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 |
|---|---|---|---|---|---|---|---|
P68400 | P30260 | 1 | phosphorylation | up-regulates | 0.378 | We report here that phosphorylation of cdc27, a core subunit of apc, in response to tgf- signaling can facilitate the activation of apc.we have demonstrated that casein kinase ii (ckii) is involved in the phosphorylation of cdc27 in response to tgf- signaling. | SIGNOR-170872 |
P28482 | P17655 | 1 | phosphorylation | up-regulates | 0.628 | 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-123079 |
P06493 | P38936 | 2 | binding | down-regulates | 0.881 | P21 and p27 are key inhibitors of both cdk1 and cdk2. | SIGNOR-128442 |
P16949 | P17612 | 0 | phosphorylation | down-regulates | 0.309 | Phosphorylation at either ser(16) or ser(63) strongly reduced or abolished the ability of stathmin to bind to and sequester soluble tubulin and its ability to act as a catastrophe factor by directly binding to the microtubules. The known in vivo phosphorylation sites of stathmin are ser-16 and ser-63 for cyclic amp-dependent protein kinase (pka). | SIGNOR-38318 |
P31749 | P04406 | 1 | phosphorylation | down-regulates activity | 0.582 | GAPDH is phosphorylated by protein kinase B (AKT) on T237, which prevents GAPDH nuclear translocation and suppresses GAPDH mediated apoptosis.|GAPDH is phosphorylated by protein kinase B (AKT) on T237, which prevents GAPDH nuclear translocation and suppresses GAPDH-mediated apoptosis ( ). | SIGNOR-280174 |
O75385 | A2RUS2 | 1 | phosphorylation | up-regulates activity | 0.435 | ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12. | SIGNOR-264731 |
Q8NER1 | Q02156 | 0 | phosphorylation | up-regulates activity | 0.2 | We found that mutation of S800 to alanine significantly reduced the PMA-induced enhancement of capsaicin-evoked currents and the direct activation of TRPV1 by PMA. Mutation of S502 to alanine reduced PMA enhancement of capsaicin-evoked currents, but had no effect on direct activation of TRPV1 by PMA. Conversely, mutation of T704 to alanine had no effect on PMA enhancement of capsaicin-evoked currents but dramatically reduced direct activation of TRPV1 by PMA. | SIGNOR-249232 |
P04406 | P31749 | 0 | phosphorylation | down-regulates activity | 0.582 | GAPDH is phosphorylated by protein kinase B (AKT) on T237, which prevents GAPDH nuclear translocation and suppresses GAPDH mediated apoptosis.|GAPDH is phosphorylated by protein kinase B (AKT) on T237, which prevents GAPDH nuclear translocation and suppresses GAPDH-mediated apoptosis ( ). | SIGNOR-280174 |
P49841 | Q68CJ9 | 1 | phosphorylation | down-regulates activity | 0.549 | It is possible that phosphorylation of CREBH by GSK3beta leads to altered CREBH conformation with a resulting decreased affinity toward the COPII coated transport complex.|Similarly, expression of dominant negative GSK3beta can rescue the decreased CREBH cleavage activity in the Bmal1 knockdown hepatocytes under the circadian clock (XREF_FIG), thus confirming that BMAL1 controls circadian regulated CREBH cleavage and activation through AKT and GSK3beta signaling in hepatocytes. | SIGNOR-279785 |
P28482 | P17676 | 1 | phosphorylation | up-regulates | 0.716 | Phosphorylation of cebpb at thr(235) peaked at 16 hours in il-1beta-stimulated cells. The mek inhibitor u0126 inhibited this phosphorylation and reduced mmp-1 gene induction. | SIGNOR-187798 |
P78317 | P61956 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.834 | Here we demonstrate that the RING-domain-containing ubiquitin E3 ligase, RNF4 (also known as SNURF), targets poly-SUMO-modified proteins for degradation mediated by ubiquitin. RNF4 depletion or proteasome inhibition led to accumulation of mixed, polyubiquitinated, poly-SUMO chains. PML protein accumulated in RNF4-depleted cells and was ubiquitinated by RNF4 in a SUMO-dependent fashion in vitro.RNF4 preferentially binds to and ubiquitinates SUMO-2 polymers over SUMO-2 monomers in vitro | SIGNOR-272640 |
Q9HCE7 | Q13485 | 1 | ubiquitination | down-regulates activity | 0.745 | Smurfs, which otherwise cannot directly bind to smad4, mediated poly-ubiquitination of smad4 in the presence of smad6 or smad7. Smad signaling is negatively regulated by inhibitory (i) smads and ubiquitin-mediated processes. | SIGNOR-236096 |
Q9UJT1 | Q8IYT4 | 2 | binding | down-regulates quantity by destabilization | 0.257 | Here we show that KATNAL2 is critical for numerous aspects of this developmental process, including the initiation of the axoneme from the basal body, suppression of the spermatid centriole duplication cycle, sperm nuclear sculpting via the manchette, the attachment of the acrosome to the nucleus and the tethering of elongated spermatids to Sertoli cells via the tubulobulbar complex and ultimately sperm release via spermiation. KATNAL2 does not sever microtubules composed of α- and β-tubulin but does interact with δ- and ε-tubulin | SIGNOR-267175 |
O94901 | P53350 | 0 | phosphorylation | down-regulates activity | 0.453 | Here, we show that SUN1, located in the INM, undergoes mitosis-specific phosphorylation on at least 3 sites within its nucleoplasmic N-terminus. We further identify Cdk1 as the kinase responsible for serine 48 and 333 phosphorylation, while serine 138 is phosphorylated by Plk1. Together, these data support a model whereby mitotic phosphorylation of SUN1 disrupts interactions with nucleoplasmic binding partners, promoting disassembly of the nuclear lamina and, potentially, its chromatin interactions. | SIGNOR-263098 |
Q92835 | P43405 | 1 | dephosphorylation | down-regulates activity | 0.418 | An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling. | SIGNOR-268456 |
P03372 | P00519 | 0 | phosphorylation | up-regulates | 0.446 | Eralpha can be phosphorylated on two sites, tyrosine 52 (y-52) and tyrosine 219 (y-219). Eralpha phosphorylation by c-abl stabilizes eralpha, resulting in enhanced eralpha transcriptional activity and increased expression of endogenous eralpha target genes. | SIGNOR-163562 |
P21731-2 | P35626 | 0 | phosphorylation | down-regulates activity | 0.2 | These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization. | SIGNOR-274091 |
P08754 | P30559 | 2 | binding | up-regulates activity | 0.448 | 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-257178 |
P51813 | P23470 | 0 | dephosphorylation | down-regulates activity | 0.26 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254693 |
Q9HC98 | P35613 | 1 | phosphorylation | down-regulates activity | 0.2 | These results indicate that NEK6 directly interacts with CD147 and phosphorylates the protein at serine-252 in Huh-7 cells. | SIGNOR-273882 |
P43320 | P02489 | 2 | binding | up-regulates activity | 0.2 | Aberrant protein interactions can lead to aggregation and insolubilization, such as occurs during cataract formation. Deamidation, a prevalent age-related modification in the lens of the eye, decreases stability of the major lens proteins, crystallins. Deamidation did not disrupt specific αA/βB2 interactions but favored aggregation before complex formation with αA. We conclude that deamidation contributes to cataract formation through destabilization of crystallins before they can be rescued by α-crystallin. | SIGNOR-252155 |
Q96P20 | Q9Y2R2 | 0 | dephosphorylation | up-regulates activity | 0.356 | Further, this explains how loss of PTPN22 and subsequent enhanced NLRP3 phosphorylation mediate a decrease in NLRP3 inflammasome activation.|Upon NLRP3 activation, PTPN22 dephosphorylates NLRP3 and thereby protects it from degradation, allowing robust inflammasome activity (summarized in Fig.S6). | SIGNOR-277056 |
P35568 | P28482 | 0 | phosphorylation | down-regulates activity | 0.68 | Rin beta-cells exposed to high glucose exhibited increased c-jun n-terminal kinase (jnk) and erk1/2 activity, which was associated with increased irs-1 phosphorylation at serine (ser)(307) and ser(612), respectively, that inhibits coupling of irs-1 to the insulin receptor and is upstream of the inhibition of irs-1 tyrosine phosphorylation. | SIGNOR-123173 |
P05556 | Q12809 | 2 | binding | up-regulates activity | 0.2 | One such mechanism is operant in colorectal cancer (CRC) cells. On integrin-dependent CRC cell adhesion, the Kv11.1/β1 integrin complex recruits the PI3K p85 subunit, which stimulates AKT phosphorylation and thus regulates autophagy | SIGNOR-277614 |
P30542 | P00813 | 2 | binding | up-regulates activity | 0.571 | The results show that human ADA, apart from reducing the adenosine concentration and thus preventing A(1)R desensitization, binds to A(1)R behaving as an allosteric effector that markedly enhances agonist affinity and increases receptor functionality. | SIGNOR-269105 |
Q9UNE7 | P56545 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.331 | Our data showed that CHIP depletion resulted in up-regulation of the steady-state level of CtBP2 ( Fig. 1 B) and that CHIP ubiquitinated CtBP2 for proteasomal degradation ( Fig. 3 A). | SIGNOR-278722 |
P43403 | Q13094 | 1 | phosphorylation | up-regulates | 0.804 | Zap-70 phosphorylates slp-76 at specific sites that allow vav sh2 domain bindingwe also show by in vitro and in vivo analysis that two slp-76 pyesp motifs (y113 and y128) mediate binding, the first being more efficient. | SIGNOR-46859 |
P15976 | Q9P286 | 0 | phosphorylation | up-regulates activity | 0.2 | In addition, we defined GATA1 Ser161, Ser187 were the main phosphorylation sites by PAK5. | SIGNOR-278297 |
O14757 | P31749 | 0 | phosphorylation | down-regulates | 0.43 | The chk1 protein phosphorylated by pkb on serine 280 does not enter into protein complexes after replication arrest. Moreover, chk1 phosphorylated by pkb fails to undergo activating phosphorylation on serine 345 by atm/atr. Phosphorylation by atm/atr and association with other checkpoint proteins are essential steps in activation of chk1. | SIGNOR-124365 |
P19544 | Q93008 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.2 | Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis. | SIGNOR-275614 |
P27361 | P37231 | 1 | relocalization | down-regulates activity | 0.398 | The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform | SIGNOR-179407 |
Q96T51 | P51813 | 0 | phosphorylation | up-regulates activity | 0.634 | Etk interacts with RUFY1 through its SH3 and SH2 domains. RUFY1 is tyrosine-phosphorylated and appears to be a substrate of Etk. Phosphorylation of the two tyrosine residues, Tyr-281 and Tyr-292, located in the linker region of the two coiled-coil domains by Etk seems to be critical for RUFY1 targeting to the endosomes. | SIGNOR-262679 |
P17612 | P01100 | 1 | phosphorylation | up-regulates activity | 0.518 | Human c-Fos protein is phosphorylated in vitro by PKA. phosphorylation of Fos occurs at serine residue 362. Modification of the Fos protein by phosphorylation with PKA then allows it to act as a regulator of its own synthesis by downregulating fos gene expression at a transcriptional level | SIGNOR-250356 |
Q96CG3 | P31749 | 0 | phosphorylation | up-regulates activity | 0.2 | For the activation of signal 2, Akt is involved in TIFA Thr9 phosphorylation, which is essential for TIFA-TIFA homophilic oligomerization. Thr9 phosphorylation-dependent TIFA oligomerization facilitates the higher-order assembly of NLRP3 inflammasome, as indicated by the interaction between TIFA and caspase-1 in the activated ECs. | SIGNOR-273542 |
Q13490 | Q12933 | 2 | ubiquitination | down-regulates quantity by destabilization | 0.873 | Traf3-binding receptors stabilize nik by activating ciap-dependent degradation of traf2 and traf3. | SIGNOR-182128 |
P25025 | P09341 | 2 | binding | up-regulates activity | 0.777 | CXCL1 produces cellular chemotactic activity by binding to the CXC chemokine receptor 2 (CXCR2). In PC, this chemokine has been associated with a variety of carcinogenic mechanisms, including oncogene-induced senescence (OIS), angiogenesis, cancer metastasis, and immunosuppressive microenvironments | SIGNOR-277717 |
P28335 | O95837 | 2 | binding | up-regulates activity | 0.435 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257295 |
P32239 | P63096 | 2 | binding | up-regulates activity | 0.274 | 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-257037 |
P09471 | P43115 | 2 | binding | up-regulates activity | 0.28 | 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-256995 |
Q01974 | Q15750 | 0 | phosphorylation | down-regulates | 0.278 | Tak1 (tgf-beta activated kinase 1), a map3k, interacts with ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich (stp) domain | SIGNOR-180566 |
P50616 | P28482 | 0 | phosphorylation | down-regulates | 0.354 | Tob is rapidly phosphorylated at ser 152, ser 154, and ser 164 by erk1 and erk2 upon growth-factor stimulation. | SIGNOR-88720 |
P28482 | P10636 | 1 | phosphorylation | down-regulates activity | 0.566 | Using nanoelectrospray mass spectrometry, we have undertaken an extensive comparison of phosphorylation in vitro by several candidate tau kinases, namely, JNK, p38, ERK2, and glycogen synthase kinase 3beta (GSK3beta). Between 10 and 15 sites were identified for each kinase. The three MAP kinases phosphorylated Ser202 and Thr205 but not detectably Ser199, whereas conversely GSK3beta phosphorylated Ser199 but not detectably Ser202 or Thr205. Phosphorylated Ser404 was found with all of these kinases except JNK. The MAP kinases may not be strictly proline specific: p38 phosphorylated the nonproline sites Ser185, Thr245, Ser305, and Ser356, whereas ERK2 was the most strict. All of the sites detected except Thr245 and Ser305 are known or suspected phosphorylation sites in paired helical filament-tau extracted from Alzheimer brains. Thus, the three MAP kinases and GSK3beta are importantly all strong candidates as tau kinases that may be involved in the pathogenic hyperphosphorylation of tau in Alzheimer's disease. | SIGNOR-249416 |
P28715 | P18074 | 2 | binding | up-regulates quantity by stabilization | 0.947 | The NER protein XPG was also found to associate with the TFIIH complex by interacting directly with XPD stabilizing the interaction between TFIIH and the CAK-XPD complex | SIGNOR-251974 |
P08047 | P78317 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.39 | Here, we identified RNF4 as the ubiquitin E3 ligase of Sp1. From in vitro and in vivo experiments, we found that sumoylated Sp1 can recruit RNF4 as a ubiquitin E3 ligase that subjects sumoylated Sp1 to proteasomal degradation. | SIGNOR-272720 |
Q9HD90 | Q9HCK8 | 0 | transcriptional regulation | down-regulates quantity | 0.2 | Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells | SIGNOR-268918 |
P29372 | Q9NRP7 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Here, we show that MID1 catalyzes the ubiquitination and proteasomal cleavage of the GLI3 regulator Fu. | SIGNOR-272466 |
Q9H2X6 | Q00987 | 1 | phosphorylation | down-regulates activity | 0.537 | HIPK2 inhibits both MDM2 gene and protein by, respectively, p53-dependent and independent regulations.|This p53-independent effect is likely mediated by HIPK2 catalytic activity and we found that HIPK2 phosphorylates MDM2 in vitro. | SIGNOR-279465 |
Q96BY2 | Q9HCM9 | 2 | binding | up-regulates quantity by stabilization | 0.483 | TRIM39 stabilizes MOAP-1 by inhibiting the poly-ubiquitination process of MOAP-1.In this study, we report the identification and characterization of TRIM39 as a binding partner of MOAP-1. TRIM39 is the first regulator of MOAP-1 protein stability identified. | SIGNOR-272911 |
P36402 | P35222 | 2 | binding | up-regulates | 0.759 | Activated dvl binds and inhibits the phosphorylation of beta catenin by gsk3beta/alfa, blocking beta catenin degradation (fig 2?2),), so that beta catenin accumulates and translocates to the nucleus, where it interacts with the t cell specific factor (tcf)/lymphoid enhancer binding factor 1 (lef-1) transcription factor and induces the transcription of target genes such as c-jun, c-myc, and cyclin d1 | SIGNOR-134282 |
Q9HCK4 | O94813 | 2 | binding | up-regulates activity | 0.863 | This observation suggests that Slit2 may require the Robo2 and Robo3 receptors in this process . Slit2 causes the miRNA miR-182 to release cofilin1 mRNA, potentiating cofilin1 local translation and resulting in growth cone collapse. The use of morpholinos or RNAi to knockdown robo2 and robo3 in X. laevis RGCs, would be useful to further confirm that Robo2 and Robo3 are the receptors involved in Slit2-dependent cofilin1 translation. | SIGNOR-268380 |
Q5S007 | Q99683 | 1 | phosphorylation | up-regulates activity | 0.325 | LRRK2 phosphorylated ASK1 at Thr832 that is adjacent to Thr845, which serves as an autophosphorylation site. | SIGNOR-277251 |
Q01518 | P49841 | 0 | phosphorylation | up-regulates activity | 0.253 | We found that GSK3 phosphorylates S307 and S309 by using inhibitors LiCl. Inhibition of GSK3beta can cause loss of cell polarity as well as accumulation of stress fibers. We propose that GSK3 regulates CAP1 through at least two mechanisms. First, GSK3 (and potentially other kinases) phosphorylate CAP1 at S309 and promote CAP1 localization to the cytosol. Second, phosphorylation at S309 affects protein-protein interactions with actin and cofilin. The loss of this phospho-regulation by GSK3 inhibition is expected to disrupt CAP1 function and actin dynamics. | SIGNOR-264822 |
P30307 | Q16539 | 0 | phosphorylation | down-regulates activity | 0.439 | P38 binds and phosphorylates Cdc25B at serines 309 and 361, and Cdc25C at serine 216; phosphorylation of these residues is required for binding to 14-3-3 proteins. | SIGNOR-250091 |
O75385 | P08237 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown). | SIGNOR-274035 |
Q13315 | P29372 | 1 | phosphorylation | up-regulates activity | 0.265 | ATM phosphorylates MPG at serine 172 (XREF_FIG).|In summary, our results show that ATM and MPG are directly associated in vitro and in vivo, phosphorylation of MPG at serine 172 is dependent on ATM and that of loss of phospho ATM reduces MPG glycosylase activity. | SIGNOR-279004 |
Q9H3R0 | P68431 | 1 | demethylation | down-regulates activity | 0.2 | As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation | SIGNOR-263864 |
P68400 | P12830 | 1 | phosphorylation | up-regulates activity | 0.401 | Casein kinase II phosphorylation of E-cadherin increases E-cadherin/beta-catenin interaction and strengthens cell-cell adhesion. | Under these conditions, phosphorylation of the E-cadherin double mutant S853A/S855A was reduced by 25% as compared with wt E-cadherin. | Expression of the E-cadherin double mutant S853A/S855A in NIH3T3 cells expressing Wnt-1 reduces cell-cell adhesion. | SIGNOR-250840 |
O00220 | Q5T0T0 | 0 | ubiquitination | down-regulates quantity | 0.2 | The collective data indicate that endogenous MARCH-8 ubiquitinates TRAIL-R1 to attenuate its cell surface expression. | SIGNOR-278570 |
P35222 | P00533 | 0 | phosphorylation | up-regulates activity | 0.773 | EGFR and TRKA effect on WNT3a mediated Topflash induction was abolished by U0126 or expression of dominant negative LRP6-5A mutant (XREF_FIG), demonstrating that both EGFR and TRKA signal via ERK and LRP6 pathway to upregulate WNT and beta-catenin signaling.|FGFR2, FGFR3, EGFR and TRKA Phosphorylate beta-catenin at Tyr142. | SIGNOR-278309 |
Q13153 | Q92934 | 1 | phosphorylation | down-regulates | 0.335 | Pak phosphorylates bad in vitro and in vivo on ser112 and ser136, resulting in a markedly reduced interaction between bad and bcl-2 or bcl-x(l) and the increased association of bad with 14-3-3tau. | SIGNOR-73533 |
P06737 | O15294 | 0 | glycosylation | up-regulates activity | 0.2 | O-GlcNAcylation at Ser-430 promotes PYGL activity | SIGNOR-267988 |
P56192 | Q9P2K8 | 0 | phosphorylation | down-regulates | 0.2 | Here we demonstrate that aimp3 is released from mrs by uv irradiation-induced stress. Dissociation was induced by phosphorylation of mrs at ser662 by general control nonrepressed-2 (gcn2) following uv irradiation. Substitution of ser662 to asp (s662d) induced a conformational change in mrs and significantly reduced its interaction with aimp3. This mutant possessed significantly reduced mrs catalytic activity because of loss of trna(met) binding, resulting in down-regulation of global translation. | SIGNOR-177648 |
Q16543 | O75385 | 0 | phosphorylation | down-regulates activity | 0.2 | Serine/Threonine Kinase Unc-51-like Kinase-1 (Ulk1) Phosphorylates the Co-chaperone Cell Division Cycle Protein 37 (Cdc37) and Thereby Disrupts the Stability of Cdc37 Client Proteins.|Ulk1-mediated phosphorylation of Ser-339 in Cdc37 compromised the recruitment of client kinases to a complex comprising Cdc37 and heat shock protein 90 (Hsp90) but only modestly affected Cdc37 binding to Hsp90. | SIGNOR-280158 |
P19174 | P43405 | 0 | phosphorylation | up-regulates activity | 0.775 | Syk isolated from antigen receptor-activated B cells phosphorylated PLC-gamma1 on Tyr-771 and the key regulatory residue Tyr-783 in vitro, whereas Lyn from the same B cells phosphorylated PLC-gamma1 only on Tyr-771. | SIGNOR-246576 |
P17612 | Q96PU5 | 1 | phosphorylation | down-regulates | 0.2 | Nedd4-2 was a substrate for phosphorylation by pka in vitro and in cells;three nedd4-2 residues were phosphorylated by pka and were required for camp to inhibit nedd4-2 (relative functional importance ser-327 > ser-221 > thr-246). | SIGNOR-128429 |
Q8TAQ5 | Q13315 | 0 | phosphorylation | down-regulates activity | 0.459 | 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-273513 |
Q2M2I8 | Q15208 | 0 | phosphorylation | up-regulates activity | 0.27 | We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation. AAK1 phosphorylation regulates dendrite branching and length | SIGNOR-263034 |
P09211 | P24723 | 0 | phosphorylation | up-regulates activity | 0.2 | Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently | SIGNOR-276014 |
P03372 | P28482 | 0 | phosphorylation | up-regulates | 0.671 | In several estrogen response element-containing genes, the s118a mutation strongly reduced induction by e(2), and u0126 did not further reduce expression. Here, we show that serines 104 (s104) and 106 (s106) are also phosphorylated by mapk in vitro and upon stimulation of mapk activity in vivo. | SIGNOR-156856 |
Q00535 | P40763 | 1 | phosphorylation | up-regulates | 0.402 | We report here that the cdk5/p35 complex associates with stat3 and phosphorylates stat3 on the ser-727 residue in vitro and in vivo. Ser phosphorylation of stat3 and transcription of stat3 target genes, such as c-fos and junb, in a cdk5-dependent manner. | SIGNOR-124325 |
P50613 | P03372 | 1 | phosphorylation | up-regulates | 0.413 | Activation of estrogen receptor alpha by s118 phosphorylation involves a ligand-dependent interaction with tfiih and participation of cdk7. | SIGNOR-81170 |
P06400 | P39687 | 2 | binding | down-regulates activity | 0.2 | We further demonstrate that pp32-Rb interaction inhibits the apoptotic activity of pp32 and stimulates proliferation. | SIGNOR-259083 |
Q8N608 | Q9NZV8 | 1 | relocalization | up-regulates activity | 0.533 | Coexpression of DPP10 changes the subcellular localization of Kv4.2 expressed in COS-7 cells by promoting surface trafficking.DPP10 accelerates Kv4.2 inactivation at high and low voltages | SIGNOR-269006 |
Q16539 | P10636 | 1 | phosphorylation | up-regulates | 0.316 | A large number of cytosolic proteins can be phosphorylated by p38 mapks, including phospholipase a2, the microtubule-associated protein tau, nhe-1, cyclin d1, cdk inhibitors, bcl2 family proteins, growth factor receptors or keratins. | SIGNOR-166611 |
P69905 | P14384 | 0 | cleavage | down-regulates activity | 0.2 | Both human plasma carboxypeptidase N (CPN) and membrane-bound carboxypeptidase M (CPM) released the C-terminal arginine (alpha-Arg141) of the alpha chain of human adult hemoglobin. Thus, the hydrolysis of hemoglobin by CPM and CPN demonstrated the contribution of the alpha-Arg141 residue to sustaining the tetrameric structure of hemoglobin and its normal oxygen affinity and vasoactivity. | SIGNOR-256507 |
Q9Y4C1 | Q16665 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.415 | 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-271568 |
O14965 | P53667 | 2 | phosphorylation | up-regulates activity | 0.262 | Because Aur-A phosphorylates and activates LIMK1 , we examined the activation status of LIMK1 during mitosis in cells treated with MLN8237.|Because Aur-A phosphorylates and activates LIMK1 [ xref ], we examined the activation status of LIMK1 during mitosis in cells treated with MLN8237. | SIGNOR-279799 |
P01100 | P14921 | 0 | transcriptional regulation | up-regulates quantity | 0.718 | Furthermore, the possible involvement of an Ets protein in the control of c-fos has interesting implications for proto-oncogene cooperation in cellular growth control. | SIGNOR-256495 |
P30304 | Q9P1W9 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.361 | The proteasome-dependent degradation of CDC25A, seen in this study upon PIM-2 over-expression, suggests that PIM-2 promotes CDC25A phosphorylation that triggers its ubiquitylation. | SIGNOR-279750 |
P35916 | P51812 | 1 | phosphorylation | down-regulates | 0.2 | Upon truncation of this c-terminal stretch, or mutation of the tyr-707 residue alone, autoinhibition is attenuated, and the kinase becomes constitutively active. Based on these findings we propose that phosphorylation of the tyr-707 represents a novel alternative regulatory mechanism for p90rsk activation. | SIGNOR-98708 |
P63215 | P42336 | 2 | binding | up-regulates | 0.385 | Gbetagamma subunits released from gi can activate pi3k (phosphoinositide 3-kinase), and can be therefore implicated in smo-dependent activation of akt | SIGNOR-145125 |
Q9NPH9 | Q9UHF4 | 2 | binding | up-regulates | 0.601 | The mrna expression level of il10, il19, il20, il22, il24, il26, il28b, il29 and their receptors il10ra, il10rb, il20ra, il20rb, il22ra1, il22ra2, il28ra was compared in skin biopsies of children and adults and in childrens' skin cells by quantitative real-time pcr (qrt-pcr). | SIGNOR-151920 |
P05129 | Q92686 | 1 | phosphorylation | up-regulates activity | 0.429 | Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM. | SIGNOR-248915 |
Q8IVH8 | P46940 | 1 | phosphorylation | up-regulates activity | 0.2 | GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration. | SIGNOR-277479 |
P28482 | P46695 | 1 | phosphorylation | up-regulates | 0.552 | Upon phosphorylation by erks, iex-1 acquires the ability to inhibit cell death induced by various stimuli. In turn, iex-1 potentiates erk activation in response to various growth factors. | SIGNOR-93740 |
Q99816 | Q6UWE0 | 0 | monoubiquitination | down-regulates quantity | 0.527 | Tal increases ubiquitylation of Tsg101 and affects its solubility in a RING- and PTAP-dependent manner. Tal-mediated ubiquitylation of Tsg101 inactivates this sorting function and concomitantly translocates Tsg101 from relatively insoluble membrane subdomains. Presumably, the coordinated action of Tal and a deubiquitylation enzyme (DUB) enables recycling of Tsg101 and reloading of cargo. | SIGNOR-271509 |
Q9P2E7 | P05556 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-269034 |
Q05513 | P35612 | 1 | phosphorylation | down-regulates | 0.275 | We now demonstrate that ptn stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (pk) c substrate domain of beta-adducin through activation of either pkc alpha or beta. | SIGNOR-139914 |
O15111 | Q9UKB1 | 2 | binding | down-regulates quantity by destabilization | 0.441 | We identified a human F-box/WD40 repeats protein (HOS), which is homologous to Slimb/h betaTrCP. Being a part of SCF complex with Skp1 and Cullin1, HOS specifically interacted with the phosphorylated IkappaB and beta-catenin, targeting these proteins for proteasome-dependent degradation in vivo. | SIGNOR-272545 |
P50148 | Q9UNW8 | 2 | binding | up-regulates activity | 0.422 | 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-257341 |
Q9UBY5 | Q14344 | 2 | binding | up-regulates | 0.4 | Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2. | SIGNOR-198547 |
P19174 | Q08881 | 0 | phosphorylation | up-regulates | 0.637 | In t cells, the predominant tec kinase is itk, which functions downstream of the t-cell receptor to regulate phospholipase c-gamma. | SIGNOR-165803 |
P28069 | Q969G2 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.514 | We show that normal LHX4 binds to a human-specific element and subsequently activates transcription from the proximal upstream regulatory sequence of POUIF1, a gene encoding a POU homeodomain transcription factor known as the main regulator of GH expression. | SIGNOR-266056 |
Q13224 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.469 | In addition, surface expression of GluN2B was not reduced in mutant mice and it remains to be investigated how the direct dephosphorylation of GluN2B Y1252 by Shp2 reduces GluN2B function.|The increased GluN2B Y1472 phosphorylation was reversed by a Src family kinase inhibitor, suggesting that Shp2 may negatively regulate GluN2B Y1472 phosphorylation through suppressing Src activity . | SIGNOR-276950 |
Q13554 | Q9UQD0 | 1 | phosphorylation | up-regulates activity | 0.272 | CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel. | SIGNOR-275788 |
P78504 | Q9UM47 | 2 | binding | up-regulates | 0.644 | Here we report the first x-ray structure of a functional fragment of a notch ligand, the dsl-egf3 domains of human jagged-1 (j-1dsl-egf3). The structure identifies a highly conserved face of the dsl domain and we show, by functional analysis of drosophila ligand mutants, that this surface is required for both cis- and trans-regulatory interactions with notch. | SIGNOR-179625 |
Q01813 | O60502 | 0 | deglycosylation | up-regulates activity | 0.2 | Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267606 |
P15976 | Q8IX07 | 2 | binding | up-regulates activity | 0.798 | GATA-2 induces the expression of GATA-1, which first activates its cofactor FOG-1, and then downregulates GATA-2 cooperatively with FOG-1. | SIGNOR-256059 |
O15530 | Q9Y243 | 1 | phosphorylation | up-regulates | 0.651 | The activation of pkbbeta and pkbgamma by pdk1 was accompanied by the phosphorylation of the residues equivalent to thr308 in pkbalpha, namely thr309 (pkbbeta) and thr305 (pkbgamma) | SIGNOR-55937 |
P19793 | P10276 | 2 | binding | up-regulates | 0.725 | Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins | SIGNOR-16665 |
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