IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q8IUC6 | O60603 | 0 | binding | up-regulates activity | 0.608 | To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group | SIGNOR-266746 |
P23443 | P27361 | 0 | phosphorylation | up-regulates activity | 0.607 | Thr 421/Ser 424 have been reported to be targeted by ERK1, 2 (39), JNK or p38 MAPKs (36). Interestingly, with a comparable kinetics, FSH represses ERK1, 2 constitutive phosphorylation in Sertoli cells isolated from 19-d-old rats | SIGNOR-134662 |
P05997 | P13497 | 0 | cleavage | up-regulates activity | 0.607 | BMP-1 Can Efficiently Cleave Pro-α1(V) N-propeptides and Pro-α2(V) C-propeptides and Less Efficiently Cleave Pro-α1(V) C-propeptides in Vitro. BMP-1 efficiently cleaves pro-α2(V) C-propeptides at a single site between residues 1250 (Glu) and 1251 (Asp). | SIGNOR-256343 |
O43186 | O15265 | 0 | binding | down-regulates activity | 0.607 | We found that ataxin-7 and CRX colocalize and coimmunoprecipitate. We observed that polyglutamine-expanded ataxin-7 can dramatically suppress CRX transactivation. | SIGNOR-223226 |
Q12778 | O00141 | 0 | phosphorylation | down-regulates activity | 0.607 | We demonstrate that SGK1 affects differentiation by direct phosphorylation of Foxo1, thereby changing its cellular localization from the nucleus to the cytosol. In addition we show that SGK1-/- cells are unable to relocalize Foxo1 to the cytosol in response to dexamethasone. | SIGNOR-255925 |
O15264 | P46734 | 0 | phosphorylation | up-regulates activity | 0.607 | p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation. | SIGNOR-273950 |
O14818 | P42684 | 0 | phosphorylation | down-regulates | 0.607 | Proteasome-mediated proteolysis is a primary protein degradation pathway in cells. The present study demonstrates that c-abl and arg (abl-related gene) tyrosine kinases associate with and phosphorylate the proteasome psma7 (alpha4) subunit at tyr-153. Consequently, proteasome-dependent proteolysis is compromised | SIGNOR-146589 |
O43464 | Q9BXM7 | 0 | phosphorylation | up-regulates | 0.607 | Htra2 is phosphorylated on activation of the p38 pathway, occurring in a pink1-dependent mannerwe suggest that pink1-dependent phosphorylation of htra2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress. | SIGNOR-158052 |
P05412 | Q8WYK2 | 0 | binding | down-regulates activity | 0.607 | JDP2 dimerizes with other AP-1 proteins such as activating transcription factor-2 (ATF2) and Jun to repress transcription from promoters that contain a cyclic AMP-responsive element (CRE). | SIGNOR-226398 |
Q13017 | P12931 | 0 | phosphorylation | up-regulates activity | 0.607 | Phosphotyrosine (p-Tyr)-dependent and -independent mechanisms of p190 RhoGAP-p120 RasGAP interaction: Tyr 1105 of p190, a substrate for c-Src, is the sole p-Tyr mediator of complex formation. Phosphorylation of Y1105, but not the minor site, was modulated in vivo to a greater extent by overexpression of c-Src than by the EGF receptor and was efficiently catalyzed by c-Src in vitro, indicating that Y1105 is a selective and preferential target of c-Src both in vitro and in vivo. | SIGNOR-276170 |
O95622 | P63096 | 0 | binding | down-regulates activity | 0.607 | Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3 | SIGNOR-278074 |
O00463 | Q15628 | 0 | binding | up-regulates | 0.607 | Upon stimulation of the tumor necrosis factor receptor1 (tnfr1), tnf-receptor-associated death domain (tradd) provides a scaffold for the assembly of complex i at the plasma membrane by binding receptor interacting protein 1 (rip1), tnfreceptor-associated factor 2 ,traf2. | SIGNOR-187058 |
Q92556 | P08631 | 0 | phosphorylation | up-regulates | 0.606 | We previously showed that elmo1 binds directly to the hck sh3 domain and is phosphorylated by hck. In this study, we used mass spectrometry to identify the following sites of elmo1 phosphorylation: tyr 18, tyr 216, tyr 511, tyr 395, and tyr 720. Mutant forms of elmo1 lacking these sites were defective in their ability to promote phagocytosis and migration in fibroblasts. | SIGNOR-138154 |
P43146 | O75962 | 0 | binding | up-regulates quantity | 0.606 | TrioY2622 is required for both netrin-1-induced activation of Rac1 and enhanced association with DCC. Phosphorylation of Trio at Tyr2622 participates in maintaining the level of surface DCC at the growth cone plasma membrane leading to axon outgrowth. Therefore, we propose that TrioY2622 is essential for the proper assembly and stability of the DCC/Trio signaling complex at the cell surface of growth cones in order to mediate netrin-1-induced cortical axon outgrowth. | SIGNOR-273856 |
Q13224 | Q13554 | 0 | phosphorylation | up-regulates activity | 0.606 | By peptide mapping, automated sequencing, and mass spectrometry, we identified the major site of phosphorylation on the fusion protein as Ser-383, corresponding to Ser-1303 of full-length NR2B. The Km for phosphorylation of this site in the fusion protein was approximately 50 nM, much lower than that of other known substrates for CaM kinase II, suggesting that the receptor is a high affinity substrate. We show that serine 1303 in the full-length NR2B and/or the cognate site in NR2A is a major site of phosphorylation of the receptor both in the postsynaptic density fraction and in living hippocampal neurons. | SIGNOR-250688 |
P0C0L4 | P48740 | 0 | cleavage | up-regulates activity | 0.606 | The classical complement activation pathway, like the MELinitiated pathway, involves the generation of a C3-converting complex, C4b2b, through enzymatic activation of C4 and C2. In the C1 complex (C1qr2s2), this specific protease activity is exhibited by C1s after activation of this enzyme by C1r. When C4 is activated, its reactive thiol ester is exposed and C4b binds covalently to nearby amino or hydroxyl groups. The C4-activating abilities of MASP-1 and MASP-2 were compared.|Activation of C4 by Ct sand MASP-2 on western blots. | SIGNOR-263438 |
O00459 | P22681 | 0 | ubiquitination | down-regulates | 0.606 | Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner. | SIGNOR-110063 |
P45984 | Q13115 | 0 | dephosphorylation | down-regulates | 0.606 | We assayed the relative ability of mkp-2, pac1, and mkp-1 to dephosphorylate erk2 and the other related map kinases, jnk2 and p38. . Mkp-2 had detectable activity against jnk2, although full inactivation of jnk2 was not observed even at the higher phosphatase concentration. | SIGNOR-40929 |
Q8N6P7 | Q9NYY1 | 0 | binding | up-regulates | 0.606 | An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis. | SIGNOR-151877 |
P98177 | P31751 | 0 | phosphorylation | down-regulates activity | 0.606 | FOXO4 transcription factor, also referred to AFX, contains three putative phosphorylation motif sites for protein kinase B (PKB), Thr32, Ser197, and Ser262, and it is proposed that phosphorylated FOXO4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression.[...]These results indicate that phosphorylation at Thr32 and Ser197 is indispensable, whereas that at Ser262 is not critical, for regulation of the nuclear localization and transcriptional activity of FOXO4 | SIGNOR-248055 |
O94979 | Q53G59 | 0 | binding | up-regulates activity | 0.606 | By analyzing mouse embryonic stem cell (mESC) division, we have identified Cul3Klhl12 as a regulator of COPII coat formation. Cul3Klhl12 monoubiquitinates Sec31 and drives assembly of large COPII-coats. As a result, ubiquitination by Cul3Klhl12 is essential for collagen export, a step that is required for integrin-dependent mESC division. | SIGNOR-272010 |
P63000 | Q9BRR9 | 0 | gtpase-activating protein | down-regulates activity | 0.606 | 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-260464 |
Q9Y6N7 | P00519 | 0 | phosphorylation | down-regulates | 0.606 | Abl functions to antagonize robo signaling both abl and ena can directly bind to robo's cytoplasmic domain. | SIGNOR-78993 |
Q676U5 | Q5MNZ9 | 0 | binding | up-regulates quantity | 0.606 | WIPI1 assists WIPI2 in recruiting ATG16L for LC3 lipidation. WIPI1-WIPI2 heterodimer may function more efficiently in ATG16L complex recruitment. | SIGNOR-268477 |
Q15303 | Q96J02 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.606 | Itch catalyzed ubiquitination of ErbB4 CYT-1, promoted its localization into intracellular vesicles, and stimulated degradation of ErbB4 CYT-1 | SIGNOR-271416 |
P04049 | Q6VAB6 | 0 | binding | up-regulates activity | 0.606 | In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. | SIGNOR-273879 |
P27361 | Q9UHA4 | 0 | binding | up-regulates | 0.606 | A protein called mp1 (mek partner 1) was identified that bound specifically to mek1 and erk1 and facilitated their activation. When overexpressed in cultured cells, mp1 enhanced activation of erk1 and activation of a reporter driven by the transcription factor elk-1. | SIGNOR-59877 |
P46531 | Q8NBL1 | 0 | glycosylation | up-regulates | 0.606 | O-glucosylation of epidermal growth factor-like (egf) repeats in the extracellular domain of notch is essential for notch function. A udp-glucose:protein o-glucosyltransferase (poglut/rumi) transfers o-glucose to serine within the o-glucose consensus. | SIGNOR-198713 |
Q9NYJ8 | Q9UDY8 | 0 | binding | up-regulates | 0.606 | Tab2/tak1 associate with ubiquitinated malt1 upon t-cell stimulation. | SIGNOR-158551 |
P04049 | P12931 | 0 | phosphorylation | up-regulates | 0.605 | We also show that phosphorylation of raf-1 on serine 338 by pak1 and tyrosines 340 and 341 by src relieves autoinhibition and that this occurs through a specific decrease in the binding of the raf-1 regulatory domain to its catalytic domain. | SIGNOR-97639 |
P16220 | O75676 | 0 | phosphorylation | up-regulates | 0.605 | Msk1 and msk2 directly phosphorilate and activete transcription factors such as creb1, atf1 msk was the kinase responsible for phosphorylation of the transcription factor creb in response to tcr stimulation. | SIGNOR-157158 |
Q07343 | P17612 | 0 | phosphorylation | up-regulates activity | 0.605 | PKA-mediated phosphorylation of Ser-56 in UCR1 of PDE4B4 leads to activation of this long isoform | SIGNOR-250024 |
P49757 | Q8N448 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.605 | Polyubiquitination of Human Numb by LNX2. The Zn-RING-Zn domain of LNX2 is a dimer and assumes a rigid elongated structure that undergoes autoubiquitination and undergoes N-terminal polyubiquitination. LNX2 can bind numb and induce its ubiquitination and subsequent proteasomal degradation | SIGNOR-272423 |
P06401 | P28482 | 0 | phosphorylation | down-regulates | 0.605 | Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26s proteasome | SIGNOR-74712 |
P42229 | P36888 | 0 | phosphorylation | up-regulates activity | 0.605 | FLT3-ITDs induced a strong activation of STAT5. FLT3-ITD mutants induce an autophosphorylation of the receptor, interleukin 3-independent growth in Ba/F3 cells, and a strong STAT5 and mitogen-activated protein kinase (MAPK) activation. | SIGNOR-261516 |
Q8NCW0 | O94907 | 0 | binding | up-regulates | 0.605 | Dkk1 has been shown to inhibitwnt by binding to and antagonizing lrp5/6. Here we show that the transmembrane proteins kremen1 and kremen2 are high-affinity dkk1 receptors that functionally cooperate with dkk1 to blockwnt/beta-catenin . Kremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of thewntreceptor lrp6 from the plasma membranekremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of the wnt receptor lrp6 from the plasma membrane | SIGNOR-88882 |
P25445 | P04637 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.605 | In an attempt to understand how CD95 expression is regulated by p53, we identified a p53-responsive element within the first intron of the CD95 gene, as well as three putative elements within the promoter. The intronic element conferred transcriptional activation by p53 and cooperated with p53-responsive elements in the promoter of the CD95 gene. wt p53 bound to and transactivated the CD95 gene, | SIGNOR-62376 |
Q9UQC2 | P06241 | 0 | phosphorylation | up-regulates activity | 0.605 | Our studies show that Gab2 is activated by Fyn kinase upon the engagement of ligand to TNFR1, IL-1R, or TLR4.|TNF\u03b1, IL-1\u03b2, and LPS induce Fyn kinase-mediated phosphorylation of Gab2. | SIGNOR-279984 |
P41597 | O60674 | 0 | phosphorylation | up-regulates activity | 0.605 | JAK2 phosphorylates CCR2 at the Tyr139 position and promotes JAK2/STAT3 complex association to the receptor. | SIGNOR-251345 |
P40189 | P42702 | 0 | binding | up-regulates | 0.605 | The binding of lif to the lifr induces its heterodimerization with gp130. The formation of this complex results in the activation of the receptor-associated janus kinases (jaks), in the phosphorylation of receptor docking sites, and finally in the recruitment of src homology-2 (sh2) domain containing proteins such as stat3 (signal transducer and activator of transcription 3). | SIGNOR-204850 |
P60484 | Q15831 | 0 | phosphorylation | down-regulates activity | 0.604 | The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity | SIGNOR-161118 |
O75676 | Q16539 | 0 | phosphorylation | up-regulates | 0.604 | Rskb, a 90-kda ribosomal s6 protein kinase family (rsk) member with two complete catalytic domains connected by a linker, is activated through p38- and erk-mitogen-activated protein kinases. unlike other rsks, the activation loop phosphorylation sites of both catalytic domains of rskb, ser(196) and thr(568), were required for activity. Rskb activation depended on phosphorylation of linker ser(343) and ser(360) and associated with phosphorylation of nonconserved ser(347), but ser(347)-deficient rskb retained partial activity. | SIGNOR-77212 |
Q13131 | Q96RR4 | 0 | phosphorylation | up-regulates | 0.604 | Ampka1 activators increased phosphorylation level and cytoplasmic localization (reduced nuclear/cytoplasmic ratio). Ampka1 activators reduced rna synthesis in the nucleoli. | SIGNOR-176602 |
P0CG48 | Q9BXM7 | 0 | phosphorylation | up-regulates activity | 0.604 | Ubiquitin is phosphorylated by PINK1 to activate parkin|PINK1 phosphorylated ubiquitin at Ser65 both in vitro and in cells | SIGNOR-249691 |
O43307 | Q9NQX3 | 0 | binding | up-regulates activity | 0.604 | 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-264973 |
P51617 | Q01638 | 0 | binding | up-regulates activity | 0.604 | As shown in Figure 3D, MyD88, IRAK, IRAK4, and TRAF6 are all recruited to ST2 upon IL-33 stimulation. | SIGNOR-277706 |
P31751 | Q6ZVD8 | 0 | dephosphorylation | down-regulates activity | 0.604 | The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells. | SIGNOR-248729 |
Q02388 | P13497 | 0 | cleavage | up-regulates quantity | 0.604 | We show that bone morphogenetic protein-1 (BMP-1), which exhibits procollagen C-proteinase activity, cleaves the C-terminal propeptide from human procollagen VII. The cleavage occurs at the BMP-1 consensus cleavage site SYAA/DTAG within the NC-2 domain. Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen. | SIGNOR-256338 |
Q3MII6 | O95166 | 0 | binding | up-regulates | 0.604 | In this study, we report evidence demonstrating that oatl1, a putative rab guanosine triphosphatase-activating protein (gap), is a novel binding partner of atg8 homologues in mammalian cells. Oatl1 is recruited to isolation membranes and autophagosomes through direct interaction with atg8 homologues and is involved in the fusion between autophagosomes and lysosomes through its gap activity. | SIGNOR-172536 |
P62993 | P36888 | 0 | binding | up-regulates activity | 0.604 | FL stimulation induces association of Grb2 with Flt3, SHP-2,and Shc | SIGNOR-245060 |
O60313 | Q96E52 | 0 | cleavage | up-regulates activity | 0.604 | YME1L cleaves OPA1 at S2 and S3 site to transform into L-OPA1 to induce fusion when cells are faced with increased oxidative phosphorylation, whereas OMA1 cleaves OPA1 at an S1 site to transform into S-OPA1, resulting in the fragmented response to cellular stress, mitochondrial dysfunction, or deletion of YME1L | SIGNOR-274139 |
P12931 | P09619 | 0 | phosphorylation | up-regulates activity | 0.604 | The increased Src activity is mainly due to the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine kinase responsible for the detachment-induced Src activation in the lung tumor cells. | SIGNOR-247979 |
Q9NWZ3 | Q01638 | 0 | binding | up-regulates activity | 0.604 | As shown in Figure 3D, MyD88, IRAK, IRAK4, and TRAF6 are all recruited to ST2 upon IL-33 stimulation. | SIGNOR-277705 |
P35052 | O94813 | 0 | binding | up-regulates | 0.604 | Slit family proteins are functional ligands of glypican-1 in nervous tissue and suggest that their interactions may be critical for certain stages of central nervous system histogenesis. | SIGNOR-68428 |
P60953 | O75044 | 0 | gtpase-activating protein | down-regulates activity | 0.604 | 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-260517 |
P45985 | Q99759 | 0 | binding | up-regulates activity | 0.604 | These data indicate that mkk3 is preferentially activated by mekk3, whereas mkk4 is activated both by mekk2 and mekk3. | SIGNOR-48628 |
Q14195 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.603 | Together, these results suggest that crmp4 is able to increase neurite formation and elongation in neurons, although not as potently as crmp2, and that this process is regulated by ser522/ser518/thr514/thr509 phosphorylation in both cases. We demonstrate that cdk5 primes crmp2 and crmp4 for subsequent phosphorylation by gsk3, whereas dyrk2, phosphorylates and primes only crmp4 in vitro | SIGNOR-145963 |
P38398 | Q13363 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.603 | Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells. | SIGNOR-259196 |
Q8N9I0 | Q9H4A3 | 0 | phosphorylation | up-regulates activity | 0.603 | Endogenous WNK1 and Syt2 coimmunoprecipitate and colocalize on a subset of secretory granules in INS-1 cells. Phosphorylation by WNK1 increases the amount of Ca2+ required for Syt2 binding to phospholipid vesicles; mutation of threonine 202, a WNK1 phosphorylation site, partially prevents this change. These findings suggest that phosphorylation of Syts by WNK1 can regulate Ca2+ sensing and the subsequent Ca2+-dependent interactions mediated by Syt C2 domains. . In contrast, WNK1 phosphorylated Syt2 on T202 and T386 within the C2 domains (Figure 6B). | SIGNOR-263049 |
Q9UHD2 | A7MCY6 | 0 | relocalization | up-regulates activity | 0.603 | TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation | SIGNOR-272469 |
P61978 | P12931 | 0 | phosphorylation | down-regulates | 0.603 | We show that hnrnp k and the c-src kinase specifically interact with each other, leading to c-src activation and tyrosine phosphorylation of hnrnp k in vivo and in vitro. c-src-mediated phosphorylation reversibly inhibits the binding of hnrnp k to the differentiation control element (dice) of the lox mrna 3' untranslated region in vitro and specifically derepresses the translation of dice-bearing mrnas in vivo.We confirmed that tyr 230, 234, 236, and 380 are phosphorylated and identified two additional targets of c-src, tyr 72 and tyr 225 (data not shown). | SIGNOR-88911 |
P48552 | P28702 | 0 | binding | up-regulates | 0.603 | Receptor interacting protein 140 (rip140) is a coregulator for a large number of transcription factors. Rip140 interacts with retinoic acid receptor (rar) and retinoid x receptor (rxr) with or without ligands | SIGNOR-95160 |
Q07817 | O00198 | 0 | binding | down-regulates | 0.603 | Hrk, physically interacts with the death-repressor proteins bcl2 and bcl2l1. Hrk activates cell death at least in part by interacting with and inhibiting the protection afforded by bcl2 and bcl2l1. | SIGNOR-47797 |
P63096 | P35372 | 0 | binding | up-regulates activity | 0.603 | 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-256711 |
O14775 | P14416 | 0 | binding | up-regulates activity | 0.603 | The D2-class dopamine receptors (D2, D3, and D4) couple to the Gi/o family of G proteins and thus induce inhibition of AC | SIGNOR-264993 |
O14733 | Q9Y2U5 | 0 | phosphorylation | up-regulates activity | 0.603 | MEKK2 can phosphorylate and activate MAP2K proteins MKK7 and MEK5, thereby promoting activation of JNK and ERK5, respectively [ xref ]. | SIGNOR-279212 |
Q9GZM8 | O14965 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.603 | Here, we show that Aurora-A phosphorylates NDEL1 at Ser251 at the beginning of mitotic entry. Interestingly, NDEL1 phosphorylated by Aurora-A was rapidly downregulated thereafter by ubiquitination-mediated protein degradation. | SIGNOR-263159 |
Q05397 | P06241 | 0 | phosphorylation | up-regulates activity | 0.602 | Because Fyn deletion prevented FAK phosphorylation at tyrosine residues 397 and 576 (XREF_FIG), we generated a phosphorylation mimicking mutant of FAK to test whether restoring FAK phosphorylation in the fyn -/- mouse lung could restore lung vascular permeability responses to PAR1 agonist to the level seen in WT mice.|Our findings that interaction of activated FAK with p120-catenins subsequent to Fyn activation of FAK facilitates reannealing of AJ leading to reestablishment of the basal endothelial barrier suggest that the Fyn-FAK pathway plays a critical role in restoring endothelial barrier function. | SIGNOR-278441 |
A7KAX9 | P04629 | 0 | relocalization | up-regulates | 0.602 | Grit translocation was regulated by receptor stimulation | SIGNOR-95809 |
Q13480 | P28482 | 0 | phosphorylation | up-regulates activity | 0.602 | Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. |serine and threonine phosphorylation are capable of modulating the initial signal | SIGNOR-249395 |
P60520 | Q8IXH6 | 0 | binding | up-regulates | 0.602 | Tp53inp2 binds to lc3 as well as to lc3-related proteins gabarap and gabarap-like2. | SIGNOR-182611 |
Q05469 | P17612 | 0 | phosphorylation | up-regulates activity | 0.602 | HSL activity is known to be regulated by phosphorylation (3). PKA increases HSL activity via phosphorylation at Ser563, Ser659, and Ser660 (14,15), although phosphorylation at Ser565 by glycogen synthase kinase, AMP-dependent protein kinase, or Ca2+/calmodulin-dependent protein kinase II has been reported to prevent activation of the enzyme | SIGNOR-249202 |
O43559 | Q16620 | 0 | phosphorylation | up-regulates activity | 0.602 | The tyrosine phosphoryla tion of FRS2/SNT2 was stimulated dependently on the TrkB activation. to explore the possibility that tyrosine residues 417 and 455 on FRS2/SNT2 function as the binding sites for Shp2, we coexpressed Y417F or Y455F phenylalanine mutants and the Y417/455F double phenylalanine mutant of Myc/Histagged FRS2/SNT2 with TrkB. The active TrkB induced somewhat reduced tyrosine phosphorylation of all of the phenylalanine mutants of FRS2/SNT2 in comparison with tyrosine phosphorylation of the wild type | SIGNOR-250202 |
O60674 | Q01344 | 0 | phosphorylation | up-regulates activity | 0.602 | Jak 2 is physically associated with the IL-5b receptor. The binding of IL-5 to its receptor results in tyrosine phosphorylation and activation of Jak 2 tyrosine kinase within 1 to 3 min. | SIGNOR-254352 |
P46531 | Q92831 | 0 | acetylation | up-regulates | 0.602 | In earlier studies, we demonstrated that maml1 enhanced p300 acetyltransferase activity, which increased the acetylation of notch by p300.Acetylation controls notch stability and function in t-cell leukemia. | SIGNOR-199024 |
P04049 | Q13153 | 0 | phosphorylation | up-regulates | 0.602 | P21-activated protein kinases (paks) are serine/threonine protein kinases that phosphorylate raf-1 at ser-338 and ser-339. | SIGNOR-180808 |
P31749 | P42574 | 0 | cleavage | down-regulates activity | 0.602 | P53 can inhibit the survival function of integrins by inducing the caspase-dependent cleavage and inactivation of the serine/threonine kinase akt/pkb;the involvement of caspase 3 in akt/pkb regulation was indicated by the ability of z-devd-fmk, a caspase 3 inhibitor, to block the alpha6beta4-associated reduction in akt/pkb levels in vivo, and by the ability of recombinant caspase 3 to promote the cleavage of akt/pkb in vitro | SIGNOR-252624 |
P10276 | P31749 | 0 | phosphorylation | down-regulates | 0.602 | We report that akt, which is constitutively activated in nsclc cells, phosphorylates raralpha and inhibits its transactivation. / mutation of ser96 to alanine abrogated the suppressive effect of akt. | SIGNOR-252489 |
P19419 | P27361 | 0 | phosphorylation | up-regulates | 0.601 | Erki phosphorylates five c-terminal sites in elk-i (s324, t336, s383, s389 and s422) with varying degrees of efficiency. | SIGNOR-34669 |
Q96EB6 | P45983 | 0 | phosphorylation | up-regulates | 0.601 | Human sirt1 was phosphorylated by jnk1 on three sites: ser27, ser47, and thr530 and this phosphorylation of sirt1 increased its nuclear localization and enzymatic activity. Surprisingly, jnk1 phosphorylation of sirt1 showed substrate specificity resulting in deacetylation of histone h3, but not p53. | SIGNOR-162314 |
P35222 | P67870 | 0 | phosphorylation | up-regulates activity | 0.601 | We show that CKII phosphorylates the N-terminal region of beta-catenin and we identified Ser29, Thr102, and Thr112 as substrates for the enzyme. We provide evidence that CKII regulates the cytoplasmic stability of beta-catenin and acts synergistically with GSK-3beta in the multi-protein complex that controls the degradation of beta-catenin | SIGNOR-251067 |
P63000 | P11274 | 0 | gtpase-activating protein | down-regulates activity | 0.601 | 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-260526 |
P12259 | P04070 | 0 | cleavage | down-regulates activity | 0.601 | The mechanism of inactivation of human factor V and human factor Va by activated protein C|Membrane-bound human factor V (250 nM) is cleaved by APC (2.5 nM) to give M(r) = 200,000, 70,000, 45,000, and 30,000 fragments and an M(r) = 22/20,000 doublet. These fragments are released after four sequential cleavages of the membrane-bound procofactor at Arg306, Arg506, Arg679, and Lys994. | SIGNOR-263629 |
Q07869 | P27361 | 0 | phosphorylation | up-regulates activity | 0.601 | We now demonstrate that amino acids 1-92 of hPPARalpha contain an activation function (AF)-1-like domain, which is further activated by insulin through a pathway involving the mitogen-activated protein kinases p42 and p44. Further analysis of the amino-terminal region of PPARalpha revealed that the insulin-induced trans-activation occurs through the phosphorylation of two mitogen-activated protein kinase sites at positions 12 and 21, both of which are conserved across evolution. | SIGNOR-249474 |
Q01094 | Q99608 | 0 | binding | down-regulates activity | 0.601 | Necdin interacts with E2F transcription factors and suppresses E2F1-dependent transcriptional activation of the cyclin-dependent kinase Cdk1 gene. Here we show that necdin serves as a suppressor of NPC proliferation in the embryonic neocortex. | SIGNOR-253382 |
P04626 | P22681 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.601 | Ligand binding to EGFR also leads to rapid internalization and proteosomal/lysosomal degradation of the receptors. This process results in a dramatic downregulation of both total and cell surface receptors. EGF-induced degradation of EGFR is thought to be initiated by phosphorylation of tyrosine 1045 of the receptor followed by binding of Cbl adaptor proteins and ubiquitination of the receptor. Internalized EGFR is transported to early endosomes where receptor-ligand complexes are sorted for either degradation or recycling to the cell surface. | SIGNOR-30794 |
O00429 | Q9GZY8 | 0 | relocalization | up-regulates activity | 0.601 | Mff functions as an essential factor in mitochondrial recruitment of Drp1. | SIGNOR-245957 |
Q9NYA1 | P27361 | 0 | phosphorylation | up-regulates | 0.601 | Activation of sphingosine kinase 1 by erk1/2-mediated phosphorylation. | SIGNOR-118550 |
Q9UHF4 | Q9NPH9 | 0 | 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 |
Q08334 | Q9NPH9 | 0 | binding | up-regulates | 0.601 | See table 2 | SIGNOR-151917 |
P00748 | P01008 | 0 | cleavage | down-regulates activity | 0.6 | Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1 | SIGNOR-264139 |
Q99704 | P06239 | 0 | phosphorylation | up-regulates activity | 0.6 | Phosphorylation of p56 dok and p62 dok is increased following CD2 stimulation and requires Lck. Phosphorylation of Dok proteins by Lck might provide a mechanism by which SH2-containing proteins can be recruited and co-localized with their substrates. | SIGNOR-251373 |
P31749 | Q96EB6 | 0 | deacetylation | up-regulates activity | 0.6 | We show that Akt and PDK1 are acetylated at lysine residues in their pleckstrin homology domains, which mediate PIP(3) binding. Acetylation blocked binding of Akt and PDK1 to PIP(3), thereby preventing membrane localization and phosphorylation of Akt. Deacetylation by SIRT1 enhanced binding of Akt and PDK1 to PIP(3) and promoted their activation. | SIGNOR-252445 |
P54132 | P52701 | 0 | binding | up-regulates | 0.6 | We show that the recombinant hmsh2/6 protein complex stimulated the ability of the bloom's syndrome gene product, blm, to process holliday junctions in vitro | SIGNOR-123705 |
Q9HBH9 | P28482 | 0 | phosphorylation | up-regulates | 0.6 | We have identified a new subfamily of murine serine/threonine kinases, whose members, map kinase-interacting kinase 1 (mnk1) and mnk2, bind tightly to the growth factor-regulated map kinases, erk1 and erk2erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity | SIGNOR-48338 |
O00429 | Q9BXM7 | 0 | phosphorylation | up-regulates activity | 0.6 | We here demonstrate that PINK1 directly phosphorylates Drp1 on S616. | SIGNOR-279548 |
P40763 | P51813 | 0 | phosphorylation | up-regulates activity | 0.6 | BMX activates STAT3 in glioblastoma stem cells.|BMX has previously been identified as an activator of STAT3, and BMX can phosphorylate STAT3 in vitro. | SIGNOR-279497 |
P12830 | Q13363 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.6 | Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells. | SIGNOR-259197 |
P17302 | P48730 | 0 | phosphorylation | up-regulates activity | 0.6 | We have examined the role of casein kinase 1 (CK1) in connexin-43 (Cx43) gap junction assembly. Cellular co-immunoprecipitation experiments and in vitro CK1 phosphorylation reactions indicate that CK1 interacted with and phosphorylated Cx43, initially on serine(s) 325, 328, or 330.| To examine CK1 function, normal rat kidney cells were treated with CKI-7, and Cx43 content was analyzed by Triton X-100 extraction, cell-surface biotinylation, and immunofluorescence. Western blot analysis indicated a slight increase in total Cx43, whereas gap junctional (Triton-insoluble) Cx43 decreased, and non-junctional plasma membrane Cx43 increased (as detected by cell surface biotinylation). | SIGNOR-249331 |
P10071 | P48729 | 0 | phosphorylation | down-regulates | 0.6 | In principle, pka, ck-1 and gsk3 can phosphorylate as many as 19 serine residues in gli3: fourpkasites, three primarygsk3sites, four primary ck-1 sites and eight secondary gsk3 and ck-1 sites | SIGNOR-116512 |
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