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 |
|---|---|---|---|---|---|---|---|
P38936 | Q00526 | 2 | binding | down-regulates | 0.664 | P21cip1 is a cyclin-dependent kinase (cdk) inhibitor that is transcriptionally activated by p53 in response to dna damage. We have explored the interaction of p21 with the currently known cdks. p21 effectively inhibits cdk2, cdk3, cdk4, and cdk6 kinases. | SIGNOR-29954 |
P54274 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.366 | Our data indicate that AURKB can phosphorylate the integral telomere DNA-binding Shelterin protein TERF1 at S404 (within the DNA-binding domain) in vitro . | SIGNOR-279440 |
P56645 | P49674 | 0 | phosphorylation | down-regulates activity | 0.74 | The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway. Moreover, CKIepsilon and CKIdelta are able to induce nuclear translocation of mPer3, which requires its nuclear localization signal. The mutation in potential phosphorylation sites on mPer3 decreased the extent of both nuclear translocation and degradation of mPer3 that are stimulated by CKIepsilon. | In mut7 in which all of the conserved serine and threonine residues in this region were mutated, the ratio of the shifted band was greatly reduced reproducibly. | SIGNOR-250816 |
Q15672 | Q15759 | 0 | 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 |
O94817 | O95352 | 2 | binding | up-regulates | 0.937 | Analogous to ubiquitination, atg12 is conjugated to atg5 by atg7--an e1-like protein--and atg10--an e2-like protein. | SIGNOR-180132 |
Q9UHD2 | Q12834 | 1 | phosphorylation | down-regulates activity | 0.2 | It was found that TBK1 phosphorylates both Cdc20 as well as Cdh1 (Figure 2F). | SIGNOR-279766 |
Q8IYD8 | Q92547 | 1 | relocalization | up-regulates | 0.418 | The enzymatic activity of fan cm is then required to remodel and stabilize the fork to allow topbp1 access to activate atr , in a 9-1-1-independent manner. | SIGNOR-164765 |
P51668 | O60291 | 2 | binding | up-regulates activity | 0.496 | Our in vivo and in vitro ubiquitylation studies demonstrate that the binding of TSG101 to Mahogunin targets the substrate TSG101 for ubiquitylation by Mahogunin E3 ligase in cooperation with its cognate E2 enzyme Ubc5a | SIGNOR-271637 |
Q9Y6Q9 | P35790 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | First, by using purified recombinant SRC-3 (XREF_FIG) and CKI proteins, we found that CKI is able to phosphorylate SRC-3 (XREF_FIG). | SIGNOR-280229 |
Q14258 | O43283 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Mechanistically, MAP3K13 phosphorylates the E3 ubiquitin ligase TRIM25 at Ser12 to decrease its polyubiquitination and proteasomal degradation. | SIGNOR-277456 |
P50750 | P10275 | 1 | phosphorylation | up-regulates activity | 0.537 | AR S81 phosphorylation by CDK9 is tightly linked to chromatin binding and transcriptional activation. | SIGNOR-279456 |
P04629 | P34130 | 2 | binding | up-regulates | 0.693 | Ngf is the preferred ligand for trka, bdnf and nt4/5 are preferred for trkb, and nt3 for trkc (barbacid 1994). These specificities are not absolute, and nt3 is also a ligand for trka and trkb. | SIGNOR-85117 |
Q13618 | P61586 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.396 | BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex. | SIGNOR-264238 |
P17252 | Q92686 | 1 | phosphorylation | up-regulates activity | 0.394 | 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-248913 |
P60953 | Q13459 | 0 | gtpase-activating protein | down-regulates activity | 0.562 | 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-260511 |
Q9NVN3 | P38405 | 2 | binding | up-regulates activity | 0.492 | In the olfactory sensory neurons located in the nasal epithelium, OR activation by odorants or other stimuli can switch on a specific olfactory G-protein (GNAL), which in turn stimulatesand ADCY3 and Ric8b leads to cyclic adenosine monophosphate (cAMP) generation from adenosine triphosphate (ATP) | SIGNOR-278071 |
P78536 | P27361 | 0 | phosphorylation | up-regulates | 0.361 | Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated sheddingwe show that extracellular signal-regulated kinase (erk) acts as an intermediate in protein kinase c-regulated trka cleavage. We report that the cytosolic tail of the tumor necrosis factor alpha-converting enzyme (tace) is phosphorylated by erk at threonine 735. In addition, we show that erk and tace associate. This association is favored by erk activation and by the presence of threonine 735. In contrast to the erk route, the p38 mapk was able to stimulate trka cleavage in cells devoid of tace activity, indicating that other proteases are also involved in trka shedding. | SIGNOR-89625 |
P07333 | Q00341 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.342 | Vigilin (Vgl1) is essential for heterochromatin formation, chromosome segregation, and mRNA stability and is associated with autism spectrum disorders and cancer: vigilin, for example, can suppress proto-oncogene c-fms expression in breast cancer. | SIGNOR-266696 |
Q9H165 | P69892 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.446 | Our findings reveal that direct γ-globin gene promoter repression by BCL11A underlies hemoglobin switching. | SIGNOR-269066 |
Q8N726 | O15119 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.395 | TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS | SIGNOR-249603 |
Q15173 | Q96M94 | 2 | binding | down-regulates quantity by destabilization | 0.2 | Here, we report that KLHL15-Cul3 specifically targets B'β to promote turnover of the PP2A subunit by ubiquitylation and proteasomal degradation. We mapped KLHL15 residues critical for homodimerization as well as interaction with Cul3 and B'β. | SIGNOR-272017 |
P45984 | P28562 | 0 | dephosphorylation | down-regulates | 0.681 | We assayed the relative ability of mkp-2, pac1, and mkp-1 to dephosphorylate erk2 and the other related map kinases, jnk2 and p38. the dual specific phosphatases pac1 and mkp-1 previously have been implicated in the in vivo inactivation of erk or of erk and jnk, respectively. | SIGNOR-40879 |
O95239 | O43663 | 2 | binding | up-regulates activity | 0.568 | These results suggest that KIF4 and its binding partner PRC1 play essential roles in the organization of central spindles and midzone formation. KIF4 deficiency leads to mislocalization of PRC1, MKLP1, CENP-E and chromosomal passenger proteins | SIGNOR-265988 |
P09237 | P07585 | 1 | cleavage | down-regulates quantity by destabilization | 0.61 | Degradation of decorin by matrix metalloproteinases. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-beta1 released from DCN in the connective tissues. | SIGNOR-256352 |
P35638 | P49715 | 1 | transcriptional regulation | down-regulates quantity | 0.519 | We find that expression of CHOP, a nuclear protein that dimerizes avidly with C/EBP isoforms alpha and beta and directs the resulting heterodimer away from classic C/EBP-binding sites, markedly inhibits this differentiation process. | SIGNOR-255913 |
O75925 | P31749 | 1 | sumoylation | up-regulates activity | 0.378 | Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity. | SIGNOR-252735 |
Q96EB6 | Q9UBK2 | 1 | deacetylation | up-regulates activity | 0.799 | SIRT1 overexpression reduces muscle wasting by blocking the activation of FoxO1 and 3 SIRT1 activation has been reported to increase dramatically endurance exercise through the activation of PGC-1_ in muscle, which stimulates fatty acid oxidation | SIGNOR-217963 |
P29992 | P35368 | 2 | binding | up-regulates activity | 0.661 | In this report, we demonstrate that in transfected cos-7 cells Gal4 and Ga16, like Gaq and Ga11, can activate PIPLC j3l and that all three al-ARs, alA, alB and alC, can activate endogenous PI-PLC by coupling to Gaq or Ga11. | SIGNOR-278122 |
Q8WTV0 | P12931 | 2 | binding | up-regulates activity | 0.368 | Importantly, coimmunoprecipitation of SR-BI and Src demonstrated that the two proteins are directly associated in WT macrophages (Fig. 7B), suggesting that SR-BI plays a direct role in activation of Src in macrophages. | SIGNOR-260314 |
Q9BXM7 | Q8IXI2 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.775 | PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. in Miro1, Ser156 (homologous to Ser182 in Drosophila) and Thr298, 299 (homologous to Ser324, 325 in Drosophila, Figure 6C). | SIGNOR-272728 |
P11802 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.569 | C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation | SIGNOR-102734 |
O00418 | P13639 | 1 | phosphorylation | down-regulates | 0.788 | Ef-2 kinase phosphorylates ef-2 at 3 threonine residues: thr-53, thr-56, thr-58. Phosphorylation of thr56 and thr58 was found to be an ordered process, modification of thr56 preceding, and apparently being required for, phosphorylation of thr58. | SIGNOR-38556 |
Q14689 | Q14247 | 1 | acetylation | up-regulates activity | 0.2 | DIP2A binds to cortactin and modulates cortactin acetylation. Autism candidate gene disconnected-interacting protein homolog 2 A (DIP2A) is known to be involved in acetylated coenzyme A (Ac-CoA) synthesis and is primarily expressed in the brain regions with abundant pyramidal neurons. We further identified that DIP2A interacted with cortactin, an activity-dependent spine remodeling protein. The binding activity of DIP2A-PXXP motifs (P, proline; X, any residue) with the cortactin-Src homology 3 (SH3) domain was critical for maintaining the level of acetylated cortactin. | SIGNOR-266589 |
O94921 | Q8ND76 | 2 | phosphorylation | down-regulates quantity by destabilization | 0.83 | Phosphorylation of cyclin Y by CDK14 induces its ubiquitination and degradation|Phosphorylation of CCNY at Serines 71 and 73 creates a putative phospho-degron that controls its association with an SCF complex | SIGNOR-273007 |
O00141 | Q9HC98 | 0 | phosphorylation | up-regulates activity | 0.338 | The present study is the first report of a protein kinase (NEK6) capable of phosphorylating the hydrophobic motif of SGK1, although our data suggest that NEK6 may not mediate this reaction in cells. Nevertheless, the phosphorylation of the hydrophobic motif of SGK1in vitro, coupled with the phosphorylation of the T-loop with PDK1, may be a useful way of generating fully active wild type SGK1. Ser377 and Ser422of SGK1, and the CDK7 T-loop peptide, which are phosphorylated by NEK6. | SIGNOR-250297 |
Q13501 | Q9UHD2 | 0 | phosphorylation | up-regulates | 0.709 | Tbk-1 coordinated assembly and function of the autophagic machinery and phosphorylated the autophagic adaptor p62 (sequestosome 1) on ser-403, a residue essential for its role in autophagic clearance. | SIGNOR-191944 |
P13861 | O43164 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.328 | Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits | SIGNOR-271856 |
O00401 | P60953 | 2 | binding | up-regulates activity | 0.919 | In the presence of Cdc42 and PI(4,5)P2, the potency of N-WASP was increased to a level approaching that of GST-VCA, suggesting that N-WASP was fully activated by the two molecules. | SIGNOR-261868 |
P35575 | P16220 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB | SIGNOR-256105 |
P63000 | P45983 | 2 | binding | up-regulates | 0.659 | The mechanism by which pak1 induced cancer growth might involve activation of jnk in the non-canonical wnt pathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor. | SIGNOR-152808 |
P31749 | P22736 | 1 | phosphorylation | down-regulates activity | 0.729 | We show that akt interacts with nur77 and inactivates nur77 by phosphorylation at ser-350 | SIGNOR-252466 |
P45984 | Q96KS0 | 1 | phosphorylation | up-regulates activity | 0.2 | Interestingly, we found that docetaxel induced JNK2 activation increased phosphorylation of PHD1 at Ser 74 and Ser 162 in hypoxic cancer cells (XREF_FIG). | SIGNOR-279077 |
Q9Y5U4 | Q8WU17 | 0 | ubiquitination | down-regulates quantity | 0.436 | Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. TRC8 destablizes SREBP precursors in a RING and proteasome-dependent manner | SIGNOR-271956 |
P10636 | O60285 | 0 | phosphorylation | up-regulates quantity | 0.249 | These results confirm that the effect of Nuak1 over tau levels is mainly due to tau phosphorylation at Ser356 by Nuak1.|Western blot analysis revealed that a 50% reduction in Nuak1 was sufficient to decrease tau levels in the brain (XREF_FIG). | SIGNOR-279306 |
Q92597 | Q96BR1 | 0 | phosphorylation | down-regulates activity | 0.402 | It has been shown that SGK3 phosphorylation of NDRG1 primes for subsequent phosphorylation by GSK-3beta.|Since NDRG1 is a direct SGK substrate, this correlation suggests that SGK3 activation and signaling may modulate NDRG1 degradation. | SIGNOR-279282 |
P27361 | Q12800 | 1 | phosphorylation | down-regulates | 0.2 | We previously established that phosphorylation of lsf in early g1 at ser-291 and ser-309 inhibits its transcriptional activity and that dephosphorylation later in g1 is required for its reactivation. At the peak activities of erk and cyclin c/cdk2 in early g1, lsf is efficiently phosphorylated on ser-291 and ser-309. | SIGNOR-184176 |
P20340 | Q7Z7G8 | 2 | binding | down-regulates activity | 0.372 | Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth. COH1 Golgi Localization Is Mediated by Active RAB6 . COH1 Interacts with All Three Mammalian RAB6 Homologues | SIGNOR-269203 |
P50148 | P20309 | 2 | binding | up-regulates activity | 0.579 | 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-257018 |
Q06187 | P51813 | 1 | phosphorylation | up-regulates | 0.335 | Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. | SIGNOR-98028 |
P49841 | P17612 | 0 | phosphorylation | down-regulates activity | 0.557 | Gsk3 is different from most kinases in that it is constitutively partially active and the most common regulatory mechanism is inhibition by phosphorylation of ser21 in gsk3alpha or ser9 in gsk3beta. This inhibitory phosphorylation can be mediated by several kinases, such as akt/protein kinase b (pkb), protein kinase c (pkc) and protein kinase a (pka). | SIGNOR-188577 |
Q13322 | Q6Y7W6 | 2 | binding | up-regulates activity | 0.596 | We demonstrated that, in cultured cells and mammalian brains, GIGYF2 interacts and colocalises with Grb10, promoting ligand‐induced ubiquitination of IGF‐1R, and thereby regulates receptor degradation | SIGNOR-260057 |
Q96KS0 | Q16665 | 1 | hydroxylation | down-regulates quantity by destabilization | 0.856 | There are three EglN family members in humans and mice (EglN1, EglN2, and EglN3). Their enzymatic activity requires oxygen, ascorbic acid, iron, and α-ketoglutarate (α-KG). Under hypoxic conditions, EglNs lose their activity and fail to hydroxylate HIFα, which leads to HIFα stabilization | SIGNOR-261999 |
P78527 | P09874 | 1 | phosphorylation | down-regulates activity | 0.525 | Therefore, through its interaction with Ku70/80 in the presence of dsDNA , DNA-PK phosphorylated PARP-1 at its catalytic CTD. | SIGNOR-280093 |
P51608 | P42262 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.323 | Bicuculline treatment also leads to an increase in the levels of the transcriptional repressor MeCP2, which binds to the GluR2 promoter along with the corepressors HDAC1 and mSin3A. | SIGNOR-264684 |
P29323 | Q13224 | 1 | phosphorylation | up-regulates quantity | 0.443 | In addition, EPHB2 signaling leads to phosphorylation of GluN2B at tyrosine residue 1472 preventing clathrin dependent endocytosis, and increasing the surface retention of GluN2B containing NMDARs. | SIGNOR-279710 |
Q13107 | O43395 | 1 | deubiquitination | down-regulates activity | 0.487 | Prp3 is deubiquitinated by Usp4 and its substrate targeting factor, the U4/U6 recycling protein Sart3, which likely facilitates ejection of U4 proteins from the spliceosome during maturation of its active site. | SIGNOR-271975 |
Q7Z6Z7 | P04637 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.495 | HUWE1 directly binds and ubiquitinates p53 to target it for proteasomal degradation, independently of MDM2 [ xref ]. | SIGNOR-278547 |
Q00534 | Q06830 | 1 | phosphorylation | down-regulates | 0.2 | Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.Prx i was also phosphorylated, with an efficiency similar to that observed with cdc2, when incubated in vitro with cdk2, cdk4, or cdk6 that had been immunoprecipitated from hela cell lysates with specific antibodies (data not shown). | SIGNOR-87113 |
P49757 | Q2M2I8 | 0 | phosphorylation | up-regulates | 0.459 | Collectively, these observations demonstrate that numb endocytic activity is regulated by aak1 and that phosphorylation may be a critical step in promoting coated pit maturation. | SIGNOR-179606 |
Q5T6F2 | P07355 | 1 | ubiquitination | down-regulates quantity | 0.341 | UBAP2 formed a complex with Annexin A2 and promoted the degradation of Annexin A2 protein by ubiquitination | SIGNOR-261314 |
Q9NXK8 | P43353 | 2 | binding | down-regulates quantity by destabilization | 0.32 | We now show that SCFFBXL12 is an authentic E3 for the ALDH3 family of enzymes. We now show that the ubiquitin-dependent degradation of ALDH3 mediated by FBXL12 (F box and leucine-rich repeat protein 12) is essential for execution of the differentiation program of trophoblast stem cells (TSCs). FBXL12 is present only in eutherian mammals, and its expression is largely restricted to the placenta during mouse embryogenesis. FBXL12 was found to interact specifically with members of the ALDH3 family and to mediate their polyubiquitylation. Finally, coimmunoprecipitation analysis revealed that FBXL12 interacted efficiently only with members of the ALDH3 family (ALDH3A1, ALDH3A2, and ALDH3B1), showing little if any association with those of the ALDH1 family (ALDH1A1, ALDH1A2, and ALDH1A3) (Fig. 2H). Collectively, these results suggested that SCFFBXL12 is an authentic E3 specific for ALDH3 family members. | SIGNOR-272815 |
P11488 | P18545 | 2 | binding | down-regulates activity | 0.764 | In the dark, PDE6 activity is suppressed by its inhibitory γ-subunit (Pγ). Rhodopsin-catalyzed activation of the G protein, transducin, relieves this inhibition and enhances PDE6 catalysis. | SIGNOR-260008 |
P35637 | Q16637 | 1 | relocalization | up-regulates activity | 0.37 | Here, we report that FUS associates with the SMN complex, mediated by U1 snRNP and by direct interactions between FUS and SMN.|The FUS IP and pulldown revealed that FUS also associates with components of the SMN complex, including SMN and Gemins 4 and 6 |Remarkably, the number of SMN-stained nuclear bodies was dramatically reduced in the FUS knockdown cells | SIGNOR-262107 |
Q9UH03 | Q13976 | 0 | phosphorylation | up-regulates activity | 0.2 | Mutation of Ser-91 to Ala in recombinant Sept3 also abolished PKG phosphorylation, confirming that Ser-91 is the major site in vitro. Therefore Sept3 is phosphorylated on Ser-91 in nerve terminals and its phosphorylation may contribute to the regulation of its subcellular localization in neurons. | SIGNOR-263183 |
Q08828 | P19086 | 2 | binding | down-regulates activity | 0.467 | Activated a z inhibits the activity of type I and type V adenylyl cyclases. | SIGNOR-278044 |
P17612 | O14813 | 1 | phosphorylation | down-regulates | 0.307 | Phox2a becomes phosphorylated by protein kinase a (pka) on ser153, which prevents association of phox2a with dna and terminates p27(kip1) transcription. | SIGNOR-186462 |
P42771 | P01106 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.766 | C-myc also directly represses transcription of cdk kinase inhibitors including p27kip1, p21cip1, p15ink4b and p16ink4a | SIGNOR-102743 |
P45973 | P84243 | 2 | binding | up-regulates activity | 0.2 | A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing. | SIGNOR-264488 |
P05091 | Q13131 | 0 | phosphorylation | up-regulates activity | 0.2 | Further studies demonstrate that in the absence of LDLR, AMPK phosphorylates ALDH2 at threonine 356 and enables its nuclear translocation. Nuclear ALDH2 interacts with HDAC3 and represses transcription of a lysosomal proton pump protein ATP6V0E2, critical for maintaining lysosomal function, autophagy, and degradation of oxidized low-density lipid protein. | SIGNOR-271863 |
P06850 | P02533 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | CRH stimulated the expression of cytokeratin 1 and involucrin, and inhibited cytokeratin 14 on both mRNA and protein levels. | SIGNOR-251899 |
Q96EB6 | Q9UPT9 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.534 | USP22 expression was regulated by c-MYC and contributed to c-MYC mediated reduction in SIRT1 polyubiquitination and degradation. USP22 directly interacted with and removing polyubiquitin chains from SIRT1 to increase SIRT1 protein stabilization and expression. These results support a role for USP22 in MYC-mediated increase in SIRT1 protein stabilization, and indicate that FLT3-ITD, c-MYC and USP22 form an oncogenic network that enhances SIRT1 expression and activity in leukemic cells. | SIGNOR-261561 |
P78368 | Q13330 | 1 | phosphorylation | up-regulates activity | 0.344 | CKI-gamma2 could further potentiate the ER corepressive function of metastasis-associated protein-1 short form.|These findings identified metastasis-associated protein-1 short form as a target of CKI-gamma2, and provided new evidence to suggest that CKI-gamma2 phosphorylates and modulates the functions of metastasis-associated protein-1 short form, and that these extranuclear effects of estrogen might have important implications in regulating the functions of metastasis-associated protein-1 short form in human mammary epithelial and cancer cells. | SIGNOR-280236 |
Q9HCP0 | O75581 | 1 | phosphorylation | up-regulates | 0.545 | Ck1gamma is associated with lrp6, which has multiple, modular ck1 phosphorylation sites. Wnt treatment induces the rapid ck1gamma-mediated phosphorylation of these sites within lrp6 | SIGNOR-143029 |
P10082 | Q15761 | 2 | binding | up-regulates | 0.643 | Maml3 forms complexes in vivo with icn and csl and functiosn as transcriptional coactivators for notch signaling. | SIGNOR-114749 |
P53355 | P10586 | 0 | dephosphorylation | up-regulates | 0.2 | Lar tyrosine phosphatase dephosphorylates dapk at py491/492 to stimulate the catalytic, proapoptotic, and antiadhesion/antimigration activities of dapk | SIGNOR-157706 |
P09429 | Q9Y6Y9 | 2 | binding | up-regulates activity | 0.63 | Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2-deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. | SIGNOR-252058 |
Q05481 | O75015 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Thus, these results indicate that these cloned ZNF140 and ZNF91 proteins function as repressors for the human Fc gamma RIIB transcription. | SIGNOR-266215 |
Q01668 | Q9UQ26 | 2 | binding | up-regulates activity | 0.347 | Here, we report an interaction of the C2B domain of RIM2α and RIM3γ with the C-terminus of the pore-forming α-subunit of CaV1.3 channels (CaV1.3α1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs). In conclusion, we propose that RIM2α and RIM3γ directly interact with the C-terminus of the pore-forming subunit of CaV1.3 Ca2+ channels and positively regulate their plasma membrane expression in HEK293 cells. | SIGNOR-264356 |
P23352 | Q14938 | 0 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268884 |
Q96EB6 | Q13627 | 0 | phosphorylation | up-regulates activity | 0.54 | DYRK1A and DYRK3 directly phosphorylate SIRT1 at Thr(522), promoting deacetylation of p53.|DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. | SIGNOR-278473 |
O15297 | O14757 | 1 | dephosphorylation | down-regulates activity | 0.473 | Here we show that the oncogenic p53-induced serine/threonine phosphatase, PPM1D (or Wip1), dephosphorylates two ATM/ATR targets, Chk1 and p53. PPM1D binds Chk1 and dephosphorylates the ATR-targeted phospho-Ser 345, leading to decreased Chk1 kinase activity. | SIGNOR-248317 |
Q96KB5 | Q06830 | 1 | phosphorylation | up-regulates | 0.26 | We report that prx1 is newly discovered direct target of topk. Our results demonstrate that topk phosphorylation of prx1 at ser-32 inhibits uvb-induced apoptosis in rpmi7951 melanoma cells by increasing prx1 peroxidase activity and decreasing the intracellular accumulation of h2o2. | SIGNOR-166901 |
P0DP25 | P48454 | 2 | binding | up-regulates | 0.525 | Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain. | SIGNOR-266340 |
Q14680 | Q14680 | 2 | phosphorylation | up-regulates | 0.2 | We have mapped no less than 16 autophosphorylation sites including serines, threonines, and a tyrosine residue and show that the phosphorylation of thr167 and ser171 is required for the activation of melk.We have not yet explored the role of autophosphorylation of nine residues in the c-terminal, autoinhibitory domain (fig. 4c). An enticing hypothesis is that these autophosphorylations decrease the inhibitory potency of this domain and thereby contribute to the activation of the kinase. | SIGNOR-141030 |
P05771 | P10636-2 | 1 | phosphorylation | down-regulates activity | 0.258 | We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs. | SIGNOR-275442 |
Q13616 | Q9UBF6 | 2 | binding | up-regulates activity | 0.857 | SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34. | SIGNOR-271444 |
Q9UBR4 | P61371 | 2 | binding | up-regulates activity | 0.623 | The Lhx3-Isl1 C terminus interaction was dependent on the LIM domains of Lhx3. The combinatorial expression of the LIM homeodomain proteins Isl1, Isl2, Lhx1, and Lhx3 in subsets of developing motor neurons correlates with the future organization of these neurons into motor columns with distinct innervation targets, implying a functional role for LIM homeodomain protein combinations in the specification of neuronal identity | SIGNOR-220169 |
Q13263 | P62136 | 0 | dephosphorylation | up-regulates activity | 0.322 | PP1\u03b1 dephosphorylates KAP1 at Ser 824 . | SIGNOR-277075 |
Q7Z6Z7 | P15172 | 1 | ubiquitination | down-regulates quantity | 0.343 | Importantly, addition of WT HUWE1 to a proteolytic reaction mixture enhanced the degradation of MyoD.|Mass-spectrometry analyses show that HUWE1 can ubiquitinate MyoD at its N-terminal residue, though the preferred sites are - at least in a cell free system - the internal lysines of the protein. | SIGNOR-278694 |
P42081 | Q8TCQ1 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Among nine family members examined, forced expression of MARCH1, -2, and -8 induced a significant reduction of surface CD86 in several cell lines.|CD86 is ubiquitinated by MARCH1. | SIGNOR-278628 |
P04049 | Q9NQU5 | 0 | phosphorylation | up-regulates activity | 0.2 | PAK5 phosphorylates Raf-1 on serine 338 and stimulates Raf-1 activity. | SIGNOR-278971 |
Q86Y13 | Q96QV6 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271761 |
P62714 | P37840 | 1 | dephosphorylation | down-regulates activity | 0.276 | α-Synuclein (α-Syn) is a key protein that accumulates as hyperphosphorylated aggregates in pathologic hallmark features of Parkinson's disease (PD) and other neurodegenerative disorders. Phosphorylation of this protein at serine 129 is believed to promote its aggregation and neurotoxicity, suggesting that this post-translational modification could be a therapeutic target. Here, we demonstrate that phosphoprotein phosphatase 2A (PP2A) dephosphorylates α-Syn at serine 129 | SIGNOR-248592 |
Q14145 | Q92560 | 2 | binding | up-regulates quantity by stabilization | 0.2 | BAP1 directly binds to and deubiquitinates KEAP1. BAP1 stabilizes KEAP1 by binding to the BTB domain. | SIGNOR-268924 |
P12931 | Q07912 | 1 | phosphorylation | up-regulates activity | 0.385 | We identified two Src phosphorylation sites within the MHR (Y859, Y860). Addition of Src-phosphorylated MHR to the Ack1 KD enhanced enzymatic activity. | SIGNOR-276342 |
Q9P107 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.643 | 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-260505 |
Q13501 | P00441 | 2 | binding | down-regulates quantity by destabilization | 0.514 | This study provides a novel molecular mechanism by which mutant SOD1 can be recognized by p62 in an ubiquitin-independent fashion and targeted for the autophagy-lysosome degradation pathway. | SIGNOR-262801 |
Q92630 | Q9UHD2 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.413 | We further found that DYRK2 phosphorylated Ser527 of TBK1, which is essential for the recruitment of NLRP4 and for the E3 ubiquitin ligase DTX4 to degrade TBK1. | SIGNOR-276939 |
Q7Z434 | Q86UT6 | 2 | binding | down-regulates activity | 0.753 | Here we describe human NLRX1, a highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family member (known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS. Expression of NLRX1 results in the potent inhibition of RLH- and MAVS-mediated interferon-beta promoter activity and in the disruption of virus-induced RLH-MAVS interactions. Co-immunoprecipitation studies demonstrate that HA–NLRX1 interacts with MAVS but not with other known mitochondrial outer membrane proteins (BCL2 and BCL2L1), indicating specificity of the NLRX1–MAVS interaction. Finally, endogenous NLRX1 associates strongly with endogenous MAVS after immunoprecipitation with two different MAVS antibodies | SIGNOR-260357 |
Q05193 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.516 | Here, we show that cyclin-dependent kinase 5 (Cdk5) phosphorylates dynamin I on Ser 774 and Ser 778 in vitro, which are identical to its endogenous phosphorylation sites in vivo. Cdk5 antagonists and expression of dominant-negative Cdk5 block phosphorylation of dynamin I, but not of amphiphysin or AP180, in nerve terminals and inhibit SVE. | SIGNOR-250661 |
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