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 |
|---|---|---|---|---|---|---|---|
P04637 | P52789 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.412 | P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway. | SIGNOR-267466 |
Q01543 | 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-260034 |
P06493 | O15392 | 1 | phosphorylation | up-regulates | 0.686 | Survivin is a member of the inhibitor of apoptosis gene family that has been implicated in both apoptosis inhibition and regulation of mitosisin synchronized cultures, cytosolic survivin abruptly increased at mitosis, physically associated with p34(cdc2), and was phosphorylated by p34(cdc2) on thr(34), in vivo | SIGNOR-115129 |
Q9NPP4 | Q5S007 | 0 | phosphorylation | up-regulates activity | 0.359 | LRRK2 phosphorylates NLRC4 at Ser533 upon inflammasome activation.|These data suggest that LRRK2 promotes NLRC4 inflammasome activation through its kinase activity. | SIGNOR-279338 |
Q9UPT6 | P53779 | 2 | binding | up-regulates | 0.745 | The c-jun nh2-terminal kinase (jnk)-interacting protein (jip) group of scaffold proteins (jip1, jip2, and jip3) can interact with components of the jnk signaling pathway and potently activate jnk. | SIGNOR-134555 |
P35548 | Q07687 | 2 | binding | down-regulates activity | 0.392 | We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities. | SIGNOR-240932 |
P08235 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.35 | Taken together, these data suggest that ERK1/2 directly phosphorylates the MR on several serine residues present in its NTD, that the upward shift of MR is mainly due to receptor phosphorylation, and finally that these sites represent the major aldosterone-inducible targets for MR phosphorylation.MR phosphorylation limits the transcriptional activity.Taken together, these results provide evidence that MR phosphorylation plays a role in aldosterone-mediated ubiquitylation and degradation. | SIGNOR-276102 |
P10586 | P56945 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.339 | LAR specifically dephosphorylates and destabilizes p130Cas and may play a role in regulating cell adhesion-mediated cell survival.|Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas. | SIGNOR-276998 |
P38936 | P28482 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.364 | Extracellular signal-regulated kinase 2-dependent phosphorylation induces cytoplasmic localization and degradation of p21cip1.|Phosphopeptide analysis of in vitro ERK2-phosphorylated p21(Cip1) revealed two phosphorylation sites, Thr57 and Ser130. | SIGNOR-185215 |
O60500 | P12931 | 0 | phosphorylation | up-regulates activity | 0.48 | Inhibition of Src kinase dependent Nephrin phosphorylation achieved by incubation of WT-Nephrin-overexpressing cells with 1 mum PP2 abolished the positive effect of Nephrin on GSIR (XREF_FIG D).|We were able to demonstrate a complete prevention of Nephrin phosphorylation, confirming that Nephrin phosphorylation is mediated by Src. | SIGNOR-280129 |
P42229 | P11309 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.375 | The results of 2 microarray experiments demonstrated that the aberrant activation of STAT proteins by Flt3-ITDs resulted in the up-regulation of several STAT5-responsive genes, such as Pim-1, Pim-2, and members of the SOCS (suppressor of cytokine signaling) protein family. These results are particularly interesting because recent data point to an important role of Pim kinases in the antiapoptosis of hematopoietic cells. | SIGNOR-249621 |
Q8NES3 | Q04721 | 2 | binding | up-regulates | 0.697 | These observations indicate that the fringe proteins directly modify notch2, which is consistent with the recent finding that fringe is a glycosyltransferase that directly modifies notch. It was further indicated that lfng does this at a site from the n terminus through the 15th egf repeat of notch2, and mfng does so at a site from the 23rd through the 29th egf repeat of notch2. | SIGNOR-107702 |
Q92934 | P11309 | 0 | phosphorylation | down-regulates activity | 0.371 | Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells. | SIGNOR-250390 |
P36776 | P31749 | 0 | phosphorylation | up-regulates activity | 0.253 | In mitochondria, LonP1 is phosphorylated by Akt on Ser173 and Ser181, enhancing its protease activity. | SIGNOR-265724 |
P49841 | O00429 | 1 | phosphorylation | up-regulates activity | 0.388 | We identified glycogen synthase kinase (GSK)3β-dependent Drp1 phosphorylation at Ser(40) and Ser(44), which increases Drp1 GTPase activity and its mitochondrial distribution and could induce mitochondrial fragmentation. | SIGNOR-276849 |
P15927 | Q8WXE1 | 2 | binding | up-regulates | 0.686 | Ssdna lesions are then coated by replication protein a (rpa), recruiting atr/atrip (atr-interacting protein) complexes via recognition and association of rpa-ssdna by atrip. | SIGNOR-163176 |
Q9GZQ6 | P19086 | 2 | binding | up-regulates activity | 0.252 | 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-257103 |
Q9H4A3 | Q9UEW8 | 1 | phosphorylation | up-regulates | 0.446 | Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1). | SIGNOR-151671 |
P05771 | P43629 | 1 | phosphorylation | down-regulates activity | 0.2 | Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII. | SIGNOR-276079 |
P46934 | Q9Y4G8 | 1 | ubiquitination | down-regulates quantity | 0.401 | In line with the previous result (XREF_FIG), overexpression of NEDD4-1 reduced the level of CNrasGEF significantly (XREF_FIG).|NEDD4-1 ubiquitinates CNrasGEF in glioma cells. | SIGNOR-278705 |
O14727 | P55211 | 2 | binding | up-regulates activity | 0.954 | Caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation. | SIGNOR-53576 |
Q03135 | P08581 | 0 | phosphorylation | up-regulates activity | 0.424 | Findings obtained using SNU-449 cells suggested that c-Met positively regulated CAV1 activity.|Inhibition of c-Met activation abolished phosphorylation of CAV1 on Tyrosine 14. | SIGNOR-279080 |
P05771 | Q9P2D0 | 1 | phosphorylation | down-regulates | 0.328 | We found that ibtk_ is phosphorylated at serines 87 and 90 by pkc on bcr engagement;this phosphorylation causes the dissociation of the btk:ibtk_ complex and allows btk to translocate to the plasma membrane. | SIGNOR-173387 |
P49841 | Q16665 | 1 | phosphorylation | down-regulates activity | 0.332 | Glycogen synthase kinase 3 \u03b2 (GSK3\u03b2) phosphorylates HIF-1\u03b1 at three serine residues (Ser-551, Ser-555, and Ser-589) located within its oxygen-dependent degradation domain (ODDD) [12] (Figure 5). Phosphorylation at these residues by GSK3\u03b2 enhances HIF-1\u03b1 degradation in a pVHL-independent manner, resulting in suppression of the HIF-1 activity [12,13].|Phosphorylation at these residues by GSK3beta enhances HIF-1alpha degradation in a pVHL independent manner, resulting in suppression of the HIF-1 activity , ]. | SIGNOR-278294 |
Q9Y625 | Q13469 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.354 | NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype. | SIGNOR-264021 |
Q9NQC7 | O43318 | 1 | deubiquitination | up-regulates activity | 0.636 | Mechanistically, CYLD interacts directly with the kinase TAK1 and removes its K63-linked polyubiquitin chain, which blocks downstream activation of the JNK-p38 cascades. | SIGNOR-266437 |
Q9BYB0 | O95886 | 0 | relocalization | up-regulates activity | 0.2 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264594 |
Q96PU5 | Q9BSA4 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.286 | Our data indicate that Nedd4-2 binds to two family members, TTYH2 and TTYH3, which contain consensus PY ((L/P)PXY) binding sites for HECT type E3 ubiquitin ligases, but not to TTYH1, which lacks this motif. Consistently, Nedd4-2 ubiquitinates both TTYH2 and TTYH3. Importantly, we have shown that endogenous TTYH2 and Nedd4-2 are binding partners and demonstrated that the TTYH2 PY motif is essential for these interactions. We have also shown that Nedd4-2-mediated ubiquitination of TTYH2 is a critical regulator of cell surface and total cellular levels of this protein. | SIGNOR-272632 |
Q7Z434 | Q86WV6 | 2 | binding | up-regulates activity | 0.2 | MAVS also interacts with STING that locates at the ER (endoplasmic reticulum), and induces the ubiquitination and dimerization of STING. The activated STING recruits TBK1 and IRF3 and contributes to the phosphorylation of IRF3 mediated by TBK1. | SIGNOR-260152 |
O95071 | P62837 | 0 | ubiquitination | up-regulates activity | 0.508 | Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks. | SIGNOR-272668 |
Q9UBE8 | Q9NQB0 | 1 | phosphorylation | down-regulates quantity | 0.772 | NLK Augments the Ubiquitylation Activity of NARF against TCF/LEF. ctivation of NLK induced by unknown ligands leads to the phosphorylation of TCF/LEF. NARF then acts on TCF/LEF as an E3 ubiquitin-ligase and, together with E1 and E2 ubiquitylation enzymes, catalyze the ubiquitylation of TCF/LEF. Finally, ubiquitylated TCF/LEF is degraded by the 26 S proteasome. | SIGNOR-271597 |
Q9UJA2 | Q9BXM7 | 0 | phosphorylation | down-regulates quantity | 0.429 | In vitro kinase assays using recombinant proteins under various control conditions indicated that PINK1 directly phosphorylates CLS1 (XREF_FIG).|Similar to Fbxo15, knockdown of PINK1 kinase using shRNA increased CLS1 levels, whereas overexpression of PINK1 plasmid decreased CLS1 levels . | SIGNOR-280065 |
Q9NQX3 | Q8NFZ4 | 2 | binding | up-regulates activity | 0.473 | Gephyrin is believed to act as a scaffold at inhibitory synapses, in a manner analogous to that of the prototypic excitatory synaptic scaffold, PSD-95. The best-known function of gephyrin is to bring the inhibitory synaptic receptors and to stabilize them at the inhibitory synapses. gephyrin interacts with NL-2 and collybistin, suggesting that it may be critical for the maturation or maintenance of inhibitory synapses. | SIGNOR-264974 |
P21860 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.341 | We demonstrated that Cdk5 phosphorylated Ser-1176 in the neuregulin receptor ErbB2 and phosphorylated Thr-871 and Ser-1120 in the ErbB3 receptor. We identified the Ser-1120 sequence RSRSPR in ErbB3 as a novel phosphorylation consensus sequence of Cdk5. Finally, we found that Cdk5 activity is involved in neuregulin-induced Akt activity and neuregulin-mediated neuronal survival. | SIGNOR-250663 |
Q6DN90 | O95819 | 0 | phosphorylation | up-regulates activity | 0.2 | Together, our results provide compelling evidence that MAP4K4 promotes FA dynamics by regulating IQSEC1 and Arf6 pathway and controlling endocytosis of integrin.|Upon targeting to FAs via MTs, MAP4K4 can bind and phosphorylate IQSEC1, which in turn activates Arf6 and endocytosis, leading to turnover of FAs. | SIGNOR-280020 |
Q9BXH1 | Q07817 | 2 | binding | down-regulates activity | 0.761 | Only bimbh3 and bbc3 had comparable strong affinities for all the prosurvival proteins. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1.Puma promotes bax translocation by both by directly interacting with bax and by competitive binding to bcl-x(l) in uv-induced apoptosis. | SIGNOR-133811 |
Q13568 | O43353 | 0 | phosphorylation | up-regulates | 0.304 | Activation of interferon regulatory factor 5 by site specific phosphorylation. Phosphorylation of carboxyl serines 451 and 462 appear the primary trigger of irf5 function in nuclear accumulation, transcription, and apoptosis. Rip2 activation of the irf5 aspartic acid substitutions showed a similar positive effect of s451d and s462d function in this assay | SIGNOR-196524 |
P46937 | Q05397 | 0 | 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 |
P62995 | P09651 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.699 | HnRNPA1 interacts with G-quadruplex in the TRA2B promoter and stimulates its transcription in human colon cancer cells. | SIGNOR-262280 |
Q06830 | P06493 | 0 | phosphorylation | down-regulates | 0.35 | Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%. | SIGNOR-87097 |
Q8TB45 | P48729 | 0 | phosphorylation | down-regulates | 0.2 | Phosphorylation of all three serine residues in the deptor degron (ser286, ser287, and ser291) is necessary for - and directly mediates - the interaction with _trcp. ck1 phosphorylated the degron of deptor, as shown by western blotting with the phospho-specific antibody (fig. S3e-f). In contrast, mtor alone was unable to induce phosphorylation of deptor on ser286, ser287, and ser291. | SIGNOR-176871 |
P17676 | P49841 | 0 | phosphorylation | up-regulates activity | 0.457 | We found that expression of srebf1a depended on GSK3β activity and that GSK3β activity was necessary for C/EBPβ phosphorylation at Thr188 | SIGNOR-251644 |
O43379 | P45983 | 2 | relocalization | up-regulates activity | 0.556 | In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis | SIGNOR-271718 |
P18075 | P18075 | 2 | binding | up-regulates | 0.2 | Bmps are dimeric proteins with a single inter-chain disulfide bond. The dimeric conformation is an absolute requirement for the biological action and interac- tion with receptors | SIGNOR-236172 |
P54753 | P98172 | 2 | binding | up-regulates | 0.762 | The activation of eph receptors by their ligands, which are membrane-anchored molecules, involves a cell-cell recognition event that often causes cell repulsion. | SIGNOR-52517 |
Q13671 | P42684 | 2 | phosphorylation | up-regulates | 0.615 | Rin1 binds to the abl sh3 and sh2 domains, and these inetractions stimulate abl2 catalytic activity. This leads to increased phosphorylation of crk and crkl | SIGNOR-136961 |
O14733 | Q99683 | 0 | phosphorylation | up-regulates | 0.594 | Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7 | SIGNOR-161766 |
Q6Y7W6 | Q13322 | 2 | binding | up-regulates activity | 0.596 | We demonstrated that, in cultured cells and mammalian brains, GIGYF2 interacts and colocalises with Grb10, promoting ligand‐induced ubiquitination of IGF‐1R, and thereby regulates receptor degradation | SIGNOR-260057 |
P10636-5 | Q96L34 | 0 | phosphorylation | down-regulates activity | 0.419 | AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A). | SIGNOR-273932 |
P03217 | Q9NR96 | 1 | post transcriptional regulation | down-regulates quantity by destabilization | 0.2 | The EBV lytic-phase protein BGLF5 reduces TLR9 expression through mRNA degradation. We established that the EBV early protein BGLF5 degrades TLR9 mRNA in vitro, providing a mechanism for its contribution to TLR9 downregulation. | SIGNOR-266633 |
Q9NQB0 | P35222 | 2 | binding | up-regulates activity | 0.9 | Hypophosphorylation of β-catenin and translocation into the nucleus leads to binding with members of the lymphoid-enhancer-binding factor/T-cell-specific transcription factor (LEF/TCF) family and activation of WNT target genesAs a member of LEF/TCF family, transcription factor 7 like 2 (Tcf7l2, formerly called Tcf4) is an important transcription factor triggering the downstream responsive genes of WNT signaling | SIGNOR-85757 |
P21802 | P08620 | 2 | binding | up-regulates | 0.758 | The nine known fgf ligands and the four signaling fgf receptors (and their alternatively spliced variants) are expressed in specific spatial and temporal patterns. The activity of this signaling pathway is regulated by ligand binding specificity, heparan sulfate proteoglycans, and the differential signaling capacity of individual fgf receptors. | SIGNOR-42377 |
Q02535 | Q99081 | 2 | binding | down-regulates activity | 0.466 | All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo. | SIGNOR-241152 |
Q15077 | P30679 | 2 | binding | up-regulates activity | 0.401 | 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-257277 |
P19086 | P32245 | 2 | binding | up-regulates activity | 0.252 | 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-257270 |
P28328 | P50542 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.579 | Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle. | SIGNOR-253021 |
Q9NPI8 | Q8IYD8 | 2 | binding | up-regulates | 0.932 | Protein interaction motifs in fancm, designated mm1 and mm2, were identified. Mm1 interacts with the fa core complex by binding to fancf, whereas mm2 interacts with rm1 and topoisomerase iiialpha, components of the bs complex. | SIGNOR-163101 |
Q92831 | Q5TEC6 | 1 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269624 |
P13569 | Q9UEW8 | 0 | phosphorylation | down-regulates activity | 0.345 | SPAK phosphorylates the transporters to reduce their surface expression and thus their activity and consequently inhibits ductal secretion to stabilize the resting state. PP1 reverses the effect of SPAK. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression. | SIGNOR-263134 |
O95863 | Q9UEW8 | 0 | phosphorylation | up-regulates activity | 0.2 | In this study, we found that STK39 also enhances SNAI1 stability by its phosphorylation at T203.|STK39 interacts with SNAI1 and phosphorylates SNAI1 on T203. | SIGNOR-279128 |
P17676 | P01024 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.259 | CCAAT/enhancer binding protein β directly regulates the expression of the complement component 3 gene in neural cells: implications for the pro-inflammatory effects of this transcription factor | SIGNOR-261927 |
Q8TE49 | Q13546 | 1 | deubiquitination | down-regulates activity | 0.2 | NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination. | SIGNOR-268410 |
Q92569 | P08069 | 2 | binding | up-regulates | 0.807 | Moreover, we found that the insulin-like growth factor-1 receptor (igf-ir) bound to p55pik;the interaction occurred at the receptor tyrosine 1316 and involved both p55pik sh2 domains. | SIGNOR-52683 |
O75888 | Q02223 | 2 | binding | up-regulates | 0.686 | April is involved in stimulation of b and t cell function. April functions via binding to bcma and taci and competes with tall-i for receptor binding. | SIGNOR-81386 |
Q9UQ52 | P46531 | 1 | relocalization | up-regulates | 0.588 | Here, we establish that nb-3, a member of the f3/contactin family, acts as a novel notch ligand to participate in oligodendrocyte generation. Nb-3 triggers nuclear translocation of the notch intracellular domain and promotes oligodendrogliogenesis from progenitor cells and differentiation of oligodendrocyte precursor cells via deltex1. | SIGNOR-124151 |
O00141 | P42568 | 1 | phosphorylation | down-regulates activity | 0.509 | In addition to Nedd4-2, Sgk1 also phosphorylates Af9, forkhead like transcription factor FOXO3a and several other substrates.|Sgk1 impairs the ability of Af9 to interact with Dot1a at these subregions without impacting Af9 DNA binding activity, leading to targeted histone H3 K79 hypomethylation. | SIGNOR-279111 |
Q8NG27 | Q15910 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.488 | Biochemical and genetic evidence demonstrates that the MYOD-induced E3 ubiquitin ligase Praja1 (PJA1) is involved in regulating EZH2 levels upon p38α activation. EZH2 premature degradation in proliferating myoblasts is prevented by low levels of PJA1, its cytoplasmic localization and the lower activity towards unphosphorylated EZH2 | SIGNOR-255664 |
Q05397 | P12814 | 2 | phosphorylation | down-regulates activity | 0.574 | The cytoskeletal/non-muscle isoform of alpha-actinin is phosphorylated on its actin-binding domain by the focal adhesion kinase tyrosine 12 is the site of phosphorylation. The wild type recombinant protein was not phosphorylated in cells lacking the focal adhesion kinase (fak).Tyrosine phosphorylation reduced the amount of alpha-actinin that cosedimented with actin filaments. | SIGNOR-108329 |
Q9Y4X5 | Q13619 | 2 | binding | up-regulates activity | 0.281 | Here, we provide evidence that Ariadne RBR E3 ubiquitin ligases such as TRIAD1 and HHARI can bind and be activated by CRL complexes. Whereas TRIAD1 specifically associates with CUL5–RBX2, HHARI is more promiscuous towards cullin types and associates with RBX1-associated cullins 1, 2, 3, and 4A. Interestingly, both TRIAD1 and HHARI show a strong preference for binding the neddylated form of the cullin. Our data suggest a novel function of NEDD8 in directing specific CRLs to Ariadne RBR ligases, which in turn exert influence on the levels of their cognate neddylated cullin. | SIGNOR-268847 |
P06241 | P17706 | 0 | dephosphorylation | down-regulates | 0.325 | Previously, we reported that sfks can serve as bona fide substrates for tcptp and that tcptp dephosphorylates the y418 activation loop autophosphorylation site (corresponding to y394 in lck and y417 in fyn) to inactivate sfks | SIGNOR-177113 |
P19784 | Q9NQB0 | 1 | phosphorylation | up-regulates activity | 0.378 | We show here that Tcf-4 can be phosphorylated in vitro by protein kinase CK2 stoichiometrically in amino acids Ser-58-Ser-59-Ser-60. Phosphorylation of these residues does not modify the interaction of Tcf-4 with beta-catenin but reduces its association to plakoglobin. | Experiments performed using a Tcf-4 mutant with decreased interaction to plakoglobin demonstrated that binding to this protein negatively affected the transcriptional activity of Tcf-4. | SIGNOR-251044 |
P30874 | P08754 | 2 | binding | up-regulates activity | 0.45 | 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-256827 |
O43293 | P38936 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.316 | ZIP kinase phosphorylates p21(WAF1) at Thr145 and alanine-substituted mutations in the p21(WAF1) phosphorylation site alter its ability to be phosphorylated by ZIP kinase. | Transfected ZIPK can promote the phosphorylation of p21(WAF1) at Thr145 in vivo and can increase the half-life of p21(WAF1) | SIGNOR-251085 |
P37231 | Q00987 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.389 | Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase. | SIGNOR-277191 |
Q8IZD2 | O95944 | 2 | binding | up-regulates activity | 0.505 | We identify natural cytotoxicity receptor NKp44 (NKp44L), a novel isoform of the mixed-lineage leukemia-5 protein, as a cellular ligand for NKp44. Unlike the other MLL family members, NKp44L is excluded from the nucleus, but expressed at the cell-surface level; its subcellular localization is being associated with the presence of a specific C-terminal motif. Strikingly, NKp44L has not been detected on circulating cells isolated from healthy individuals, but it is expressed on a large panel of the tumor and transformed cells. | SIGNOR-260045 |
Q15831 | P43268 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.622 | LKB1 phosphorylated PEA3 and promoted its degradation through a proteasome-mediated mechanism. | SIGNOR-279293 |
P14859 | P78527 | 0 | phosphorylation | down-regulates | 0.33 | Through a similar strategy, t226 and s232 were characterized as the dna-pk phosphorylation sites | SIGNOR-53258 |
P38405 | Q96LB1 | 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-256930 |
Q8NHW3 | P28482 | 0 | phosphorylation | up-regulates activity | 0.334 | These residues are phosphorylated by erk2 but not by p38, jnk, and erk5 in vitro. However, the contribution of the mek/erk pathway to mafa phosphorylation in vivo appears to be moderate, implicating another kinase. The integrity of serine 14 and serine 65 residues is required for transcriptional activity, since their mutation into alanine severely impairs mafa capacity to activate transcription. | SIGNOR-108564 |
Q04721 | O00548 | 2 | binding | up-regulates | 0.636 | In this study, we demonstrate that dll1 can activate notch signaling mostly through notch2 receptor and can contribute to drug resistance to bortezomib, both in murine and human mm cells. | SIGNOR-199320 |
Q6UXX9 | Q9ULV1 | 1 | ubiquitination | down-regulates quantity | 0.313 | Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. | SIGNOR-260117 |
O15550 | P31269 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.323 | 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-260025 |
P49761 | Q92995 | 1 | phosphorylation | up-regulates activity | 0.2 | CLK3 directly phosphorylated USP13 at Y708, which promoted its binding to c-Myc, thereby preventing Fbxl14-mediated c-Myc ubiquitination and activating the transcription of purine metabolic genes. | SIGNOR-274122 |
Q9Y653 | P02461 | 2 | binding | up-regulates activity | 0.2 | Using the N-terminal fragment of GPR56 (GPR56(N)) as a probe, we have recently demonstrated that collagen III is the ligand of GPR56 in the developing brain. In this report, we discover a new functional domain in GPR56(N), the ligand binding domain. | SIGNOR-253979 |
Q13315 | Q96P70 | 1 | phosphorylation | up-regulates activity | 0.2 | In line with our previous results, IR exposure induced the nuclear accumulation of RanBP9, which was prevented by ATM inhibition using KU-55933.|Taken together these data indicate that RanBP9 is a novel target of ATM and that ATM phosphorylates at least two different residues (S181 and S603) of RanBP9 following IR exposure. | SIGNOR-278910 |
Q9UHD2 | Q96AQ6 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.29 | Phosphorylation of HPIP on serine 147 by TBK1 promotes E2-mediated GREB1 expression. Accordingly, we identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1. | SIGNOR-273643 |
P07948 | P00533 | 2 | phosphorylation | up-regulates activity | 0.586 | Taken together, our findings demonstrate that Yes and Lyn phosphorylate EGFR at Y1101 which influences EGFR nuclear translocation in this model of cetuximab resistance. | SIGNOR-279205 |
P07333 | O60716 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.27 | In our study, CSF-1R induced the tyrosine phosphorylation of p120 Y904 and Y228 in a SRC-dependent manner ( xref ). | SIGNOR-278929 |
P53779 | O43521 | 1 | phosphorylation | up-regulates activity | 0.689 | JNKs specifically phosphorylate BIMEL at Ser55, 65, and/or 73. several observations demonstrate that the phosphorylation of BIMEL is a physiologically important mechanism for enhancing its proapoptotic activity. | SIGNOR-250130 |
P10644 | Q13976 | 0 | phosphorylation | up-regulates activity | 0.234 | In this study, we further examined the potential of RIα phosphorylation to regulate physiologically relevant "desensitization" of PKAc activity. First, the serine 101 site of RIα was validated as a target of PKGIα phosphorylation both in vitro and in cells.These findings suggest that RIα phosphorylation may be a novel mechanism to circumvent the requirement of cAMP stimulus to activate type I PKA in cells. | SIGNOR-277383 |
P35240 | Q96PU5 | 0 | ubiquitination | up-regulates activity | 0.261 | Merlin ubiquitination is mediated by the E3 ubiquitin ligase, NEDD4L, which requires a scaffold protein, AMOTL1, to approach Merlin. Several NF2-patient-derived Merlin mutations disrupt its binding to AMOTL1 and its regulation by the AMOTL1-NEDD4L apparatus. Lysine (K) 396 is the major ubiquitin conjugation residue. Disruption of Merlin ubiquitination by the K396R mutation or NEDD4L depletion diminishes its binding to Lats1 and inhibits Lats1 activation. These effects are also accompanied by loss of Merlin's anti-mitogenic and tumor suppressive properties. Thus, we propose that dephosphorylation and ubiquitination compose an intramolecular relay to activate Merlin functions in activating the Hippo pathway during growth control. | SIGNOR-263662 |
Q9P0L2 | P10636 | 1 | phosphorylation | down-regulates activity | 0.429 | We have studied the relationship between the phosphorylation of tau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. MARK and PKA phosphorylate several sites within the repeats (notably the KXGS motifs including Ser262, Ser324, and Ser356, plus Ser320). This type of phosphorylation strongly reduces tau's affinity for microtubules, and at the same time inhibits tau's assembly into PHFs. | SIGNOR-250173 |
Q9NZS9 | Q14790 | 2 | binding | down-regulates | 0.37 | We also demonstrate that the mitochondrial protein bar, which has been shown to simultaneously bind caspase-8 and bcl-2 | SIGNOR-112585 |
P01106 | P06733 | 2 | transcriptional regulation | up-regulates quantity | 0.411 | C-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway. | SIGNOR-259989 |
P62993 | Q07890 | 2 | binding | up-regulates | 0.88 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. | SIGNOR-175180 |
Q9NVW2 | Q86U70 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.566 | Here we identify RLIM as a ubiquitin protein ligase that is able to target CLIM cofactors for degradation through the 26S proteasome pathway. | SIGNOR-272617 |
Q14938 | Q13562 | 1 | transcriptional regulation | up-regulates quantity | 0.265 | 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-268904 |
Q9UGP5 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.354 | We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ. | SIGNOR-273836 |
P17252 | P49407 | 1 | phosphorylation | up-regulates activity | 0.2 | We demonstrate that β-arrestin-1 recruitment to the TCR, and bystander TCR and CXCR4 downregulation, are mechanistically mediated by the TCR-triggered PKC-mediated phosphorylation of β-arrestin-1 at Ser163. | SIGNOR-276619 |
P83916 | 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-264492 |
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