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 |
|---|---|---|---|---|---|---|---|
Q9NR82 | P17612 | 0 | phosphorylation | up-regulates activity | 0.2 | We conclude that phosphorylation of S53 on the amino terminus of Kv7.5 is essential for PKA-dependent enhancement of channel activity in response to βAR activation in vascular and airway smooth muscle cells. | SIGNOR-265980 |
O43815 | P62714 | 2 | binding | up-regulates activity | 0.595 | The striatin family proteins interact with the structural (A) and catalytic (C) subunits of the protein phosphatase, PP2A, and are also termed the B‴ family of PP2A subunits (4). Within heterotrimeric PP2A complexes, striatins function as one of many regulatory B subunits thought to be responsible for substrate selection and localization of PP2A isoforms | SIGNOR-261700 |
Q06187 | P19174 | 1 | phosphorylation | up-regulates activity | 0.581 | Then, BTK and ITK are activated by Src kinases and proceed to phosphorylate the lipase PLCgamma2 / PLCgamma1, which cleaves PIP2 in the plasma membrane and generates the secondary messengers IP3 and DAG. | SIGNOR-279444 |
P04637 | P36873 | 0 | dephosphorylation | down-regulates activity | 0.318 | Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities|In addition, our results reveal that one of the molecular mechanisms by which PP-1 promotes cell survival is to dephosphorylate p53, and thus negatively regulate p53-dependent death pathway. | SIGNOR-248499 |
P17612 | P15924 | 1 | phosphorylation | down-regulates activity | 0.328 | HeLa cells treated with forskolin indicated that stimulation of protein kinase A in transfected cells could decrease the interaction of DP.AN.SerC23 with keratin IF networks. phosphorylation of Ser-C23 could destabilize interactions that occur either directly through this 20 residue sequence or that are dependent on its correct conformation | SIGNOR-250353 |
Q16620 | Q6UB99 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Ankrd11 knockdown decreases the levels of bdnf and Trkb mRNAs. Next, we examine whether ANKRD11 accesses the Trkb promoter in cortical neurons. We performed the chromatin immunoprecipitation assay (ChIP) using an ANKRD11 antibody followed by PCR to amplify the Trkb promoter region. We found that ANKRD11 binds to the Trkb promoter (Fig. 6E). As expected, the level of ANKRD11 binding was decreased in the Ankrd11 knockdown condition. | SIGNOR-266731 |
Q9Y6W8 | P27986 | 2 | binding | up-regulates activity | 0.497 | ICOS ligation in concert with TCR stimulation results in strong PI3K activation in T lymphocytes. The ICOS cytoplasmic tail contains an YMFM motif that binds the p85alpha subunit of class IA PI3K, similar to the YMNM motif of CD28, suggesting a redundant function of the two receptors in PI3K signaling. | SIGNOR-272539 |
O43613 | P30679 | 2 | binding | up-regulates activity | 0.449 | 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-257354 |
Q9H0X6 | P11474 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Furthermore, RNF208 was induced by 17β-estradiol (E2) treatment in an estrogen receptor alpha (ΕRα)-dependent manner | SIGNOR-269052 |
Q99062 | P09919 | 2 | binding | up-regulates | 0.766 | The gcsf:gcsf-r complex formed a 2:2 stoichiometry by means of a cross-over interaction between the ig-like domains of gcsf-r and gcsf. the ig-like domain cross-over structure necessary for gcsf-r activation is consistent with previously reported thermodynamic and mutational analyses. | SIGNOR-144743 |
P42224 | O60674 | 0 | phosphorylation | up-regulates | 0.806 | Phosphorylation at tyr701 by the janus family of tyrosine kinases (jak) leads to stat1 dimerization via its src homology 2 domains, exposure of a dimer-specific nuclear localization signal, and subsequent nuclear translocation. | SIGNOR-235709 |
P07954 | O96013 | 0 | phosphorylation | down-regulates quantity | 0.2 | FH is massively phosphorylated at the Ser 46 by PAK4 in non-small cell lung cancer (NSCLC) cells, and PAK4-phosphorylated FH binds to 14-3-3, resulting in cytosolic detention of FH and prohibition of FH/CSL/p53 complex formation. | SIGNOR-266315 |
P30411 | P63096 | 2 | binding | up-regulates activity | 0.385 | 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-256695 |
Q9Y3S1 | O95198 | 2 | binding | down-regulates quantity by destabilization | 0.44 | We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body. | SIGNOR-272120 |
P17676 | P21291 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We conclude that c-Rel regulates CRP expression without the requirement of binding to a kappaB site, and binds directly to C/EBPbeta to facilitate the binding of C/EBPbeta to the CRP promoter | SIGNOR-254049 |
P15311 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.464 | Increased ezrin expression and activation by CDK5 coincident with acquisition of the senescent phenotype. | SIGNOR-250665 |
P14138 | P23946 | 0 | cleavage | up-regulates activity | 0.374 | Chymase from human mast cells selectively cleaved big endothelins (ETs) at the Tyr31-Gly32 bond and produced novel trachea-constricting 31-amino acid-length endothelins, ETs(1-31), without any further degradation products. | SIGNOR-256355 |
P04637 | Q86XK2 | 0 | neddylation | down-regulates | 0.671 | Fbxo11 promotes the neddylation of p53 and inhibits its transcriptional activity / we found that fbxo11 also neddylates p53 on two lysines, lys-320 and lys-321 | SIGNOR-150669 |
P0C725 | Q92985 | 2 | binding | down-regulates activity | 0.2 | EBV LF2 tegument protein specifically interacts with the central inhibitory association domain of IRF7, and this interaction leads to inhibition of the dimerization of IRF7, which suppresses IFN-alpha production and IFN-mediated immunity. | SIGNOR-266632 |
Q6PGQ7 | P53350 | 2 | phosphorylation | up-regulates | 0.788 | Bora/aurora-a-dependent phosphorylation is a prerequisite for plk1 to promote mitotic entry after a checkpoint-dependent arrest. | SIGNOR-179425 |
P08912 | P19086 | 2 | binding | up-regulates activity | 0.253 | 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-257125 |
Q00535 | F7VJQ1 | 1 | phosphorylation | up-regulates quantity | 0.332 | Cdk5 phosphorylated PrP induces the aggregation of non phosphorylated PrP.|Together, these results indicate that S43 is a major Cdk5 phosphorylation site in PrP. | SIGNOR-278920 |
Q9UK22 | O00459 | 2 | binding | down-regulates quantity by destabilization | 0.2 | FBXL2 interacts with the pool of p85β that is free of p110 PI(3)K catalytic subunits and targets this pool for ubiquitylation and subsequent proteasomal degradation. | SIGNOR-271936 |
O75460 | Q9NX47 | 0 | ubiquitination | down-regulates activity | 0.2 | MITOL promotes K63-linked chain ubiquitination of IRE1\u03b1 at lysine 481 (K481), thereby preventing hyper-oligomerization of IRE1\u03b1 and regulated IRE1\u03b1-dependent decay (RIDD). | SIGNOR-278609 |
P19484 | P42345 | 0 | phosphorylation | down-regulates activity | 0.477 | Our data points to the lysosome as the site where mTORC1-dependent phosphorylation of TFEB occurs. [...]Our study has revealed a specific role for phosphorylation of TFEB S211 in the negative regulation of the nuclear abundance of TFEB. This occurs through the promotion of 14-3-3 binding and the masking of the nearby NLS on TFEB. | SIGNOR-248270 |
P49810 | P55210 | 0 | cleavage | up-regulates activity | 0.318 | In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329. | SIGNOR-261751 |
Q14247 | P18031 | 0 | dephosphorylation | up-regulates activity | 0.516 | We conclude that Mena INV promotes invadopodium maturation by inhibiting normal dephosphorylation of cortactin at tyrosine 421 by the phosphatase PTP1B. | SIGNOR-277027 |
P24941 | Q96EB6 | 1 | phosphorylation | up-regulates activity | 0.465 | Sirt1 is in turn phosphorylated by Cdk2, which may further regulate its activity.|Taken together, these data demonstrate that Cdk2 deletion does not decrease Hif1\u03b1 expression induced by HX, and strongly suggests that the phosphorylation of Sirt1 at Ser47 by Cdk2 requires Sirt1 deacetylase activity. | SIGNOR-279513 |
Q15418 | P03372 | 1 | phosphorylation | up-regulates | 0.494 | Serine 167 is the major phosphorylation site on the human estrogen receptor. Phosphorylation is mediated by casein kinase ii. | SIGNOR-34113 |
Q15759 | Q15672 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness. this ser 68 is phosphorylated by p38, c-jun n-terminal kinases (jnk), and extracellular signal-regulated kinases1/2 in vitro | SIGNOR-173405 |
P42336 | Q92569 | 2 | binding | up-regulates | 0.846 | The region between the src homology 2 (sh2) domains of p55pik bound to the nh2 terminus region of p110alpha | SIGNOR-53597 |
P01111 | P49842 | 0 | phosphorylation | up-regulates activity | 0.306 | STK19 Phosphorylates NRAS Protein at Serine 89|STK19 phosphorylates NRAS to enhance its binding to its downstream effectors and promotes oncogenic NRAS-mediated melanocyte malignant transformation.| | SIGNOR-264566 |
P28702 | P10589 | 2 | binding | up-regulates | 0.274 | Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site | SIGNOR-79449 |
Q13188 | P53350 | 0 | phosphorylation | down-regulates activity | 0.331 | We conclude that TRIM69A promotes multi-site phosphorylation of MST2.We demonstrate that TRIM69 stimulates formation of an MST2-PLK1 complex and promotes phosphorylation of MST2 at S15, a known PLK1 site. PLK1-mediated MST2 phosphorylation at S15 is necessary for subsequent phosphorylation of NEK2A to dissociate c-NAP1 from daughter centrioles (7). Thus, we provide a new molecular mechanism by which TRIM69 promotes MST2- and PLK1-mediated centrosome disjunction. | SIGNOR-277904 |
Q16665 | Q00987 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.643 | We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1alpha subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation. | SIGNOR-271385 |
Q9Y261 | P80370 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.332 | Taken together, these data suggest that Foxa-2 is a direct transcriptional activator of the Pref-1 gene. | SIGNOR-254971 |
Q92597 | O00141 | 0 | phosphorylation | up-regulates | 0.569 | Transient expression of active (sgk1-s422d) and inactive (sgk1-k127a) sgk1 mutants confirmed that activating sgk1 stimulates ndrg1-thr(346/356/366) phosphorylation. dexamethasone (0.2 mum) acutely activated sgk1 and the peak of this response (2-3 h) coincided with the induction of g (na), and both responses were pi3k-dependent. While these data suggest that sgk1 might mediate the rise in g (na), transient expression of the inactive sgk1-k127a mutant did not affect the hormonal induction of g (na) but did suppress the activation of sgk1. | SIGNOR-180821 |
Q969H0 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.425 | In response to ionizing radiation, ATM phosphorylates FBXW7 at serine 26 to recruit it to DNA double-strand break (DSB) sites, whereas activated DNA-PKcs phosphorylates XRCC4 at serines 325/326, which promotes binding of XRCC4 to FBXW7 | SIGNOR-259942 |
P21579 | Q8WXE9 | 2 | binding | up-regulates quantity | 0.777 | the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively .Stonin-2 and AP-2 are also Required for Efficient Synaptotagmin-1 Retrieval. the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively. | SIGNOR-264115 |
Q9Y463 | P24385 | 1 | phosphorylation | down-regulates | 0.41 | Further, we found that not only gsk-3beta but also dyrk1b modulates cyclin d1 subcellular localization by the phosphorylation of thr(288). These results suggest that dif-3 induces degradation of cyclin d1 through the gsk-3beta- and dyrk1b-mediated threonine phosphorylation in hela cells | SIGNOR-150126 |
P06493 | P06748 | 1 | phosphorylation | down-regulates activity | 0.518 | However, under the experimental conditions used here, the t199 residue was the most likely candidate to be phosphorylated by cyclin b/cdc2 these results strongly support the concept that the rna binding activity of b23.1 is inactivated by cyclin b/cdc2-mediated phosphorylation. | SIGNOR-89605 |
O95071 | P23193 | 2 | binding | up-regulates | 0.358 | We show that the e3 ubiquitin ligase ubr5 associates with the cdk9 subunit of positive transcription elongation factor b to mediate its polyubiquitination in human cells. Tfiis also binds ubr5 to stimulate cdk9 polyubiquitination. | SIGNOR-170258 |
Q15746 | P17481 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively | SIGNOR-261640 |
Q15596 | P50750 | 0 | phosphorylation | up-regulates activity | 0.246 | Interestingly, GRIP1 is phosphorylated at an N-terminal serine cluster by cyclin-dependent kinase-9 (CDK9), which is recruited into GC-induced GR:GRIP1:CDK9 hetero-complexes, producing distinct GRE-specific GRIP1 phospho-isoforms. Phosphorylation potentiates GRIP1 coactivator but, remarkably, not its corepressor properties. | SIGNOR-256098 |
P06493 | O00429 | 1 | phosphorylation | up-regulates activity | 0.466 | Drp1 is phosphorylated at the Ser616 position and activated predominantly by CDK1. | SIGNOR-279394 |
P31260 | Q15910 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.438 | 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-260070 |
P17612 | P16144 | 1 | phosphorylation | down-regulates | 0.2 | Additionally, we show that s1360 and s1364 of beta4 are the only residues phosphorylated by pkc and pka in cells, respectivelywe have defined three regions on beta4 that together harbor all the serine and threonine phosphorylation sites and show that three serines (s1356, s1360, and s1364), previously implicated in hd regulation, prevent the interaction of beta4 with the plectin actin-binding domain when phosphorylated | SIGNOR-156873 |
P42681 | P42681 | 2 | phosphorylation | up-regulates | 0.2 | Evidence of autophosphorylation in txk: y91 is an autophosphorylation site. the results suggest that phosphorylated txk is an active form to promote ifn-gamma synthesis | SIGNOR-89844 |
P06239 | P51692 | 1 | phosphorylation | up-regulates activity | 0.643 | A constitutively active Lck kinase promotes cell proliferation and resistance to apoptosis through signal transducer and activator of transcription 5b activation.|Expression of the active Lck kinase induces both tyrosine phosphorylation and DNA binding activity of signal transducer and activator of transcription 5b (STAT5b), a STAT family member activated in a variety of tumor cells. | SIGNOR-279056 |
P04626 | Q05397 | 1 | phosphorylation | up-regulates activity | 0.657 | HER2, EGFR, and additional RTKs directly phosphorylate FAK FERM at Y397.|To further confirm the mechanism of direct FAK activation by HER2, we performed a series of GST pull-down assays with purified recombinant proteins. | SIGNOR-278475 |
O15530 | P31749 | 1 | phosphorylation | up-regulates | 0.748 | We have partially purified a kinase from brain extract that phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that is immunoprecipitated with PDK1 antibodies. | SIGNOR-67367 |
P02647 | P00738 | 2 | binding | up-regulates quantity by stabilization | 0.726 | Haptoglobin binding to apolipoprotein A-I prevents damage from hydroxyl radicals on its stimulatory activity of the enzyme lecithin-cholesterol acyl-transferase. haptoglobin, when circulating at enhanced levels with free Hb during the acute phase of inflammation, might protect ApoA-I structure and function against hydroxyl radicals. | SIGNOR-252106 |
P35236 | P27361 | 0 | phosphorylation | up-regulates activity | 0.693 | First, Erk phosphorylates HePTP at residues Thr45 and Ser72. Second, HePTP dephosphorylates Erk at PTyr185.| | SIGNOR-249475 |
O60566 | Q02224 | 2 | binding | up-regulates activity | 0.846 | Without CENP-E, diminished levels of BubR1 are recruited to kinetochores and BubR1 kinase activity remains at basal levels. CENP-E binds to and directly stimulates the kinase activity of purified BubR1 in vitro. Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal. | SIGNOR-252043 |
P08754 | P25116 | 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-256875 |
Q15418 | Q15418 | 2 | phosphorylation | up-regulates activity | 0.2 | Herein, we demonstrate that the n-terminal kinase domain (ntk) of rsk1 is necessary for interactions with pkarialpha. Substitution of the activation loop phosphorylation site (ser-221) in the ntk with the negatively charged asp residue abrogated the association between rsk1 and pkarialpha. | SIGNOR-162681 |
Q9Y6I7 | Q9H2X6 | 1 | ubiquitination | down-regulates | 0.568 | Ubiquitination and degradation of homeodomain-interacting protein kinase 2 by wd40 repeat/socs box protein wsb-1 | SIGNOR-160032 |
Q04206 | Q13315 | 0 | phosphorylation | down-regulates activity | 0.502 | Interestingly, another group has identified that in the VP-16 induced NF-\u03baB activation, ATM binds to RelA directly and phosphorylates RelA on Ser 547, a post-translational modification that represses a subset of NF-\u03baB-dependent genes ( xref ).|Our findings that ablation of ATM reduces RelA serine 276 phosphorylation, suggests a mechanism for how ROS mediates RelA serine 276 phosphorylation in the TNF pathway (Figure -D). | SIGNOR-279006 |
Q9BYT3 | P32754 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation. | SIGNOR-272958 |
Q96DA2 | Q9NRD5 | 2 | binding | up-regulates activity | 0.374 | GTP-bound RAB39B interacts with PICK1. In line with evidence that PICK1 can dimerize, the structural model suggests that dimerization of PICK1 is a prerequisite for simultaneous recognition of both RAB39B and GluA2 each by one of the PICK1 molecules in the PICK1 dimer (Fig. 6a–c). The existence of such complex is supported by our co-immunoprecipitation experiments shown above. | SIGNOR-264045 |
P46527 | P54753 | 0 | phosphorylation | down-regulates activity | 0.2 | In accord with this concept are the findings of Vlach et al. , who have studied point mutants of p27 deficient in their interactions with EK2, and have found that T187 phosphorylation of p27 by EK2 requires an interaction of p27 with the cyclin E subunit, while inhibition of the kinase activity requires an additional interaction with the CDK2 subunit.|The question considered here is the theoretical question whether deactivation of p27 by EK2 can produce binary EK2 release, and if so what biochemical kinetic features are required for this behavior. | SIGNOR-279406 |
Q92915 | P19784 | 0 | phosphorylation | up-regulates activity | 0.307 | Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents. | SIGNOR-275741 |
Q15139 | Q9GZY8 | 1 | phosphorylation | up-regulates activity | 0.2 | PKD directly phosphorylates MFF on serines 155, 172, and 275 | SIGNOR-277559 |
P11309 | O43524 | 1 | phosphorylation | down-regulates activity | 0.387 | Pim1s expression induced the phosphorylation of foxo3a (fig. 5a and b) and inactivated its transcriptional activity (fig. 5c). A previous report showed that phosphorylation at t32, s253, and s315 residues in foxo3a induced 14-3-3 binding, nuclear export, and proteasomemediated degradation (42). | SIGNOR-179308 |
P31749 | Q05195 | 1 | phosphorylation | down-regulates | 0.363 | Here, we present evidence that akt inhibits mad1-mediated transcription repression by physical interaction with and phosphorylation of mad1. | SIGNOR-252525 |
P35568 | O14920 | 0 | phosphorylation | down-regulates activity | 0.654 | IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways. | SIGNOR-251297 |
Q15019 | P68400 | 0 | phosphorylation | down-regulates | 0.2 | Here we show that human septin 2 is phosphorylated in vivo at ser218 by casein kinase ii. Septin 2 binds and hydrolyses gtp. The purified protein has the capacity to polymerize into long filaments when loaded with gtp or gdp. Moreover, we show that the endogenous protein in hela cells, like that produced in insect cells, is phosphorylated by casein kinase ii and that this phosphorylation alters nucleotide binding. | SIGNOR-148010 |
Q14344 | Q9Y653 | 2 | binding | up-regulates activity | 0.2 | Binding of collagen III to ADGRG1 provides a canonical example of adhesion GPCR interactions with ECM proteins (Luo et al., 2011). Identified by an in vitro biotinylation/proteomics approach, extracellular interactions with collagen III were subsequently proven capable of activating ADGRG1-mediated signaling via Gα12/13 followed by RhoA activation to regulate corticogenesis | SIGNOR-272345 |
P10275 | Q15858 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In neuroblastoma ND7 cells, a nuclear interaction between the developmentally regulated transcription factor Brn-3a and AR resulted in a complex which bound to multiple elements within the promoter region of SCN9A (Nav1.7) and upregulated channel expression. | SIGNOR-253466 |
P15056 | P00519 | 1 | phosphorylation | up-regulates activity | 0.275 | BRAF V600E activates Abl and Arg.|Rather, BRAF V600E, a serine threonine kinase, induced Abl threonine phosphorylation (XREF_FIG), and tyrosine phosphorylation of kinase-inactive Abl or Arg, which lack the ability to autophosphorylate (XREF_FIG). | SIGNOR-278914 |
P63000 | Q13177 | 2 | binding | up-regulates activity | 0.75 | A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways. | SIGNOR-248250 |
Q9NP77 | Q96GD4 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.254 | Here we report that Aurora B kinase directly interacts with and phosphorylates Ssu72, a new cohesin-binding phosphatase, at Ser 19 in vitro and in vivo. The Aurora B-mediated phosphorylation of Ssu72 causes the structural modification of Ssu72 protein, downregulates phosphatase activity and triggers the ubiquitin-dependent degradation of Ssu72. | SIGNOR-275529 |
Q96A26 | Q16665 | 0 | 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 |
Q8TAQ5 | Q12888 | 2 | binding | down-regulates activity | 0.2 | These results indicate that Apak is a genuine substrate of ATM kinase. Apak phosphorylation on Ser 68 is critical for p53-mediated apoptosis. in response to DNA damage, ATM is rapidly activated by autophosphorylation and mediates p53 activation through disruption of the Apak–p53 complex by phosphorylating Apak on Ser 68. | SIGNOR-273512 |
P17252 | Q9UQ13 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PKCalpha/delta phosphorylate Sur8 at Thr-71 and Ser-297, respectively. This phosphorylation is essential for polyubiquitin-dependent degradation of Sur8. | SIGNOR-275568 |
Q92813 | Q9Y385 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.379 | ER residency places D2 physically close to an array of proteins that interact and modify the D2 molecule via ubiquitination and targeting to the proteasomal system, explaining its relatively short half-life. Both ubiquitin conjugases UBC6 and or UBC7 interact with D2 and support D2 ubiquitination. Two Lys residues in D2 are involved in this process, K237 and K244. | SIGNOR-267481 |
Q9NV58 | Q9Y6H5 | 1 | ubiquitination | up-regulates quantity | 0.453 | Ubiquitylation of synphilin-1 by Dorfin. A, synphilin-1 is ubiquitylated in HEK293 cells. Several lines of evidence have suggested that derangements in the ubiquitin-proteasome protein degradation pathway may have a prominent role in the pathogenesis of PD (5). Our present study shows that Dorfin, an E3 ubiquityl ligase, is colocalized with ubiquitin in LBs of PD and physically binds to ubiquitylate synphilin-1, which is known to be a major component of LBs | SIGNOR-271455 |
P31749 | P45983 | 0 | phosphorylation | up-regulates activity | 0.427 | We report that JNKs are necessary for the reactivation of Akt after ischemic injury. We identified Thr450 of Akt as a residue that is phosphorylated by JNKs, and the phosphorylation status of Thr450 regulates reactivation of Akt after hypoxia, apparently by priming Akt for subsequent phosphorylation by 3-phosphoinositide-dependent protein kinase. | SIGNOR-252426 |
Q02577 | Q8TAP4 | 2 | binding | up-regulates activity | 0.411 | Here we found that LMO3 forms a complex with HEN2 and acts as an upstream mediator for transcription of Mash1 in neuroblastoma. | SIGNOR-254827 |
P32239 | P30679 | 2 | binding | up-regulates activity | 0.509 | 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-257412 |
P05412 | P45984 | 2 | binding | up-regulates | 0.884 | C-jun is targeted for ubiquitination by its association with inactive c-jun nh2-terminal kinase (jnk).Phosphorylation By activated jnk protects c-jun from ubiquitination. | SIGNOR-53791 |
P06493 | Q16584 | 1 | phosphorylation | down-regulates activity | 0.2 | Using in vitro kinase assays and phosphomutants, we determined that CDK1 phosphorylates MLK3 on Ser548 and decreases MLK3 activity during mitosis, whereas CDK2 phosphorylates MLK3 on Ser770 and increases MLK3 activity during G1/S and G2 phases. | SIGNOR-277603 |
O00311 | Q8TEA8 | 1 | phosphorylation | up-regulates activity | 0.321 | 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-273967 |
Q86XI6 | Q6VVB1 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.398 | Here, we show that the laforin-malin complex downregulates PTG-induced glycogen synthesis in FTO2B hepatoma cells through a mechanism involving ubiquitination and degradation of PTG. We show here that laforin and malin play a crucial role in the regulation of glycogen biosynthesis in FTO2B hepatoma cells. In these cells, the laforin–malin complex counteracts the glycogenic effect of PTG because it promotes its ubiquitination and degradation. | SIGNOR-271728 |
P23560 | Q6UB99 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons. | SIGNOR-266732 |
P50148 | P30989 | 2 | binding | up-regulates activity | 0.471 | Altogether, these results reveal for the first time the ability of hNTS1 to directly activate the Gαq-, Gαi1-, GαoA-, and Gα13-mediated signaling pathways | SIGNOR-278058 |
P31749 | Q99497 | 1 | phosphorylation | up-regulates activity | 0.465 | Using a proteomic approach, we identified on DJ-1 a novel threonine phosphorylation (T125) that was found, by the in-silico tool scansite 4, as part of a putative Akt consensus. |Deglycase activity of DJ-1 on histones proteins, investigated by coupling 2D tau gel with LC-MS/MS and 2D-TAU (Triton-Acid-Urea)-Western blot, was found correlated with its phosphorylation status that, in turn, depends from Akt activation. | SIGNOR-275582 |
Q99504 | P16104 | 1 | dephosphorylation | down-regulates | 0.2 | Tyr142 is dephosphorylated by the tyr phosphatases eya1 and eya3. | SIGNOR-168927 |
P35670 | Q15139 | 0 | phosphorylation | up-regulates activity | 0.296 | ATP7B trafficking was markedly reduced by the Ser-478/481/1121/1453 to Ala mutation. We conclude that PKD plays a key role in copper-dependent serine phosphorylation, permitting high levels of ATP7B protein expression and trafficking. | SIGNOR-272295 |
P27361 | P17655 | 1 | phosphorylation | up-regulates | 0.565 | Epidermal growth factor activates m-calpain (calpain ii), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation.We now show that erk directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (egf)-induced calpain activation in vitro and in vivo. | SIGNOR-123083 |
P25103 | P09471 | 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-257249 |
P56159 | P39905 | 2 | binding | up-regulates | 0.8 | A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling | SIGNOR-49091 |
Q9Y613 | Q13464 | 0 | phosphorylation | up-regulates | 0.309 | Rock phosphorylates the c-terminal residues ser1131, ser1137, and thr1141 of formin homology domain protein 1 (fhod1). Phosphorylation of fhod1 at the three residues fully disrupts the autoinhibitory interaction, which culminates in formation of stress fibres. | SIGNOR-160548 |
P04049 | P06400 | 1 | phosphorylation | down-regulates activity | 0.578 | Further, Raf-1 was able to phosphorylate Rb in vitro quite efficiently.|Raf-1 can inactivate Rb function and can reverse Rb mediated repression of E2F1 transcription and cell proliferation efficiently. | SIGNOR-279481 |
P61586 | O43182 | 0 | gtpase-activating protein | down-regulates activity | 0.581 | 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-260462 |
P06493 | P50613 | 0 | phosphorylation | up-regulates | 0.581 | The mo15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (cdks) through phosphorylation of thr161 and its homologues | SIGNOR-38307 |
Q15797 | O96004 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation | SIGNOR-268936 |
Q05513 | P27448 | 1 | phosphorylation | down-regulates | 0.2 | Hpar-1a, t564, is phosphorylated in vivo and by apkc in vitro.This study establishes a novel functional link between two central determinants of cellular polarity, apkc and par-1, and suggests a model by which apkc may regulate par-1 in polarized cells | SIGNOR-124221 |
P62714 | P30153 | 2 | binding | up-regulates | 0.891 | Pr65/a acts as a scaffold protein for binding pp2ac and regulatory b subunits in a heterotrimeric holoenzyme | SIGNOR-138886 |
Q7Z6Z7 | O14757 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.298 | Taken together, these results are consistent with our hypothesis that HUWE1 directly poly-ubiquitinates and targets Chk1 to the proteasome. | SIGNOR-278568 |
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