeleton leading to spine formation. | SIGNOR-262861 |
P17612 | Q7Z434 | 1 | phosphorylation | down-regulates activity | 0.283 | Mutagenesis indicated that PKACalpha phosphorylated wild-type VISA and the VISA mutants VISA (S100A), VISA (T234A) and VISA (S238A) but not VISA (T54A) (XREF_FIG, panel C).|We found that PKACalpha caused degradation of wild-type VISA but not VISA (T54A) or VISA (K7/500R), in which either the PKACs mediated phosphorylation or MARCH5 mediated K48 linked polyubiquitination residues are mutated (XREF_FIG, panel G). | SIGNOR-279649 |
P11802 | Q06413 | 1 | binding | down-regulates | 0.283 | In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms. | SIGNOR-176518 |
P09668 | P02818 | 1 | cleavage | down-regulates quantity by destabilization | 0.283 | This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42. | SIGNOR-256325 |
P28482 | Q96KB5 | 2 | phosphorylation | up-regulates activity | 0.283 | In the present study, Ser32 was revealed to be a novel phosphorylated site on TOPK that could be activated by ERK2.|TOPK/PBK is phosphorylated by ERK2 at serine 32, promotes tumorigenesis and is involved in sorafenib resistance in RCC. | SIGNOR-279744 |
P29371 | Q03113 | 1 | binding | up-regulates activity | 0.283 | 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-257389 |
P20794 | P12830 | 1 | phosphorylation | down-regulates | 0.283 | Finally, we speculate that there are two mechanisms whereby MAK inactivates CDH1 : the first is kinase dependent inactivation, modeled after CDK, where phosphorylation dissociates CDH1 from APC/C; the second is through physical binding of CDH1 with MAK.|These results suggest a cell cycle-dependent phosphorylation of CDH1 by MAK. | SIGNOR-278486 |
P29371 | Q14344 | 1 | binding | up-regulates activity | 0.283 | 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-257438 |
Q8TBB1 | P22459 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.283 | We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo.The C-terminal LNX1 PDZ1-binding motifs of the ATP-binding cassette, subfamily A member 1 (ABC-1), PBK, glutamate receptor, ionotropic, N-methyl d-aspartate 1 (GRIN1), and Claudin-17 significantly promoted the ubiquitination of the corresponding artificial degrons by LNX1ΔPDZ234. | SIGNOR-272899 |
P09958 | P06213 | 1 | cleavage | up-regulates activity | 0.283 | Here we demonstrate that the two IR isoforms are similarly cleaved by furin, but when this furin-dependent maturation is inefficient, IR proforms move to the cell surface where the proprotein convertase PACE4 selectively supports IRB maturation. | SIGNOR-260365 |
Q9H2K8 | Q13043 | 1 | phosphorylation | up-regulates | 0.283 | In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2 | SIGNOR-192762 |
Q5VWQ8 | P27986 | 1 | binding | down-regulates activity | 0.283 | DAB2IP binds the p85 subunit of PI3K through its PR domain and prevents PI3K-p85 relocation from the cytoplasm to the membrane, a necessary step for PI3K activation and signaling to AKT. Notably, DAB2IP reinforces this inhibitory effect by directly binding AKT.2 | SIGNOR-254757 |
Q96GD4 | O14578 | 1 | phosphorylation | down-regulates activity | 0.283 | Finally, Aurora B phosphorylates CIT-K to control its localization and interaction with central spindle partners.|Together these findings indicate that CIT-K is an Aurora B substrate and that Aurora B phosphorylation at S699 dampens the association of CIT-K with KIF23 and the chromosomal passenger complex in order to reduce CIT-K accumulation at the spindle midzone in early cytokinesis. | SIGNOR-279140 |
Q9HCK8 | P04818 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.283 | In order to identify CHD8 target genes, we performed a transcriptomic analysis of CHD8-depleted cells, finding out that CHD8 controls the expression of cyclin E2 (CCNE2) and thymidylate synthetase (TYMS), two genes expressed in the G1/S transition of the cell cycle. CHD8 was also able to co-activate the CCNE2 promoter in transient transfection experiments. Chromatin immunoprecipitation experiments demonstrated that CHD8 binds directly to the 5' region of both CCNE2 and TYMS genes. | SIGNOR-268805 |
P49841 | Q9NQX3 | 1 | phosphorylation | down-regulates | 0.283 | Identification of gsk3_ as the kinase targeting ser-270 /phosphorylation at ser-270 promotes gephyrin processing by calpain | SIGNOR-200957 |
Q96PU5 | Q9NY46 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.283 | 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-253464 |
Q7Z6J0 | Q9UQF2 | 1 | binding | up-regulates | 0.283 | We find that posh and jips directly associate with one another to form a multiprotein complex, pjac (posh-jip apoptotic complex), that includes all of the known kinase components of the pathway. Our observations indicate that this complex is required for jnk activation and cell death in response to apoptotic stimuli. | SIGNOR-145393 |
P17612 | P14136 | 1 | phosphorylation | down-regulates activity | 0.283 | GFAP can serve as a substrate for phosphorylation by CAMP-dependent protein kinase. CAMP-dependent protein kinase or protein kinase C phosphorylated Ser-8, Ser-13, and Ser-34.each phosphorylation was shown to induce disassembly of the glial filaments. | SIGNOR-249713 |
P17612 | Q9BZE0 | 1 | phosphorylation | down-regulates activity | 0.283 | Protein kinase a (pka) and glycogen synthase kinase 3beta sequentially phosphorylate gli2 at multiple sites, identified by mutagenesis, thus resulting in a reduction of its transcriptional activity | SIGNOR-145131 |
Q9H0M0 | O15350 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.283 | WWP1 in complex with WWP2 specifically regulates ΔNp73. In our study, we identified WWP2, an E3 ligase, as a novel p73-associated protein that ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3 ligase, WWP1, which specifically ubiquitinates and degrades ΔNp73. | SIGNOR-272232 |
O60216 | Q01196 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.283 | We observed that depletion of RAD21 (but not CTCF) enhanced RUNX1 transcription in human HL-60 myelocytic leukemia cells | SIGNOR-259973 |
Q12968 | P05231 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.283 | The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway has been found to play a role in regulating growth and differentiation in several cell types. However, the functional significance of NFAT in the vasculature is largely unclear. Here we show that NFATc1, NFATc3, and NFATc4 are expressed in human myometrial arteries. |Chronic inhibition of NFAT significantly reduced IL-6 production in intact myometrial arteries and inhibited cell proliferation in vascular smooth muscle cells cultured from explants from the same arteries. | SIGNOR-251732 |
P49841 | Q15853 | 1 | phosphorylation | up-regulates activity | 0.283 | Although no study has yet correlated the activity of GSK3beta with the activity of USF2 in a certain tumor setting, the findings of the present study would favor the tumor promoting aspects of GSK3beta and USF2 since GSK3beta activated USF2 enhanced cell migration which may be important in terms of tumor cell metastasis.|Together, these data show that there are two residues within USF2, namely S155 and T230, which can be phosphorylated by GSK3beta. | SIGNOR-278158 |
Q8IXJ9 | Q15788 | 2 | binding | up-regulates activity | 0.283 | We also show that ASXL1 associates specifically with SRC-1 and cooperates synergistically in the transcriptional activation. Further data indicated that the transactivation domain (AD; amino acids 300–655) of ASXL1, newly defined in this study, interacts with the C-terminal AD2 (amino acids 1217–1441) of SRC-1, suggesting that one AD cooperates with the other AD in transcriptional activation by RAR. | SIGNOR-255931 |
P17612 | P35612 | 1 | phosphorylation | down-regulates activity | 0.283 | Ser-726 and Ser-713 in the C-terminal MARCKS-related domains of - and -adducin, respectively, were identified as the major phosphorylation sites common for PKA and PKC. Phosphorylation by PKA, but not PKC, reduced the affinity of adducin for spectrin-F-actin complexes as well as the activity of adducin in promoting binding of spectrin to F-actin. | SIGNOR-250332 |
Q99814 | Q9UGL1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.283 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271578 |
O00141 | O14686 | 1 | phosphorylation | down-regulates activity | 0.283 | Elevated SGK1, in turn, phosphorylates KMT2D, suppressing its function, leading to a loss of methylation of lysine 4 on histone H3 (H3K4) and a repressive chromatin state at ER loci to attenuate ER activity. | SIGNOR-277447 |
P28482 | Q14934 | 1 | phosphorylation | up-regulates | 0.283 | We demonstrate that p90 ribosomal s6 kinase (rsk) is recruited to the nfat-dna transcription complex upon activation.Bound Rsk phosphorylates ser(676) and potentiates nfatc4 dna binding. Ser(676) is also targeted by the erk map kinase. | SIGNOR-133272 |
O00308 | O15350 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.283 | WWP2 ubiquitinates p73 and controls its protein stability. In our study, we identified WWP2, an E3 ligase, as a novel p73-associated protein that ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3 ligase, WWP1, which specifically ubiquitinates and degrades ΔNp73. | SIGNOR-272233 |
Q92847 | P63092 | 1 | binding | up-regulates activity | 0.283 | 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-256782 |
Q13131 | P29474 | 1 | phosphorylation | up-regulates | 0.283 | The central finding of this report is that rosiglitazone rapidly stimulates no production and enos ser-1177 phosphorylation in an ampk-dependent manner | SIGNOR-160838 |
P49841 | Q12888 | 1 | phosphorylation | up-regulates activity | 0.283 | Based on these observations, we hypothesized that the IR induced GSK3beta nuclear translocation may activate 53BP1 via phosphorylation at the S/T-Q motif.|Importantly, our in vivo and in vitro data clearly indicated that GSK3\u03b2 induced the phosphorylation of 53BP1 at the Ser166 site. | SIGNOR-278226 |
O15294 | P46937 | 1 | glycosylation | up-regulates activity | 0.283 | Mass spectrometry analysis showed that YAP was the effector protein modified by OGT. In details, YAP Ser109 O-GlcNAcylation promoted the malignant phenotypes in PTC cells by inducing YAP Ser127 dephosphorylation and activation. | SIGNOR-276942 |
P15173 | Q13683 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.283 | Only myogenin and MyoD were able to efficiently trans-activate the alpha7 promoter-CAT construct (Fig. 7). Myogenin trans-activated the promoter by _2-fold whereas MyoD was able to trans-activate by nearly 4-fold, indicating that both of these factors may play a role in alpha7 gene expression during muscle development. | SIGNOR-241521 |
P21127 | Q07955 | 1 | phosphorylation | up-regulates activity | 0.283 | In comparison, CLK1 expression leads to speckle dissolution and diffuse GFP-SRSF1 localization in the nucleus.|We showed that CLK1 phosphorylates SRSF1 at approximately 18 sites inducing a gel shift from 35 to about 38 kDa on SDS-PAGE (XREF_FIG, upper panel). | SIGNOR-279499 |
P49841 | P16615 | 1 | phosphorylation | down-regulates activity | 0.283 | GSK3β-dependent phosphorylation of SERCA2 at serine 663 in human and mouse hearts. Phosphorylation of SERCA2 at serine 663 regulates SERCA2 activity. | SIGNOR-277886 |
P53355 | Q96RR4 | 1 | phosphorylation | down-regulates | 0.283 | Dapk phosphorylates camkk. S511 was identified as the phosphorylation site . a potential mechanism of action was identified on the basis of the location of s511 near the cam recognition domain of camkk and demonstrated by attenuation of cam-stimulated camkk autophosphorylation after dapk phosphorylation. | SIGNOR-126241 |
Q96KB5 | P28482 | 2 | phosphorylation | up-regulates activity | 0.283 | Phosphorylation of ELK1 or ERK2 increased dramatically compared with controls and suggested that TOPK or ERK2 could enhance ERK2 or TOPK kinase activity by respective and mutual phosphorylation of each other.|The results indicated that active TOPK could strongly phosphorylate ERK2 and very weakly phosphorylate ERK1. | SIGNOR-278417 |
Q15788 | Q8IXJ9 | 2 | binding | up-regulates activity | 0.283 | We also show that ASXL1 associates specifically with SRC-1 and cooperates synergistically in the transcriptional activation.Therefore, both the ability to bind SRC-1 and the autonomous activation of ASXL1 are required for its coactivator function. Further data indicated that the transactivation domain (AD; amino acids 300–655) of ASXL1, newly defined in this study, interacts with the C-terminal AD2 (amino acids 1217–1441) of SRC-1, suggesting that one AD cooperates with the other AD in transcriptional activation by RAR. | SIGNOR-255924 |
O96013 | P16949 | 1 | phosphorylation | down-regulates activity | 0.283 | Indeed, we show here that inactivating phosphorylation of the endogenous stathmin on serine-16 is also induced by the active PAK4 in mitotic egg extract and is likely to participate in the observed stabilization of the MT asters ( xref , right). | SIGNOR-280058 |
Q14164 | Q9UNN5 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.283 | Upon virus infection, the kinase IKKɛ directly phosphorylates FAF1 at Ser556 and triggers FAF1 de-aggregation. Moreover, Ser556 phosphorylation promotes FAF1 lysosomal degradation, consequently relieving FAF1-dependent suppression of MAVS. | SIGNOR-277618 |
Q01664 | Q13547 | 1 | binding | up-regulates activity | 0.282 | We also observed moderately increased recruitment of CTCF, HDAC1, and SP1 by the full-length AP-4 onto the WT DNA beads. | SIGNOR-226590 |
Q92915 | Q14524 | 1 | binding | down-regulates activity | 0.282 | 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-253417 |
P49841 | P20393 | 1 | phosphorylation | up-regulates | 0.282 | We show here that gsk3beta phosphorylates and stabilizes the orphan nuclear receptor rev-erbalpha, a negative component of the circadian clock. | SIGNOR-144570 |
Q96PY6 | Q8WXE1 | 1 | binding | up-regulates activity | 0.282 | It was reported that NEK1 associates with ATR/ATRIP and primes it for activation in response to a variety of genotoxic agents | SIGNOR-275842 |
Q15208 | P01106 | 1 | phosphorylation | down-regulates activity | 0.282 | Previously, we demonstrated that STK38 kinase mediates MYC phosphorylation.|STK38-WT overexpression dramatically reduced MYC half-life (4-fold), compared to control un induced cells (XREF_FIG), while STK38-KD overexpression led to increased MYC half-life (1.7 fold), illustrating an involvement in MYC protein turnover regulation (XREF_FIG). | SIGNOR-280142 |
Q01484 | Q15172 | 1 | relocalization | up-regulates quantity | 0.282 | 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-266729 |
Q86X55 | Q01196 | 1 | methylation | down-regulates activity | 0.282 | We have found that PRMT4 is highly expressed in HSPCs, where it functions as an inhibitor of myeloid differentiation (Figure 7G). In these cells, PRMT4 methylates RUNX1 at R223, promoting the assembly of a DPF2-containing transcriptional co-repressive complex, and repressing transcription at the miR-223 locus. | SIGNOR-261967 |
Q16665 | Q96A26 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.282 | In this work, we report the identification of an HIF-1 alpha-responsive proapoptotic molecule, HGTD-P. Its expression was directly regulated by HIF-1 alpha through a hypoxia-responsive element on the HGTD-P promoter region. | SIGNOR-260292 |
P21728 | P08754 | 1 | binding | up-regulates activity | 0.282 | 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-257181 |
Q9UJD0 | P20336 | 1 | relocalization | up-regulates activity | 0.282 | N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle | SIGNOR-264379 |
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